Palladium-Mediated CH Activations

Palladium-Mediated C-H Activations

DISSERTATION

Presented in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of The Ohio State University

William Howell Henderson

Graduate Program in Chemistry

The Ohio State University

2011

Dissertation Committee:

Professor James P. Stambuli, Advisor

Professor Dennis Bong

Professor Craig Forsyth

William Howell Henderson

2011

Abstract

A selective allylic oxidation of terminal alkenes using novel alkyl aryl sulfides as ligands for Pd(OAc) 2 was developed, which allows for lower catalyst loadings and significantly decreased reaction times. Reactions utilizing alkyl aryl sulfide ligands selectively provide the linear allylic acetates in yields comparable to previously reported methods. Additionally, a greener method allowing for the use of oxygen as the stoichiometric oxidant is also reported. Attempts to isolate intermediate complexes led to isolable palladium chloride complexes, but no diacetate complexes could be isolated as pure compounds. Mechanistic studies conducted allude to an acetoxypalladation mechanism rather than a mechanism containing π-allyl palladium intermediates. 1

Typically, allylic oxidations of internal alkenes either fail to provide any allylic oxidation products or provide a mixture of allylic acetate isomers. The previously mentioned methodology has led to the discovery that cis -vinylsilanes, in the absence of external ligand, undergo allylic oxidations to provide branched allylic acetate trans - vinylsilane as the sole diastereomer and regioisomer. Attempting to apply the allylic oxidations to other internal alkenes it was discovered that vinyl fluorides and alkyl enol ethers form α,β-unsaturated aldehydes in good yields requiring low loadings (1-5 mol %) of Pd(OAc) 2. Previously reported Saegusa oxidations utilize anywhere from 0.5-1 equivalent of Pd(OAc) 2 to form α,β-unsaturated aldehydes and ketones. A modification reported by Larock uses 10 mol % Pd(OAc) 2, however, DMSO is used as a solvent and ii reactions require up to 3 days to proceed to completion. This new method tolerates a broad range of functional groups. Initial mechanistic studies of this new catalyst system were undertaken.

Palladium acetate has been shown to form a novel palladacycle with tri-tert - butylphosphine through a facile room temperature C-H activation. This palladacycle is stable to reduction to Pd(0) species under typical aryl-amination conditions requiring base and amine. As a result, coordinated tri-tert -butylphosphine is easily displaced by less basic phosphines and even secondary amines. The kinetic stability of this complex indicates that it is likely a catalyst decomposition product rather than a predominant catalytic intermediate and as a result formation of this complex likely inhibits quantitative formation of active catalytic intermediates. 2

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Dedication

This document is dedicated to my family and friends.

Acknowledgments

I would like to thank all of The Stambuli Research Group members as well as other students in the department for all of their help during my graduate school career.

Dr. Nicolas Proust was a fantastic post-doc to have around the lab. He was interested in answering questions and solving problems within the group and thoroughly enjoyed talking about chemistry and ongoing projects. He was one of my favorite people to talk to about research and I am lucky to have worked with him on a couple of projects.

In addition, he may be the best editor/reviewer I have ever worked with.

Dr. Chad Eichman was an integral part of my graduate Ph.D. He was always someone I could bounce ideas off of and made lab work manageable. I spent more hours in lab with him than any other person. He is the only person that could make it through

24 h of lab with me. Honestly, he is a great friend and colleague. Also, as a senior member of our group Dr. Carla Councellor was always helpful and made joining a new group much easier.

Kamala was always willing to help me whenever I asked, and was kind enough to give me rides to my house when it was freezing outside. She has reviewed and edited every document I have produced over the last year since Nico and Chad have left. I would also like to thank Kamala, Sean, Check, Chip and Lauer for all of the discussions and help in lab as well as financial support during tough times when all I had was a v useless American Express credit card. Check and Lauer are great people to work with on projects and as bothersome as I was, Matheiu never hesitated to help me with any computer problems or read any document, no matter how busy he looked. Brenda was kind enough to make a cheesecake every year for my birthday.

With regards to friends from home, Justin Jones is the best friend I could have asked for. Though not in Columbus, he made sure to clear his schedule so that he had time to go fishing every time I visited Richmond and made an effort just to call and say hi regularly. Carrie supported me through most of my graduate career and some of the toughest times. She was an incredible girlfriend and I am grateful for every minute we spent together. Veronica is always great at giving advice and provided me with insight into life after graduate school. The help she has given me is priceless. All of my friends, including Christine, Pritesh, Chris, Jeff Brad, Ryan, Fraser, and Colin, are also great friends to have and made visiting home something to look forward to every vacation.

I appreciate the support my family has given me including my sister and brother.

Additionally, my mother and father have been extremely supportive in every endeavor that I have undertaken. If I told my mother I was going to the moon she would probably tell me he believed I could make it. I love them all.

Most importantly, I would like to thank my advisor, James Stambuli, for allowing me to learn and perform research in The Stambuli Research Group. Over my graduate career he has taught me how to approach problems, pay attention to detail, and think critically. Being one of the first students to join his group was tough, but I can honestly

vi say that it was an incredible experience. I am certain that under his instruction and with his help all of his students will be successful in their future endeavors.

Lastly, I would like to thank the other professors and staff at The Ohio State

University for their instruction, guidance, and help. Dr. Tanya Young entrusted me with maintaining the NMR facilities which was a welcome break from teaching. I would especially like to thank Professor Craig Foryth and Professor Dennis Bong for serving on my dissertation committee,

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Vita

September 10, 1984 ...... Born – Richmond, Virginia

May 2006...... B.S. Chemistry, Virginia Polytechnic

Institute and State University

August 2006 – March 2010 ...... Graduate Teaching Assistant

The Ohio State University

March 2010 to present ...... Graduate NMR Facilities Assistant

The Ohio State University

Publications

Henderson, W. H.; Alvarez, J.: Eichman, C. C.; Stambuli, J. P. “Characterization,

Reactivity and Potential Catalytic Intermediacy of a Cyclometalated Tri-tert- butylphosphine Palladium Acetate Complex” Organometallics , 2011 , 30 , 5038.

Check, C. T.; Henderson, W. H.; Vanden Eynden, M.: Stambuli, J. P. “Regio- and

Stereoselective Silyl-Directed C-H Allylic Oxidations of Olefins” J. Am. Chem. Soc.

2011 Submitted.

viii

Henderson, W. H.; Check, C. T.; Proust, N.; Stambuli, J. P. “Allylic Oxidations of

Olefins Using a Palladium Thioether Catalyst” Org. Lett. 2010 , 12 (4), 824.

Henderson, W. H.; Stambuli, J. P. “Lithium 2,2,2-Trifluoroethoxide” EROS 2009 .

Fields of Study

Major Field: Chemistry

Table of Contents

Abstract ...... ii

Dedication ...... iv

Acknowledgments ...... v

Vita ...... viii

Publications ...... viii

Fields of Study ...... ix

Table of Contents ...... x

List of Tables ...... xiii

List of Figures ...... xv

List of Schemes ...... xvii

List of Abbreviations ...... xx

Chapter 1: Introduction ...... 1

1.1 Early Reports of Allylic Oxidations ...... 1

1.2 Palladium-catalyzed Allylic Oxidations ...... 7

1.3 Later Work ...... 14

Chapter 2: Allylic Oxidations of Olefins ...... 20

2.1 Abstract ...... 20

2.2 Results and Discussion ...... 21

2.2.1 Synthesis and Reactivity of Sulfoxide and Sulfide Pincer Ligands ...... 21

2.2.2 Reactivity of Nitrogen Based Ligands ...... 27

2.2.3 Reactivity of Sulfur Ligands ...... 28

2.2.4 Reactivity and Optimization Using a Hemilabile Thioether Ligand...... 44

2.2.5 Isolation of Ligand Bound Palladium Complexes ...... 57

2.2.6 Mechanistic Work ...... 66

2.2.7 Alkyl Aryl Sulfides ...... 69

2.2.8 Heck-arylations ...... 71

2.2.9 Allylic Oxidations of cis -Vinylsilanes ...... 75

2.3 Conclusion ...... 85

2.4 Future work ...... 86

Chapter 3: Synthesis of α,β-Unsaturated Aldehydes from Alkyl Enol Ethers ...... 89

3.1 Abstract ...... 89

3.2 Background ...... 89

3.3 Results and Discussion ...... 94

3.4 Conclusion ...... 113

3.5 Future work ...... 113

Chapter 4: Characterization, Reactivity and Potential Catalytic Intermediacy of a

Cyclometalated Tri-tert -butylphosphine Palladium Acetate Complex ...... 114

4.1 Abstract ...... 114

4.2 Background ...... 114

4.3 Results and Discussion ...... 117

4.4 Conclusion ...... 129

Chapter 5: Experimental Details ...... 131

5.1 General Methods ...... 131

5.2 Chapter 2: Experimental Details...... 133

5.3 Chapter 3: Experimental Details...... 183

5.4 Chapter 4: Experimental Details...... 202

References and Notes ...... 209

Appendix A: 1H NMR and 13 C NMR for Selected Compounds ...... 216

Appendix B: X-Ray Crystallographic Information ...... 404

xii

List of Tables

Table 1.1: Mechanistic studies using a π-allyl palladium complex ...... 13

Table 2.1: Reactivity of SCS and SNS pincer ligands ...... 25

Table 2.2: Reactivity of pyridyl sulfoxides and o-xylene based bis-sulfoxide ...... 26

Table 2.3: Reactivity of SNS and SCS pincer sulfide ligands ...... 30

Table 2.4: Reactivity of commercial sulfides...... 31

Table 2.5: Reactivity of bis-sulfides ...... 34

Table 2.6: Screening of metal salts with 1,2-bis(phenylthio)ethane ...... 35

Table 2.7: Oxidant screen...... 37

Table 2.8: Acetic acid screen ...... 38

Table 2.9: Solvent screen ...... 39

Table 2.10: Lewis and Brønsted acid screen ...... 40

Table 2.11: Ligand screen of mixed sulfides ...... 45

Table 2.12: Solvent Screen with ligand 2.49 ...... 46

Table 2.13: Acid and base screen ...... 48

Table 2.14: Alkali metal salts screen ...... 49

Table 2.15: Palladium salt screen ...... 50

Table 2.16: The allylic oxidation of terminal olefins ...... 52

Table 2.17: Competitive binding of amides to palladium ...... 53 xiii

Table 2.18: Allylic oxidations using stoichiometric O 2 as an oxidant ...... 55

Table 2.19: Reactivity of the sulfide ligand and analogous sulfoxide ...... 65

Table 2.20: Reactivity of π-allyl palladium acetate dimers ...... 68

Table 2.21: Divergent reactivity of an alkyl aryl sulfide and corresponding sulfoxide .... 70

Table 2.22: Screening alkyl aryl sulfides as ligands ...... 71

Table 2.23: Optimization of Heck-arylations with BQ ...... 73

Table 2.24: Solvent screen of Heck-Arylations ...... 74

Table 2.25: Optimization of reaction conditions with cis -vinylsilanes ...... 78

Table 2.26: Screening of silyl groups ...... 79

Table 2.27: Substrate screen using cis -vinylsilanes ...... 81

Table 3.1: Formation of α,β-unsaturated aldehydes from alkyl enol ethers...... 93

Table 3.2: Optimization of conditions using vinyl fluorides ...... 97

Table 3.3: Optimization of conditions using an alkyl enol ether ...... 100

Table 3.4: Substrate screen in AcOH…………………………………………...………101

Table 3.5: Solvent screen with an alkyl enol ether………………………………..……102

Table 3.6: Substrate screen of alkyl enol ethers ...... 104

Table 3.7: Substrate screen of alkyl enol ethers usng O 2 ...... 106

Table 3.8: Formation of cyclohexenone from alkyl enol ethers ...... 108

Table 4.1: Aryl aminations with complex 4.1 , complex 4.2 , and Pd(P tBu 3)2 ...... 122

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List of Figures

Figure 1.1: Products commonly formed in allylic oxidation reactions ...... 2

Figure 1.2: Mechanism for copper-catalyzed allylic oxidations ...... 4

Figure 1.3: Acetoxypalladation mechanism for allylic oxidations ...... 7

Figure 1.4: Mechanistic studies of allylic oxidations of cyclohexene ...... 10

Figure 1.5: Ligand controlled regioselectivity ...... 12

Figure 1.6: Proposed catalytic cycle using (vinylsulfinyl)benzene...... 14

Figure 1.7: Intramolecular allylic oxidations of alkenes with Pd(OAc) 2 ...... 18

Figure 1.8: Observation and isolation of palladium complexes ...... 19

Figure 2.1: Synthesis of SCS pincer ligands ...... 22

Figure 2.2: Synthesis of SNS pincer ligands ...... 23

Figure 2.3: Nitrogen based ligands for allylic oxidations ...... 28

Figure 2.4: Binding strength of different sulfur based ligands ...... 29

Figure 2.5: Conversion of 1-dodecene using 1,2-bis(phenylthio)ethane and Pd(OAc)2...42

Figure 2.6: Reactivity of complex 2.46 ...... 43

Figure 2.7: Formation of dodec-1-en-2-yl acetate with a 1:1 and 2:1 ligand to Pd(OAc) 2 ratio….…………………………………………………………………………………...47

Figure 2.8: 2.49 in AcOD d 4 ...... 58

Figure 2.9: 2.49 with Pd(OAc) 2 in AcOD d 4 ...... 58 xv

Figure 2.10: 2.49 with Pd(OAc) 2 and BQ in AcOD d 4 ...... 59

Figure 2.11: X-Ray crystal structure of the actual dichloride complex 2.82 ...... 62

Figure 2.12: Attempts to form diacetate complexes ...... 63

Figure 2.13: Reactivity of sulfide ligated palladium complexes ...... 64

Figure 2.14: Entering a proposed catalytic cycle from complex 2.90 ...... 68

Figure 2.15: Allylic oxidations of disubstituted alkenes ...... 75

Figure 2.16: Synthesis of ( E) and ( Z) vinylsilanes ...... 76

Figure 2.17: Allylic oxidations of vinylsilanes ...... 77

Figure 2.18: Proposed mechanism for allylic oxidations of vinylsilanes ...... 84

Figure 3.1: Mechanism of a Saegusa Oxidation ...... 91

Figure 3.2: Alternative syntheses of enals ...... 94

Figure 3.3: Formation of an enal from a vinyl fluoride ...... 96

Figure 3.4: Formation of α,β-unsaturated aldehyde over time…………………...…….105

Figure 3.5: Substrates that perform poorly under optimized conditions ...... 107

Figure 3.6: Possbile mechanistic pathways for enal formation from enol ethers ...... 110

Figure 3.7: KIE of α,β-unsaturated aldehydes over time…………………...…….…….112

Figure 4.1: 31 P NMR of complex 4.1 at a) 33 °C, b) 16 °C, c) 6 °C, d) -14 °C ...... 119

Figure 4.2: X-ray crystal structure of complex 4.1 ...... 120

Figure 4.3: Reduction of complex 4.1 using NaO tBu and HNBu 2 ...... 125

Figure 4.4: Displacement of P tBu 3 with morpholine, PPh 3, and dppe ...... 126

Figure 4.5: Direct synthesis of complexes 4.5 and 4.6 from Pd(OAc) 2 ...... 127

xvi

List of Schemes

Scheme 1.1: Selenium dioxide mediated allylic oxidation ...... 2

Scheme 1.2: Catalyic selenium dioxide-mediated allylic oxidation ...... 3

Scheme 1.3: Copper-catalyzed allylic oxidation of 1-octene with tert -butyl perbenzoate . 3

Scheme 1.4: Copper-catalyzed allylic oxidation using tert -butyl peracetate ...... 4

Scheme 1.5: Allylic oxidations using CrO 3-(pyridine) 2 ...... 5

Scheme 1.6: Allylic oxidations using stoichiometric Hg(OAc) 2 ...... 5

Scheme 1.7: Mechanism of Hg(OAc) 2 mediated allylic oxidations ...... 6

Scheme 1.8: Allylic oxidations using stoichiometric Pd(OAc) 2 ...... 6

Scheme 1.9: Catalytic Pd(OCOCF 3)2 mediated allylic oxidations ...... 8

Scheme 1.10: Allylic oxidations of cyclic alkenes ...... 9

Scheme 1.11: Oxygen as a stoichiometric oxidant ...... 9

Scheme 1.12: Decomposition of bisulfoxide 1.37 to 1.38 ...... 11

Scheme 1.13: 2,2’-Bipyrimidine as a ligand for allylic oxidations ...... 15

Scheme 1.14: Allylic oxidations using LiOH•H 2O and Pd(OAc) 2...... 16

Scheme 1.15: Allylic oxidations using 4,5-diazafluorenone...... 17

Scheme 2.1: Allylic oxidations of 1-dodecene...... 23

Scheme 2.2: 1,2-bis(phenylthio)ethane as a ligand for allylic oxidations ...... 32

Scheme 2.3: Synthesis of bis-sulfides ...... 32 xvii

Scheme 2.4: Isomerization studies using 1,2-bis(phenylthio)ethane ...... 41

Scheme 2.5: Synthesis of 1,2-bis(phenylthio)ethane ligated palladium complex...... 43

Scheme 2.6: Wacker oxidation of 2-allylphenol ...... 54

Scheme 2.7: Isomerization experiment with phenyl(2-(p-tolyloxy)ethyl)sulfane ...... 57

Scheme 2.8: Attempted synthesis of a sulfide ligated palladium diacetate complex ...... 60

Scheme 2.9: Synthesis of a proposed palladium dichloride complex ...... 61

Scheme 2.10: Previously reported palladium-mediated oxidation of sulfides ...... 64

Scheme 2.11: An alkyl aryl sulfide as a ligand ...... 69

Scheme 2.12: Heck-arylation with 1,3,5-trimethoxybenzene ...... 72

Scheme 2.13: Allylic oxidations of vinylsilanes using BAIB as an oxidant...... 82

Scheme 2.14: Intramolecular etherifications of vinylsilanes ...... 82

Scheme 2.15: Possible rearrangement of linear allylic acetates ...... 85

Scheme 3.1: Larock’s modification of Saegusa Oxidations ...... 92

Scheme 3.2: Formation of enals using PdCl 2 and H 2O ...... 93

Scheme 3.3: Synthesis of vinyl fluorides ...... 95

Scheme 3.4: Attempted enal formation from vinyl halides and boronic acids ...... 98

Scheme 3.5: Synthesis of (methoxymethyl)triphenylphosphonium chloride ...... 98

Scheme 3.6: Synthesis of methyl enol ethers ...... 99

Scheme 3.7: Conversion of methyl enol ethers to enals using Pd(OAc) 2 ...... 99

Scheme 3.8: O18 incorporation into enals...... 111

Scheme 4.1: Formation of complex 4.1 from P tBu 3 and Pd(OAc) 2 ...... 118

Scheme 4.2: Equilibrium between complex 4.1 and complex 4.2 ...... 118

xviii

Scheme 4.3: Reduction of complex 4.1 to Pd(P tBu 3)2 ...... 121

Scheme 4.4: Formation of 4.8 ...... 128

xix

List of Abbreviations

α alpha

Ǻ angstrom

β beta

δ chemical shift in parts per million

π pi

µ micro

°C degrees Celsius

1H NMR proton nucliear magnetic resonance

13 C NMR carbon 13 nuclear magnetic resonance

31 P NMR phosphorus 31 nuclear magnetic resonance acac acetoacetate atm atmosphere(s)

Ac acetyl

AcOH acetic acid aq aqueous

BAIB bis-acetoxy iodobenzene

Bn benzyl xx

BPM 2,2’-bipyrimidine

BQ benzoquinone cat catalytic

COD cyclooctadiene

Cp cyclopentadienyl d doublet; days dd doublet of doublets dt doublet of triplets dba dibenzylideneacetone

DCE 1,2-dichloroethane

DCM dichloromethane

DDQ 2,3-dichloro-5,6-dicyano-1,4-benzoquinone

DHQ dihydroquinone

DIBAL diisobutylaluminum hydride

DMAP N,N-dimethylaminopyridine

DME 1,2-dimethoxyethane

DMF N,N-dimethylformamide

DMSO dimethylsulfoxide dppe diphenylphosphinoethane

E entgenen

Et ethyl

Et 2O diethyl ether

xxi equiv equivalents g gram(s)

GC gas chromatography h hour(s)

Hz hertz iPr isopropyl

IR infrared

J coupling constant in Hz

KIE kinetic isotope effect

L liter m meta m milli

M molarity; mega

Me methyl

MeCN acetonitrile

MeOH methanol min minute(s) mol mole(s)

MS mass spectrometry; molecular sieves m/z mass to charge ratio nBu normal butyl

Nu nucleophile

xxii o ortho

OAc acetate

OBz benzoate p para

Pd(OAc) 2 palladium acetate

Pd(TFA) 2 palladium trifluoroacetate

Ph phenyl

PhMe toluene

PMB para -methoxybenzyl ppm parts per million p-TSA para -toluenesulfonic acid py pyridine q quartet s singlet t triplet

TBDPS tert -butyldiphenylsilyl

TBS tert -butyldimethylsilyl tBu tert -butyl

THF tetrahydrofuran

TFA trifluoroacetate

TLC thin layer chromatograhy

UV ultraviolet

xxiii

Z zusammen

xxiv

Chapter 1: Introduction

1.1 Early Reports of Allylic Oxidations

The purpose of this introduction is to provide background for the subsequent chapters focusing on advancements made in palladium-catalyzed allylic oxidations.

Allylic oxidation reactions rarely form the desired product exclusively and a number of undesired regioisomers and side products are usually prevalent. Typically, regioisomer issues stem from the fact that formation of products can occur by substitution at the sp 3 position or substitution with transposition of the double bond. When π-allyl intermediates are involved regioisomers may be formed from reductive elimination/substitution of either C1 or C3 of the π-allyl species. When terminal alkenes are used, these products are referred to as branched ( 1.2 ) and linear products ( 1.3 ).

Additionally, transition metals can act as Lewis acids, coordinating to and promoting addition across the alkene followed by β-hydride elimination to give Wacker-type products rather than allylic oxidation products. 3 If water is the nucleophile, the resulting enol ether tautomerizes to form the corresponding ketone, 1.5 (Figure 1.1).

Figure 1.1: Products commonly formed in allylic oxidation reactions

The first reported allylic oxidations of alkenes were selenium dioxide-mediated and initially stoichiometric quantities of selenium dioxide were used to prepare allylic alcohols (Scheme 1.1). 4 The use of stoichiometric selenium is undesirable because while selenium is an essential trace element, it is toxic in larger doses. 5

Scheme 1.1: Selenium dioxide mediated allylic oxidation

Advances eventually led to reaction conditions in which peroxides were used to reoxidize catalytic amounts of selenium dioxide (Scheme 1.2). 6 Typically, selenium dioxide-mediated allylic oxidations oxidize α to the more substituted end of the double

7 bond with a preference for CH 2 > CH 3 > CH without transposition of the alkene. While reaction conditions using selenium are mild, overoxidation leading to α,β-unsaturated 2 aldehydes and ketones as well as epoxidation of alkenes can prove detrimental to yields. 7b

Additionally, the reaction is substrate controlled leaving no way to externally control the regioselectivity of the reaction.

Scheme 1.2: Catalyic selenium dioxide-mediated allylic oxidation

In the late 1950s, copper (II) salts were shown to catalyze the formation of branched allylic benzoates using peracids under an inert atmosphere. 8 In the initial report, tert - butyl perbenzoate was used to oxidize 1-octene ( 1.10 ) to a mixture of oct-1-en-3-yl benzoate ( 1.11 ) and ( E)-oct-2-en-1-yl benzoate ( 1.12 ) (Scheme 1.3). 8a

Scheme 1.3: Copper-catalyzed allylic oxidation of 1-octene with tert -butyl perbenzoate

This method was later expanded to form allylic acetates ( 1.13 and 1.14 ) using tert -butyl peracetate and various copper salts (Scheme 1.4). 8b

Scheme 1.4: Copper-catalyzed allylic oxidation using tert -butyl peracetate

The reaction was believed to proceed through a radical mechanism where the copper salt is recycled through a Cu(I)/Cu(II) pathway. The tert -butoxy radicals facilitate the formation of allylic radicals and tert -butanol, which can be converted to the allylic acetate via copper (Figure 1.2).

Figure 1.2: Mechanism for copper-catalyzed allylic oxidations

The reactivity of peroxides and peracids limits functional group compatibility.

Additionally, the use of peracids provides a major drawback upon scale-up due to the shock-sensitive and spontaneous explosive nature of peroxides. 9

Seminal reports of chromium mediated allylic oxidations required super- stoichiometric amounts of chromium trioxide-pyridine complex to oxidize the allylic position of cyclic alkenes to α, β-unsaturated ketones. 10 An evident drawback of these

4 reactions is the high toxicity of chromium salts that are used in excess (often greater than

10 equivalents) to complete the transformation (Scheme 1.5).

Scheme 1.5: Allylic oxidations using CrO 3-(pyridine) 2

In 1949, Treibs et al. reported mercury acetate-mediated allylic acetoxylations of olefins using stoichiometric amounts of mercuric acetate (Scheme 1.6). 11

Scheme 1.6: Allylic oxidations using stoichiometric Hg(OAc) 2

Rappoport and co-workers studied the mechanism of these reactions and concluded that the reactions likely proceed through an ή 1-allyl mercury intermediate, 1.17 , via

12 elimination of acetic acid from Hg(OAc) 2 (Scheme 1.7).

Scheme 1.7: Mechanism of Hg(OAc) 2 mediated allylic oxidations

Shortly thereafter, Rappoport reported allylic acetoxylations of olefins using

13 Pd(OAc) 2. Using Pd(OAc) 2 in neat acetic acid produced primarily the Wacker-type vinylic substitution product along with minor amounts of the linear allylic acetate ( 1.20 ); however, when DMSO was used as a co-solvent the linear allylic acetate ( 1.20 ) was the major product, formed in a 73% yield (Scheme 1.8).

Scheme 1.8: Allylic oxidations using stoichiometric Pd(OAc) 2

Contrary to prior studies with mercuric acetate, Rappoport and coworkers believed that Pd(OAc) 2 mediated reactions proceeded via an acetoxypalladation mechanism rather than π-allyl palladium intermediates to form the linear allylic acetate (Figure 1.3). 6

R R Pd(OAc)2

Pd(OAc)2 1.21

H -hydride R AcO R elimination AcO PdOAc 1.20 1.22

Figure 1.3: Acetoxypalladation mechanism for allylic oxidations

Mercury salts are toxic 14 and palladium salts are costly, therefore, the need for a catalytic transition metal mediated protocol lacking explosive peroxides or toxic metals was evident.

1.2 Palladium-catalyzed Allylic Oxidations

In 1984, McMurry reported the first palladium-catalyzed allylic acetoxylation of acyclic alkenes using 2 equivalents of benzoquinone, as a palladium reoxidant, and

15 Pd(TFA) 2 in acetic acid. Various ligands including triphenylphosphine, diethylmalonate, and an aryl ether were tested. Under these conditions, reactions suffered from generally long times, high temperatures, and low selectivities of branched and linear allylic acetates, but offered a vast improvement over unselective stoichiometric

7 alternatives. McMurry proposed that this reaction proceeded through a π-allyl palladium intermediate, 1.26 , since Trost et al. had previously reported 16 the isolation of π-allyl palladium complexes prepared from Pd(OCOCF 3)2 and alkenes (Scheme 1.9).

Pd(OCOCF3)2 (5 mol %), BQ, Ligand, AcOH, temp. R R R H OAc OAc 1.23 1.24 1.25 O R = L B

R Pd 1.26 Ligand Temp Time Products (L:B) Yield

No ligand 80 °C 96 h 1:1.5 56%

PPh3 60 °C 48 h 1:1.1 67% O

20 °C 48 h 1.9:1 85% O

Scheme 1.9: Catalytic Pd(OCOCF 3)2 mediated allylic oxidations

Ǻkermark and Bäckvall published a series of papers on palladium catalyzed allylic oxidations of cyclic alkenes. 17 The oxidation of symmetrical cyclic alkenes, such as cyclohexene, gives only one allylic acetate product. Additionally, it was found that when cyclic alkenes are used with catalytic Pd(OAc) 2, no additional ligand is necessary to form cyclohex-2-en-1-yl acetate in good yield. Reaction times for various cyclic

8 alkenes ranged from 16 to 300 h and, under these conditions, linear alkenes provided a

1:1 (L:B) mixture of allylic acetate regioisomers. 17f Substrates containing functional groups or substituted cyclic alkenes gave low yields or were unreactive (Scheme 1.10).

Scheme 1.10: Allylic oxidations of cyclic alkenes

Initially, 10 mol % of benzoquinone was used with 2 equivalents of MnO 2 to reoxidize palladium; however, a later report details the use of oxygen as a stoichiometric oxidant. When oxygen was used as an oxidant, 5 mol % Cu(OAc) 2 and 10 mol %

17c dihydroquinone were required in place of benzoquinone and MnO 2 (Scheme 1.11).

Scheme 1.11: Oxygen as a stoichiometric oxidant

Mechanisic studies of allylic acetoxylations using palladium by Ǻkerman were inconclusive but indicated that both acetoxypalladation and π-allyl palladium

9 mechanisms may be operating concurrently and that small changes in the substrate may cause one mechanism to be favored over the other. 17f

Bäckvall further probed the mechanism by preparing 1,2-dideuterocyclohexane

(1.31 , 55-70% D) and submitting it to reported reaction conditions from previous work (5 mol % Pd(OAc) 2 and 2 equivalents of benzoquinone in acetic acid at 25 °C). Depending on the functioning mechanism a different ratio of products was expected. If a π-allyl palladium mechanism proceeding through 1.33 was operating a 1:1 ( 1.34:1.35) ratio was expected while an acetoxypalladation mechanism proceeding through 1.36 would give a

2.70:1 ( 1.34 :1.35 ) ratio of products. Bäckvall observed a 1:1 ( 1.34 :1.35 ) ratio of products indicating that π-allyl palladium intermediate 1.33 was likely responsible for the allylic oxidation of cyclohexene (Figure 1.4). 17a

Figure 1.4: Mechanistic studies of allylic oxidations of cyclohexene

White and co-workers reported selective allylic oxidations of terminal olefins using

10 mol % Pd(OAc) 2, ligand, and benzoquinone in a dioxane/AcOH solvent mixture at 40

°C. 18 By changing the ligand from DMSO to bidentate ligand, 1,2- 10 bis(phenylmethanesulfinyl)ethane ( 1.37 ) or (vinylsulfinyl)benzene ( 1.38 ), the regiochemical outcome of the reaction could be altered to afford either the linear or branched allylic acetate, respectively. White also showed that under the reaction conditions 1,2-bis(phenylmethanesulfinyl)ethane ( 1.37 ), decomposes to

(vinylsulfinyl)benzene ( 1.38 ) (Scheme 1.12).

Scheme 1.12: Decomposition of bisulfoxide 1.37 to 1.38

Directly using (vinylsulfinyl)benzene as a ligand gave higher branched to linear ratios ranging from 1:16 to 1:46 (L:B) with yields from 56-83%. Using DMSO as a ligand linear to branched ratios (L:B) ratios were typically around 11:1 and yields were modest ranging from 50-65% (Figure 1.5). More hindered quinones such as 1,4-naphthoquinone or duroquinone were found to be ineffective at catalyzing these allylic oxidations.

Figure 1.5: Ligand controlled regioselectivity

Mechanistic studies using (vinylsulfinyl)benzene to form the branched allylic acetates were performed by stirring the ligand with Pd(OAc) 2 and 1-decene in CDCl 3. A

π-allyl palladium intermediate was observed by 1H NMR spectroscopy. In subsequent studies the observed π-allyl palladium acetate dimer, 1.39 , was synthesized using alternate methods and submitted to various reaction conditions. The complex ( 1.39 ) was unreactive in dioxane and acetic acid without any additives. When only ligand was added to the palladium complex in acetic acid, no products resulting from reductive elimination to form allylic acetates were observed. Interestingly, if the π-allyl palladium complex was stirred in AcOH with 20 equivalents of benzoquinone, a 58% yield of a

1:32 (L:B) mixture of allylic acetates was seen and when ligand and benzoquinone were added a similar yield and L:B ratio was observed (Table 1.1).

Table 1.1: Mechanistic studies using a π-allyl palladium complex

Based on the above results a catalytic cycle was proposed in which the ligand was only coordinated to palladium during C-H activation to form a π-allyl palladium intermediate

(1.43 ). It was determined that benzoquinone was necessary not only to reoxidize the palladium species from Pd(0) to Pd(II), completing the catalytic cycle, but also to promote reductive elimination of the π-allyl and acetate ligands (Figure 1.6). 18a

Figure 1.6: Proposed catalytic cycle using (vinylsulfinyl)benzene

Prior to this report, no catalytic protocols using mild conditions to selectively form branched or linear allylic acetates existed. The ability to alter the outcome of the reaction by changing the ligand provided an important advancement in this field; however, there was still room for improvement. Low catalyst turnover (<10), long reaction times and super-stoichiometric amounts of oxidant are disadvantages, limiting the usefulness of this methodology.

1.3 Later Work

Additional reports of allylic oxidations by Bercaw, 19 Le Bras, 20 Stahl, 21 and

Sheppard 22 were published contemporaneously with studies in our lab. Bercaw showed that a pre-formed catalyst created from Pd(OAc) 2 and commercially available nitrogen ligands such as pyridine, 1,10-phenanthroline, and 2,2’-bipyrimidine at 70 °C in acetic acid provide linear allylic acetates. Yields ranged from 45-78% using 2,2’-bipyrimidine but substrates contained limited functionality with most substrates bearing simple hydrocarbon motifs (Scheme 1.13). 19

Scheme 1.13: 2,2’-Bipyrimidine as a ligand for allylic oxidations

An ensuing mechanistic study proposed that the reaction proceeded through π- allyl palladium intermediates and that based on the lack of a kinetic isotope effect, coordination of the olefin or reoxidation of palladium was the rate limiting step.

Le Bras and coworkers discovered that addition of 2 equivalents of LiOH•H 2O to reactions employing 10 mol % Pd(OAc) 2 and 2 equivalents of BQ in EtCO 2H proceeded with complete conversion to form the allylic oxidation product of allyl benzene in 24 h.

When LiOH•H 2O was omitted from the reaction conditions lower conversions and much lower yields were noted. Reactions with allylbenzene were highly selective for the ( E) isomer of the linear allylic oxidation product with 99:1 (L:B) ratios and 21:1 ( E:Z) ratios.

LiOH•H 2O was unique as a base for this reaction, and when other alkali metal bases were

15 used, yields were lower and more inconsistent. This methodology is well suited for allylbenzenes ( 1.47 ) and homoallylic alcohols ( 1.49 ), but when other substrates such as

1-decene were submitted to the reaction conditions, selectivity decreased dramatically to

8:1 (L:B) and 7:1 ( E:Z). Only when iPrCOOH and MeCN were used as co-solvents could selectivities be increased to 17:1 (L:B) and 19:1 ( E:Z) without a significant decrease in conversion (Scheme 1.14). 20

Scheme 1.14: Allylic oxidations using LiOH•H 2O and Pd(OAc) 2.

Stahl and coworkers reported that Pd(OAc) 2 and 4,5-diazafluorenone promote the allylic acetoxylation of terminal olefins to form linear allylic acetates. This report proposes that the 4,5-diazafluorenone ligand not only promotes C-H insertion into an allylic C-H bond but also promotes reductive elimination of the π-allyl intermediate and acetate ligands by forming a Pd(IV) complex, 1.52 , from a Pd(II) complex ( 1.51 ). This circumvents the need for benzoquinone as a reoxidant completely and 1 atmosphere of O 2 can be used as the stoichiometric oxidant. Reactions are run in dioxane, and require 16 equiv AcOH with 20 mol % NaOAc at 60 °C for complete consumption of starting

16 material. These conditions show excellent selectivity for the linear allylic acetates with

E:Z ratios ranging from 6:1 to 36:1 and give moderate yields of 52-84%. A broad range of functionalities are tolerated including tert -butyldimethylsilylethers, methylesters, amides, carbamates, and ketals (Scheme 1.15). 21

Scheme 1.15: Allylic oxidations using 4,5-diazafluorenone

More recently, a report has been published that outlines the reaction of dithianes with Pd(OAc) 2 in intramolecular allylic acetoxylations. If the analogous ketone, 1.55 , was submitted to the reaction conditions only slow oxidation to multiple products occurred. Moreover, external alkene ( 1.57 ) added to the reaction mixture failed to react

(Figure 1.7). Typically, sulfur is thought to poison metal catalysts; however, these results are indicative of sulfur promoting catalyst reactivity. 22

Figure 1.7: Intramolecular allylic oxidations of alkenes with Pd(OAc) 2

Observation of π-allyl palladium intermediate 1.60 when stoichiometric palladium acetate was employed and isolation of palladium σ-complex 1.62 supports the notion that a palladium-sulfide complex actively catalyzes these reactions (Figure 1.8). Furthermore, these results reinforce our previously reported work in this area. 1

Figure 1.8: Observation and isolation of palladium complexes

Despite the advancements made over the past few decades, there remained room for improvement. Our initial interest in this field stemmed from the fact that our group had previously synthesized a library of sulfoxide and sulfide pincer ligands for use in iridium catalysis. We postulated that these ligands might be able to improve selectivity, reaction times, or catalyst loadings of allylic oxidations where other ligands had failed.

Chapter 2: Allylic Oxidations of Olefins

2.1 Abstract

As described in the preceding chapter, research over the last few decades has led to a number of advancements in the field of allylic oxidations. 1-15 Despite these advancements, there remains a number of limitations concerning palladium-catalyzed allylic oxidations, including high catalyst loadings, low regioselectivity between linear and branched allylic acetates, formation of side products, long reaction times, and super- stoichiometric amounts of oxidant. Furthermore, internal olefins are usually unreactive or give a complex mixture of products.

Our research in this field has led to a number of significant advancements while exploring sulfoxides and sulfides as ligands for this transformation. New sulfur based ligands for palladium allow for 5 mol % Pd(OAc) 2 loadings in allylic oxidations, lower than previous methods to selectively form linear allylic acetates. In addition, sulfur ligands provide a considerable rate enhancement compared to previous systems.

Reactions utilizing sulfide based ligands are complete within 14-21 h compared to other

20 reports requiring 2-3 days. Moreover, using alkyl aryl sulfide ligands allows for alternative reaction conditions that employ O 2 as the stoichiometric oxidant. Yields and regioselectivities using our newly discovered sulfur ligands are comparable to previous reports of allylic oxidations. This methodology has been extended to cis -vinylsilanes.

The cis -vinylsilanes are selectively converted to branched allylic acetates containing a trans-olefin.

Preliminary reactivity studies employing π-allyl palladium acetate dimers under our reaction conditions do not provide results similar to those obtained in the catalytic reaction, which may suggest an alternative reaction pathway. While mechanistic studies were inconclusive, many discoveries were made that lend insight into details regarding palladium-catalyzed allylic oxidations. Of equal importance is the discovery of a novel sulfide scaffold for ligands in palladium catalysis. Sulfur is typically considered a catalyst poison and only a few examples of sulfides acting as ligands in catalysis exist. 23

2.2 Results and Discussion

2.2.1 Synthesis and Reactivity of Sulfoxide and Sulfide Pincer Ligands

Our study of allylic acetoxylations commenced with a variety of sulfoxide pincer ligands. These ligands have the ability to bind to palladium as a tridentate ligand through coordination to nitrogen as with 2,6-disubstituted pyridines or a C-H insertion in the case of disubstituted m-xylene derived ligands. The electronic nature of these sulfoxide

21 ligands is similar to previously reported systems. However, we postulated that the rigid backbone of the aryl rings and tighter binding to palladium might increase selectivities and yields. Additionally, while White et al. demonstrated that bis-sulfoxides containing an ethylene backbone can decompose to vinyl sulfoxides under their reported reaction conditions, pincer type ligands would be unable to undergo this decomposition to the vinyl sulfoxide. 18a

Bis-sulfides derived from 1,3-bis(bromomethyl)benzene and 2,6- bis(chloromethyl)pyridine are easily accessed from previously reported chemistry and it was possible to quickly and efficiently build a diverse library of SCS and SNS bis- sulfoxide pincer ligands. 24 The synthesis of SCS ligands was easily accomplished by thiolate displacement of bromide from 1,2-bis(bromomethyl)benzene. The resulting bis- sulfides were oxidized by either sodium periodate or hydrogen peroxide in methanol.

Most bis-sulfide syntheses and oxidations proceeded in high yields (Figure 2.1).

Figure 2.1: Synthesis of SCS pincer ligands

An analogous route was employed for the synthesis of SNS based pincer ligands starting from 2,6-bis(chloromethyl)pyridine (Figure 2.2).

Figure 2.2: Synthesis of SNS pincer ligands

A ligand screen was initiated with 1-dodecene as the substrate using slightly modified reported reaction conditions (10 mol % Pd(OAc) 2, 2 equivalents of benzoquinone, 4 equivalents of AcOH in 0.3 or 0.6 mL of dioxane at 40 °C). 1-

Dodecene was chosen as an ideal test substrate because of prior examples found in the literature and lack of functional groups that could adversely affect the reaction outcome.

After 48 h, the reactions were evaluated by GC analysis and peak areas of the linear allylic acetate ( L), vinyl acetate ( V), and branched allylic acetate ( B) were compared to any remaining 1-dodecene ( 2.7 ).

Scheme 2.1: Allylic oxidations of 1-dodecene

Pincer ligands with the SCS backbone (2.8 and 2.9 ) showed primarily a mixture of branched allylic and vinyl acetates with only a small amount of the linear allylic 23 acetate observed (Table 2.1, entries 1-3). Overall, conversions were low, but when reactions were run in 0.3 mL dioxane (0.67 M) higher conversions were observed than when 0.6 mL of dioxane (0.33 M) was used (entries 1-3). Interestingly, pincer ligands with a SNS backbone (2.10 , 2.11, and 2.12 ) showed good selectivity for the branched allylic acetate with only very minor amounts of the vinyl acetate seen (entries 4-7). No linear allylic acetate products were observed by GC analysis. Conversions were considerably higher than for the SCS based pincer ligands ( 2.8 and 2.9) and when 0.3 mL dioxane was used with SNS ligands conversions as high as 69% were noticed (entry 4).

The divergence in selectivity between SCS and SNS based pincer ligands remains unexplained, although it is possible that the pyridine component of SNS ligands binds more tightly to the palladium center, remaining bound to palladium more than SCS ligands. An unselective background reaction exists in which Pd(OAc)2, BQ, and AcOH are able to slowly oxidize terminal alkenes to allylic acetates, and if the SNS ligand remains bound to palladium for a higher percentage of time this could explain the increased selectivity in formation of products.

Table 2.1: Reactivity of SCS and SNS pincer ligands

Pd(OAc)2 (10 mol %), Ligand (10 mol %) BQ (2 equiv), AcOH (4 equiv) dioxane, 40 °C, 48 h

8 OAc 8 2.7 L

Entry Ligand Dioxane Conversiona L:B:V

O 1 S S 0.3 mL 43% 0:1:2 Me Me 2.8

2 O O 0.3 mL 41% 1:8:10 S S 3 Bn Bn 0.6 mL 22% 0:1:2 2.9

O O 4 0.3 mL 69% 0:11:1 S S 5 Bn N Bn 0.6 mL 34% 0:6:1 2.10

O O 6 S S 0.3 mL 20% 0:7:1 Me N Me 2.11

O O 7 S S 0.6 mL 36% 0:9:1 Et N Et 2.12

a) Conversions determined by GC analysis.

In addition to SNS and SCS pincer ligands, a bidentate sulfoxide o-xylene analog containing an aromatic backbone and pyridyl sulfoxide analogs were also screened. In general, pyridyl sulfoxide based ligands showed selectivity for the branched allylic acetate, supporting the above hypothesis that the tighter binding pyridyl functionality in addition to a weakly binding sulfoxide may help to increase selectivity (entries 1-6).

While the pyridyl sulfoxide ligands gave good selectivities, they suffered from low

25 conversions. At lower concentrations, the methyl sulfoxide, 2.14 , performed better than the ethyl and benzyl sulfoxides ( 2.13 and 2.15) giving 41% conversion with a 1:18 (L:B) ratio (entry 4). The o-xylene derived bis-sulfoxide ( 2.16 ) showed similar conversions and selectivities as the aforementioned analogous m-xylene derived bis-sulfoxide ( 2.9 ), giving a higher conversion of 1-dodecene, 46%, at a higher concentration (entry 7).

Table2.2: Reactivity of pyridyl sulfoxides and o-xylene based bis-sulfoxide

While pincer based ligands in conjunction with Pd(OAc) 2 were modestly effective in converting 1-dodecene to allylic acetates, the low conversions and selectivites left much to be desired. Nonetheless, valuable information was gained from these results.

The ability of pyridyl containing sulfoxides to selectively form branched allylic acetates lent insight into requirements for selectivity in these reactions.

2.2.2 Reactivity of Nitrogen Based Ligands

Based on the previous results, it was thought that nitrogen based ligands may be effective at facilitating palladium mediated allylic oxidations. No conversion of 1- dodecene was observed when nitrogen based ligands such as 1,10-phenanthroline, 2,2’- bipyridine and imines were submitted to the reaction conditions using Pd(OAc) 2, BQ, and

AcOH in dioxane at 40 °C. Bercaw would later report the use of 2,2’-bipyrazine as a ligand for selective formation of linear allylic acetates (Pd(OAc) 2, BQ, bipyrazine,

AcOH, 80 °C). 19 Additional attempts to form allylic oxidation products employing these ligands with Pd(OAc) 2 and BQ in dioxane with AcOH at 40 °C showed no conversion of

1-dodecene to any allylic oxidation products.

Figure 2.3: Nitrogen based ligands for allylic oxidations

2.2.3 Reactivity of Sulfur Ligands

After examining the literature and utilizing knowledge gained from previous results, we postulated that sulfides might prove to be superior ligands to sulfoxide based ligands. While at first glance sulfides may seem similar to sulfoxides, their reactivities are quite different. Sulfoxides are used extensively in catalysis as weakly bound electron-deficient ligands. In contrast, sulfides are usually thought of as catalyst poisons and rarely used as ligands for catalysis, with only very few examples found in the literature. We thought the ability of sulfides to bind strongly to a metal center might help to increase the selectivity of allylic oxidations, despite the perception that sulfides are attributed with poisoning metal catalysts. 23

Figure 2.4: Binding strength of different sulfur based ligands

Studies were initiated with sulfide precursors from previously mentioned sulfoxide ligands. In contrast to previous results, whereas pyridyl sulfoxides performed better than xylene based bis-sulfoxides, the pyridyl sulfides ( 2.24-2.27) gave no conversion to any vinylic or allylic acetate products (entries 4-8). The xylene based sulfides showed selectivity for the linear allylic acetate product, however, conversions were extremely low (entries 1-3 and 9-10). m-Xylene based bis-sulfides gave only trace amounts of allylic oxidation products for methyl ( 2.21 ), ethyl ( 2.22 ), and benzyl ( 2.23 ) derivatives. o-Xylene based ligands gave 7% conversion for the benzyl derivative ( 2.29 ) and the ethyl derivative ( 2.29 ), the best ligand, reached only 10% conversion (entry 9).

The lack of reactivity from aromatic nitrogen sulfide ligands mirrors the results previously described using nitrogen ligands such as 2,2’-bipyridine. The pyridine and sulfide moieties likely bind too strongly to palladium, saturating the metal center and preventing coordination of the terminal olefin.

Table 2.3: Reactivity of SNS and SCS pincer sulfide ligands

Commercially available symmetrical sulfides were also tested (Table 2.4).

Diethyl sulfide and diphenyl sulfide were used in a 1:1 and 2:1 ligand to Pd(OAc) 2 ratio.

When 10 mol % diethyl sulfide and diphenyl sulfide were used 23% and 60% conversion

30 was achieved, respectively, with the vinylic acetate and linear allylic acetate as the major products (entries 1 and 3). Only 6% conversion was seen when diethyl sulfide was increased to 20 mol % and 49% conversion seen when 20 mol % diphenyl sulfide was used. The reactions were not appreciably selective with the major products again being the vinylic acetate and linear allylic acetate (entries 2 and 4). Diallyl sulfide, used in a

1:1 ratio of ligand to Pd(OAc) 2, gave a better conversion of 75% after 111 h (entry 5).

Unfortunately, the selectivity between linear and branched allylic acetates remained poor with the predominant products being the vinyl acetate and linear allylic acetate.

Table 2.4: Reactivity of commercial sulfides

In an attempt to improve the selectivity of these reactions we chose to submit 1,2- bis(phenylthio)ethane to the reaction conditions (Scheme 2.2). Allylic oxidations using this ligand and metal combination proceeded with 51% conversion and a high selectivity 31 for the linear allylic acetate after 48 h. Typical selectivities were 55:1 (L:B) with very little formation of the vinylic acetate, which is unprecedented for palladium-catalyzed allylic oxidations. In previous reports using DMSO as a co-solvent, selectivities of around 20:1 (L:B) 18b were obtained while reports utilizing nitrogen-based ligands realized a mixture of isomers. 19

Scheme 2.2: 1,2-bis(phenylthio)ethane as a ligand for allylic oxidations

These results prompted the synthesis and screening of a variety of bis-sulfides.

Bis-sulfides are easily prepared by stirring the aryl or alkyl sulfide with KOH in MeOH before adding the dibromoalkane and stirring at 23 °C for an additional 16 h.

Scheme 2.3: Synthesis of bis-sulfides

If 20 mol % 1,2-bis(phenylthio)ethane ( 2.35) was used with 10 mol % Pd(OAc) 2 conversion to product decreased to 42% while maintaining a 58:1 (L:B) ratio (entry 2). If 32 the phenyl sulfide moieties were replaced with other aryl and benzyl sulfides, conversions and selectivities were typically lower. When 1,2-bis(benzylthio)ethane

(2.36) was used, only a 3% conversion and a 6:1 mixture of linear and branched allylic acetates was obtained (entry 3). 1,2-Bis(naphthalene-1-ylthio)ethane ( 2.37), a bulkier aryl sulfide, gave a conversion of 24% and a 26:1 (L:V) ratio (entry 4). Electron- deficient ligand, 1,2-bis((4-fluorophenyl)thio)ethane ( 2.38), performed better than the naphthyl ligand with a 41% conversion and a selectivity of 28:1 L:B (entry 5). 1,2-

Bis((4-methoxyphenyl)thio)ethane ( 2.39), an electron-rich ligand, gave similar selectivity

(56:1 L:B) as 1,2-bis(phenylthio)ethane, however, conversions were lower at 28% (entry

6). The ethylene linker was also varied to see if better conversions and selectivities could be achieved. When diphenyldisulfide ( 2.40 ) was used, the reaction was unselective giving a 1:1 mixture of linear and branched allylic acetates with a small amount of vinyl acetate and lower overall conversion, 14% (entry 7). A methylene linked bis-sulfide

(2.41), bis(phenylthio)methane, gave 20% conversion with the vinyl acetate as the predominant product (entry 8). Using a propylene linker ( 2.42) gave 39% conversion in a

20:1 (L:B) ratio while extending the linker further to butylene ( 2.43) gave only 19% conversion with a 1:1 (L:V) ratio (entries 9 and 10). Ethane-1,2-dithiol (2.44) with

Pd(OAc) 2 failed to catalyze the reaction (entry 11). When 1,2-bis(ethylthio)ethane ( 2.45) was used as a ligand, the reaction failed to proceed with more than 1% conversion, lower conversion than when no external ligand is added (entry 12). Based on the ligand screen above, it was concluded that the initial ligand, 1,2-bis(phenylthio)ethane, would be used for optimization of the reaction conditions.

Table 2.5: Reactivity of bis-sulfides

Optimization of reaction conditions commenced with screening various metal salts with PhSCH 2CH 2SPh under standard reaction conditions. Only trace amounts of vinyl acetate were observed for all palladium salts. Pd(OAc) 2 provided superior conversions to other complexes, however, Pd(dba) 2 gave slightly better L:B ratios

(entries 1 and 2). Using Pd/C only low conversions were obtained and other metals such as nickel and copper failed to catalyze the reaction (entries 3-5).

Table 2.6: Screening of metal salts with 1,2-bis(phenylthio)ethane

Most reported examples using benzoquinone require excess oxidant, usually 2 equivalents. It would be advantageous to find conditions where an alternate oxidant or less oxidant was required. Not surprisingly, quinones such as 2,3,5,6-tetramethylbenzo-

1,4-quinone and 1,4-napthoquinone inhibit reactivity (entries 1 and 2), likely as a result of steric hinderance from the bulkier quinones preventing coordination and ultimately preventing reoxidation of Pd(0) species to Pd(OAc) 2. Varying the amount of benzoquinone from 0 to 2.0 equivalents showed that with no benzoquinone reactions were unselective (entry 3). This result is reflected in entries 8 and 10 in which Cu(OAc) 2 and MnO 2 were used as oxidants in the absence of benzoquinone and unusually low selectivities for this system were noted. Adding 0.5 equivalents of benzoquinone showed

35 increased conversions and selectivity increased to 45:1 (L:B) (entry 4). Increasing the amount of benzoquinone above 1.0 equivalents had little effect on conversion or selectivity (entries 5-7). Since the absence of benzoquinone resulted in low selectivities for linear allylic acetates, an oxidant screen utilizing 10 mol % benzoquinone in conjunction with other oxidants was investigated. Other oxidants used in conjunction with 10 mol % benzoquinone gave lower conversions than when only 2 equivalents of benzoquinone was used, but retained fairly good selectivities in most cases (entries 8, 10, and 12-16). Interestingly, the use of oxygen and 10 mol % benzoquinone gave 43% conversion with good L:B ratios (17:1), slightly lower than reactions employing 2 equivalents of benzoquinone (entry 13). These results lend insight into the ability of benzoquinone to affect the reaction outcome, with only 10 mol % (1:1 BQ:Pd(OAc) 2) required for excellent selectivities for the linear allylic acetate. Additionally, there appears to be a synergistic effect between the bis-sulfide ligand and benzoquinone since when either is absent there is a significant decrease in selectivity for the linear allylic acetate product. Employing 2 equivalents of benzoquinone was chosen for further studies in order to ensure adequate amounts of oxidant were present in case reactions proceeded with complete conversion.

Table 2.7: Oxidant screen

It was thought that increasing the concentration of acetic acid should increase the rate of reaction, potentially allowing the reaction to proceed to completion. Increasing the equivalents of acetic acid improved conversion when up to 12 equivalents were used

(entry 4). If more acetic acid was added, consumption of 1-dodecene decreased.

Table 2.8: Acetic acid screen

Screening various solvents with this reaction established that many solvents were superior to dioxane, with acetonitrile, THF, and tert -butyl methyl ether giving the highest conversions while maintaining good selectivities (entries 3, 4 and 10). Surprisingly,

DMSO which has previously been employed as a co-solvent with acetic acid gave decreased conversion and selectivity (entry 1). DMF also gave low conversion of starting material, most likely due to competitive binding of DMF and the bis-sulfide with palladium, saturating the metal center (entry 2). In all cases, the vinyl acetate was only observed in trace amounts.

Table 2.9: Solvent screen

Attempts to increase the rate of reaction by adding Lewis acids, metal salts, and protic acids resulted in inhibition of the reaction (entries 1, 3, and 4), or similar conversion (entry 2). In the case of trifluoroacetic acid, a higher conversion was observed, but ~15% was conversion of starting material to an unreactive internal alkene isomer (entry 3).

Table 2.10: Lewis and Brønsted acid screen

Isomerization of allylic acetates by palladium (II) salts is known 25 and it is possible that during allylic acetoxylations the branched allylic acetate is formed first, and then isomerized to the linear allylic acetate. A study focusing on the ability of the ligand and palladium salt to isomerize branched allylic acetates to linear allylic acetates was conducted. If dodec-1-en-3-yl acetate, the branched allylic acetate, was submitted to the reaction conditions for 48 h only 12% of the linear allylic acetate, dodec-1-enyl acetate, was formed in a 1:1 ( E:Z) ratio. This indicates that the linear allylic acetate is formed directly from an allylic oxidation, rather than an allylic oxidation to form the branched allylic acetate followed by isomerization from the branched to linear allylic acetate.

Scheme 2.4: Isomerization studies using 1,2-bis(phenylthio)ethane

In any reaction utilizing a catalyst the lifetime of the catalyst is a concern. Over time, unproductive reactions consume intermediates along a catalytic pathway limiting turnover, and often times requiring higher catalyst loadings. In some reactions, catalytic activity may expire after only a few minutes while other catalysts remain active for days.

To gain further insight into the durability of catalytic species operating in allylic oxidations, the progress of conversion to dodec-3-en-1-yl acetate was monitored by GC analysis and plotted as a function of time. While the catalyst in these reactions tends to react relatively slowly, after 50 h the catalyst remains active, a testament to the robustness of this system. The continued activity likely results from a combination of the strongly coordinating sulfide and acetic acid, keeping any Pd(0) species soluble and preventing colloidal palladium black formation. As long as Pd(0) species remain in solution, a propensity exists for oxidation to an active Pd(II) species.

Figure 2.5: Conversion of 1-dodecene using 1,2-bis(phenylthio)ethane and Pd(OAc) 2

Reaction systems utilizing a transition metal salt and external ligand can suffer from incomplete formation of intermediate complexes along the reaction pathway to an active catalyst, resulting in lower yields and requiring higher loadings of expensive metal salts. In many cases, pre-forming a precursor to the active catalyst where a ligand is bound to the metal center in advance, gives cleaner reactions and better results.

Therefore, a complex with 1,2-bis(thiophenyl)ethane prebound to palladium was desired.

If Pd(OAc) 2 and 1,2-bis(phenylthio)ethane are stirred in MeCN at 23 °C for 5 h a yellow- orange solution forms. Reduction of MeCN under vacuum and crystallization of the resulting yellow precipitate results in formation of (PhSCH 2CH 2SPh)Pd(OAc) 2 as a

13 yellow microcrystalline solid in a 91% yield. Analysis of the yellow solid by C NMR

42 showed 1,2-bis(phenylthio)ethane to be symmetrically bound through both sulfurs, as evidenced by a resonance at 22.6 ppm corresponding to equivalent ethylene carbons.

Scheme 2.5: Synthesis of 1,2-bis(phenylthio)ethane ligated palladium complex

When complex 2.46 was submitted to the reaction conditions with 1-dodecene, a

49% conversion to allylic acetates was observed in a 42:1 (L:B) ratio. The results employing complex 2.46 are similar to results seen when 1,2-bis(phenylthio)ethane and

Pd(OAc) 2 are added independently, indicating that complexation of the ligand to palladium is facile and likely not hindered by the reaction conditions.

Figure 2.6 Reactivity of complex 2.46

While a variety of bis-sulfides were explored, 1,2-bis(phenylthio)ethane gave the best conversions of 1-dodecene to the linear allylic acetate product. Optimized conditions showed that increasing the equivalents of AcOH gave comparable selectivities with improved yields for the linear allylic acetate product. While we were unable to find a superior catalyst re-oxidant, there appears to be a synergistic effect between the 1,2- bis(phenylthio)ethane ligand and benzoquinone. In spite of the high selectivity for the linear allylic acetate, the inability of 1,2-bis(phenylthio)ethane to give complete conversion in a reasonable timeframe remains a drawback of this ligand.

2.2.4 Reactivity and Optimization Using a Hemilabile Thioether Ligand

Bis-sulfides represented a new and interesting class of ligands for catalysis, but a ligand that could promote higher and faster conversions was desired. Since ethylene linked bis-sulfides demonstrated high selectivities for the linear allylic acetates, we postulated that a bidentate ligand containing a sulfide and a more hemi-labile functional group might promote higher conversions, while retaining good selectivities.

Contemporaneously, while optimizing conditions for bis-sulfides, a ligand screen using more weakly coordinating phosphine-, amine- and ether-sulfide analogs ( 2.47, 2.48 and

2.49) of 1,2-bis(phenylthio)ethane was conducted. It was discovered that using Pd(OAc) 2 with a sulfide ligand containing a hemi-labile ether group ( 2.49) gave complete conversion in 9 h, albeit with slightly lower L:B selectivities than when 1,2- bis(phenylthio)ethane was used. 44

Table 2.11: Ligand screen of mixed sulfides

A solvent screen revealed AcOH as the optimal solvent. Using AcOH, catalyst loadings could be lowered to 5 mol % with 85% conversion after 14 h. The allylic oxidation of 1-dodecene using 10 mol % Pd(OAc) 2 and the hemi-labile ether ligand provided dodec-2-en-1-yl acetate as a mixture of E and Z isomers in a 70% isolated yield and when the loading was dropped to 5 mol % the linear E and Z products were isolated in a 61% yield. 1-Dodecene was unreactive in the absence of Pd(OAc) 2. This represents one of the fastest examples of an allylic acetoxylation to date and uses loadings equivalent to the lowest reported catalyst loadings. Using 10 mol % Pd(OAc) 2, other co- solvents such as CH 2Cl 2, DME, toluene, THF and Et 2O gave moderate conversions, with

Et 2O giving a conversion of 77% (entries 3-7). There was no appreciable difference in reactivity when the reactions were conducted under an N 2, O 2, or air atmosphere.

Table 2.12: Solvent Screen

Proceeding to optimize reaction conditions, the ratio of palladium to sulfur ligand was varied. When a 1:1 ratio of ligand to metal utilizing 5 mol % Pd(OAc) 2 was monitored by GC a 70% yield was observed. If the ligand to Pd(OAc) 2 ratio was increased to 2:1 in AcOH, the reaction proceeded more slowly showing a 64% yield of dodec-3-en-1-yl acetate by GC after 13 h. The slower conversion is expected and additionally, this helps to justify the slower conversions seen when a 1:1 ratio of strongly coordinating 1,2-bis(phenylthio)ethane to Pd(OAc) 2 was used.

Figure 2.7: Formation of dodec-2-en-1-yl acetate with a 1:1 and 2:1 ligand to Pd(OAc) 2 ratio

Additives such as acids, bases and salts were added to reactions in an attempt to increase reactivity. Strong acids have been shown to speed up conversions in previous

26 reports of allylic oxidations, however, when used in conjunction with Pd(OAc) 2 and

PhSCH 2CH 2O( p-tolyl) in acetic acid, 1 equivalent of MeSO 3H isomerized 1-dodecene to a mixture of internal alkenes (entry 1) while 20 mol % TFA gave a complex mixture of products (entry 2). In both cases, reaction of 1-dodecene was slower than reactions without additional acid. The addition of KI drastically inhibited conversion to any product (entry 3) and when 20 mol % NEt 3 was added, slower conversion to product was also noted (entry 4). The ability of added halide salts to deleteriously effect these reactions appears in other instances too. Halides are potentially able to undergo 47 metathesis with palladium acetate forming catalytically inactive PdX 2 (X = I, Br, Cl) complexes, unable to undergo reductive elimination or halopalladation to form C-X bonds.

Table 2.13: Acid and base screen

While investigating allylic oxidation reactions, a publication detailing the formation of linear allylic acetates using Pd(OAc) 2 in MeCN with a LiOH•H 2O additive was published. Investigation into alkali metal salt additives in conjunction with a thioether ligand revealed LiOH•H 2O to be unique in this reaction. Addition of lithium halides gave no conversion to allylic acetate products and instead small amounts of unidentified products were observed by GC analysis (entries 1-3). LiOH•H 2O gave 94% conversion of 4-phenylbut-1-ene to ( E)-4-phenylbut-2-en-1-yl acetate regardless of whether or not the thioether ligand ( 2.49) was present (entries 4 and 5). It was thought that LiOH•H 2O would form LiOAc in acetic acid, and that other acetate salts may

48 effectively promote allylic acetate formation as well. Interestingly, decreased conversions to acetate products were observed with 2 equivalents of KOAc and NaOAc after 24 h, but when LiOAc was added the reaction proceeded in 89% conversion with a

24:1 (L:B) ratio in 18 h (entries 6-8). A clear trend emerges; as the cationic radius of the acetate salt becomes smaller and the cation harder, the reaction proceeds faster. It is not fully understood why, but it appears that this reactivity is unique to lithium, the smallest and hardest alkali metal. One possibility is formation of a bimetallic lithium-palladium complex.

Table 2.14: Alkali metal salts screen

The efficacy of other palladium salts towards allylic acetoxylations was examined. In addition to Pd(OAc) 2, Pd(dba) 2 successfully formed dodec-3-enyl acetate 49 in a 52:1 (L:B) ratio with complete conversion of 1-dodecene after 24 h, although the vinyl acetate side product remained prevalent (entry 2). Highly reactive CpPd(C 3H5) gave complete conversion of 1-dodecene after 24 h, but was less selective. The linear allylic acetate remained the major product but a 9:1:1 (L:B:V) ratio of products was realized (entry 3). Pd(acac) 2 was less reactive giving only a 61% conversion to allylic acetate products, however, ratios of linear, branched, and vinyl acetates were comparable to those seen when Pd(OAc) 2 was used (entry 4).

Table 2.15: Palladium salt screen

Submitting a variety of terminal alkenes to the optimized reaction conditions (5 mol % Pd(OAc) 2, 5 mol % thioether ligand, and 2 equivalents of benzoquinone in AcOH at 40 °C) gave good yields with selectivities of 20:1 for the linear allylic acetate for most substrates (Table 2.16). All of the compounds in the table were isolated as the pure

(>95% by 1H NMR spectroscopy) linear ( E)-allylic acetate unless noted, and the yields are an average of two 1 mmol reactions. The reaction times were optimized to favor the 50 greatest conversion with the least amount of branched allylic acetate, vinyl acetate, and ketone side products. Nonetheless, all of the alkenes underwent ≥85% conversion in all reactions. Allylic and homoallylic arenes ( 2.54, 2.56, 2.58, and 2.50 ) provided the corresponding linear products in good yields regardless of the substitution present on the arene (entries 1-4). The reaction conditions also tolerated amides ( 2.61), carbamates

(2.65), esters ( 2.63 and 2.67), ethers ( 2.69 and 2.71) and acetals ( 2.73) (entries 6-12).

The only substrates that did not provide good L:B sectivity contained an amide ( 2.61), which likely coordinates to the metal center and disrupts the Pd-S dative bond present in the high selectivity catalyst in these reactions. The low yield obtained for the PMB-ester

(2.67) may be a result of some type of oligomerization as >90% conversion of the alkene was observed. The GC spectrum contained only minor amounts of the corresponding vinyl acetate and methyl ketone products, and attempts to isolate any other major products was fruitless.

Table 2.16: The allylic oxidation of terminal olefins

To test the hypothesis that amides present during the reaction may competitively bind to palladium decreasing selectivity and yields, two amides were tested under standard reaction conditions. N-Phenylbenzamide ( 2.75) and N,N-dimethylbenzamide

(2.76) were both used in a 1:1 ratio with Pd(OAc) 2 and sulfide ligand. In both cases, complete consumption of 1-dodecene was observed resulting in a mixture of products with the vinyl acetate being the predominant oxidation product. These results are further supported by the fact that when DMA was used as a solvent in the absence of a thioether ligand, very little conversion was seen, but the vinyl acetate remained the major product.

Based on these results it is clear that amides possess the ability to competitively bind to palladium, displacing the sulfide ligand, and are able to alter the reaction outcome.

Table 2.17: Competitive binding of amides to palladium

Palladium chloride has previously been used to form 2-methylbenzofuran from 2- allylphenol. However, divergent reactivity of 2-allylphenols under allylic acetoxylation conditions using thioether ligand, 2.49, could result in useful chromenes. Attempts to 53 perform an intramolecular allylic etherification with 2-allylphenol ( 2.77 ) were unsuccessful, giving 2-methylbenzofuran ( 2.79 ), resulting from Wacker type oxidation, as the sole product from these reactions.

Scheme 2.6: Wacker oxidation of 2-allylphenol

While using a hemi-labile thioether ligand allowed for conversion of terminal olefins to linear allylic acetates in significantly faster times with high selectivity using lower catalyst loadings than previously reported conditions for the linear allylic acetate, the super-stoichiometric amounts of oxidant remained an obstacle. In order to avoid the need for excess oxidant, alternative conditions using oxygen as an oxidant were explored.

Conditions using 5 mol % iron phthalocyanine, 10 mol % benzoquinone, and O 2 (1 atm) in AcOH with 5 mol % Pd(OAc) 2 and 5 mol % 2.49 were attempted to no avail. Under these conditions only a 34% conversion of 1-dodecene to allylic acetate products was observed with a L:V ratio of 2:1. A Cu(OAc) 2/dihydroquinone system with O 2 and 5 mol

% Pd(OAc) 2 and 5 mol % 2.49, resulted in a 73% conversion after 24 h and was selective for the linear product. In order for complete conversion to occur, 10 mol % Pd(OAc) 2 was required. Under these conditions, Cu(OAc) 2 and oxygen oxidize dihydroquinone to benzoquinone, which is able to re-oxidize Pd(0) to Pd(II). Additionally, as shown with 54

1,2-bis(phenylthio)ethane, benzoquinone helps encourage high selectivity for the linear product, and mechanistic studies mentioned later give evidence that it also promotes reductive elimination.

With these modified conditions, slightly longer reaction times are required to obtain similar yields when compared to previous results using benzoquinone. The allylic oxidation product from allylbenzene ( 2.55) was isolated in 58% yield, while 4- phenylbutene ( 2.50 ), containing an extended alkyl chain, was isolated in 60% yield. An acetate protected alcohol ( 2.64) also gave a good yield of 62%. The substrate used to optimize reaction conditions, 1-dodecene, was converted to ( E)-dodec-3-enyl acetate

(2.64) in a 50% yield. These alternative conditions offer a greener approach to allylic acetoxylations, using catalytic amounts of all reagents other than acetic acid and oxygen, two environmentally benign compounds.

Table 2.18: Allylic oxidations using stoichiometric O 2 as an oxidant

Because the linear to branched allylic acetate ratios were lower when

PhSCH 2CH 2O( p-tolyl) (2.49) was used than those found with 1,2-bis(phenylthio)ethane

(2.35), it was thought that either these reactions could operate through different mechanisms or there could possibly be a background isomerization reaction. Pd(II) isomerizations of allylic acetates have been reported in the literature 25 and a proposed alternative mechanism would be if the branched allylic acetate is formed first through an allylic oxidation followed by a Pd(II) catalyzed isomerization to form the linear allylic acetate.

If the linear allylic acetate (48:1 L:B) is submitted to the optimized reaction conditions, it deteriorates to a 30:1 (L:B) mixture after 12 h. When dodec-1-en-3-yl acetate was submitted to the standard reaction conditions using 2.49, after 12 h, a 1:2

(L:B) ratio was seen compared to a 1:7 (L:B) ratio with 1,2-bis(phenylthio)ethane after

48 h. Monitoring the progression of an allylic oxidation of 1-dodecene by GC analysis shows that the branched allylic acetate does not appear until 3 h when a 58:1 (L:B) ratio is observed. This L:B ratio slowly erodes to 43:1 after 5 h, 34:1 after 8 h, and finally to

20:1 after 12 h. While due to the slow isomerization it does not appear that this reaction proceeds through a mechanism in which the branched allylic acetate is formed first, phenyl(2-(p-tolyloxy)ethyl)sulfane does allow for increased isomerization of allylic acetates when compared to 1,2-bis(phenylthio)ethane.

Scheme 2.7: Isomerization experiment with phenyl(2-(p-tolyloxy)ethyl)sulfane

2.2.5 Isolation of Ligand Bound Palladium Complexes

A more complete understanding of intermediate metal species was desired in order to gain insight into the mechanistic pathway. Analysis of the ligand in the presence of Pd(OAc) 2 in AcOD d 4 as well as analysis of the ligand in the presence of Pd(OAc) 2

1 and BQ in AcOD d 4 was performed. In AcOD using H NMR analysis, the free ligand shows sharp resonances corresponding to the ethylene backbone and aromatic protons

(Figure 2.6). When Pd(OAc) 2 is added, the ligand can be seen coordinated to Pd(OAc) 2, as noted by a shift in the aromatic and ethylene protons which now appear as broad resonances (Figure 2.7). When BQ was added, no change in the 1H NMR spectrum other than a singlet corresponding to BQ was noticed, and even heating to 40 °C gave no change by 1H NMR spectroscopy (Figure 2.8).

Figure 2.8: 2.49 in AcOD d 4

Figure 2.9: 2.49 with Pd(OAc) 2 in AcOD d 4 58

Figure 2.10: 2.49 with Pd(OAc) 2 and BQ in AcOD d 4

Because evidence pointed towards coordination of the ligand to Pd(OAc)2 in

AcOD, there remained the possibility of isolating an intermediate palladium species.

Unfortunately, mixing either one or two equivalents of ligand with Pd(OAc) 2 in various solvents resulted in a reddish intractable oil, proposed to contain a palladium center bound the sulfide ligand and two acetate groups ( 2.80). All attempts to recrystallize or isolate a pure complex from this oil failed.

Scheme 2.8: Attempted synthesis of a sulfide ligated palladium diacetate complex

An alternative route was therefore needed to isolate this complex. Addition of the ligand to PdCl 2 in toluene failed to form the analogous dichloride complex. One equivalent of ligand in toluene was added to a stirring solution of Pd(COD)Cl 2 in toluene and the reaction refluxed for 16 h. The solution turned an orange color. Reduction of solvent followed by layering with hexanes gave orange flaky crystals initially thought to be (PhSCH 2CH 2O(p-tolyl))PdCl 2 (2.81) with the ligand coordinated through both the

1 sulfur and hemi-labile oxygen. The H NMR of this complex in CDCl 3 showed two multiplets at 4.12 ppm and 3.57 ppm corresponding to the ethylene backbone, a singlet at

2.26 ppm representing the tolyl methyl group, and resonances in the aromatic region integrating to 9H. No other resonances were noted in the 1H NMR spectrum.

Scheme 2.9: Synthesis of a proposed palladium dichloride complex

Changing the initial palladium complex to Pd(MeCN) 2Cl 2 gave a much greater amount of the flaky orange crystals, matching the 1H NMR spectrum obtained from reaction of the ligand with Pd(COD)Cl 2. Recrystallization of this complex by layering of hexanes over toluene gave X-ray quality crystals. Upon analysis, the X-ray crystal structure showed the actual complex to contain a square planar palladium center with two chlorides trans to each other and two coordinated ligands bound through sulfur ( 2.82).

The “hemi-labile” ether moieties appear to have little if any contact with the palladium center. Using this knowledge, two equivalents of ligand were added to Pd(MeCN) 2Cl 2 in toluene and upon removal of the solvent and recrystallization by layering hexanes over toluene, (PhSCH 2CH 2O( p-tolyl)) 2PdCl 2 (2.88) was isolated in an 83% yield.

Figure 2.11: X-Ray crystal structure of the actual dichloride complex 2.82

In an attempt to synthesize the diacetate analog ( 2.83), complex 2.82 was stirred in CH 2Cl 2 and two equivalents of AgOAc added. The reaction was allowed to stir at 23

°C in the absence of light. Upon filtration and reduction of solvent, only a red intractable oil was recovered. All attempts to isolate a pure complex from this oil were unsuccessful. It has been previously reported that palladium(II) acetate-dialkyl sulfide systems can form acetate and sulfur bridged palladium oligomers consisting of di-, tri-, and tetra-nuclear palladium complexes. 27 If complex 2.83 is formed in situ, oligomerization may form multiple products preventing isolation of the desired mono- nuclear diacetate complex.

Figure 2.12: Attempts to form diacetate complexes

The dichloride complex, 2.82, showed no reactivity towards allylic oxidations when stirred in AcOH with 1-dodecene and benzoquinone. However, catalytic competency could be obtained if 2.82 was stirred in CH 2Cl 2 with two equivalents of

AgOAc followed by removal of CH 2Cl 2 and addition of AcOH, benzoquinone, and 1- dodecene. Under these conditions the intermediate complex could catalyze the allylic oxidation of 1-dodecene in a 37% yield. As noted in the abovementioned chart (Figure

2.7), using Pd(OAc) 2 and PhSCH 2CH 2O( p-tolyl) in a metal to ligand ratio of 2:1 gave

50% conversion by GC analysis. The lower yield using the complex pretreated with

AgOAc is likely a result of incomplete formation of the active diacetate catalyst.

Figure 2.13: Reactivity of sulfide ligated palladium complexes

Phosphine ligated palladium catalysts such as 2.86 in THF under an atmosphere of oxygen have been shown to oxidize a variety of sulfides ( 2.84 ) selectively to

28 corresponding sulfoxides, 2.85 (Scheme 2.10). Questions arose as to whether Pd(OAc) 2 and benzoquinone in acetic acid could potentially be oxidizing thioether ligand, 2.49, to sulfoxide, 2.88 .

Scheme 2.10: Previously reported palladium-mediated oxidation of sulfides

To dismiss any perception of in situ sulfoxide formation, ligand 2.49 was oxidized to the sulfoxide using H 2O2 in acetic acid. Submission of sulfoxide, 2.88 , to the optimized reaction conditions using 1-dodecene resulted in formation of primarily the vinyl acetate ( 2.87 ) in a 46% yield, insinuating that under our reaction conditions

PhCH 2CH 2O( p-tolyl) ( 2.49) is not converted to sulfoxide, 2.88 . This reaction did not proceed to completion during the 12 h reaction time. In retrospect, these results are not surprising. It is entirely possible that previously reported conditions oxidizing sulfides to sulfoxides under an atmosphere of oxygen proceed through a radical mechanism. In contrast, allylic oxidations involving benzoquinone unavoidably form dihydroquinone, a radical scavenger. Thus, the presence of dihydroquinone would inhibit any radical oxidations of sulfides to sulfoxides.

Table2.19: Reactivity of the sulfide ligand and analogous sulfoxide

2.2.6 Mechanistic Work

Many allylic acetoxylations are proposed to proceed through π-allyl palladium intermediates ( 2.89 ) resulting from insertion into the allylic C-H bond. 15,17a,17f,18a In order to help determine the mechanism driving our reported reactions, we attempted to enter the catalytic cycle through a preformed π-allyl palladium acetate dimer formed from 1- dodecene. If the active mechanism went through a π-allyl palladium intermediate then upon addition of benzoquinone, acetic acid and ligand at 40 °C, similar yields and L:B ratios of the allylic acetates should be observed. To ensure the consistency of mechanistic assessments between these results and White’s, the π-allyl palladium dimer was also submitted to White’s reported conditions using dioxane as a solvent. 18a If stirred with benzoquinone in dioxane, complete conversion of 1-dodecene to the branched allylic acetate was observed, consistent with White’s previously reported results. When the π- allyl palladium dimer ( 2.99) was stirred in acetic acid with no additives or added

PhSCH 2CH 2O( p-tolyl), only minor amounts of allylic acetate products were seen.

Interestingly, if the dimer ( 2.90) was stirred in acetic acetate with benzoquinone, a 0.4:1 mixture of linear and branched allylic acetates was observed. Lastly, when the π-allyl palladium dimer ( 2.90) was stirred in acetic acid with added ligand and benzoquinone, full conversion of the π-allyl palladium was noted with a slight preference for the linear allylic acetate. Consistent with White’s results, it appears that benzoquinone aids reductive elimination. However, experimental L:B ratios could not be replicated using π- 66 allyl palladium acetate dimer, 2.90, and all further attempts to achieve higher L:B ratios using a π-allyl palladium acetate dimer failed. Based on these results, the π-allyl palladium mechanism cannot be conclusively verified and likely, an alternate mechanism is at work. An alternative mechanism, similar to one proposed by Rappoport to form linear allylic acetates, is acetoxypalladation, in which palladium and acetate are added across the alkene, followed by a regioselective β-hydride elimination. 13 The only apparent experiment that could adequately lend evidence to this mechanism includes the allylic oxidation of 1,2-dideutero-cyclohex-1-ene. However, this reaction proceeds under our optimized reaction conditions at a similar rate as in the absence of thioether ligand, rendering any results inconclusive due to a considerable background reaction.

In Bercaw’s mechanistic studies of allylic acetoxylations using 2,2’-bipyrazine as a ligand for palladium, no kinetic isotope effect was seen, providing evidence that either coordination of the alkene to palladium or re-oxidation of Pd(0) to Pd(II) was the rate limiting step. 19 Kinetic isotope experiments using our standard reaction conditions showed the rate of reaction for 3,3-dideutero-1-dodecene to be similar to 1-dodecene.

Figure 2.14: Entering a proposed catalytic cycle from complex 2.90

Table 2.20: Reactivity of π-allyl palladium acetate dimers

While no predominant pathway can be identified, studies lend insight into mechanistic requirements, and potentially troublesome steps of this reaction.

2.2.7 Alkyl Aryl Sulfides

Close examination of the X-ray crystal structure of complex 2.82 had indicated little contact if any between the oxygen of the ether moiety and the palladium center.

Therefore, the possibility existed that the ether moiety was not necessary for good conversions. Indeed, if the analogous ligand containing CH 2 (2.93 ) in place of O was submitted to optimized reaction conditions using 1-dodecene, dodec-2-en-1-yl acetate was formed in a similar yield. Moreover, similar ratios of linear, branched, and vinylic products were noted.

Scheme 2.11: An alkyl aryl sulfide as a ligand

Analogous alkyl aryl sulfoxide 2.94 primarily formed the vinyl acetate, similar to the aforementioned sulfoxide ( 2.88 ).

Table 2.21: Divergent reactivity of an alkyl aryl sulfide and corresponding sulfoxide

OAc Pd(OAc)2 (5 mol %) Ligand (5 mol %) V BQ (2 equiv) 2.87 AcOH, 40 C, 13 h OAc 2.50 L 2.51 Entry Ligand Major Product Yielda

1 PhS Ph L 63% O 2.93 2 S Ph V Ph 20% 2.94 a) Isolated yields based on an average of two 1 mmol reactions.

The synthesis and reactivity of a small library of alky aryl sulfides was studied.

Various alkyl aryl sulfides in conjunction with Pd(OAc) 2 were able to catalyze the allylic oxidation of 1-dodecene in similar yields as (2-(p-tolyloxy)ethyl) phenyl sulfide ( 2.49).

The length of the alkyl chain ( 2.93 and 2.95 ) had little effect on yield although the benzyl phenyl sulfide ( 2.96 ) helped to catalyze the reaction faster than methyl phenyl sulfide

(2.95 ). When the sulfide ligand incorporating a pyridinium iodide salt ( 2.97 ) was used the reaction formed only trace amounts of any allylic oxidation products and <5% of the vinyl acetate ( 2.87 ). It is unlikely that the nitrogen in the pyridinium ligand inhibits reactivity. However, previous attempts to catalyze this reaction in the presence of halides salts have failed, so likely the iodide is the cause for lack of reactivity when using this ligand. It is not fully understood why alkyl aryl sulfide ligands promote this selective transformation while diaryl sulfides tend to favor vinylic acetates and dialkyl sulfides are both extremely slow and unselective at forming allylic acetates.

Table 2.22: Screening alkyl aryl sulfides as ligands

2.2.8 Heck-arylations

While testing the reactivity of different electron-deficient benzoquinones in allylic oxidations, it was noticed that when 1,3,5-trimethoxybenzene was used as an internal standard the reactions proceeded much more slowly than without internal standard.

Additionally, a new unidentified peak appeared in many of the GC chromatograms.

Crude 1H NMR gave little indication of the identity of any side products other than a few resonances found in the vicinity of an alkene’s chemical shift. Isolation of the unknown 71 product showed a compound in which benzoquinone was coupled with 1,3,5- trimethoxybenzene. This product likely occurs through a Heck-arylation mechanism in which C-H activation of 1,3,5-trimethoxybenzene occurs followed by addition to benzoquinone. Subsequent β-hydride elimination would give the isolated product. Heck reactions of aryl-halides with benzoquinone have been previously reported but there have no reports of the C-H activation of an electron rich benzene ring followed by a Heck reaction with benzoquinone. Therefore, we decided to optimize conditions and explore the generality of this reaction.

Scheme 2.12: Heck-arylation with 1,3,5-trimethoxybenzene

In the absence of ligand, conversions were much slower than when 5 mol %

PhSCH 2CH 2O( p-tolyl) was added (entries 1 and 2). Conversion decreased accordingly with a decrease in Pd(OAc) 2 and ligand loadings (entry 3). Decreasing the equivalents of benzoquinone also decreased the rate of reaction (entry 4). When the reaction was heated to either 60 °C or 90 °C with 1.2 equivalents of benzoquinone a new unidentified product was formed instead of the arylated benzoquinone (entries 6 and 7).

Table 2.23: Optimization of Heck-arylations with BQ

A solvent screen was conducted using 1,2,4-trimethoxybenzene, which also showed reactivity to form the arylated product. All solvents except AcOH gave trace amounts of product while AcOH gave a 45% yield by internal standard with a 39% isolated yield.

Table 2.24: Solvent screen of Heck-Arylations

OMe MeO OMe Pd(OAc)2 (5 mol %) O MeO PhSCH2CH2(p-tolyl) (5 mol %) BQ (2 equiv), Solvent, 40 °C, 21 h OMe

OMe O 2.100 2.101 Entry Solvent Yield 1 dioxane 4% 2 CH2Cl2 4% 3 acetone 3% 4 THF 2% 5 toluene 3% 6 DME 4% 7 H2O 3% 8 AcOH 45% (39%) a) Yields determined by GC analysis. b) Yields in brackets are isolated yields.

Examining the substrate scope of this reaction revealed that this transformation was restricted to only very electron rich aromatic substrates. While 1,3,5- trimethoxybenzene and 1,2,4-trimethoxybenzene fared well in this reaction, toluene, phenol, anisole, and 3,5-dimethylanisole failed to react at all. This method could not be extended to the Heck-arylation of alkenes such as methyl acrylate. The low yields obtained may be a result of the reduction of arylated benzoquinone products to the corresponding dihydroquinone by Pd(0) species over the course of the reaction.

2.2.9 Allylic Oxidations of cis -Vinylsilanes

An extension of this allylic acetoxylation methodology to disubstituted alkenes would be useful since current methods suffer from low yields and selectivities. In general, this transformation is more challenging due to the diminished ability of palladium to chelate more hindered alkenes. A compilation of disubstituted alkenes

(2.104 -2.107 ), with varying functional groups, were submitted to the allylic acetoxylation reaction conditions. Unfortunately, disubstituted alkenes failed to react selectively, and in many cases, not at all, under conditions using a sulfide ligand, Pd(OAc) 2 or Pd(TFA) 2, and benzoquinone.

Figure 2.15: Allylic oxidations of disubstituted alkenes

Disubstituted alkenes likely suffer from inhibition of binding to palladium. The C-C bond of an allylic alkene is ~1.3 Ǻ while the C-Si bond of a vinylsilane is ~1.8 Ǻ. We proposed that the longer C-Si bond could potentially make coordination of the alkene to

75 palladium more facile and that the coordinated alkene might be able to undergo an allylic oxidation to form the linear allylic acetate.

cis -Vinylsilanes were easily synthesized in one or two steps from terminal alkynes using previously reported conditions. 29 The corresponding silane was stirred in ethyl aluminum dichloride (1 M in hexanes) in toluene at 0 °C for 15 min before adding the alkyne ( 2.108 ) to give the cis -vinylsilane ( 2.109). Alternatively, the terminal alkyne was lithiated with n-butyl lithium and then reacted with the appropriate chlorosilane to give the silyl protected alkyne. The resulting alkyne could then be reduced to the cis - vinylsilane ( 2.109 ) using dicyclohexylborane in THF at 0 °C. 30 Isomerically pure trans - vinylsilanes ( 2.110) were more difficult to prepare. Formation required stirring the alkyne, silane, and 0.1 mol % Wilkinson’s catalyst in a polar solvent for 2 d. 31

Additionally, the best selectivity obtained in our lab was a 10:1 ( E:Z) mixture of inseparable isomers.

Figure 2.16: Synthesis of ( E) and ( Z) vinylsilanes

When isomerically pure cis - or trans -triethyl(hept-1-en-1-yl)silane ( 2.111 and

2.112 ) was submitted to our previously reported allylic oxidation conditions (Pd(OAc) 2,

PhSCH 2CH 2O( p-tolyl), BQ, AcOH) at 23 °C only starting material was observed by GC or 1H NMR analysis. When trans -triethyl(hept-1-en-1-yl)silane ( 2.111 ) was submitted to the same conditions at 70 °C, again no reaction to any products was observed. However, if cis -triethyl(hept-1-en-1-yl)silane ( 2.112 ) was submitted to the above reaction conditions and heated to 70 °C for 24 h, surprisingly ( E)-1-(triethylsilyl)hept-1-en-3-yl acetate ( 2.113 ) was isolated in a 40% yield. This reaction proceeded with clean isomerization of the ( Z)-alkene to the ( E)-alkene to give the branched allylic acetate, with no other regioisomers or side products observed in the crude 1H NMR.

Figure 2.17: Allylic oxidations of vinylsilanes

If cis -triethyl(hept-1-en-1-yl)silane ( 2.112 ) was submitted to the reaction conditions in the absence of any external ligand at 70 °C the yield increased to 56%

(entry 3). The reaction required 48 h to proceed to completion at 50 °C but the yield of

(E)-1-(triethylsilyl)hept-1-en-3-yl acetate increased to 64% (entry 4). If the reaction was heated to 90 °C, the branched allylic acetate was formed in a 51% yield after 3 h (entry

5). Heating to 110 °C led to a complex mixture of products. When the reaction was run at 90 °C with 2 mol % Pd(OAc) 2, the reaction time was increased to 6 h and provided

(E)-1-(triethylsilyl)hept-1-en-3-yl acetate ( 2.113 ) in a 66% yield (entries 6 and 7). The loading could be decreased further to 1 mol % Pd(OAc) 2 without a decrease in yield

(entry 8). The fact that all starting material was consumed over the course of these reactions, but yields remained around 66% for the optimized conditions alluded to the fact that there may be a decomposition pathway that forms some type of polymeric side product.

Table 2.25: Optimization of reaction conditions with cis -vinylsilanes

Various silyl groups were tested to see if higher yields could be obtained. When cis -hept-1-en-1yltrimethylsilane (2.119 )was used the yield decreased to 41% (entry 2).

Bulkier groups such as SiPh 3, Si(Me) 2tBu, and Si(Me) 2Bn also gave decreased yields of

16%, 44% and 57% respectively (entries 3-5). When cis -hept-1-en-1yltriisopropylsilane was submitted to the optimized reaction conditions no reaction to any products was seen

(entry 6). The lack of reactivity for triisopropylsilane may be due to the large steric bulk preventing coordination to the alkene.

Table 2.26: Screening of silyl groups

A substrate screen using various (Z)-vinyltrialkylsilanes was performed. ( Z)-Dec-

1-en-1-yltriethylsilane ( 2.129) provided ( E)-1-(triethylsilyl)dec-1-en-3-yl acetate ( 2.130 ) 79 in a 69% yield (entry 1). tert -Butyldimethylsilyl ethers ( 2.131 ) tolerated the reaction conditions, however, when the silylether was in a closer proximity to the vinylsilane

(2.133 ) yields were lower (entries 2 and 3). Internal vinylsilanes ( 2.135) reacted to give a mixture of isomers ( 2.136 and 2.137) in a 56% yield (entry 4). ( Z)-Triethyl(5- phenylpent-1-en-1-yl)silane ( 2.138) gave the corresponding allylic acetate ( 2.139) in a

47% yield (entry 5). Analogous ( Z)-tert -butyldimethyl(3-phenylprop-1-en-1-yl)silane

(2.140 ) and ( Z)-triethyl(3-phenylprop-1-en-1-yl)silane ( 2.142 ) were unreactive, probably due to the bulky phenyl ring in the allylic position as well as the bulky silane, in the case of the tert -butyldimethylsilane (entries 6 and 7). Triethylvinylsilane containing an isopropyl group ( 2.144 ) gave the product ( 2.145 ) in a 53% yield (entry 8). Acetate esters tolerated the reaction conditions giving a 50% yield of 2.147 . Additionally, silanes containing phthalimide ( 2.148 ) gave a 48% yield of product ( 2.149 ) when 5 mol %

Pd(OAc) 2 was used (entry 10).

Table 2.27: Substrate screen using cis -vinylsilanes

Recently it has been discovered that changing the oxidant from benzoquinone to

BAIB alters the outcome of the reaction to favor formation of the (Z)-allylic acetate

(2.151 ). Additionally reaction times are decreased from 12-24 h to 1.5 h. Yields are comparable or higher than when benzoquinone is used as an oxidant. The divergent 81 reactivity alludes to the possibility of an alternative mechanism. It is possible that BAIB speeds up the C-O bond forming step enough to predominate over isomerization, from syn to anti, of an intermediate π-allyl palladium complex.

2 mol % Pd(OAc)2 BAIB (2 equiv), AcOH

OAc SiEt3 90 °C, 1.5 h OAc

R R SiEt3 2.150 2.151 up to 1:5 (E:Z)

Scheme 2.13: Allylic oxidations of vinylsilanes using BAIB as an oxidant

This methodology has also allowed for intramolecular allylic etherifications using

Pd(dba) 2 and benzoquinone in acetone to form tetrahydrofuran, tetrahydropyran, and benzofuran rings containing a pendant trans -vinylsilane ( 2.152 ).

Scheme 2.14: Intramolecular etherifications of vinylsilanes

These results could be rationalized by the following mechanism (Figure 2.16).

First, C-H insertion would form the π-allyl palladium acetate complex ( 2.153 ). These reactions require no external ligand, but typically external ligands are required in allylic oxidations of terminal olefins to assist palladium inserting into the allylic C-H bond. 82

Therefore, it is likely that the silyl group promotes the C-H insertion. An electronic effect from the silane may aid the insertion by making the alkene more electron rich; however, if this was the sole explanation then likely trans -vinylsilanes would show some reactivity as well. An additional effect unique to cis -vinylsilanes is 1,3-allylic strain between the silyl group and an allylic hydrogen which could weaken the C-H bond promoting insertion by palladium. This could explain the trend seen when different vinylsilanes were tested. The trimethylsilyl group would lack the necessary steric bulk to effectively weaken the C-H bond while other more bulky silanes would prevent any palladium species from coordinating to the alkene.

No ( Z)-allylic acetates ( 2.154 ) are observed in the reaction mixture which would result from reductive elimination from the anti complex ( 2.153 ). Reductive elimination of acetate and the anti complex to form the ( Z)-allylic acetate is probably hindered by the large 1,3-allylic strain incurred between the resulting acetate and silyl group. Instead, once the anti π-allyl palladium complex has formed, at temperatures above 50 °C the complex could isomerize to the more thermodynamically favored syn complex ( 2.155 ).

This temperature dependant isomerization is similar to the one proposed by Murahashi. 32

Reductive elimination of acetate and the syn complex would give the more stable ( E)- allylic acetate ( 2.113 ). This is supported, in part, by optimization results where at room temperature no reaction is observed.

Figure 2.18: Proposed mechanism for allylic oxidations of vinylsilanes

It is also possible that reductive elimination could occur to give the linear allylic acetate ( 2.156 ) which then isomerizes via a [3,3] sigmatropic rearrangement to the branched allylic acetate ( 2.113 ). 33 When the linear allylic acetate was submitted to the optimized reaction conditions, after 10 h the branched allylic acetate was formed in a

65% yield. These results do not definitively confirm that the linear allylic acetate is formed first, but do verify the linear allylic acetate as a kinetically competent intermediate in the reaction.

Scheme 2.15: Possible rearrangement of linear allylic acetates

2.3 Conclusion

In conclusion, a more thorough understanding of allylic acetoxylations is presented. Significant improvements and contributions have been made in the area of palladium catalyzed allylic acetoxylations. Reactions employing Pd(OAc) 2 and alkyl aryl sulfides proceed with faster rates than any currently reported methods at lower catalyst loadings. The ability to use oxygen as a stoichiometric oxidant offers a greener alternative to a reaction that traditionally requires excess benzoquinone.

Allylic oxidations and etherifications of cis -vinylsilanes represent a new niche in the scope of allylic oxidations and opens the door for further studies. Reactions of cis - vinylsilanes proceed with excellent regio- and stereoselectivity for the branched ( E)- allylic acetates. This methodology has been expanded to include intramolecular etherifications as well as expanded to form branched ( Z)-allylic acetates if BAIB is used as the oxidant.

Of equal importance are the serendipitous discoveries found during optimization and screening. The cooperation of benzoquinone and ligand when forming linear allylic

85 acetates was unexpected but valuable for further investigations. Also of significance are discoveries relating to nitrogen containing ligands and substrates present in the reaction, which tend to inhibit reactivity and selectivity. Addition of halides unexpectedly shuts down reactivity as seen by the addition of alkali halide salts, palladium chloride complexes, and a pyridinium iodide ligand. Furthermore, the discovery of easily prepared alkyl aryl sulfides as powerful ligands for this transformation allows for further studies.

2.4 Future work

While our method for converting terminal olefins to linear allylic acetates offered improved conditions, a milder faster method for formation of branched allylic acetates is still a challenge. Initial studies using bis-sulfoxides were promising, and results provide a foundation for further research towards discovery of a ligand that rapidly converts alkenes to branched allylic acetates using lower catalyst loadings. Additionally, the formation of branched allylic acetates creates a stereogenic center, which could be exploited to perform asymmetric allylic oxidations. A more ambitious goal would be discovery of a practical method for regioselective acetoxylations of acyclic unfunctionalized disubstituted alkenes. The toughest obstacle to completing this goal appears to be binding of the alkene to the metal center.

With respect to the formation of linear allylic acetates, catalyst loadings while lower than previous reports, are still generally higher than typical loadings utilized for 86

Heck or Suzuki cross-coupling reactions. Results show that catalysts formed from

Pd(OAc) 2 and sulfides are fairly robust, showing conversion of alkenes to product after

48 h in the case of 1,2-bis(phenylthio)ethane. However, reaction rates slow appreciably and likely a more active catalyst, able to efficiently catalyze allylic acetoxylations at low concentrations, would need to be generated in order to further reduce loadings.

In regard to the allylic oxidation of cis -vinylsilanes, branched allylic acetates contain a stereogenic center and the ability to perform this reaction asymmetrically to provide enantio-enriched products would be useful. Previous attempts to perform asymmetric allylic oxidations through C-H bond activation have led to low enantioselectivities. Allylic oxidations with vinylsilanes offer the advantage of a proximal silyl group, versus terminal alkenes which have no substitution. Therefore, in addition to attempting an asymmetric version of this reaction using chiral ligands, allylic oxidations of substrates with chiral silyl groups could be attempted. It would also be useful to employ vinylsilanes as a handle for further functionalization in a one pot procedure. Vinylsilanes are known to undergo palladium-catalyzed Hiyama cross- coupling reactions. Additionally, there are numerous reports using mild conditions to convert vinylsilanes to vinyliodides and ketones.

Lastly, while commercially available dialkyl or diaryl sulfides have been used in catalysis, albeit rarely, the discovery of alkyl aryl sulfides as ligands for catalysis is completely novel. As described, alkyl aryl sulfides are able to promote allylic acetoxylations and Heck-arylations but the scope of this unique ligand motif has yet to be completely explored, and the generality to which this ligand could potentially be

87 employed is appealing. Moreover, further studies regarding alkyl aryl sulfide derivatives related to electronics and steric bulk are required.

Chapter 3: Synthesis of α,β-Unsaturated Aldehydes from Alkyl

Enol Ethers

3.1 Abstract

Our lab has recently discovered a new method to synthesize α,β-unsaturated aldehydes from alkyl enol ethers using 1-5 mol % Pd(OAc) 2 in dichloromethane or acetone using benzoquinone as a palladium oxidant. This represents a significant advancement over current systems, most of which require 0.5 to 1 equivalents of a palladium salt. 34 Additionally, this methodology has been extended to more environmentally friendly conditions using a Cu(OAc) 2/O 2 system to reoxidize Pd(0), circumventing the need for stoichiometric benzoquinone.

3.2 Background

Seminal reports by Saegusa detailed the synthesis of α,β-unsaturated ketones and aldehydes from silyl enol ethers using 50 mol % Pd(OAc) 2 and 0.5 equivalents of benzoquinone in acetonitrile. 34a This was indeed an improvement over previous methods that used harsher conditions and stronger oxidants to complete this transformation. 35 A major limitation of this methodology is the inability to decrease catalyst loadings , thus stoichiometric amounts of expensive Pd(OAc) 2 are required to achieve good yields.

Lowering the amount of Pd(OAc) 2 under these reaction conditions results in a significant decrease in yield and the inability to decrease catalyst loading to levels that would encourage larger scale reactions remains a drawback to this methodology. Additionally, silyl enol ethers are unstable under many reaction conditions. Despite these limitations,

Saegusa oxidations have seen use in numerous syntheses, a testament to the usefulness of this transformation. 36

The accepted mechanism for a Saegusa oxidation begins with attack of the alkene on palladium, displacing an acetate. This intermediate ( 3.3 ) is stabilized by a lone pair from the oxygen of the silyl enol ether. The free acetate then bonds to silicon forming

TMSOAc, subsequently cleaving the silicon-oxygen bond ( 3.4 and 3.5 ). β-Hydride elimination from the palladium bound cyclohexanone forms the enone ( 3.2 ), completing the transformation.

Figure 3.1 Mechanism of a Saegusa Oxidation

A report by Larock utilized oxygen to reoxidize Pd(0) species to Pd(II) in DMSO

(Scheme 3.1). Under these conditions, catalyst loadings as low as 10 mol % were achieved, however, reaction times were increased to 72 h. 37 While this method is environmentally friendly, it still requires a large amount of expensive palladium catalyst and DMSO as a solvent can sometimes be problematic in the isolation of organic substrates when compared to more traditional organic solvents, i.e. dichloromethane or diethyl ether.

Scheme 3.1: Larock’s modification of Saegusa Oxidations

In 1992, Takayama reported the conversion of methyl enol ethers to α,β-unsaturated aldehydes using 0.5 to 1 equivalents of Pd(OAc) 2 and 1 equivalent of Cu(OAc) 2•H 2O

34b under basic conditions (Table 3.1). Lowering the amount of Pd(OAc) 2 under these reaction conditions results in a significant decrease in yield. Methyl enol ethers provide a more stable enolate equivalent, but the inability to decrease catalyst loading to levels that would encourage larger scale reactions, inhibits its utility. In all of the aforementioned methodologies, enones are primarily formed with only a few examples of α,β-unsaturated aldehydes.

Table 3.1: Formation of α,β-unsaturated aldehydes from alkyl enol ethers

More recently it has been shown that 10 mol % PdCl 2 and DDQ can convert alkenes ( 3.11 ) to α,β-unsaturated aldehydes ( 3.12 ). Substrates must contain an allylic or benzylic alkene and functional group compatibility is extremely limited to alkyl, methoxy, and fluoro substituted aromatic rings. 38

Scheme 3.2: Formation of enals using PdCl 2 and H 2O

Common indirect methods of forming α,β-unsaturated aldehydes ( 3.15 ) include a three step modification beginning with a Wittig reaction, employing methyl or ethyl

(diethoxyphosphoryl)acetate ( 3.14 ), followed by a DIBAL reduction of the α,β- 93 unsatutrated ester, to form the allylic alcohol. The allylic alcohol is then oxidized to the

39 aldehyde using an oxidant such as MnO 2. Additionally, formation of the propargylic alcohol from a lithiated alkyne and formaldehyde followed by a reduction/oxidation sequence has been used to form enals. 40

Figure 3.2: Alternative syntheses of enals

3.3 Results and Discussion

Allylic oxidations of internal olefins are more difficult than terminal olefins, requiring higher catalyst loadings and longer reaction times while suffering from low yields and regioselectivities. However, our lab recently discovered that allylic oxidations of cis - vinylsilanes proceed with low catalyst loadings in moderate yields and high regioselectivity. The unusual reactivity of cis -vinylsilanes can be attributed to the

94 decreased steric bulk about the alkene due to the longer vinylic C-Si bond (1.8 Ǻ) which results in stronger coordination of palladium to the alkene. 32 We initially hypothesized that vinyl fluorides would also make good substrates for allylic oxidations due to the small atomic radius of fluorine. The linear products resulting from an allylic oxidation of vinyl fluorides would provide 1-fluoroallylic acetates, which are known to undergo addition elimination reactions in the presence of a nucleophile to form α,β-unsaturated aldehydes. 41 Additionally, whereas silyl enol ethers commonly used in Saegusa oxidations are acid labile, vinyl fluorides could be carried through multi-step syntheses as a masked aldehyde equivalent, withstanding acidic and oxidative conditions.

Using trifluorochloromethane and 4 equivalents of tributylphosphine, 1-fluorotridec-

1-ene ( 3.18 ) was synthesized from 1-dodecanal ( 3.17 ). 42 Isolation of the product required distillation from the crude reaction mixture and was somewhat troublesome due to the high boiling point of the product.

Scheme 3.3: Synthesis of vinyl fluorides

Submitting 1-fluorotridecene to our original allylic oxidation conditions of terminal olefins (Pd(OAc) 2, PhSCH 2CH 2O( p-tolyl), and benzoquinone (BQ) in acetic acid) unexpectedly directly produced ( E)-tridec-2-enal ( 3.21 ), in the absence of an added

95 nucleophile, rather than the expected product, ( E)-1-fluorotridec-2-en-1-yl acetate ( 3.19 ), albeit in low yield. It was proposed that first an allylic oxidation occurred to form the linear allylic acetate followed by addition/elimination from 3.20 to form the α,β- unsaturated aldehyde, initiated by water present in the acetic acid.

Figure 3.3: Formation of an enal from a vinyl fluoride

Optimization of the reaction conditions showed that increasing the metal to ligand ratio increased conversion to the enal, 3.21 . Increasing loadings of Pd(OAc) 2 only gave full conversion after 25 mol % of Pd(OAc) 2 with 8% PhSCH 2CH 2O( p-tolyl) (entries 1-3,

6, and 8). If other solvents were used very little product formation was observed (entry

4). Molecular sieves also inhibited product formation (entry 5). When no ligand was included, only 0.1:1 ratio of P:SM was noted.

Table 3.2: Optimization of conditions using a vinyl fluoride

Even though the transformation of 1-fluorotridec-1-ene ( 3.18 ) to ( E)-tridec-2-enal

(3.21 ) was successful, the lower catalyst loadings (compared to traditional Saegusa oxidations) were outweighed by the troublesome, expensive syntheses of vinyl fluorides and low yields of the aldehyde. Methods to synthesize vinyl fluorides often require expensive reagents such as Selectfluor or tedious purification procedures. 42-43 Therefore, we began to search for an alternative reagent for the synthesis of α,β-unsaturated aldehydes.

The most common synthesis of vinyl chlorides, the Takai olefination, requires an

44 excess of expensive CrCl 2 salts. Other vinyl halides such as vinyl iodides and vinyl bromides are more commonly found in the literature and easily synthesized from vinylsilanes 45 or vinylboranes 46 . Submission of ( E)-1-iodohept-1-ene or ( Z)-1- bromohept-1-ene to the reaction conditions yielded no α,β-unsaturated aldehyde.

Additionally, 1,1-dibromohept-1-ene 47 and ( E)-hept-1-en-1-ylboronic acid also showed no formation of the α,β-unsaturated aldehyde under the aforementioned reaction conditions. The radius of iodine, bromine, and boronic acids are large, and the resulting steric interactions may prevent alkene coordination to a metal center, likely the first step in these reactions.

Scheme 3.4: Attempted enal formation from vinyl halides and boronic acids

We postulated that in addition to possessing the ability to withstand a variety of reaction conditions, methyl enol ethers would be susceptible to allylic oxidations because of the decreased steric bulk of the ether moiety. Substrates could be easily formed through a Wittig olefination using (methoxymethyl)triphenylphosphonium chloride

(3.25 ) which is easily and inexpensively formed from PPh 3, AcCl, Ac 2O, and (MeO) 2CH 2 in toluene. 48

Scheme 3.5: Synthesis of (methoxymethyl)triphenylphosphonium chloride 98

Additionally, methyl enol ethers could be synthesized through formation of dimethyl ketals using trialkyl orthoformates followed by elimination of MeOH with p-

TSA. 49

Scheme 3.6: Synthesis of methyl enol ethers

Initial investigations commenced with ( E)-1-methoxytridec-1-ene ( 3.29 ), in

AcOH with 5 mol % Pd(OAc) 2, 5 mol % PhSCH 2CH 2O( p-tolyl) and 2 equivalents of benzoquinone. The reaction mixture was monitored by GC analysis and indicated the formation of a major product, which was determined to be ( E)-tridec-2-enal ( 3.21 ) upon isolation.

Scheme 3.7: Conversion of methyl enol ethers to enals using Pd(OAc) 2

Using (4-(methoxymethylene)cyclohexyl)benzene ( 3.30) to optimize conditions, the reaction was found to be effective in the absence of the thioether ligand (entries 2 and

3). If Pd(OAc) 2 was excluded from the reaction, no conversion to the enal ( 3.31) was observed (entry 1). When the catalyst loading was decreased to 0.5 mol %, yields suffered as well (entry 4). Heating the reaction to 90 °C was also detrimental to yields

(entry 5). The addition of 1.1 equivalents of water was necessary for good conversions when using 0.5 mol % Pd(OAc) 2 (entry 6). Increasing the catalyst loading slightly to 1.5 mol % with the addition of water gave satisfactory yields of enal and under these conditions the amount of benzoquinone could be reduced to 1.2 equivalents (entries 7 and

8). Moreover, when the reaction was run at 23 °C, a slight increase in yield was noted

(entry 9).

Table 3.3: Optimization of conditions using an alkyl enol ether

100

In order to quickly evaluate the scope of this reaction, 1-methoxytridec-1-ene

(3.29 ), (4-methoxybut-3-en-1-yl)benzene ( 3.9 ), and (4-

(methoxymethylene)cyclohexyl)benzene ( 3.30) were submitted to the conditions using

AcOH and H 2O at 23 °C. The corresponding enals of 1-methoxytridec-1-ene, (4- methoxybut-3-en-1-yl)benzene, and (4-(methoxymethylene)cyclohexyl)benzene ( 3.21 ,

3.10 , and 3.31) were isolated in a 71%, 65%, and 81% yield, respectively. Under these conditions isolated yields were comparable to GC yields using an internal standard.

Table 3.4: Substrate screen in AcOH

A solvent screen revealed acetic acid to be the best solvent, however, CH 2Cl 2 and acetone with 4 equivalents of AcOH were found to be only slightly lower yielding

(entries 1,2 and 6). The advantage of using less acetic acid to achieve milder conditions

101 outweighed the marginal difference in yield. Dioxane and toluene also performed well, albeit with slightly lower yields, while MeCN gave poor conversions (entries 3-5).

Table 3.5: Solvent screen an alkyl enol ether

Gratifyingly, upon continued screening of substrates, this methodology was found to tolerate a broad array of functional groups. Methyl enol ethers of hydrocarbons (3.29 and 3.9 ) formed the corresponding enals in relatively good yields (entries 1 and 2). Silyl ethers (3.34) and acetate esters (3.36) tolerated the mild reaction conditions (entries 3 and

4). cis -Vinylsilanes (3.38 ) proceeded to form the α,β-unsaturated aldehyde (3.39 ) in a

67% yield (entry 6). Methoxy methylene cyclohexanes (3.30, 3.40, 3.41, and 3.43) also behaved well, giving high yields of the desired trisubstituted α,β-unsaturated aldehydes

(entries 7-10). Imides in the form of phthalimide (3.45) and succinimide (3.47 ) gave the product in good yields as well (entries 11 and 12). Trisubstituted alkenes ( 3.50) could also be formed in benzo-fused 7-membered rings (entry 13). Additionally, 102 tetrasubstituted alkenes (3.52) could also be formed in a 57% yield (entry 14). This represents the first example of a tetrasubstituted alkene formed from an enol ether.

103

Table 3.6: Substrate screen of alkyl enol ethers

104

Most reactions proceeded to complete conversion of staring material to saturated and unsaturated aldehydes, but yields did not always reflect this product distribution.

Reactions were monitored to see if any decomposition of product or starting material was present during the reaction. The reaction was monitored by GC analysis and plotted as a function of time. Results indicate that there is a slight decrease in the total amount of product and starting material, however, this decrease is likely within error of the GC.

Figure 3.4: Formation of α,β-unsaturated aldehyde over time

Oxygen as a stoichiometric oxidant would provide an obvious advantage over benzoquinone. Alternate reaction conditions comprised of 10 mol % dihydroquinone, 5 mol % Cu(OAc) 2, and one atmosphere of oxygen could be utilized as a reoxidant for palladium instead of stoichiometric benzoquinone. Under these conditions a higher

105 loading of palladium acetate is required and yields tend to be slightly lower than with benzoquinone (Table 2, Entries 1-4).

Table 3.7: Substrate screen of alky enol ethers using O 2

While most enol ether substrates underwent oxidation smoothly to the enal, some substrates failed to react, decomposed, or reacted slowly under the reaction conditions.

The dibenzyl substrate ( 3.53) was completely unreactive under the reaction conditions most likely due to steric hindrance around the alkene. The carbamate and acetonide ( 3.54 and 3.55) were either unstable under the reaction conditions or the resulting products were unstable since at the end of the reaction time only small amounts of any product were observed by GC analysis. The enol ether formed from α-tetralone ( 3.56 ) formed product but was never able to give complete conversion with 5 mol % Pd(OAc) 2.

106

Figure 3.5: Substrates that perform poorly under optimized conditions

Methyl enol ethers derived from ketones, such as cyclohexanone, primarily resulted in formation of the saturated ketone with little (<10%) formation of the desired

α,β-unsaturated ketone (entry 1). If THF was used as a solvent with 1.1 equivalents of

H2O, a 0.5:1 cyclohexenone ( 3.58 ) to cyclohexanone (3.59 ) ratio was observed, however, the reaction required 72 h to proceed to completion (entry 2). The ratio of cyclohexenone product could be improved if 5.5 equivalents of H 2O were used, but conversion remained low (entry 3). Other solvents such as CH 2Cl 2 and acetone proved less effective than THF

(entries 4 and 5). Currently, the best conversions and ratio of cyclohexenone to cyclohexanone are obtained when 5.5 equivalents of H 2O, 0.07 equivalents of AcOH and

THF is used as a solvent (entry 7). It is possible that ketones may allow protonation of an

107 intermediate palladium species by acetic acid, which could persevere over β-hydride elimination, forming the undesired saturated product.

Table 3.8: Formation of cyclohexenone from alkyl enol ethers

The formation of unsaturated aldehydes could proceed through a variety of mechanisms. Potentially isolable intermediates contain boxes around them. The simplest mechanism is an acetoxypalladation/Wacker mechanism where either acetate or water and palladium are regioselectively added across the alkene ( 3.61 and 3.64) (pathways 1 and 2). The resulting intermediate could undergo β-hydride elimination and either a nucleophilic addition elimination mechanism or loss of water to form the respective complexes ( 3.63 and 3.66 ). Proceeding through a π-allyl palladium mechanism requires an initial C-H activation followed by a regioselective reductive elimination of acetate or water (pathways 4 and 5). The reductive elimination would provide the same 108 intermediates as shown in the acetoxypalladation mechanism ( 3.62 and 3.65) which would undergo an addition elimination sequence or loss of water to form the α,β- unsatuarated product ( 3.63 and 3.66) . The last proposed mechanisms are similar to the

Saegusa mechanism except rather than acetate attacking the enol ether, the acetate traps an alkylated aldehyde intermediate to form 3.61 or 3.64 (pathways 5 and 6). Again, these intermediates are similar to those proposed for the acetoxypalladation/Wacker mechanism.

109

Figure 3.6: Possbile mechanistic pathways for enal formation from enol ethers

110

18 To test whether water or acetate was responsible for aldehyde formation H 2O

(60-65%) was added to dry AcOH used in the reaction. The product of these reactions showed O 18 incorporation into the aldehyde ( 3.70). Unfortunately a control experiment,

18 submitting the product to the reaction conditions using H 2O also showed incorporation of O 18 , likely due to the equilibrium and exchange of water with aldehyde during these reactions.

Scheme 3.8: O 18 incorporation into enals

Further, investigation of the mechanism showed no evidence of 1-methoxy acetate intermediates, which would result from an allylic oxidation of the alkyl enol ether. Lack of a KIE for the oxidation of deuterated 4-

(methoxymethylene)cyclohexyl)benzene alluded to the fact that coordination of the alkene to palladium could be the rate limiting step.

111

Figure 3.7: KIE of α,β-unsaturated aldehyde formation

No reaction was seen in the absence of AcOH or under anhydrous conditions.

Analysis of the crude reaction mixture revealed formation of MeOH with no MeOAc present, excluding the possibility of a mechanism analogous to Saegusa oxidations, where acetate from Pd(OAc) 2 results in formation of TMSOAc and an intermediate palladium species (3.4 and 3.5 ). Stirring 4-(methoxymethylene)cyclohexyl)benzene in

CH 2Cl 2 in the presence of a stoichiometric amount of Pd(OAc) 2 followed by addition of nBu 4NCl gave <5% formation of π-allyl palladium chloride species. Therefore, the simplest mechanism consistent with our findings is coordination of the alkyl enol ether to palladium followed by a regioselective Wacker oxidation directed by the ether moiety.

The resulting hemiacetal palladium species (3.61) could then undergo β-hydride eliminaton (3.62) and dissociation to form the α,β-unsaturated aldehyde (3.63) and methanol. 112

3.4 Conclusion

In conclusion we have demonstrated an efficient conversion of alkyl enol ethers to

α,β-unsaturated aldehydes. The stability of alkyl enol ethers increases the utility of this transformation. Catalyst loadings are significantly lower than any previously reported

Saegusa oxidations and the mild reaction conditions tolerate a broad array of functional groups. A method employing oxygen as a replacement for benzoquinone has also been demonstrated.

3.5 Future work

Currently, ongoing efforts to further develop this methodology using vinyl fluorides are underway. Vinyl fluorides would offer the advantage of a masked α,β- unsaturated aldehyde equivalent. Additionally, vinyl fluorides can be synthesized without a one carbon homologation under neutral conditions.

The limitation of this method to terminal alkyl enol ethers prevents its utility and expansion to alkyl enol ethers which could yield α,β-unsaturated ketones would be useful. Under conditions optimized for enal formation, saturated ketones are the predominant product, and unfortunately premliminary work has yielded only modest results.

113

Chapter 4: Characterization, Reactivity and Potential Catalytic

Intermediacy of a Cyclometalated Tri-tert -butylphosphine Palladium

Acetate Complex

4.1 Abstract

Palladium acetate and tri-tert -butylphosphine react at room temperature via C-H activation to form a novel cyclometalated complex. This complex can be reduced to

Pd(P tBu 3)2 by either heat or hydrogen but is resistant to reduction by alkoxide bases and amines. As a result, this complex prevents quantitative formation of active Pd(0) species in room temperature amination reactions. Additionally, complexed tri-tert - butylphosphine can be displaced by nitrogen and phosphine ligands to form a series of novel cyclometalated complexes.

4.2 Background

114

Development and application of palladium-catalyzed cross-coupling reactions is a dominant area of research in synthetic chemistry. The utility of these classes of reactions was punctuated in 2010 with the awarding of the Nobel Prize in Chemistry to three pioneers in cross-coupling chemistry, Richard Heck, Ei-ichi Negishi, and Akira Suzuki. 50

At the forefront of the advancement of these reactions was the discovery that the combination of palladium salts with bulky, electron-rich trialkylphosphines created highly unsaturated and reactive catalysts. 51 One of the first widely applicable bulky, electron-rich ligands was tri-tert -butylphosphine (P tBu 3). The increased activity of P tBu 3 is highlighted by its ability to form stable unsaturated T-shaped monomeric palladium complexes, which are proposed catalytic intermediates in many reactions. 52 In 1997, the

Tosoh Corporation reported that Pd(dba) 2 (dba = dibenzylideneacetone) or Pd(OAc) 2, when used with P tBu 3, effectively catalyzes the amination of aryl halides with piperazines. 53 More recently, Hartwig and co-workers have expanded the scope of

54 palladium-catalyzed reactions using PtBu 3 in aryl aminations as well as α-arylations of

55 56 carbonyls and nitriles. Additionally, Fu and co-workers have shown that P tBu 3 and a palladium salt effectively catalyze Suzuki-Miyaura, 57 Negishi, 58 Heck, 59 Sonogashira, 60 and Stille 61 cross-coupling reactions with arylbromides and arylchlorides. 62

Most of the catalytic cycles proposed in palladium-catalyzed cross-coupling reactions are believed to operate on a Pd(0)/Pd(II) platform. The favored starting palladium pre- catalysts are Pd(dba) 2 and Pd(OAc) 2 as they are readily available or easily prepared, and are stable to air and moisture. The widespread use of Pd(dba)2 as a precatalyst is interesting because of the ability of dba to deleteriously affect a reaction outcome. 63

115

Moreover, the actual composition of Pd(dba) 2 is subject to preparatory method of choice, can vary from batch to batch and is difficult to quantify its purity spectroscopically.

However, Pd(dba) 2 provides a more direct route to generating a desired palladium catalyst than Pd(OAc) 2 because one can imagine that a mixture of Pd(dba) 2 and externally added phosphine react together and the weaker dba ligand is replaced at the metal by the phosphine. The second dba ligand can then be displaced by another phosphine or by the incoming substrate. 64 Moreover, the oxidation state at palladium goes unchanged upon addition of ligand and once the catalyst is formed, oxidative addition can occur resulting in a change in oxidation state from Pd(0) to Pd(II).

The formation of palladium catalysts from Pd(OAc) 2 is not as straightforward in this regard. From a structural standpoint, palladium acetate is well defined, 65 however, the oxidation state of Pd(OAc) 2 is Pd(II) and the mode of reduction to Pd(0) upon addition of phosphine is still unclear in many cases. 66 Typically, no intermediate palladium species are isolated during these reductions and studies relating to the reduction of

Pd(OAc) 2/P tBu 3 combinations have not been reported.

If one charges 5 mol % of Pd(OAc) 2 and a corresponding ligand into a cross-coupling reaction, the intermediate reactions that follow are unlikely to produce the active catalytic species with quantitative conversion. Therefore, the identification of intermediate complexes during these transformations is important to understand how to more cleanly generate a complex that better resembles the active catalyst, 67 while avoiding any potential reactions that unproductively consume Pd(OAc) 2 and ligand. The identification and isolation of these complexes may help to design catalysts that allow for decreased

116 catalyst loading and increased catalyst turnover. We have recently discovered one of these complexes, a cyclometalated complex formed from the facile C-H insertion of

Pd(OAc) 2 with P tBu 3 at room temperature.

4.3 Results and Discussion

While repeating a procedure using a catalyst formed from five equivalents of P tBu 3 and one equivalent of Pd(OAc) 2, employing a smaller amount of expensive P tBu 3 was desired. Moreover, it was unclear what the identity of the product of this reaction would be. Initially, one would expect Pd(P tBu 3)2 to somehow form. The formation of this Pd(0) complex could arise from the generation of Pd[(P tBu 3)2(OAc) 2] that further reacts to form

Pd(P tBu 3)2. However, the existence of metal complexes containing two bulky P tBu 3 ligands on a single palladium center is rare. 68 A quick investigation of this reaction by 31 P

NMR spectroscopy did not show any evidence of the diacetate complex or Pd(P tBu 3)2. A large signal corresponding to uncoordinated P tBu 3 at 63.1 ppm was observed along with broad signals near 68.1 ppm and -8.0 ppm. The downfield resonances closer to uncomplexed P tBu 3 are in the area of datively bound P tBu 3, while PtBu 3 resonances upfield from 0 ppm typically correspond to cyclometalated phosphines. Therefore, it was believed that there were at least two distinct complexes present in this reaction.

Repeating the reaction using two equivalents of P tBu 3 produced the same resonances in the 31 P NMR spectrum, less the free phosphine peak at 63.1 ppm. Crystallization of the crude reaction mixture from pentane unexpectedly provided the single novel complex 117

[(P tBu 3)Pd(CH 2C(CH 3)2PtBu 2)(OAc)]HOAc (4.1 ), in 81% yield, resulting from insertion into the C-H bond of P tBu 3 and formation of AcOH. Because complex 4.1 was formed from mixing P tBu 3 and Pd(OAc) 2 at room temperature, it either functions as a precatalyst to the active catalytic species or as a product of the catalyst deactivation pathway, and may provide insight into how Pd(OAc) 2 is reduced to Pd(0) in cross- coupling reactions that employ PtBu 3 as a ligand.

Scheme 4.1: Formation of complex 4.1 from P tBu 3 and Pd(OAc) 2

The seemingly complex 31 P NMR spectrum is caused by the equilibrium of 4.1 and known dimeric complex 4.2 (Scheme 2). At -14 °C the broad resonances in the 31 P NMR and 1H NMR spectra coalesce to form two sharp, distinct signals that correspond to datively bound PtBu 3 at 68.1 ppm and the cyclometalated P tBu 3, which appears at -8.0 ppm (Figure 1).

Scheme 4.2: Equilibrium between complex 4.1 and complex 4.2 118

If one equivalent of PtBu 3 is added to Pd(OAc) 2 the known cyclometalated palladium dimer 4.2 is formed in situ and is identified by a broad resonance at -8.9 ppm. Addition of another equivalent of P tBu 3 causes dimer 4.2 to dissociate forming complex 4.1 . Any additional P tBu 3 remains as free ligand exchanging with bound P tBu 3, noted by the broad signal at 63.1 ppm.

Figure 4.1: 31 P NMR of complex 4.1 at a) 33 °C, b) 16 °C, c) 6 °C, d) -14 °C

An X-ray crystal structure of complex 4.1 was obtained (Figure 1). The geometry about the palladium center is distorted square planar with C(2)-Pd-O(1) and P(1)-Pd-P(2) bond angles of 162.3° and 167.0°, respectively. The cyclometalated phosphine has a bite angle of 68.3°, slightly more strained than observed in the previously reported X-ray crystal structure of the cyclometalated dimer, bis(µ-chloro)bis[2-(di-tert - butylphosphino)-2-methylpropyl]dipalladium, 69 which has a bite angle of 70.0°. The Pd-

C(2) and Pd-P(1) bond lengths are 2.066 Å and 2.279 Å respectively, compared to 2.052

119

Å and 2.209 Å in bis(µ-chloro)bis[2-(di-tert -butylphosphino)-2- methylpropyl]dipalladium. The Pd-O(1) bond is 2.156 Å, and slightly elongated compared to the known Herrmann-Beller palladacycle with bridging acetates which have

Pd-O bond distances of 2.147 and 2.111 Å.70

Figure 4.2: X-ray crystal structure of complex 4.1

In order to better understand how complex 4.1 may function as a catalyst precursor, we attempted to affect its reduction to Pd(0) by adding bases typically utilized in cross- coupling reactions. In THF at 23 °C, K 2CO 3, Cs 2CO 3, K 3PO 4, and NaOAc do not promote reduction to Pd(0) as observed by 31 P NMR spectroscopy. Interestingly, the addition of NaO tBu created a new unidentifiable complex with a sharp 31 P NMR signal at

120

-2.4 ppm and free P tBu 3. All attempts to isolate this complex were unsuccessful. This complex could potentially be formed via tert -butoxide coordinating to palladium, displacing either the acetate, P tBu 3, or both.

Complex 4.1 was then submitted directly to a hydrogen atmosphere, since hydrogenations have been reported with Pd(OAc) 2 and excess P tBu 3 in the presence of formic acid in THF. 71 Interestingly, when complex 4.1 is stirred in either THF or toluene at 23 °C under a hydrogen atmosphere it was cleanly converted to Pd(P tBu 3)2 in 12 h.

Further investigations into the reactivity of complex 4.1 showed that in the presence of

O2 and air the complex decomposes forming tri-tert -butylphosphine oxide and minor amounts of unidentified products. Not surprisingly, complex 4.1 is unreactive towards aryl bromides and aryl iodides at room temperature.

Since many reactions containing Pd(OAc) 2/P tBu 3 combinations require elevated temperatures, we postulated that thermal decomposition to Pd(0) might be possible.

Complex 1 is stable in toluene at 23 °C for days, however, when heated to 90 °C, decomposes within 12 h to form Pd(P tBu 3)2.

Scheme 4.3: Reduction of complex 4.1 to Pd(P tBu 3)2

121

To study the reactivity of complex 4.1 in cross-coupling reactions, we submitted 4.1 to previously reported reaction conditions that do not require elevated temperatures, thus preventing thermal decomposition to Pd(0) complexes. Hartwig has shown that

Pd(OAc) 2 and 0.8 equivalents of PtBu 3 catalyze the amination of ortho -substituted aryl bromides at room temperature. 54 We submitted complex 4.1, cyclometalated dimer 4.2, and Pd(P tBu 3)2 to the reported reaction conditions using 2-bromotoluene and dibutylamine (Table 1, entries 1-3)). Surprisingly, all three complexes gave poor yields of N,N-dibutyl-o-toluidine. These reactions were then repeated at 60 °C and 110 °C. At

60 °C, the reaction proceeds in higher yields and faster reaction times for all complexes; however, none of the complexes catalyzed the reaction in yields comparable to reported conditions (entries 4-6). At 110 °C, yields and reaction times suffer, perhaps due to rapid catalyst decomposition (entries 7-9).

Table 4.1: Aryl aminations with complex 4.1, complex 4.2, and Pd(P tBu 3)2

122

To identify the active catalyst in the amination reaction, Pd(OAc) 2 and 0.8 equivalents

31 PtBu 3 were stirred in toluene for 1 h. The P NMR spectrum showed an unidentified resonance at -11.3 ppm and 4.2. Attempts to isolate the source of the signal at -11.3 ppm were unsuccessful. If five equivalents of NaO tBu are added to complex 4.1 or complex

4.2, a resonance at -2.4 ppm appears, indicating formation of the unknown complex.

Surprisingly, if Pd(OAc) 2, 0.8 equivalents of P tBu 3 and five equivalents of NaO tBu are stirred together in toluene, a resonance at -2.4 ppm appears as well as a much smaller resonance at 85.7 ppm corresponding to Pd(P tBu 3)2.

Secondary and tertiary amines are known to promote the reduction of Pd(OAc) 2 to

66c Pd(0) when used in conjunction with alkoxide bases. Indeed, when Pd(OAc) 2, 0.8 equivalents of P tBu 3, 5 equivalents of NaO tBu, and HNBu 2 are stirred in toluene the only phosphine resonance present is at 85.7 ppm, indicating formation of Pd(P tBu 3)2. Lastly, 123 if 5 equivalents of NaO tBu, HNBu 2, and either complex 4.1 or complex 4.2 are stirred together in toluene, initially, only a very small amount of Pd(P tBu 3)2 is seen along with a large signal at-2.4 ppm. After 18 h at room temperature, complex 4.1 showed only a

31 small amount of Pd(P tBu 3)2 by P NMR spectroscopy, while complex 4.2 continues to slowly form Pd(P tBu 3)2. The low yields of arylamines combined with the ability of complex 4.1 to withstand conditions that would typically reduce Pd(II) sources to Pd(0) lead to the conclusion that complex 4.1 is not an intermediate that leads to formation of the active catalyst under these conditions. Instead, complex 4.1 is likely a product along the catalyst decomposition pathway.

124

Figure 4.3: Reduction of complex 4.1 using NaO tBu and HNBu 2

Because complex 4.1 is able to withstand reduction to Pd(0) in the presence of amines, we chose to examine whether secondary amines were unreactive towards complex 4.1 or potentially formed new complexes, preventing reduction to Pd(0). The addition of morpholine to complex 4.1 results in displacement of coordinated P tBu 3, forming a new cyclometalated complex rather than a Pd(0) species. The morpholine-containing complex 4.5 was isolated by recrystallization from pentane in 58% yield. We hypothesized that because of the bulkiness of P tBu 3 at the palladium center, this ligand

125 could also be displaced by smaller, less basic phosphines. Indeed, the addition of PPh 3 to

4.1 readily displaces P tBu 3 after 2 h at 23 °C to form the PPh 3 ligated complex 4.6 in 93% yield. Spectroscopically, complex 4.6 is well defined in the 31 P NMR spectrum, showing two sharp doublets at 23 °C. Other phosphines such as dppe (1,2- bis(diphenylphosphino)ethane) are also able to displace P tBu 3 forming the corresponding complex 4.7 in 98% yield.

Figure 4.4: Displacement of P tBu 3 with morpholine, PPh 3, and dppe

Complexes 4.5 and 4.6 are alternatively formed from the addition of 1 equivalent of P tBu 3 and 1 equivalent of PPh 3 or morpholine respectively in THF to a stirring solution of Pd(OAc) 2. The addition of dppe and P tBu 3 to Pd(OAc) 2 primarily forms

72 previously reported (dppe) 2Pd(OAc) 2.

126

Figure 4.5: Direct synthesis of complexes 4.5 and 4.6 from Pd(OAc) 2

73 Recently, P tBu 2Me has seen expanded use as a ligand in cross-coupling reactions.

While P tBu 2Me is similar to P tBu 3 electronically, it has a significantly smaller cone angle

(161° for P tBu 2Me vs. 182° for P tBu 3), and when 2.3 equivalents are stirred with

Pd(OAc) 2 in THF for 2 h, no cyclometalated complexes resulting from C-H activation are seen. Instead, previously unreported, Pd[(P tBu 2Me) 2(OAc) 2] ( 4.8 ) is formed in 69% yield, which may lend insight into the steric requirements for facile C-H activation.

Indeed, some complexes containing bulky P tBu 3 show an agostic C-H interaction that may allude to a low barrier of activation towards cyclometalation. 52 Additionally, the inability of P tBu 2Me to form stable cyclometalated complexes with Pd(OAc) 2 may explain enhanced yields in certain cross-coupling reactions when PtBu 2Me was used instead of P tBu 3.

127

Scheme 4.4: Formation of 4.8

Cyclometalated complexes are reported in the literature and occasionally lead to highly reactive catalysts, such as allylic substitutions catalyzed by iridium and a cyclometalated phosphoramidite ligand. 74 In contrast, the results provided herein indicate that complex

4.1 is likely a catalyst decomposition product at room temperature, unable to form Pd(0) species in catalytically useful amounts. However, prior to cyclometalation, Pd(OAc) 2 in

t the presence of NaO Bu, dibutylamine, and P tBu 3 is readily reduced to Pd(0). Moreover, the stability of complex 4.1 is demonstrated in its ability to withstand reduction to Pd(0) under conditions which reduce Pd(OAc) 2/P tBu 3 and complex 4.2 to Pd(P tBu 3)2, a Pd(0) species.

The analysis and identification of catalyst decomposition pathways is often overlooked and understudied. However, the importance in identifying such species lies in the ability to engineer long-lived catalysts that avoid rapid decomposition pathways. For example, it is common in the literature to find procedures in which a metal salt and ligand are pre- mixed, prior to the addition of substrate and other reactants, to effectively form a catalyst 128

19,75 precursor or the active catalyst. However, if Pd(OAc) 2 and two equivalents of P tBu 3 are pre-mixed, reactions may proceed slowly or not at all at room temperature, thus requiring elevated temperatures in order to effectively catalyze reactions. Procedurally, since the cyclometalation of Pd(OAc) 2 and P tBu 3 occurs at room temperature, it would be pertinent to avoid combining Pd(OAc) 2 and P tBu 3 in solution without base, or a combination of amine and base present. Furthermore, the stoichiometry of Pd(OAc) 2 to

PtBu 3 must be considered. In many cases the optimal stoichiometry of P tBu 3 to

Pd(OAc) 2 is less than 2:1, with greater amounts of P tBu 3 requiring higher temperatures. 51,54,76 The ability of 4.1 to thermally decompose to a zero-valent palladium species should also be noted. While triarylphosphine ligands readily form Pd(0) complexes from Pd(OAc) 2, even at room temperature, it would be worthwhile to identify a bulky electron rich trialkylphosphine ligand that would readily form a zero-valent palladium complex from Pd(OAc) 2 without the addition of external reagents.

4.4 Conclusion

In conclusion we have demonstrated that Pd(OAc) 2 and P tBu 3, which are commonly used in cross-coupling reactions, form the novel palladacyclic complex 4.1 through a facile C-H insertion step at room temperature. The formation of this complex prevents quantitative formation of the precatalyst to the active Pd(0) species. This C-H insertion is likely due to the pronounced steric nature of P tBu 3, as P tBu 2Me, another electron rich trialkylphosphine, does not form cyclometalated products with Pd(OAc) 2 at room 129 temperature. With respect to aminations of ortho -substituted aryl bromides, palladacycle

4.1 is catalytically active. However, 4.1 appears to move further away from the predominant active catalytic species as reactions conducted with this complex are slower and significantly lower yielding than reactions using in situ generated catalyst from

Pd(OAc) 2 and PtBu 3. While complex 4.1 is stable to reduction in the presence of amine and base, we have shown that it may be reduced to Pd(PtBu 3)2 with heat or hydrogen.

The ability of 4.1 to form Pd(0) complexes at elevated temperatures provides an avenue for entry into general Pd(0)/Pd(II) catalysis. Typically, strongly coordinating PtBu 3 is easily displaced from palladacycle 4.1 by smaller, more weakly binding nitrogen and phosphorus containing ligands. Utilizing the ability to easily displace P tBu 3, we have prepared a series of novel cyclometalated complexes

130

Chapter 5: Experimental Details

5.1 General Methods

All reactions were performed in oven dried glassware or 4 mL borosilicate glass vials with a Teflon septum cap. Allylic oxidations of terminal alkenes and vinylsilanes as well as reactions of alkyl enol ethers to form α,β-unsaturated aldehydes were run under an air atmosphere. All other reactions were run under nitrogen (N 2) or argon (Ar) unless otherwise stated. All solvents were reagent grade and predried or distilled. 1,2-

(benzylthio)ethane, 77 bis(phenylthio)methane, 78 1,3-bis(phenylthio)propane, 79 1,4- bis(phenylthio)butane, 79 1,2-bis(ethylthio)ethane, 80 N-methyl-N-(2-

(phenylthio)ethyl)aniline, 81 diphenyl(2-(phenylthio)ethyl)phosphine, 82 1-allyl-4- fluorobenzene, 83 N-phenylpent-4-enamide, 84 2-(but-3-enyl)-2-methyl-1,3-dioxolane, 85

((pent-4-enyloxy)methyl)benzene, 86 (tert -butyldiphenylsiloxy)-1-pentene, 87 N- phenylbenzamide, 88 N,N-diethylbenzamide, 89 bis[acetate(1,2,3-trihapto-1- dodecene)palladium (II)], 18a phenyl(3-phenylpropyl)sulfane, 90 methyl(phenyl)sulfane, 91 benzyl(phenyl)sulfane, 92 (E)-triethyl(hept-1-en-1-yl)silane,31 (Z)-hept-1-en-1- yltrimethylsilane, 30 (Z)-triethyl(hex-3-en-3-yl)silane,93 and 131

(methylmethoxy)triphenylphosphonium chloride 48 were prepared according to known literature procedures. Palladium acetate was purified by recrystallization from hot benzene. 1,4-Benzoquinone was sublimed before use in reactions. All other commercially obtained reagents were used as received. Thin-layer chromatography

(TLC) was conducted with Sorbent Technologies silica gel UV254 precoated plates (0.25 mm), and visualized using UV lamps and anisaldehyde or potassium permanganate staining. 1H and 13 C NMR spectra were recorded on Bruker spectrometers and are reported relative to TMS. IR spectra were recorded on a Perkin Elmer 1600 FT-IR spectrometer. High resolution mass spectra were obtained from the mass spectrometry facility at The Ohio State University.

132

5.2 Chapter 2: Experimental Details

General Procedure for the Formation of Sulfoxides Method A: To a stirring solution of NaIO 4 (2.05 equiv) in H 2O (2 M) was added the necessary bis-sulfide (1 equiv) in

MeOH (1 M). The reaction was warmed to 60 °C and stirred for 12 h. The MeOH was then removed under reduced pressure and the reaction diluted with H 2O. The aqueous layer was extracted with CH 2Cl 2 (5x50 mL) and the organic layers combined. The organic layer was then dried over Na 2SO 4, filtered, and the organic layer removed under reduced pressure. The resulting solid was purified by recrystallization or flash chromatography on silica gel.

Method B: H2O2 (30% aq) was added dropwise to a stirring solution of sulfide in AcOH

(0.3 M) at 0 °C. The reaction was stirred for 16 h as it warmed to 23 °C. The acetic acid was removed under reduced pressure and the resulting crude sulfoxide was purified by flash chromatography on silica gel to provide the pure sulfoxide

Methyl(3-((methylsulfinyl)methyl)benzyl)sulfane (2.8) : Using method A, NaIO 4 (2.17 g, 10.1 mmol, 2.09 equiv) in H 2O (4 mL) was added to 1,3- bis((methylthio)methyl)benzene (0.800 g, 4.81 mmol) in MeOH (17 mL). After the reaction time and workup, the crude product was purified by column chromatography on

133 silica gel (10% MeOH/EtOAc) to give methyl(3-((methylsulfinyl)methyl)benzyl)sulfane

(0.279 g, 1.29 mmol, 27%) as a white crystalline solid.

-1 1 FTIR (film, cm ): 3032, 2929, 1316, 1118, 1048; H NMR (CDCl 3, 400 MHz): δ 7.47-

7.40 (m, 2H), 7.37-7.40 (m, 2H), 4.28-4.26 (m, 2H), 3.98 (q, J = 13.2 Hz, 2H), 2.80 (s,

13 3H), 2.48 (s, 3H); C NMR (CDCl 3, 100 MHz): δ 132.6, 131.1, 130.9, 130.8, 129.8,

129.1, 61.1, 59.5, 39.5, 37.6.

1,3-Bis((benzylsulfinyl)methyl)benzene (2.9): Using method B, 1,3- bis((benzylthio)methyl)benzene (750 mg, 2.14 mmol) was dissolved in glacial acetic acid

(5 mL) and the solution was cooled to 0 °C. H 2O2 (30% aq, 0.485 mL, 4.28 mmol, 2.00 equiv) was added dropwise and the solution was slowly warmed to 23 °C with stirring.

After stirring for 16 h the acetic acid was removed under vacuum and the crude product purified by flash chromatography on silica gel (10% MeOH/EtOAc) to give 1,3- bis((benzylsulfinyl)methyl)benzene (739 mg, 1.93 mmol, 90%) as a white crystalline solid.

-1 1 FTIR (film, cm ): 3161, 2928, 1096, 1044; H NMR (CDCl 3, 400 MHz): δ 7.41-7.20 (m,

13 14H), 3.93-3.78 (m, 8H); C NMR (CDCl 3, 100 MHz): δ 132.2, 131.2, 130.4, 130.3,

130.1, 129.6, 129.2, 128.6, 57.9, 56.9.

134

2,6-bis((benzylsulfinyl)methyl)pyridine (2.10): Using Method B, 2,6- bis((benzylthio)methyl)pyridine (751 mg, 2.14 mmol) was dissolved in glacial acetic acid

(5 mL) and the solution was cooled to 0 °C. H 2O2 (30% aq, 0.484 mL, 4.27 mmol, 2 equiv) was added dropwise and the solution was slowly warmed to 23 °C with stirring.

After stirring for 16 h the acetic acid was removed under vacuum and the crude product purified by flash chromatography on silica gel to give 2,6- bis((benzylsulfinyl)methyl)pyridine (704 mg, 1.84 mmol, 86%) as a white crystalline solid.

-1 1 FTIR (film, cm ): 3065, 3031, 2923, 1589, 1573, 1454, 1041; H NMR (CDCl 3, 400

MHz): δ 7.72-7.68 (m, 1H), 7.36-7.29 (m, 12H), 4.18-4.10 (m, 4H), 3.99-3.95 (m, 4H);

13 C NMR (CDCl 3, 100 MHz): δ 154.5, 137.6, 137.5, 130.4 (2), 129.8 (2), 128.9, 128.4,

124.8 (2), 57.9, 57.8, 57.6, 57.5.

2,6-bis((methylsulfinyl)methyl)pyridine (2.11): To a stirring solution of NaIO 4 (1.65 g,

7.69 mmol, 2.10 equiv) in H 2O (8 mL) at 0 °C was added 2,6- bis((methylthio)methyl)pyridine (730 mg, 3.66 mmol) in MeOH (5 mL). The reaction was stirred for 12 h while warming from 0 °C to 23 °C. The MeOH was then removed under reduced pressure and the reaction diluted with H 2O. The aqueous layer was extracted with CH 2Cl 2 (5x50 mL) and the organic layers combined. The organic layer was then dried over Na 2SO 4, filtered, and the organic layer removed under reduced

135 pressure. The resulting solid was purified by flash chromatography on silica gel (10%

MeOH/EtOAc) to give 2,6-bis((benzylsulfinyl)methyl)pyridine (237 mg, 1.01 mmol,

28%) as a clear oil.

-1 1 FTIR (film, cm ): 2987, 2854, 1591, 1455, 1088, 1047; H NMR (CDCl 3, 400 MHz): δ

7.74 (t, J = 7.6 Hz, 1H), 7.36-7.34 (d, J = 7.6 Hz, 2H), 4.19-4.09 (m, 4H), 2.60 (s, 6H);

13 C NMR (CDCl 3, 100 MHz): δ 151.4 (2), 137.9, 137.8, 124.76, 61.7 (2), 38.4.

2,6-bis((ethylsulfinyl)methyl)pyridine (2.12): To a stirring solution of NaIO 4 (1.17 g,

5.48 mmol, 2.08 equiv) in H 2O (2 mL) was added 2,6-bis((methylthio)methyl)pyridine

(601 mg, 2.64 mmol) in MeOH (10 mL). The reaction was warmed to 60 °C and stirred for 12 h. The MeOH was then removed under reduced pressure and the reaction diluted with H 2O. The aqueous layer was extracted with CH 2Cl 2 (5x50 mL) and the organic layers combined. The organic layer was then dried over Na 2SO 4, filtered, and the organic layer removed under reduced pressure. The resulting solid was purified by flash chromatography on silica gel (10% MeOH/EtOAc) to give 2,6- bis((ethylsulfinyl)methyl)pyridine (23 %) as a clear oil.

-1 1 FTIR (film, cm ): 2981, 2937, 1591, 1381, 1087, 1045, 1021; H NMR (CDCl 3, 400

MHz): δ 7.72 (t, J = 8 Hz, 1H), 7.34-7.30 (m, 2H), 4.18-4.05 (m, 4H), 2.85-2.67 (m, 4H),

13 1.37 (t, J = 7.2 Hz, 6H); C NMR (CDCl 3, 100 MHz): δ 151.6, 151.5, 137.7 (2), 124.6

(2), 58.9 (2), 45.2, 45.1, 6.8 (2).

136

2-((ethylsulfinyl)methyl)pyridine (2.13): Using method B, 2-

((ethylthio)methyl)pyridine (1.04 g, 6.80 mmol) was dissolved in glacial acetic acid (16 mL) and the solution was cooled to 0 °C. H 2O2 (30% aq, 0.771 mL, 6.80 mmol, 1 equiv) was added dropwise and the solution was slowly warmed to 23 °C with stirring. After stirring for 16 h the acetic acid was removed under vacuum and the crude product purified by flash chromatography on silica gel to give 2-((ethylsulfinyl)methyl)pyridine

(1.13 g, 6.68 mmol, 98%) as a clear oil.

-1 1 FTIR (film, cm ): 3020, 2980, 2937, 1593, 1437, 1047; H NMR (CDCl 3, 400 MHz): δ

8.61-8.59 (m, 1H), 7.71 (td, J = 7.6, 1.6 Hz, 1H), 7.37 (dd, J = 7.6, 0.4 Hz, 1H), 7.26 (dd,

J = 7.6, 4.8 Hz, 1H), 4.19-4.08 (m, 2H), 2.84-2.64 (m, 2H), 1.35 (t, J = 7.6 Hz, 3H); 13C

NMR (CDCl 3, 100 MHz): δ 151.0, 149.9, 136.9, 125.3, 123.1, 59.0, 44.9, 6.7.

2-((methylsulfinyl)methyl)pyridine (2.14): Using method B, 2-

((methylthio)methyl)pyridine (801 mg, 5.75 mmol) was dissolved in glacial acetic acid

(12 mL) and the solution was cooled to 0 °C. H 2O2 (30% aq, 0.652 mL, 5.75 mmol, 1 equiv) was added dropwise and the solution was slowly warmed to 23 °C with stirring.

After stirring for 16 h the acetic acid was removed under vacuum and the crude product

137 purified by flash chromatography on silica gel to give 2-((methylsulfinyl)methyl)pyridine

(620 mg, 4.00 mmol, 69%) as a clear oil.

-1 1 FTIR (film, cm ): 3013, 2918, 1588, 1475, 1436, 1046; H NMR (CDCl 3, 400 MHz): δ

8.62-8.61 (m, 1H), 7.72 (td, J = 7.6, 1.6 Hz, 1H), 7.37 (d, J = 7.6 Hz, 1H), 7.29-7.26 (m,

13 1H), 4.21-4.11 (m, 2H), 2.58 (s, 6H); C NMR (CDCl 3, 100 MHz): δ 150.7, 149.9, 136.9,

125.3, 123.1, 61.5, 37.9.

2-((benzylsulfinyl)methyl)pyridine (2.15): 2-((benzylthio)methyl)pyridine (1.02 g, 4.72 mmol) was dissolved in glacial acetic acid (10 mL) and the solution was cooled to 0 °C.

H2O2 (30% aq, 0.536 mL, 4.72 mmol, 1.00 equiv) was added dropwise and the solution was slowly warmed to 23 °C with stirring. After stirring for 16 h the acetic acid was removed under vacuum and the crude product purified by flash chromatography on silica gel to give 2-((benzylsulfinyl)methyl)pyridine (835 mg, 3.61 mmol, 76%) as a white crystalline solid.

-1 1 FTIR (film, cm ): 3061, 3031, 2973, 2922, 1586, 1472, 1435, 1044; H NMR (CDCl 3,

400 MHz): δ 8.62 (dt, J = 4, 0.8 Hz, 1H), 7.69-7.65 (m, 1H), 7.39-7.29 (m, 6H), 7.26-7.23

13 (m 1H), 4.16-4.10 (m, 2H), 3.98-3.92 (m, 2H); C NMR (CDCl 3, 100 MHz): δ 150.8,

149.7, 136.5, 130.2, 129.7, 128.7, 128.1, 125.4, 122.8, 57.7, 57.1.

138

1,2-bis((benzylsulfinyl)methyl)benzene (2.16): 1,2-bis((benzylthio)methyl)benzene

(746 mg, 2.13 mmol) was dissolved in glacial acetic acid (5 mL) and the solution was cooled to 0 °C. H 2O2 (30% aq, 0.483 mL, 4.26 mmol, 2.00 equiv) was added dropwise and the solution was slowly warmed to 23 °C with stirring. After stirring for 16 h the acetic acid was removed under vacuum and the crude product purified by flash chromatography on silica gel to give 1,2-bis((benzylsulfinyl)methyl)benzene (653 mg,

1.71 mmol, 80%) as a white crystalline solid.

-1 1 FTIR (film, cm ): 3065, 2925, 1495, 1454, 1041; H NMR (CDCl 3, 400 MHz): δ 7.42-

13 7.23 (m, 14H), 4.12 (t, J = 13.6 Hz, 2H), 3.96-3.77 (m, 6H); C NMR (CDCl 3, 100

MHz): δ 132.3, 132.1, 131.5, 131.4, 130.4 (2), 130.2, 130.1, 129.2, 129.0, 128.6, 58.6 (2),

55.2, 55.1.

1,3-bis((methylthio)methyl)benzene (2.21): A solution of 1,3- bis(bromomethyl)benzene (2.67 g, 10.1 mmol) in methanol (40 mL) was added to a stirring solution of sodium methanethiolate (1.76 g, 25.1 mmol, 2.50 equiv) in H 2O (10 mL). The reaction was heated to 55 °C and allowed to stir 16 h. The solvent was reduced and the product extracted with benzene (3x60 mL). The organic layers were

139 combined, dried over MgSO 4 and reduced to yield 1,3-bis((methylthio)methyl)benzene

(1.67 g, 10.1 mmol, 100%) as a clear colorless oil.

FTIR (film, cm -1): 3057, 2977, 2917, 2030, 1605, 1486, 1437, 1237, 1085; 1H NMR

13 (CDCl 3, 400 MHz): δ 7.28-7.17 (m, 4H), 3.66 (s, 4H), 1.99 (s, 6H); C NMR (CDCl 3,

100 MHz): δ 138.6, 129.5, 128.7, 127.7, 38.4, 15.1.

1,3-bis((ethylthio)methyl)benzene (2.22): A solution of 1,3-bis(bromomethyl)benzene

(601 mg, 2.28 mmol) in methanol (16 mL) was added to a stirring solution of potassium ethanethiolate (581 mg, 5.81 mmol, 2.55 equiv) in H 2O (3 mL). Methanol (16 mL) was added and the reaction was heated to 55 °C and allowed to stir 16 h. The solvent was reduced and the product extracted with benzene (3x60 mL). The organic layers were combined, dried over MgSO 4 and reduced to yield 1,3-bis((ethylthio)methyl)benzene

(397 mg, 1.75 mmol, 77%) as a clear colorless oil.

-1 1 FTIR (film, cm ): 2972, 2927, 1605, 1451, 1267, 1085; H NMR (CDCl 3, 400 MHz): δ

7.27-7.17 (m, 4H), 3.71 (s, 4H), 2.43 (q, J = 7.2 Hz, 4H), 1.22 (t, J = 18 Hz, 6H); 13C

NMR (CDCl 3, 100 MHz): δ 139.0, 129.4, 128.7, 127.6, 35.9, 25.5, 14.6.

140

1,3-bis((benzylthio)methyl)benzene (2.23): Potassium phenylmethanethiolate (1.59 g,

9.80 mmol, 2.23 equiv) in methanol (7 mL) was added dropwise to a stirring solution of

1,3-bis(bromomethyl)benzene (1.16 g, 4.40 mmol) in methanol (7 mL). The reaction was heated to 60 °C and allowed to stir 16 h. The solvent was reduced, H 2O (20 mL) was added, and the product extracted with benzene (3x75 mL). The organic layers were combined, dried over MgSO 4 and reduced to yield 1,3-bis((benzylthio)methyl)benzene

(1.53 g, 4.37 mmol, 99%) as a white crystalline solid.

-1 1 FTIR (film, cm ): 3064, 2919, 1602, 1494, 1071; H NMR (CDCl 3, 400 MHz): δ 7.31-

13 7.14 (m, 14H), 3.59 (s, 4H), 3.57 (s, 4H); C NMR (CDCl 3, 100 MHz): δ 138.6, 138.4,

129.9, 129.3, 128.8, 128.7, 127.9, 127.2, 35.9, 35.8.

2,6-bis((methylthio)methyl)pyridine (2.24): 2,6-bis(chloromethyl)pyridine (925 mg,

5.25 mmol) was added to a stirring solution of sodium methanethiolate (923 mg, 13.2 mmol, 2.51 equiv) in H 2O (5 mL). Methanol (33 mL) was added and the reaction was allowed to stir at 23 °C for 16 h. The solvent was reduced and the product extracted with benzene (3x60 mL). The organic layers were combined, dried over MgSO 4 and reduced to yield 2,6-bis((ethylthio)methyl)pyridine (984 mg, 4.94 mmol, 94%) as a clear colorless oil

141

-1 1 FTIR (film, cm ): 3058, 2972, 2915, 2830, 1590, 1573, 1218; H NMR (CDCl 3, 400

13 MHz): δ 7.63 (t, J = 7.6 Hz, 1H), 7.24 (d, J = 7.6 Hz, 2H), 3.78 (s, 4H), 2.06 (s, 6H); C

NMR (CDCl 3, 100 MHz): δ 158.1, 137.2, 120.9, 39.9, 15.2

2,6-bis((ethylthio)methyl)pyridine (2.25): 2,6-bis(chloromethyl)pyridine (403 mg, 2.29 mmol) was added to a stirring solution of potassium ethanethiolate (469 mg, 4.68 mmol,

2.05 equiv) in H 2O (3 mL). Methanol (7 mL) was added and the reaction was allowed to stir at 23 °C for 16 h. The solvent was reduced and the product extracted with benzene

(3x60 mL). The organic layers were combined, dried over MgSO 4 and reduced to yield crude 2,6-bis((ethylthio)methyl)pyridine which was purified by column chromatography on silica gel (10% EtOAc/hexanes) to give pure 2,6-bis((ethylthio)methyl)pyridine (349 mg, 1.54 mmol, 67%), as a clear colorless oil.

-1 1 FTIR (film, cm ): 2971, 2928, 2872, 1591, 1573, 1453, 1267; H NMR (CDCl 3, 400

MHz): δ 7.61 (t, J = 7.6 Hz, 1H), 7.24 (d, J = 7.6 Hz, 2H), 3.83 (s, 4H), 2.52 (q, J = 7.6

13 Hz, 4H), 1.24 (t, J = 7.6 Hz, 6H); C NMR (CDCl 3, 100 MHz): δ 158.5, 137.3, 121.0,

37.8, 25.7, 14.5.

142

2,6-bis(( tert -butylthio)methyl)pyridine (2.26): 2,6-bis(chloromethyl)pyridine (1.54 g,

8.75 mmol) was added to a stirring solution of potassium 2-methyl-2-propanethiolate

(2.95 g, 23.0 mmol, 2.49 equiv) in H 2O (10 mL). Methanol (35 mL) was added and the reaction was heated to 55 °C and allowed to stir for 16 h. The reaction was cooled to ambient temperature, the solvent reduced and the product extracted with benzene (3x60 mL). The organic layers were combined, dried over MgSO 4 and reduced to yield 2,6- bis((tert-butylthio)methyl)pyridine (2.44 g, 8.6 mmol, 93%) as a clear colorless oil.

-1 1 FTIR (film, cm ): 2960, 2900, 1590, 1574, 1454, 1365, 1163; H NMR (CDCl 3, 400

13 MHz): δ 7.56 (t, J = 7.6 Hz, 1H), 7.28 (d, J = 7.6 Hz, 2), 3.89 (s, 4H), 1.33 (s, 18H); C

NMR (CDCl 3, 100 MHz): δ 158.8, 136.9, 121.1, 42.9, 35.5, 30.9.

2,6-bis((benzylthio)methyl)pyridine (2.27): Potassium phenylmethanethiolate (0.800 g,

10.7 mmol, 2.35 equiv) in methanol (7 mL) was added dropwise to a stirring solution of

2,6-bis(chloromethyl)pyridine (1.73 g, 4.55 mmol) in methanol (7 mL). The reaction was heated to 60 °C and allowed to stir for 16 h. The reaction was cooled to ambient temperature, the solvent reduced and the product extracted with benzene (3x60 mL). The organic layers were combined, dried over MgSO 4 and reduced to yield 2,6- bis((benzylthio)methyl)pyridine (1.59 g, 4.54 mmol, 99%) as a yellow oil.

-1 1 FTIR (film, cm ): 3062, 3029, 2920, 1590, 1573, 1452; H NMR (CDCl 3, 400 MHz): δ

7.53 (t, J = 7.6 Hz, 1H), 7.33-7.18 (m, 10H), 7.14 (d, J = 7.6 Hz, 2H), 3.72 (s, 4H), 3.69 143

13 (s, 4H); C NMR (CDCl 3, 100 MHz): δ 158.3, 138.2, 137.3, 129.2, 128.5, 127.0, 121.2,

37.4, 35.9.

2-((benzylthio)methyl)pyridine (2.28): Potassium phenylmethanethiolate (2.20 g, 13.6 mmol, 1.16 equiv) in methanol (7 mL) was added dropwise to a stirring solution of 2-

(chloromethyl)pyridine (1.49 g, 11.7 mmol) in methanol (7 mL). The reaction was allowed to stir at 23 °C for 16 h. The solvent was reduced, H 2O (20 mL) added and the product extracted with benzene (3x75 mL). The organic layers were combined, dried over MgSO 4 and reduced to yield 2-((benzylthio)methyl)pyridine (2.32 g, 10.8 mmol,

93%) as a clear colorless oil. The clear oil over an extended period of time turned deep purple upon standing.

-1 1 FTIR (film, cm ): 3064, 3030, 2923, 1592, 1473, 1435, 1088; H NMR (CDCl 3, 400

MHz): δ 8.56 (m, 1H), 7.56 (td, J = 7.6, 1.6 Hz, 1H), 7.31-7.17 (m, 6H), 7.09 (td, J = 4.8,

13 3 0.8 Hz, 1H), 3.72 (s, 2H), 3.67 (s, 2H); C NMR (CDCl , 100 MHz): δ 158.6, 149.2,

138.0, 136.5, 128.9, 128.4, 126.9, 122.9, 121.7, 37.4, 35.8.

144

1,2-bis((ethylthio)methyl)benzene (2.29): Potassium ethanethiolate (1.79 g, 17.86 mmol, 2.48 equiv) dissolved in methanol (10 mL) was added dropwise to a stirring solution of 1,2-bis(chloromethyl)benzene (1.26 g, 7.19 mmol) in methanol (10 mL). The solution was stirred at 23 °C for 18 h. The solvent was reduced, H2O (20 mL) added and the product extracted with benzene (3x75 mL). The organic layers were combined, dried over MgSO 4 and reduced to yield 1,2-bis((ethylthio)methyl)benzene (1.35 g, 5.93 mmol,

82%)as a clear colorless oil.

-1 1 FTIR (film, cm ): 3068, 2971, 2928, 1487, 1453, 1266, 1234; H NMR (CDCl 3, 400

MHz): δ 7.25-7.18 (m, 4H), 3.90 (s, 4H), 2.49 (q, J = 7.6 Hz, 4H), 1.26 (t, J = 7.6 Hz,

13 6H); C NMR (CDCl 3, 100 MHz): δ 136.7, 130.7, 127.3, 33.4, 26.1, 14.8.

1,2-bis((ethylthio)methyl)benzene (2.30): Potassium phenylmethanethiolate (1.83 g,

11.25 mmol, 2.34 equiv) dissolved in methanol (7 mL) was added dropwise to a stirring solution of 1,2-bis(chloromethyl)benzene (0.842 mg, 4.81 mmol) in methanol (7 mL).

The solution was stirred at 23 °C for 16 h. The solvent was reduced, H 2O (20 mL) added and the product extracted with benzene (3x75 mL). The organic layers were combined, dried over MgSO 4 and reduced to yield 1,2-bis((benzylthio)methyl)benzene (1.65 g, 4.70 mmol, 98%) as a white crystalline solid.

145

-1 1 FTIR (film, cm ): 3063, 3028, 2920, 1493, 14453, 127, 1071; H NMR (CDCl 3, 400

13 MHz): δ 7.31-7.13 (m, 14H), 3.66 (s, 4H), 3.58 (s, 4H); C NMR (CDCl 3, 100 MHz): δ

138.3, 136.3, 130.7, 129.1, 128.6, 127.4, 127.2, 36.63, 33.2.

1,2-bis(naphthalene-1-ylthio)ethane (2.37): Naphthalen-1-thiol (0.908 mg, 5.67 mmol,

2.13 equiv) was added to a stirring solution of KOH (480 mg, 8.56 mmol, 3.22 equiv) in

MeOH (12 mL) at 0 °C. After stirring for 10 min 1,2-dibromoethane (0.23 mL, 2.66 mmol) was added and the reaction stirred at 23 °C for 16 h. MeOH was removed under vacuum, H 2O (20 mL)added and the aqueous layer extracted with EtOAc (3x40 mL).

The organic layers were combined, dried over MgSO 4, and the solvent removed under vacuum. The off-white solid was purified by recrystallization from hot hexanes to give

1,2-bis(naphthalene-1-ylthio)ethane (701 mg, 2.02 mmol, 76%) as a white crystalline solid.

-1 1 FTIR (film, cm ): 3057, 1792, 1558, 1505, 1381; H NMR (CDCl 3, 400 MHz): δ 8.37-

8.36 (m, 2H), 7.84-7.82 (m, 2H), 7.73 (d, J = 8.4 Hz, 2H), 7.54-7.43 (m, 6H), 7.29 (t, J =

13 7.6 Hz, 2H); C NMR (CDCl 3, 100 MHz): δ 134.2, 133.5, 132.2, 129.6, 128.8, 128.1,

126.8, 126.5, 125.7, 125.4, 34.0.

146

1,2-bis((4-fluorophenyl)thio)ethane (2.38): 4-fluorobenzenethiol (732 mg, 5.69 mmol,

2.10 equiv) was added to a stirring solution of KOH (271 mg, 6.77 mmol, 2.5 equiv) in

MeOH (5 mL) at 0 °C. After stirring for 10 min 1,2-dibromoethane (233 µL, 2.70 mmol) was added and the reaction stirred at 23 °C for 16 h. MeOH was removed under vacuum,

H2O (50 mL) added and the aqueous layer extracted with EtOAc (3x40 mL). The organic layers were combined, dried over MgSO 4, and the solvent removed under vacuum. The off-white solid was purified by recrystallization from hot hexanes to give 1,2-bis((4- fluorophenyl)thio)ethane (543 mg, 1.92 mmol, 71%) as a white crystalline solid.

-1 1 FTIR (film, cm ): 3057, 1590, 1490, 1230, 1156; H NMR (CDCl 3, 400 MHz): δ 7.33-

13 7.28 (m, 4H), 7.01-6.95 (m, 4H), 2.98 (s, 4H); C NMR (CDCl 3, 100 MHz): δ 163.6,

161.1, 133.4, 133.3, 130.1, 130.0, 116.5, 116.3, 34.8.

1,2-bis((4-methoxyphenyl)thio)ethane (2.39): 4-methoxybenzenethiol (3.42 g, 24.4 mmol, 2.10 equiv) was added to a stirring solution of KOH (1.63 g, 29.0 mmol, 2.5 equiv) in MeOH (23 mL) at 0 °C. After stirring for 10 min 1,2-dibromoethane (1.00 mL,

11.6 mmol) was added and the reaction stirred at 23 °C for 16 h. MeOH was removed under vacuum, H 2O (20 mL)added and the aqueous layer extracted with EtOAc (3x40 mL). The organic layers were combined, dried over MgSO 4, and the solvent removed under vacuum. The off-white solid was purified by recrystallization from hot hexanes to give 1,2-bis((4-methoxyphenyl)thio)ethane (2.35 g, 7.66 mmol, 66%) as a white crystalline solid. 147

-1 1 FTIR (film, cm ): 3006, 2959, 2940, 2837, 1592, 1493, 1285, 1245; H NMR (CDCl 3,

13 400 MHz): δ 7.29-7.27 (m, 4H), 6.83-6.80 (m, 4H), 3.79 (s, 6H), 2.92 (s, 4H); C NMR

(CDCl 3, 100 MHz): δ 159.2, 133.7, 125.2, 114.7, 55.3, 35.3.

Complex 2.46: To a stirring solution of Pd(OAc) 2 (157 mg, 0.70 mmol) in MeCN (3 mL) was added 1,2-bis(phenylthio)ethane (172 mg, 0.69 mmol, 1.00 equiv) in MeCN (2 mL). The solution turned yellow after stirring for 1 h at 23 °C. The solution was then filtered and the yellow solid washed with MeCN. Complex 2.46 (300 mg, 0.64 mmol,

91%) was found to be analytically pure by 1H NMR.

-1 1 FTIR (film, cm ): 3154, 3063, 2982, 1618, 1595, 1442, 1371, 1312; H NMR (CDCl 3,

13 400 MHz): δ 8.24 (s, 4H), 7.51 (s, 6H), 3.08-2.90 (m, 4H), 1.88 (s, 6H); C NMR

(CDCl 3, 100 MHz): δ 177.6, 132.7, 131.2, 130.2, 129.4, 42.2, 22.6.

Phenyl(2-(p-tolyloxy)ethyl)sulfane (2.49): To a solution of 2-chloroethyl phenyl sulfide

(4.29 mL, 29.0 mmol) in EtOH (25 mL) was added a mixture of p-cresol (4.14 g, 38.4 mmol, 1.34 equiv), KOH (1.76 g, 31.0 mmol, 1.10 equiv), EtOH (50 mL), and water (25 mL) dropwise at ambient temperature. The resultant mixture was heated to reflux,

148 maintained overnight, and then cooled to ambient temperature leading to the formation of an off-white precipitate. The solid was filtered, washed with water (3x30 mL) and air dried. The solid was dissolved in hot hexanes, filtered hot and cooled to recrystallize phenyl(2-(p-tolyloxy)ethyl)sulfane (4.67 g, 19.1 mmol, 67%) as a white crystalline solid.

-1 1 FTIR (film, cm ): 3054, 2987, 1511, 1439, 1422, 1265, 747, 1232; H NMR (CDCl 3, 400

MHz): δ 7.41-7.39 (m, 2H), 7.30-7.26 (m, 2H), 7.23-7.18 (m, 1H), 7.05 (d, J = 8.0 Hz,

2H), 6.76-6.74 (m, 2H), 4.10 (t, J = 7.2 Hz, 2H), 3.26 (t, J = 7.2 Hz, 2H), 2.27 (s, 3H);

13 C NMR (CDCl 3, 100 MHz): δ 156.2, 135.5, 130.3, 129.9, 129.8, 129.0, 126.4, 114.5,

+ 66.7, 32.8, 20.4; HRMS (ES) calcd for [C 15H16OS + Na] 267.0814, found 267.0801.

General procedure for the preparation of linear allylic acetate (P) with

Pd(OAc) 2:To a stirred mixture of Pd(OAc) 2 (11 mg, 0.050 mmol, 0.050 equiv), 6 (12 mg, 0.050 mmol, 0.050 equiv) and benzoquinone (216 mg, 2.00 mmol, 2.0 equiv) in

AcOH (0.75 mL) was added substrate S (1.00 mmol) in one portion at ambient temperature. The resultant mixture was stirred at 40 °C for 15 to 20 h then was cooled to ambient temperature, quenched with saturated aqueous NaHSO 3 (10 mL) and diluted with water (20 mL) and CH 2Cl 2 (100 mL). The organic layer was separated and the aqueous layer was extracted with CH 2Cl 2 (50 mL) again. The combined organic layers were dried over Na 2SO 4, filtered, and freed of solvent under reduced pressure to afford a

149 brown oil, which was purified by column chromatography on silica gel (CH 2Cl 2/hexane or EtOAc/hexane) to afford allylic acetate P as a colorless to pale yellow oil in good yield.

OAc

(2 E)-3-phenylprop-2-en-1-yl acetate (2.55): This reaction was performed according to the general procedure for Pd(OAc) 2 using allylbenzene (132 µL, 1.00 mmol). The crude product was purified by column chromatography (silica gel, 2%

EtOAc/hexanes) to give 64% of the product (113 mg, 0.641 mmol) as a pale yellow oil.

-1 1 FTIR (film, cm ): 3027, 2938, 1740, 1230; H NMR (CDCl 3, 400 MHz): δ 7.39-7.37 (m,

2H), 7.33-7.29 (m, 2H), 7.26-7.24 (m, 1H), 6.40 (d, J = 16.0 Hz, 1H), 6.27 (dt, J = 16.0,

13 6.4 Hz, 1H), 4.71 (dd, J = 6.4, 1.6 Hz, 2H), 2.08 (s, 3H); C NMR (CDCl 3, 100 MHz): δ

170.6, 136.1, 134.0, 128.5, 128.3, 126.5, 123.1, 64.9, 20.8; HRMS (ES) calcd for

+ [C 11 H12 O2 + Na] 199.0730, found 199.0727.

(2 E)-3-(4-methoxyphenyl)prop-2-en-1-yl acetate (2.57): This reaction was performed according to the general procedure for Pd(OAc) 2 using 1-allyl-4- methoxybenzene (148 mg, 1.00 mmol). The crude product was purified by column chromatography (silica gel, 3/1 CH 2Cl 2/hexanes) to give 72% of the product (149 mg,

0.722 mmol) as a pale yellow oil. FTIR (film, cm -1): 3055, 2958, 1736, 1608, 1513,

1 1265, 1247, 739; H NMR (CDCl 3, 400 MHz): δ 7.36-7.32 (m, 2H), 6.89-6.86 (m, 2H),

6.61 (d, J = 15.6 Hz, 1H), 6.17 (dt, J = 15.6, 6.4 Hz, 1H), 4.71 (dd, J = 6.4, 1.2 Hz, 2H), 150

13 3.82-3.80 (m, 3H), 2.11 (s, 3H); C NMR (CDCl 3, 100 MHz): δ 170.7, 159.5, 133.9,

+ 128.8, 127.7, 120.7, 113.9, 65.2, 55.1, 20.9; HRMS (ES) calcd for [C 12 H14 O3 + Na]

229.0835, found 229.0828.

(2 E)-3-(4-fluorophenyl)prop-2-en-1-yl acetate (2.59): This reaction was performed according to the general procedure for Pd(OAc) 2 using 1-allyl-4- fluorobenzene (136 mg, 1.00 mmol). The crude product was purified by column chromatography (silica gel, 2% EtOAc/hexanes) to give 68% of the product (133 mg,

0.684 mmol) as a pale yellow oil. FTIR (film, cm -1): 3042, 2938, 1740, 1601, 1510,

1 1229; H NMR (CDCl 3, 400 MHz): δ 7.36-7.31 (m, 2H),7.02-6.97 (m, 2H), 6.60 (d, J =

15.6 Hz, 1H), 6.22-6.15 (dt, J = 16.0, 2.4 Hz, 1H), 4.70 (d, J = 6.4 Hz, 2H), 2.08 (s, 3H);

13 C NMR (CDCl 3, 100 MHz): δ 170.9, 164.0, 133.2, 132.5 (d, J = 14Hz), 128.3 (d, J =

32Hz), 123.1 (d, J = 9Hz), 115.7 (d, J = 85Hz), 65.1, 21.1; HRMS (ES) calcd for

+ [C 11 H11 FO 2 + Na] 217.0635, found 217.0636.

(2 E)-4-phenylbut-2-en-1-yl acetate (2.51): This reaction was performed according to the general procedure for Pd(OAc)2 using 4-phenyl-1-butene (150 µL, 1.00 mmol). The crude product was purified by column chromatography (silica gel, 3/1

CH 2Cl 2/hexanes) to give 61% of the product (117 mg, 0.615 mmol) as a pale yellow oil.

-1 1 FTIR (film, cm ): 3028, 2940, 1739, 1495, 1453, 1364, 1232; H NMR (CDCl 3, 400

MHz): δ 7.39-7.32 (m, 2H), 7.28-7.22 (m, 3H), 6.01-5.94 (m, 1H), 5.71-5,65 (m, 1H), 151

13 4.60 (dd, J = 6.8, 1.2 Hz, 2H), 3.44 (d, J = 6.8 Hz, 2H), 2.12 (s, 3H); C NMR (CDCl 3,

100 MHz): δ 170.6, 139.4, 134.4, 128.5, 128.4, 126.1, 125.2, 64.7, 38.5, 20.8; HRMS

+ (ES) calcd for [C12 H14 O2 + Na] 213.0886, found 213.0889.

(2 E)-dodec-2-en-1-yl acetate (2.60): This reaction was performed according to the general procedure for Pd(OAc) 2 using 1-dodecene (224 µL, 1.00 mmol). The crude product was purified by column chromatography (silica gel, 2% EtOAc/hexanes) to give

58% of the product (131 mg, 0.578 mmol) as a pale yellow oil. FTIR (film, cm -1): 2926,

1 2855, 1741, 1458, 1363, 1233; H NMR (CDCl 3, 400 MHz): δ 5.77-5.71 (m, 1H), 5.58-

5.52 (m, 1H), 4.48 (dd, J = 6.8, 1.2 Hz, 2H), 2.03 (s, 3H), 1.25 (br s, 16H), 0.87 (t, J = 6.8

13 Hz, 3H); C NMR (CDCl 3, 100 MHz): δ 170.6, 136.5, 123.7, 65.2, 32.2, 31.8, 29.5, 29.4,

+ 29.3, 29.1, 28.8, 22.6, 20.8, 14.0; HRMS (ES) calcd for [C 14 H26 O2 + Na] 249.1825, found 249.1820.

(E)-5-oxo-5-(phenylamino)pent-2-enyl acetate (2.62): This reaction was performed according to the general procedure for Pd(OAc) 2 using N-phenylpent-4- enamide (175 mg, 1.00 mmol). The crude product was purified by column chromatography (silica gel, 3/1 CH 2Cl 2/hexanes) to give 76% of the product as a 2:1 mixture of linear to branched allylic acetate (177 mg, 0.758 mmol) as a pale yellow oil.

Note: An analytically pure sample of the ( E)-linear acetate was obtained by column chromatography (silica gel, 9/1 CH 2Cl 2/Et 2O) for characterization purposes. FTIR (film,

152 cm -1): 3429, 1734, 1685, 1526, 1441, 1238, 909, 733; 1H NMR (CDCl3, 400 MHz): δ

7.73 (s 1H), 7.53 (d, J = 8 Hz, 2H), 7.32-7.27 (m 2H), 7.12-7.084 (t, J = 7.2 Hz, 2H),

5.99-5.91 (m 1H), 5.82-5.75 (m 1H), 4.59 (d, J = 5.6 Hz, 2H), 3.17 (d, J = 6.8 Hz, 2H),

13 2.08 (s, 3H); C NMR (CDCl 3, 100 MHz): δ 171.1, 168.7, 137.8, 129.6, 128.9, 127.4,

+ 124.5, 119.9, 64.6, 40.9, 21.0; HRMS (ES) calcd for [C 13 H15NO 3 + Na] 256.0944, found

256.0942.

(2 E)-pent-2-en-1,5-diyl diacetate (2.64): This reaction was performed according to the general procedure for Pd(OAc) 2 using pent-4-enyl acetate (128 mg, 1.00 mmol).

The crude product was purified by column chromatography (silica gel, 15%

EtOAc/hexanes) to give 68% of the product (127 mg, 0.682 mmol) as a pale yellow oil.

-1 1 FTIR (film, cm ): 2958, 1741, 1383, 1365, 1236, 1030, 970; H NMR (CDCl 3, 400

MHz): δ 5.79-5.63 (m, 2H), 4.52 (d, J = 5.6 Hz, 2H), 4.13-4.08 (m, 2H), 2.40 (q, J = 6.4

13 Hz, 2H), 2.06 (s, 3H), 2.04 (s, 3H); C NMR (CDCl 3, 100 MHz): δ 170.6, 170.3, 130.7,

+ 126.5, 64.3, 63.0, 31.3, 20.6, 20.5; HRMS (ES) calcd for [C 9H14 O4 + Na] 209.0784, found 209.0774.

(2 E)-6-[(diethylcarbamoyl)oxy]hex-2-en-1-yl acetate (2.66): This reaction was performed according to the general procedure for Pd(OAc) 2 using hex-5-enyl diethylcarbamate (199 mg, 1.00 mmol). The crude product was purified by column chromatography (silica gel, 15% EtOAc/hexanes) to give 70% of the product (180 mg,

153

0.700 mmol) as a pale yellow oil. FTIR (film, cm -1): 3054, 2985, 1735, 1689, 1429,

1 1265; H NMR (CDCl 3, 400 MHz): δ 5.72-5.65 (m, 1H), 5.53-5.46 (m, 1H), 4.50 (d, J =

6.4 Hz, 2H), 3.98 (t, J = 6.8 Hz, 3H), 3.16 (br s, 4H), 2.08-2.02 (m, 2H), 1.95 (s, 3H),

13 1.66-1.61 (m, 2H), 1.01 (t, J = 7.2 Hz, 6H); C NMR (CDCl 3, 100 MHz): δ 170.4, 155.6,

134.7, 124.3, 64.7, 63.9, 41.5(m), 28.4, 28.1, 20.6, 13.5 (m); HRMS (ES) calcd for

+ [C 13 H23 NO 4 + Na] 280.1519, found 280.1514.

(3 E)-4-methoxybenzyl-5-(acetyloxy)pent-3-enoate (2.68): This reaction was performed according to the general procedure for Pd(OAc) 2 using 4-methoxybenzyl pent-

4-enoate (220 mg, 1.00 mmol). The crude product was purified by column chromatography (silica gel, 3/1 CH 2Cl 2/hexanes) to give 30% of the product (85 mg,

0.305 mmol) as a pale yellow oil. FTIR (film, cm -1): 3057, 2963, 1737, 1614, 1516,

1 1266, 1249, 736; H NMR (CDCl 3, 400 MHz): δ 7.31-7.27 (m, 2H), 6.90-6.87 (m, 2H),

5.92-5.85 (m, 1H), 5.73-5.66 (m, 1H), 5.06 (s, 2H), 4.53 (dd, J = 6,0, 1.2 Hz, 2H), 3.80

13 (s, 3H), 3.12 (dd, J = 6.8, 0.8 Hz, 2H), 2.04 (s, 3H); C NMR (CDCl 3, 100 MHz): δ

171.0, 170.6, 159.7, 130.1, 127.9, 127.8, 126.8; 113.9, 66.4, 64.3, 55.2, 37.6, 20.8;

+ HRMS (ES) calcd for [C 15H18O5 + Na] 301.1050, found 301.1046.

(2 E)-5-(benzyloxy)pent-2-en-1-yl acetate (2.70): This reaction was performed according to the general procedure for Pd(OAc) 2 using ((pent-4-enyloxy)methyl)benzene

154

(176 mg, 1.00 mmol). The crude product was purified by column chromatography (silica gel, 5% EtOAc/hexanes) to give 65% of the product (152 mg, 0.649 mmol) as a pale yellow oil. FTIR (film, cm -1): 3054, 2936, 2860, 1736, 1266, 1236, 738; 1H NMR

(CDCl 3, 400 MHz): δ 7.36-7.28 (m, 5H), 5.86-5.79 (m, 1H), 5.71-5.64 (m, 1H), 4.55-4.53

(m, 4H), 3.54 (t, J = 6.4 Hz, 2H), 2.40 (q, J = 6.4 Hz, 2H), 2.07 (s, 3H); 13 C NMR

(CDCl 3, 100 MHz): δ 170.4, 138.2, 132.2, 128.1, 127.36, 127.31, 125.6, 72.6, 69.0, 64.7,

+ 32.5, 20.6; HRMS (ES) calcd for [C 14 H18 O3 + Na] 257.1148, found 257.1141.

(4 E)-6-(acetyloxy)hex-4-en-1-(tert -butyldiphenylsilyl)oxy (2.72): This reaction was performed according to the general procedure for Pd(OAc) 2 using tert -butyl(hex-5- enyloxy)diphenylsilane (338 mg, 1.00 mmol). The crude product was purified by column chromatography (silica gel, 3/1 CH 2Cl 2/hexanes) to give 43% of the product (170 mg,

0.428 mmol) as a pale yellow oil. FTIR (film, cm -1): 3054, 2933, 2859, 1735, 1265, 739;

1 H NMR (CDCl 3, 400 MHz): δ 7.66 (d, J = 2.8 Hz, 4H), 7.42-7.34 (m, 6H), 5.76-5.70 (m,

1H), 5.59-5.54 (m, 1H), 4.48 (d, J = 2.4 Hz, 2H), 3.67 (t, J = 2.4 Hz, 2H), 2.16 (q, J = 3.2

13 Hz, 2H), 2.01 (s, 3H), 1.64 (m, 2H), 1.06 (s, 9H); C NMR (CDCl 3, 100 MHz): δ 170.6,

135.8, 135.5, 133.9, 129.5, 127.5, 124.0, 65.1, 63.0, 31.6, 28.5, 26.8, 20.9, 19.1; HRMS

+ (ES) calcd for [C 24 H32 O3Si + Na] 419.2013, found 419.2001.

(2 E)-4-(2-methyl-1,3-dioxolan-2-yl)but-2-en-1-yl acetate (2.74): This reaction was performed according to the general procedure for Pd(OAc)2 using 2-(but-3-enyl)-2-

155 methyl-1,3-dioxolane (142 mg, 1.00 mmol). The crude product was purified by column chromatography (silica gel, 15% EtOAc/hexanes) to give 50% of the product (101 mg,

0.504 mmol) as a pale yellow oil. FTIR (film, cm -1): 2985, 2886, 1739, 1446, 1378,

1 1231; H NMR (CDCl 3, 400 MHz): δ 5.82-5.75 (m, 1H), 5.70-5.62 (m, 1H), 4.53 (dd, J =

6.4, 0.8 Hz, 2H), 3.97-3.91 (m, 4H), 2.40 (d, J = 7.2 Hz, 2H), 2.14 (s, 3H), 1.32 (s, 3H);

13 C NMR (CDCl 3, 100 MHz): δ 170.8, 130.3, 127.4, 109.2, 64.9, 64.7, 42.2, 23.9, 20.9;

+ HRMS (ES) calcd for [C 10 H16 O4 + Na] 223.0941, found 223.0942.

General procedure for allylic oxidations using oxygen: To a stirred mixture of

Pd(OAc) 2 (22.4 mg, 0.100 mmol, 0.100 equiv), 6 (24.4 mg, 0.100 mmol, 0.100 equiv),

Cu(OAc) 2 (9.1 mg, 0.05 mmol, 0.05 equiv) and dihydroquinone (11.0 mg, 0.100 mmol,

0.100 equiv) in AcOH (0.75 mL) was added 4-phenyl-1-butene (132 mg, 1.00 mmol) in one portion at ambient temperature. The reaction was purged with oxygen for 5 min. and placed under an O 2 atmosphere using a balloon. The resultant mixture was stirred at 40

°C for 20 – 28 h then was cooled to ambient temperature and diluted with water (20 mL) and CH 2Cl 2 (100 mL). The organic layer was separated and the aqueous layer was extracted with CH 2Cl 2 (50 mL) again. The combined organic layers were dried over

Na 2SO 4, filtered, and freed of solvent under reduced pressure to afford a brown oil, which

156 was purified by column chromatography on silica gel to afford the product as a colorless to pale yellow oil.

(2 E)-3-phenylprop-2-en-1-yl acetate (2.55): This reaction was performed according to the general procedure for Cu(OAc) 2 and O 2 using allylbenzene (132 µL, 1.00 mmol).

The crude product was purified by column chromatography (silica gel, 2%

EtOAc/hexanes) to give 59% of the product (104 mg, 0.590 mmol) as a pale yellow oil.

(2 E)-4-phenylbut-2-en-1-yl acetate (2.50): This reaction was performed according to the general procedure for Cu(OAc) 2 and O 2 using 4-phenyl-1-butene (150 µL, 1.00 mmol). The crude product was purified by column chromatography (silica gel, 3/1

CH 2Cl 2/hexanes) to give 61% of the product (116 mg, 0.609 mmol) as a pale yellow oil.

(2 E)-dodec-2-en-1-yl acetate (2.60): This reaction was performed according to the general procedure for Cu(OAc) 2 and O 2 using 1-dodecene (224 µL, 1.00 mmol). The crude product was purified by column chromatography (silica gel, 2% EtOAc/hexanes) to give 55% of the product (125 mg, 0.553 mmol) as a pale yellow oil.

(2 E)-pent-2-en-1,5-diyl diacetate (2.64): This reaction was performed according to the general procedure for Cu(OAc) 2 and O 2 using pent-4-enyl acetate (128 mg, 1.00 mmol).

The crude product was purified by column chromatography (silica gel, 15%

EtOAc/hexanes) to give 67% of the product (125 mg, 0.671 mmol) as a pale yellow oil.

157

Dichlorobis(phenyl(2-(p-tolyloxy)ethyl)sulfane)palladium(II) (2.82):

Pd(MeCN)2Cl 2 (408 mg, 1.57 mmol), phenyl(2-(p-tolyloxy)ethyl)sulfane (779 mg, 3.18 mmol, 2.02 equiv), and CH 2Cl 2 (20 mL), were stirred for 5 h at ambient temperature. The solvent was removed under reduced pressure and toluene added. The solution was then filtered and the product recrystallized from hexanes to give 75% of the product (790 mg,

1.18 mmol) as an orange crystalline solid. FTIR (film, cm -1): 3055, 3004, 2919, 2865,

1 1608, 1509, 1243, 1070, 1026, 816, 742, 684; H NMR (CDCl 3, 400 MHz): δ 7.88 (d,

4H), 7.44 (m, 2H), 7.37 (m, 4H), 7.03 (d, 4H), 6.69 (d, 4H), 4.12 (t, 4H), 3.57 (t, 4H),

2.26 (s, 6H); Anal. Calcd for C 30 H32 Cl 2O2PdS 2: C, 54.10; H, 4.84. Found: C, 53.98; H,

4.92.

Reactions with dichlorobis(phenyl(2-(p-tolyloxy)ethyl)sulfane)palladium(II):

Dichlorobis(phenyl(2-(p-tolyloxy)ethyl)sulfane)palladium(II) (33.3 mg, 0.050 mmol) was placed in a 4 mL septum cap borosilicate glass vial and dissolved in CHCl 3 (0.5 mL).

AgOAc (16.7 mg, 0.100 mmol) in CHCl3 (0.5 mL) was added and the solution stirred for

4 h at ambient temperature. The solution was filtered over Celite and the solvent removed under reduced pressure to give a deep reddish oil. The oil was then dissolved in 158

AcOH (0.75 mL) and added to a vial containing benzoquinone (216 mg, 2.00 mmol), 4- phenyl-1-butene (150 µL, 1.00 mmol), and nitrobenzene (100 µL, 0.971 mmol). The reactions were then heated at 40 ˚C for 14 h. An aliquot (10 µL) was taken and analyzed by GC. The yield of (2E)-4-phenylbut-2-en-1-yl acetate (0.37 mmol, 37%) was calculated using NO 2C6H5 as an internal standard.

1-Methyl-4-(2-(phenylsulfinyl)ethoxy)benzene (2.88): Phenyl(2-(p- tolyloxy)ethyl)sulfane (200 mg, 0.768 mmol) was added to acetic acid (2 mL) and cooled to 0 ˚C. Hydrogen peroxide (30 % aq, 95.0 µL, 0.838 mmol, 1.02 equiv) was added and the solution was allowed to warm to ambient temperature and stirred for 16 h. After the reaction was complete the acetic acid was removed under reduced pressure and the product purified by column chromatography (silica gel, 25% EtOAc/hexanes) to give

52% of the product (104 mg, 0.399 mmol) as a white solid. FTIR (film, cm -1): 3036,

1 2919, 2877, 1608, 1511, 1234, 1041, 824, 754, 508; H NMR (CDCl 3, 400 MHz): δ 7.66

(m, 2H), 7.52 (d, 3H), 7.07 (d, 2H), 6.77 (d, 2H), 4.44 (m, 1H), 4.18 (m, 1H), 3.18 (m,

13 2H), 2.28 (s, 3H); C NMR (CDCl 3, 100 MHz): δ 156.1, 144.0, 131.3, 130.9, 130.2,

+ 129.5, 124.2, 114.7, 61.1, 57.5, 20.7; HRMS (ES) calcd for [C 15 H16 O2S + Na] calcd

283.0763, found 283.0768.

159

Reactions with bis[acetate(1,2,3-trihapto-1-dodecene)palladium (II)] (9) :

These reactions were carried out using a modified procedure from White et al. 7 A solution of 74 mL AcOH containing 1.0 mL nitrobenzene was prepared. A 4 mL vial with septum cap was charged with bis[acetate(1,2,3-trihapto-1-dodecene)palladium (II)]

(10.0 mg, 0.03 mmol of Pd), 2.46 (7.3 mg, 0.03 mmol), and the AcOH/NO 2C6H5 (0.45 mL) solution. Benzoquinone (130 mg, 1.20 mmol) was then added and the solution stirred at 40 ˚C for 2 h. An aliquot (10 µL) was taken and analyzed by GC. The yield of

(2E)-dodec-2-en-1-yl acetate (0.012 mmol, 40.1%) and dodec-1-en-3-yl acetate (0.012 mmol, 40.1%) were calculated using NO 2C6H5 as an internal standard.

((3-Phenylpropyl)sulfinyl)benzene (2.94): Phenyl(3-phenylpropyl)sulfane (679 mg,

2.97 mmol) was added to acetic acid (7 mL) and cooled to 0 ˚C. Hydrogen peroxide (30

% aq, 350 µL, 3.10 mmol, 1.01 equiv) was added and the solution was allowed to warm to ambient temperature and stirred for 16 h. After the reaction was complete the acetic acid was removed under reduced pressure and the product purified by column chromatography (silica gel, 25% EtOAc/hexanes) to give 77% of the product (562 mg,

2.30 mmol) as a white solid.

-1 1 FTIR (film, cm ): 3062, 3027, 2937, 1496, 1443, 1086, 1041; H NMR (CDCl 3, 400

MHz): δ 7.57-7.55 (m, 2H), 7.51-7.44 (m, 3H), 7.28-7.24 (m, 2H), 7.20-7.16 (m, 1H),

7.14-7.11 (m, 2H), 2.83-2.67 (m, 4H), 2.15-2.04 (m, 1H), 1.99-1.89 (m, 1H); 13C NMR

160

(CDCl 3, 100 MHz): δ 143.9, 140.5, 131.0, 129.3, 128.6, 128.5, 126.4, 124.1, 56.4, 34.6,

23.7.

1-ethyl-4-(ethylthio)pyridin-1-ium iodide (2.97): In a 10 mL round bottomed flask, 4-

(ethylthio)pyridine (130.2, 1.00 mmol), and iodoethane (80 µL, 1.00 mmol, 1 equiv) were dissolved in CH 2Cl 2 (5 mL). The reaction was stirred at 23 °C for 24 h. The CH 2Cl 2 was removed under reduced pressure to give a deep red-orange oil. The oil was washed with diethyl ether (3x15 mL) by adding it to the crude oil, stirring vigorously for 10 min, and then decanting off the diethyl ether layer. The oil was dried under reduced pressure to give pure 1-ethyl-4-(ethylthio)pyridin-1-ium iodide (178.3 mg, 0.604 mmol, 60% ) as a red oil.

-1 1 FTIR (film, cm ): 3107, 3019, 2976, 2930, 1632, 1494, 1461, 1111; H NMR (CDCl 3,

400 MHz): δ 9.08 (d, J = 6.8 Hz, 2H), 7.82 (d, J = 7.2 Hz, 2H), 4.78 (q, J = 7.2 Hz, 2H),

3.25 (q, J = 6.8 Hz, 2H), 1.68 (t, J = 7.2 Hz, 3H), 1.47 (t, J = 6.8 Hz, 3H); 13 C NMR

(CDCl 3, 100 MHz): δ 163.3, 142.0, 122.9, 55.5, 25.9, 16.7, 12.8.

161

2',4',6'-trimethoxy-[1,1'-biphenyl]-2,5-dione (2.99): To a stirred mixture of Pd(OAc) 2

(12 mg, 0.05 mmol, 0.05 equiv), 2.46 (13 mg, 0.060 mmol, 0.060 equiv) and benzoquinone (202 mg, 1.86 mmol, 1.86 equiv) in AcOH (0.75 mL) was added substrate

1,3,5-trimethoxybenzene (1.00 mmol) in one portion at ambient temperature. The resultant mixture was stirred at 40 °C for 24 h then was cooled to ambient temperature, and diluted with water (20 mL) and CH 2Cl 2 (100 mL). The organic layer was separated and the aqueous layer was extracted with CH 2Cl 2 (50 mL) again. The combined organic layers were dried over Na 2SO 4, filtered, and freed of solvent under reduced pressure to afford brown solid, which was purified by column chromatography on silica gel (1:6

EtOAc/hexanes) to afford 2',4',6'-trimethoxy-[1,1'-biphenyl]-2,5-dione (75 mg, 0.27 mmol, 27%) as a deep red solid. Spectral data of the product matched reported literature values.

1 H NMR (CDCl 3, 400 MHz): δ 6.82-6.74 (m, 3H), 6.17 (s, 2H), 3.84 (s, 3H), 3.73 (s, 6H);

13 C NMR (CDCl 3, 100 MHz): δ 188.0, 185.9, 162.6, 158.7, 142.6, 137.2, 136.3, 135.9,

90.8, 55.8, 55.4.

2',4',5'-trimethoxy-[1,1'-biphenyl]-2,5-dione (2.101): To a stirred mixture of Pd(OAc) 2

(1.00 mg, 0.05 mmol, 0.05 equiv), 2.46 (11 mg, 0.050 mmol, 0.050 equiv) and

162 benzoquinone (206 mg, 1.89 mmol, 1.89 equiv) in AcOH (0.75 mL) was added substrate

1,2,4-trimethoxybenzene (1.00 mmol) in one portion at ambient temperature. The resultant mixture was stirred at 40 °C for 24 h then was cooled to ambient temperature, and diluted with water (20 mL) and CH 2Cl 2 (100 mL). The organic layer was separated and the aqueous layer was extracted with CH 2Cl 2 (50 mL) again. The combined organic layers were dried over Na 2SO 4, filtered, and freed of solvent under reduced pressure to afford brown solid, which was purified by column chromatography on silica gel (30%

EtOAc/hexanes) to afford 2',4',5'-trimethoxy-[1,1'-biphenyl]-2,5-dione (101 mg, 0.37 mmol, 37%) as a deep red solid. Spectral data of the product matched reported literature values.

General procedure for the preparation of cis -vinylsilanes: The cis -vinylsilanes were prepared with a slight modification to a known literature procedure. 29 To a solution of ethylaluminum dichloride in hexane (1 M, 0.2 mL, 0.20 mmol) and toluene (1.0 mL) under N 2 at 0 °C was slowly added triethylsilane (140 mg, 100 µL, 1.20 mmol). The solution was allowed to stir for 10 min at 0 °C. The alkyne (1.00 mmol) was then slowly added to the solution and the reaction mixture was allowed to stir for 1.5 h at 0 °C. To the reaction was then added triethylamine (0.20 mL, 1.5 mmol) and allowed to stir for an additional 5 min. The reaction was then diluted with Et 2O (10 mL) and carefully washed with sat. NaHCO 3 (3 x 10 mL), brine (10 mL), dried over MgSO 4 and concentrated. The crude products were then ran through a plug of silca and concentrated to give pure cis - vinylsilanes.

163

(Z)-triethyl(hept-1-en-1-yl)silane (2.112): This reaction was performed according to the general procedure for cis -vinylsilanes using 1-heptyne (2.62 mL, 1.92 g, 20.0 mmol).

The crude product was purified by eluting through a plug of silica gel (hexanes) to give

71% of the product (3.03 g, 14.3 mmol) as a clear oil.

FTIR (film, cm -1): 2955, 2877, 1701, 1606, 1458, 1417, 1378, 1237, 1016, 732; 1H NMR

(CDCl 3, 400 MHz): δ 6.37 (dt, J = 14.0, 7.2 Hz, 1H), 5.39 (dt, J = 14.0, 1.2 Hz, 1H),

2.11-2.06 (m, 2H), 1.41-1.27 (m, 6H), 0.94 (t, J = 8.0 Hz, 9H), 0.91-0.87 (m, 3H), 0.61

13 (q, J = 7.6 Hz, 6H); C NMR (CDCl 3, 100 MHz): δ 150.6, 125.1, 34.3, 31.9, 29.7, 22.8,

14.2, 7.7, 4.9.

(Z)-hept-1-en-1-yltriphenylsilane (2.121): This reaction was performed according to the general procedure for cis -vinylsilanes using 1-heptyne (1.31 mL, 960 mg, 10.0 mmol) and triphenysilane (3.13 g, 12.0 mmol). The crude product was purified by column chromatography on silica gel (hexanes) to give 35% of the product (1.24 g, 3.50 mmol) as a clear oil.

-1 1 FTIR (film, cm ): 3048, 2955, 2925, 2855, 1601, 1427, 1109, 699; H NMR (CDCl 3,

400 MHz): δ 7.56-7.55 (m, 6H), 7.40-7.31 (m, 9H), 6.70 (dt, J = 13.6, 7.6 Hz, 1H), 6.02

(dt, J = 13.6, 1.2, 1H), 1.91 (qd, J = 7.6, 1.2 Hz, 2H), 1.18-1.10 (m , 2H), 1.08-1.00 (m,

13 2H), 0.97-0.91 (m, 2H), 0.74 (t, J = 7.2 Hz, 3H); C NMR (CDCl 3, 100 MHz): δ 154.2,

164

136.0, 135.5, 129.4, 128.0, 122.8, 34.7, 31.6, 28.9, 22.5, 14.1; HRMS (ESI) calcd for

+ C25 H28 Si [M+Na] : 379.1852, found 379.1846.

(Z)-tert -butyl(hept-1-en-1-yl)dimethylsilane (2.123): This reaction was performed according to the general procedure for cis -vinylsilanes using 1-heptyne (1.31 mL, 960 mg, 10.0 mmol) and tert -butyldimethylsilane (1.99 mL, 1.39 g, 12.0 mmol). The crude product was purified through a plug of silica gel (hexanes) to give 64% of the product

(1.36 g, 6.40 mmol) as a clear oil.

-1 1 FTIR (film, cm ): 2927, 2855, 1606, 1469, 1248, 1007, 825, 774, 688; H NMR (CDCl 3,

400 MHz): δ 6.35 (dt, J = 14.4, 7.2 Hz, 1H), 5.45 (dt, J = 14.0, 1.2 Hz, 1H), 2.09 (qd, J =

13 6.0, 1.2 Hz, 2H), 1.37-1.24 (m, 6H), 0.91-0.84 (m, 12H), 0.07 (s, 6H); C NMR (CDCl 3,

100 MHz): δ 150.4, 125.9, 33.8, 31.8, 29.7, 26.6, 22.8, 17.0, 14.2, -3.8; GC MS (CI) m/z

(relative intensity): 212 (M +, 100).

(Z)-benzyl(hept-1-en-1-yl)dimethylsilane (2.125): This reaction was performed according to the general procedure for cis -vinylsilanes using 1-heptyne (0.66 mL, 484 mg, 5.0 mmol) and benzyldimethylsilane (0.95 mL, 902 mg, 6.0 mmol). The crude product was purified through a plug of silica gel (hexanes) to give 42% of the product

(523 mg, 2.12 mmol) as a clear oil.

165

FTIR (film, cm -1): 3080, 3060, 3024, 2957, 2925, 2856, 2119, 1601, 1493, 1452, 1408,

1 1378, 1249, 1207, 1155, 1056, 1030, 885, 835, 762, 698; H NMR (CDCl 3, 400 MHz): δ

7.25 (t, J = 7.6 Hz, 2H), 7.11 (t, J = 7.2 Hz, 1H), 7.07 (d, J = 8.0 Hz, 2H), 6.39 (dt, J =

14.0, 7.2 Hz, 1H), 5.49 (d, J = 14.0 Hz, 1H), 2.22 (s, 2H), 2.10 (q, J = 7.6 Hz, 2H), 1.42-

13 1.31 (m, 6H), 0.95 (t, J = 6.8 Hz, 3H), 0.15 (s, 6H); C NMR (CDCl 3, 100 MHz): δ

150.7, 140,4, 128.5, 128.3, 126.8, 124.2, 34.0, 31.8, 29.6, 27.0, 22.8, 14.3, -1.4; HRMS

+ (ESI) calcd for C 16 H26 Si [M+Na] : 269.1701, found 269.1696.

(Z)-dec-1-en-1-yltriethylsilane (2.129): This reaction was performed according to the general procedure for cis -vinylsilanes using 1-decyne (1.80 mL, 1.40 g, 10.0 mmol). The crude product was purified through a plug of silica gel (hexanes) to give 60% of the product (1.54 g, 6.00 mmol) as a clear oil.

FTIR (film, cm-1): 2924, 1604, 1461, 1415, 1377, 1235, 1015, 971, 730; 1H NMR

(CDCl 3, 400 MHz): δ 6.37 (dt, J = 14.4, 7.2 Hz, 1H), 5.37 (dt, J = 14, 1.2 Hz, 1H), 2.11-

2.05 (m, 2H), 1.38-1.32 (m, 12H), 0.94 (t, J = 8.0 Hz, 9H), 0.88 (t, J = 3.2, 3H), 0.60 (q, J

13 = 8.0 Hz, 6H); C NMR (CDCl 3, 100 MHz): δ 150.6, 125.1, 34.4, 32.2, 30.1, 29.8, 29.7,

29.5, 22.9, 14.3, 7.8, 4.9.

(Z)-tert -butyldimethyl((6-(triethylsilyl)hex-5-en-1-yl)oxy)silane (2.131): To a solution of (Z)-6-(triethylsilyl)hex-5-en-1-ol (2.37 g, 11.1 mmol) and tert -

166 butyl(chloro)dimethylsilane (2.09 g, 13.9 mmol) in DMF (24 mL) was added imidazole

(842 mg, 12.4 mmol). The reaction mixture was allowed to stir at ambient temperature for 1 h. Sat. aq. NH 4Cl (20 mL) and Et 2O (50 mL) were added to the reaction mixture and the organic layer was separated. The aqueous layer was then extracted with Et 2O (3 x 10 mL). The combined organic layers were washed with water (3 x 30 mL), brine (20 mL), dried over MgSO 4 and concentrated. The crude product was purified by column chromatography on silica gel (2% EtOAc/hexanes) and concentrated to give 99% of the pure product (3.58 g, 10.9 mmol).

FTIR (film, cm -1): 2953, 2877, 1605, 1462, 1416, 1388, 1361, 1255, 1105, 1005, 909,

1 837, 776, 734; H NMR (CDCl 3, 400 MHz): δ 6.35 (dt, J = 14.4, 7.2 Hz, 1H), 5.39 (dt, J

= 14.0, 1.2 Hz, 1H), 3.59 (t, J = 6.4 Hz, 2H), 2.10 (qd, J = 7.2, 1.2 Hz, 2H), 1.56-1.49 (m,

2H), 1.44-1.37 (m, 2H), 0.93 (t, J = 8.0 Hz, 9H), 0.89 (s, 9H), 0.59 (q, J = 8.0 Hz, 6H),

13 0.03 (s, 6H); C NMR (CDCl 3, 100 MHz): δ 150.0, 125.2, 63.0, 33.8, 32.6, 26.0, 25.9,

+ 18.3, 7.5, 4.7, -5.3; HRMS (ESI) calcd for C 18 H48 OSi 2 [M+Na] : 351.2510, found

351.2508.

(Z)-tert -butyldimethyl((4-(triethylsilyl)but-3-en-1-yl)oxy)silane (2.133): This reaction was performed with a slight modification to the general procedure for cis -vinylsilanes using (but-3-yn-1-yloxy)( tert -butyl)dimethylsilane (2.50 g, 13.5 mmol) and EtAlCl 2 in hexanes (1 M, 17.6 mL, 17.6 mmol). The crude product was purified by column chromatography on silica gel (5% EtOAc/hexanes) to give 46% of the product (1.87 g,

6.20 mmol) as a clear oil. 167

-1 1 FTIR (film, cm ): 2953, 1606, 1471, 1255, 1102, 1005, 836, 775, 734; H NMR (CDCl 3,

400 MHz): δ 6.37 (dt, J = 14.4, 7.2 Hz, 1H), 5.49 (dt, J = 14.4, 1.2 Hz, 1H), 3.63 (t, J =

6.8 Hz, 2H), 3.32 (dq, J = 7.2, 1.2 Hz, 2H), 0.93 (t, J = 8.0 Hz, 9H), 0.88 (s, 9H), 0.59 (q,

13 J = 8.0 Hz, 2H), 0.04 (s, 6H); C NMR (CDCl 3, 100 MHz): δ 146.3, 127.5, 63.2, 37.7,

+ 26.1, 18.6, 7.7, 4.9, -5.0; HRMS (ESI) calcd for C 16 H36 OSi 2 [M+Na] : 323.2197, found

323.2197.

(Z)-triethyl(5-phenylpent-1-en-1-yl)silane (2.138): This reaction was performed according to the general procedure for cis-vinylsilanes using 5-phenyl-1-pentyne (2.40 mL, 2.21 g, 15.3 mmol). The crude product was purified through a plug of silica gel

(hexanes) to give 71% of the product (2.83 g, 10.9 mmol) as a clear oil. FTIR (film, cm -

1 1 ): 3062, 3026, 2952, 2873, 1604, 1454, 1235, 1015, 731; H NMR (CDCl 3, 400 MHz): δ

7.29-7.25 (m, 2H), 7.18-7.16 (m, 3H), 6.39 (dt, J = 14, 3.2 Hz, 1H), 5.42 (d, J = 14.0 Hz),

2.63 (t, J = 7.6 Hz, 2H), 2.16-2.11 (m, 2H), 1.74-1.66 (m, 2H), 0.92 (t, J = 8.0 Hz, 9H),

13 0.56 (q, J = 7.6 Hz, 6H); C NMR (CDCl 3, 100 MHz): δ 149.8, 142.6, 128.6, 128.5,

+ 125.9, 125.8, 35.9, 33.9, 31.8, 7.1, 4.9; HRMS (ESI) calcd for C 17 H28 Si [M+Na] :

283.1852, found 283.1854.

168

(Z)-tert-butyldimethyl(3-phenylprop-1-en-1-yl)silane (2.140): This reaction was performed according to the general procedure for cis -vinylsilanes using 3-phenyl-1- propyne (0.630 mL, 613 mg, 5.07 mmol). The crude product was purified through a plug of silica gel (hexanes) to give 82% of the product (961 mg, 4.16 mmol) as a clear oil.

1 H NMR (CDCl 3, 400 MHz): δ 7.38-7.35 (m, 2H), 7.29-7.25 (3H), 6.57 (dtf, J = 14, 7.6

Hz, 1H), 5.71 (dt, J = 14, 1.2 Hz, 1H), 3.56 (d, J = 7.6 Hz), 1.00 (s, 9H), 0.24 (s, 6H);

13 C NMR (CDCl 3, 100 MHz): δ 147.9, 140.7, 128.6 (2), 127.5, 126.3, 39.9, 26.7, 17.1, -

3.7.

(Z)-triethyl(4-methylpent-1-en-1-yl)silane (2.144): This reaction was performed according to the general procedure for cis -vinylsilanes using 4-methyl-1-pentyne (1.20 mL, 838 mg, 10.2 mmol). The crude product was purified through a plug of silica gel

(hexanes) to give 73% of the product (1.48 g, 7.50 mmol) as a clear oil.

-1 1 FTIR (film, cm ): 2953, 1605, 1463, 1415, 1015, 725; H NMR (CDCl 3, 400 MHz): δ

6.39 (dt, J = 14.0, 7.2 Hz, 1H), 5.46 (dt, J = 14.0, 1.2 Hz, 1H), 2.00 (dt, J = 7.2, 1.2 Hz,

2H), 1.65 (septet, J = 6.4 Hz, 1H), 0.97-0.90 (m, 15H), 0.61 (q, J = 4.0 Hz, 6H); 13 C

NMR (CDCl 3, 100 MHz): δ 149.5, 126.1, 43.2, 29.0, 22.7, 7.7, 4.9; Anal. Calcd for

C12 H26 Si: C, 72.64; H, 13.21. Found: C, 72.78; H, 13.34.

169

(Z)-6-(triethylsilyl)hex-5-en-1-ol: To a solution of EtAlCl 2 in hexanes (1 M, 37.5 mL,

37.5 mmol) and toluene (15 mL) under N 2 at 0 °C was slowly added triethylsilane (2.90 mL, 2.11 g, 18.2 mmol). The solution was allowed to stir for 10 min at 0 °C. 5-Hexyn-1- ol (1.65 mL, 1.47 g, 15.0 mmol) was then slowly added to the solution and the reaction mixture was allowed to stir for 1.5 h at 0 °C. To the reaction was then added triethylamine (8.0 mL, 60 mmol) and the reaction was allowed to stir for an additional 5 min. The reaction was then diluted with Et 2O (100 mL) and carefully washed with sat. aq.

NaHCO 3 (8 x 40 mL), brine (100 mL), dried over MgSO 4 and concentrated. The crude product was purified by column chromatography on silica gel (20% EtOAc/hexanes) and concentrated to give 90% of the pure product (2.88 g, 13.5 mmol).

FTIR (film, cm -1): 3327, 2953, 2874, 1605, 1460, 1415, 1378, 1236, 1067, 1016; 1H

NMR (CDCl3, 400 MHz): δ 6.37 (dt, J = 14.4, 7.2 Hz, 1H), 5.42 (dt, J = 14.4, 1.2 Hz,

1H), 3.64 (t, J = 6.4 Hz, 2H), 2.14 (qd, J = 7.6, 1.2 Hz, 2H), 1.85 (s, 1H), 1.63-1.56 (m,

2H), 1.49-1.41 (m, 2H), 0.95 (t, J = 8.0 Hz, 9H), 0.61 (q, J = 8.0 Hz, 6H); 13 C NMR

(CDCl 3, 100 MHz): δ 149.9, 125.7, 62.9, 33.9, 32.6, 26.1, 7.7, 4.9; HRMS (ESI) calcd for

+ C12 H26 OSi [M+Na] : 237.1645, found 237.1642.

(Z)-6-(triethylsilyl)hex-5-en-1-yl acetate (2.146): A solution of (Z)-6-(triethylsilyl)hex-

5-en-1-ol (1.29 g, 6.0 mmol), NEt 3 (2.1 mL, 15 mmol), and DCM (5 mL) was stirred at ambient temperature for 30 min, after which DMAP (40.0 mg, 0.32 mmol) was added.

The solution was then cooled to 0 °C and acetic anhydride (1.42 mL, 15 mmol) was slowly added. The reaction mixture was then stirred for 12 h at ambient temperature. The 170 solution was then diluted with DCM (30 mL), washed with sat. aq. NaHCO 3 (2 x 30 mL), brine (30 mL), and then dried over MgSO 4. The solution was then concentrated and the crude product was purified through a short silica gel column (10% EtOAc/hexanes) to give 90% of the pure product (1.39 g, 5.42 mmol) as a colorless oil.

FTIR (film, cm -1): 2952, 2910, 2874, 1744, 1605, 1458, 1416, 1365, 1239, 1042, 1016,

1 972, 728; H NMR (CDCl 3, 400 MHz): δ 6.37 (dt, J = 16.0, 8.0 Hz, 1H), 5.45 (d, J =

12.0 Hz, 1H), 4.08 (t, J = 8.0 Hz, 2H), 2.15 (q, J = 8.0 Hz, 2H), 2.06 (s, 3H), 1.70-1.63

(m, 2H), 1.50-1.44 (m, 2H), 0.95 (t, J = 4.0 Hz, 9H), 0.62 (q, J = 4.0 Hz, 6H); 13 C NMR

(CDCl 3, 100 MHz): δ 171.3, 149.5, 126.0, 64.6, 33.7, 28.5, 26.3, 21.2, 7.7, 4.9; HRMS

+ (ESI) calcd for C14 H28 O2Si [M+Na] : 279.1756, found 279.1751.

(Z)-2-(6-(triethylsilyl)hex-5-en-1-yl)isoindoline-1,3-dione (2.148): Diisopropyl azodicarboxylate (1.10 mL, 5.59 mmol) was slowly added to a mixture of (Z)-6-

(triethylsilyl)hex-5-en-1-ol (1.07 g, 5.00 mmol), THF (10 mL), phthalimide (811 mg,

5.51 mmol), and triphenylphosphine (1.46 g, 5.55 mmol) at ambient temperature. After being stirred 48 h, the reaction mixture was concentrated, rinsed with Et 2O-hexane (1:1, 2 x 20 mL), and the white precipitate was filtered off. The filtrate was then concentrated and the crude product was purified by column chromatography on silica gel (10%

EtOAc/hexanes) to give 77% of the pure product (1.33 g, 3.86 mmol).

-1 1 FTIR (film, cm ): 2953, 1605, 1463, 1415, 1015, 725; H NMR (CDCl 3, 400 MHz): δ

6.39 (dt, J = 14.0, 7.2 Hz, 1H), 5.46 (dt, J = 14.0, 1.2 Hz, 1H), 2.00 (dt, J = 7.2, 1.2 Hz, 171

2H), 1.65 (septet, J = 6.4 Hz, 1H), 0.97-0.90 (m, 15H), 0.61 (q, J = 4.0 Hz, 6H); 13 C

NMR (CDCl 3, 100 MHz): δ 149.5, 126.1, 43.2, 29.0, 22.7, 7.7, 4.9; HRMS (ESI) calcd

+ for C 20 H29 NO2Si [M+Na] :366.1865, found 366.1860.

The reaction was then diluted with hexanes (20 mL), washed with sat. aq. NaHSO 3 (2 x

20 mL), brine (10 mL), dried over MgSO 4 and concentrated. The crude product was then purified by column chromatography on silica gel (2% EtOAc/hexanes).

General procedure for allylic oxidations of cis-vinylsilanes with BQ: To a small borosilicate glass vial equipped with a stir bar was added the corresponding cis- vinylsilane (1.00 mmol), Pd(OAc) 2 (4.5 mg, 0.02 mmol), benzoquinone (216 mg, 2.00 mmol), and acetic acid (0.8 mL). The vial was then placed in an oil bath at 90 °C and stirred until the reaction was determined to be complete by GC analysis. The reaction was then diluted with hexanes (20 mL), washed with sat. aq. NaHSO 3 (2 x 20 mL), brine (10 mL), dried over MgSO 4 and concentrated. The crude product was then purified by column chromatography on silica gel.

172

(E)-1-(trimethylsilyl)hept-1-en-3-yl acetate (2.116): This reaction was performed according to the general procedure for allylic oxidations of cis-vinylsilanes using (Z)- triethyl(hept-1-en-1-yl)silane (213 mg, 1.00 mmol) and Pd(OAc) 2 (4.5 mg, 0.02 mmol).

The crude product was purified by column chromatography on silica gel (2%

EtOAc/hexanes) to give 66% of the product (179 mg, 0.660 mmol) as a pale yellow oil.

FTIR (film, cm -1): 2955, 2874, 1744, 1622, 1460, 1416, 1370, 1236, 1017, 781, 722; 1H

NMR (CDCl 3, 400 MHz): δ 5.94 (dd, J = 18.8, 5.6 Hz, 1H), 5.76 (d, J = 18.8 Hz, 1H),

5.22, (q, J = 6.0 Hz, 1H), 2.06 (s, 3H), 1.62-1.58 (m, 2H), 1.40-1.20 (m, 4H), 0.95-0.91

13 (m, 12H), 0.59 (q, J = 8.0 Hz, 6H); C NMR (CDCl 3, 100 MHz): δ 170.3, 145.3, 127.7,

76.6, 34.0, 27.4, 22.6, 21.4, 14.1, 7.4, 3.5; Anal. Calcd for C15 H30 O2Si: C, 66.61; H,

11.18. Found: C, 66.50; H, 11.14.

(E)-1-(trimethylsilyl)hept-1-en-3-yl acetate (2.119): This reaction was performed according to the general procedure for allylic oxidations of cis-vinylsilanes using (Z)- hept-1-en-1-yltrimethylsilane (171 mg, 1.00 mmol) and Pd(OAc) 2 (4.5 mg, 0.02 mmol).

The crude product was purified by column chromatography on silica gel (2%

EtOAc/hexanes) to give 41% of the product (94 mg, 0.41 mmol) as a pale yellow oil.

-1 1 FTIR (film, cm ): 2957, 2862, 1743, 1371, 1237, 1020, 988, 866, 839; H NMR (CDCl 3,

400 MHz): δ 5.93 (dd, J = 18.8, 5.2 Hz, 1H), 5.82 (dd, J = 18.8, 0.8 Hz, 1H), 5.22 (q, J =

6.0 Hz, 1H), 2.08 (s, 3H), 1.61-1.58 (m, 2H), 1.31-1.27 (m, 4H), 0.89 (t, J = 6.4 Hz, 3H),

13 0.07 (s, 9H); C NMR (CDCl 3, 100 MHz): δ 170.4, 143.7, 131.2, 76.2, 33.8, 27.3, 22.5,

+ 21.3, 13.9, -1.4; HRMS (ESI) calcd for C12 H24 O2Si [M+Na] : 251.1438, found 251.1438. 173

(E)-1-(triphenylsilyl)hept-1-en-3-yl acetate (2.122): This reaction was performed according to the general procedure for allylic oxidations of cis-vinylsilanes using (Z)- hept-1-en-1-yltriphenylsilane (357 mg, 1.00 mmol) and Pd(OAc) 2 (4.5 mg, 0.02 mmol).

The crude product was purified by column chromatography on silica gel (2%

EtOAc/hexanes) to give 16% of the product (66 mg, 0.16 mmol) as a pale yellow oil.

FTIR (film, cm -1): 3068, 3049, 2998, 2955, 2932, 2860, 1738, 1622, 1466, 1428, 1372,

1 1238, 1111, 1028, 997, 909, 777, 735, 700; H NMR (CDCl 3, 400 MHz): δ 7.51-7.33 (m,

15H), 6.37 (dd, J = 18.6, 1.2 Hz, 1H), 6.08 (dd, J = 18.6, 3.3 Hz, 1H), 5.38-5.33 (m, 1H),

2.075 (s, 3H), 1.65-1.59 (m, 2H), 1.32-1.29 (m, 4H), 0.90-0.87 (m, 3H); 13 C NMR

(CDCl 3, 100 MHz): δ 170.5, 149.9, 136.1, 134.4, 129.8, 128.1, 124.8, 76.1, 34.0, 27.5,

+ 22.7, 21.4, 14.2; HRMS (ESI) calcd for C 27 H30 O2Si [M+Na] : 437.1907, found 437.1900.

(E)-1-(tert -butyldimethylsilyl)hept-1-en-3-yl acetate (2.124) : This reaction was performed according to the general procedure for allylic oxidations of cis-vinylsilanes using (Z)-tert -butyl(hept-1-en-1-yl)dimethylsilane (213 mg, 1.00 mmol) and Pd(OAc) 2

(4.5 mg, 0.02 mmol). The crude product was purified by column chromatography on silica gel (2% EtOAc/hexanes) to give 44% of the product (119 mg, 0.440 mmol) as a pale yellow oil.

174

FTIR (film, cm -1): 2954, 2857, 1745, 1620, 1470, 1371, 1235, 1019, 989, 839; 1H NMR

(CDCl 3, 400 MHz): δ 5.94 (dd, J = 18.8, 5.2 Hz, 1H), 5.81 (dd, J = 18.8, 1.2 Hz, 1H),

5.24-5.19 (m, 1H), 2.07 (s, 3H), 1.62-1.57 (m, 2H), 1.35-1.25 (m, 5H), 0.91-0.86 (m,

13 14H), 0.02 (s, 6H); C NMR (CDCl 3, 100 MHz): δ 170.5, 145.3, 128.8, 76.6, 34.1, 27.5,

26.6, 22.7, 21.5, 16.7, 14.2; Anal. Calcd for C15 H30 O2Si: C, 66.61; H, 11.18. Found: C,

66.89; H, 11.34.

(E)-1-(benzyldimethylsilyl)hept-1-en-3-yl acetate (2.126): This reaction was performed according to the general procedure for allylic oxidations of cis-vinylsilanes using (Z)- benzyl(hept-1-en-1-yl)dimethylsilane (247 mg, 1.00 mmol) and and Pd(OAc) 2 (4.5 mg,

0.02 mmol). The crude product was purified by column chromatography on silica gel

(5% EtOAc/hexanes) to give 57% of the product (172 mg, 0.570 mmol) as a pale yellow oil.

FTIR (film, cm -1): 3081, 3060, 3024, 2956, 2933, 2861, 1741, 1622, 1600, 1493, 1452,

1 1371, 1237, 1207, 1154, 1055, 1019, 988, 834, 699; H NMR (CDCl 3, 400 MHz): δ 7.22

(t, J = 7.2 Hz, 2H), 7.09 (t, J = 7.2 Hz, 1H), 7.00 (t, J = 8.0 Hz, 2H), 5.92 (dd, J = 18.8,

5.6 Hz, 1H), 5.80 (dd, J = 18.8, 1.2 Hz, 1H), 5.24 (q, J = 6.0 Hz, 1H), 2.15 (s, 2H), 2.10

(s, 3H), 1.62-1.58 (m, 2H), 1.37-1.28 (m, 4H), 0.93 (t, J = 6.8 Hz, 3 H), 0.80 (s, 6H); 13 C

NMR (CDCl 3, 100 MHz): δ 170.5, 145.3, 140.0, 129.3, 128.5, 128.3, 124.3, 76.4, 34.1,

+ 27.5, 26.2, 22.7, 21.5, 14.2, -3.2; HRMS (ESI) calcd for C 18 H28 O2Si [M+Na] : 327.1756, found 327.1751.

175

(E)-1-(triethylsilyl)dec-1-en-3-yl acetate (2.130) : This reaction was performed according to the general procedure for allylic oxidations of cis-vinylsilanes using (Z)-dec-

1-en-1-yltriethylsilane (255 mg, 1.00 mmol) and Pd(OAc) 2 (4.5 mg, 0.02 mmol). The crude product was purified by column chromatography on silica gel (2% EtOAc/hexanes) to give 69% of the product (216 mg, 0.690 mmol) as a pale yellow oil.

FTIR (film, cm -1): 2953, 2919, 2873, 1743, 1622, 1461, 1416, 1370, 1236, 1017, 989,

1 781, 722; H NMR (CDCl 3, 400 MHz): δ 5.96-5.73 (m, 2H), 5.24-5.19 (m, 1H), 2.07 (s,

3H), 1.62-1.56 (m, 2H), 1.28-1.27 (m, 10H), 0.94-0.86 (m, 12H), 0.57 (q, J = 8.0 Hz,

13 6H); C NMR (CDCl 3, 100 MHz): δ 170.5, 145.3, 127.9, 76.7, 34.4, 31.9, 29.5, 29.4,

+ 25.3, 22.8, 21.5, 14.3, 7.5, 3.5; HRMS (ESI) calcd for C 18 H36 O2Si [M+Na] : 335.2377, found 335.2375.

(E)-6-(( tert -butyldimethylsilyl)oxy)-1-(triethylsilyl)hex-1-en-3-yl acetate (2.132) : This reaction was performed according to the general procedure for allylic oxidations of cis- vinylsilanes using (Z)-tert -butyldimethyl((6-(triethylsilyl)hex-5-en-1-yl)oxy)silane (329 mg, 1.00 mmol) and Pd(OAc) 2 (11 mg, 0.05 mmol). The crude product was purified by column chromatography on silica gel (5% EtOAc/hexanes) to give 49% of the product

(190 mg, 0.490 mmol) as a pale yellow oil.

FTIR (film, cm -1): 2951, 1748, 1622, 1463, 1416, 1370, 1234, 1102, 1007, 938, 838, 777,

1 722, 667; H NMR (CDCl 3, 400 MHz): δ 6.05 (dd, J = 19.0, 5.6 Hz, 1H), 5.87 (dd, J =

176

18.8, 1.2 Hz, 1H), 5.38-5.33 (m, 1H), 3.72 (t, J = 6.4 Hz, 2H), 2.17 (s, 1H), 1.79-1.75 (m,

2H), 1.66-1.61 (m, 2H), 1.05-0.99 (m, 19H), 0.67 (q, J = 8.0 Hz, 6H), 0.15 (s, 6H); 13 C

NMR (CDCl 3, 100 MHz): δ 170.0, 145.1, 127.8, 76.1, 62.7, 30.7, 28.4, 25.9, 21.2, 18.3,

+ 7.3, 3.4, -5.3; HRMS (ESI) calcd for C 20 H42 O3Si 2 [M+Na] : 409.2565, found 409.2564.

(E)-1-(( tert -butyldimethylsilyl)oxy)-4-(triethylsilyl)but-3-en-2-yl acetate (2.134): This reaction was performed according to the general procedure for allylic oxidations of cis- vinylsilanes using (Z)-tert -butyldimethyl((4-(triethylsilyl)but-3-en-1-yl)oxy)silane (301 mg, 1.00 mmol) and Pd(OAc) 2 (4.5 mg, 0.02 mmol). The crude product was purified by column chromatography on silica gel (5% EtOAc/hexanes) to give 38% of the product

(136 mg, 0.380 mmol) as a pale yellow oil.

FTIR (film, cm -1): 3234, 2954, 2874, 2388, 2279, 1745, 1618, 1454, 1329, 1235, 812; 1H

NMR (CDCl 3, 400 MHz): δ 6.01-5.82 (m, 2H), 5.34-5.29 (m, 1H), 3.67 (d, J = 6.0 Hz,

2H), 2.09 (s, 3H), 0.92 (t, J = 8.0 Hz, 9H), 0.88 (s, 9H), 0.57 (q, J = 8.0 Hz, 6H), 0.05 (s,

13 6H); C NMR (C 6D6, 100 MHz): δ 169.1, 143.0, 129.1, 76.7, 64.9, 25.8, 20.6, 18.3, 7.4,

+ 3.5, -5.4; HRMS (ESI) calcd for C 18 H38 O3Si 2 [M+Na] : 381.2252, found 381.2254.

(Z)-4-(triethylsilyl)hex-4-en-3-yl acetate and ( E)-3-(triethylsilyl)hex-3-en-2-yl acetate

(2.136 and 2.137): This reaction was performed according to the general procedure for allylic oxidations of cis-vinylsilanes using (Z)-triethyl(hex-3-en-3-yl)silane (198 mg, 1.00

177 mmol) and Pd(OAc) 2 (11.0 mg, 0.05 mmol). The crude product was purified by column chromatography on silica gel (2% EtOAc/hexanes) to give 56% of the mixture of products (144 mg, 0.560 mmol) as a clear oil.

FTIR (film, cm -1): 2955, 2875, 1739, 1608, 1459, 1418, 1368, 1242, 1173, 1050, 1016,

1 961, 732; H NMR (CDCl 3, 400 MHz): δ 6.35 (q, J = 6.8 Hz, 1H), 5.85 (q, J = 5.6 Hz,

1H), 5.67 (t, J = 6.4 Hz, 1H), 5.09 (t, J = 6.8 Hz, 1 H), 2.40-2.05 (m, 2H), 2.03 (s, 3H),

1.83-1.76 (m, 4H), 1.27 (d, J= 6.8 Hz, 3H), 1.02-0.84 (m, 12H), 0.75-0.62 (m, 6H); 13 C

NMR (CDCl 3, 100 MHz): δ 170.4, 170.4, 144.6, 138.8, 138.1, 137.4, 137.4, 80.5, 76.4,

72.1, 28.9, 28.3, 22.7, 21.6, 21.5, 21.5, 21.4, 17.5, 15.6, 14.1, 10.5, 10.4, 7.7, 7.5, 4.3, 4.3,

+ 4.1, 4.0; HRMS (ESI) calcd for C14 H28 O2Si [M+ Na] : 279.1751, found 279.1751.

(E)-5-phenyl-1-(triethylsilyl)pent-1-en-3-yl acetate (2.139) : This reaction was performed according to the general procedure for allylic oxidations of cis-vinylsilanes using (Z)-triethyl(5-phenylpent-1-en-1-yl)silane (261 mg, 1.00 mmol) and Pd(OAc) 2 (4.5 mg, 0.02 mmol). The crude product was purified by column chromatography on silica gel

(2% EtOAc/hexanes) to give 47% of the product (150 mg, 0.470 mmol) as a pale yellow oil.

FTIR (film, cm -1): 3085, 3062, 3026, 2951, 2870, 1756, 1604, 1496, 1455, 1416, 1369,

1 1236, 1090, 1017, 972, 731; H NMR (CDCl 3, 400 MHz): δ 7.28-7.15 (m, 5H), 5.98 (dd,

J = 19.0, 5.6 Hz, 1H), 5.80 (dd, J = 19.0, 0.8 Hz, 1H), 5.29-5.25 (m, 1H), 2.69-2.58 (m,

2H), 2.05 (s, 3H), 2.02-1.86 (m, 2H), 0.93 (t, J = 8.0 Hz, 9H), 0.59 (q, J = 8.0 Hz, 6H);

13 C NMR (CDCl 3, 100 MHz): δ 170.3, 144.9, 141.6, 128.6, 128.5, 128.3, 126.1, 76.0, 178

+ 36.0, 31.7, 21.3, 7.5, 3.5; HRMS (ESI) calcd for C19 H30 O2Si [M+Na] : 341.1907, found

341.1907.

(E)-4-methyl-1-(triethylsilyl)pent-1-en-3-yl acetate (2.145) : This reaction was performed according to the general procedure for allylic oxidations of cis-vinylsilanes using (Z)-triethyl(4-methylpent-1-en-1-yl)silane (198 mg, 1.00 mmol) and Pd(OAc) 2 (4.5 mg, 0.02 mmol). The crude product was purified by column chromatography on silica gel

(2% EtOAc/hexanes) to give 53% of the product (136 mg, 0.530 mmol) as a pale yellow oil.

FTIR (film, cm -1): 2956, 2875, 1741, 1622, 1464, 1416, 1370, 1238, 1123, 1018, 774,

1 722; H NMR (CDCl 3, 400 MHz): δ 5.92 (dd, J = 19.0, 6.0 Hz, 1H), 5.76 (dd, J = 19.0,

0.8 Hz, 1H), 5.05 (td, J = 6.0 Hz, 0.8 Hz, 1H), 2.07 (s, 3H), 1.87 (sex, J = 6.8 Hz, 1H),

13 0.95-0.89 (m, 15H), 0.57 (q, J = 8.0 Hz, 6H); C NMR (CDCl 3, 100 MHz): δ 170.4,

143.5, 129.0, 81.1, 32.0, 21.3, 18.3, 18.1, 7.5, 3.5; HRMS (ESI) calcd for C 14 H28 O2Si

[M+Na]+: 279.1751, found 279.1741.

(E)-6-(triethylsilyl)hex-5-ene-1,4-diyl diacetate (2.147): This reaction was performed according to the general procedure for allylic oxidations of cis-vinylsilanes using (Z)-6-

(triethylsilyl)hex-5-en-1-yl acetate (256 mg, 1.00 mmol) and Pd(OAc) 2 (4.5 mg, 0.05 mmol). The crude product was purified by column chromatography on silica gel (2%

EtOAc/hexanes) to give 50% of the product (156 mg, 0.50 mmol) as a pale yellow oil. 179

FTIR (film, cm -1): 3462, 2952, 2874, 1738, 1622, 1461, 1416, 1370, 1235, 1019, 780,

1 732; H NMR (CDCl 3, 400 MHz): δ 5.94 (dd, J = 19.0, 5.2 Hz, 1H), 5.79 (dd, J = 19.0,

0.8 Hz, 1H), 5.26 (q, J = 4.8 Hz, 1H), 4.07 (t, J = 6 Hz, 2H), 2.07 (s, 3H), 2.04 (s, 3H),

13 1.69-1.67 (m, 4H), 0.93 (t, J = 8.0 Hz, 9H), 0.58 (q, J = 8.0 Hz, 6H); C NMR (CDCl 3,

100 MHz): δ 171.1, 170.2, 144.6, 128.4, 75.9, 64.2, 30.7, 24.5, 21.3, 20.9, 7.4, 3.4;

+ HRMS (ESI) calcd for C 16 H30 O4Si [M+Na] : 337.1811, found 337.1806.

(E)-6-(1,3-dioxoisoindolin-2-yl)-1-(triethylsilyl)hex-1-en-3-yl acetate (2.149) : This reaction was performed according to the general procedure for allylic oxidations of cis- vinylsilanes using (Z)-2-(6-(triethylsilyl)hex-5-en-1-yl)isoindoline-1,3-dione (344 mg,

1.00 mmol) and Pd(OAc) 2 (11.2 mg, 0.02 mmol). The crude product was purified by column chromatography on silica gel (10% EtOAc/hexanes) to give 46% of the product

(186 mg, 0.460 mmol) as a pale yellow oil.

FTIR (film, cm -1): 2956, 2875, 1741, 1622, 1464, 1416, 1370, 1238, 1123, 1018, 774,

1 722; H NMR (CDCl 3, 400 MHz): δ 5.92 (dd, J = 19.0, 6.0 Hz, 1H), 5.76 (dd, J = 19.0,

0.8 Hz, 1H), 5.05 (td, J = 6.0 Hz, 0.8 Hz, 1H), 2.07 (s, 3H), 1.87 (sex, J = 6.8 Hz, 1H),

13 0.95-0.89 (m, 15H), 0.57 (q, J = 8.0 Hz, 6H); C NMR (CDCl 3, 100 MHz): δ 170.4,

143.5, 129.0, 81.1, 32.0, 21.3, 18.3, 18.1, 7.5, 3.5; HRMS (ESI) calcd for C 22 H34 NO 4Si

[M+Na]+: 424.1920, found 424.1915.

180

(E)-1-(triethylsilyl)hept-2-en-1-yl acetate (2.156): The product was prepared according to a modified literature procedure. 12 A solution of trans -2-hepten-1-ol (506 mg, 4.44 mmol) in THF (5 mL) was cooled to -78 oC. To the stirring solution, n-BuLi (3.1 mL,

1.6M, 5.0 mmol) was added dropwise and the solution was then allowed to stir for 1 h.

Chlorotriethylsilane (738 mg, 4.90 mmol) was then added in one portion to the stirring solution, and the solution was allowed to continue to stir at -78 oC for 2 h. To the solution was added sec -BuLi in cyclohexane (4.1 mL, 1.3 M, 5.3 mmol) dropwise, over a 10 min period. After 2 h the cooling bath was removed and sat. aq. NH 4Cl (10 mL) was added to the solution. The solution was extracted with Et 2O (2 x 15 mL). The combined organic layers were washed with H 2O (2 x 10 mL), brine (2 x 10 mL), dried over MgSO 4, and concentrated. The crude alcohol (942 mg, 4.10 mmol), triethylamine (1.25 mL, 908 mg,

9.00 mmol), and dry DCM (4 mL) were added to a round bottom flask equipped with a stir bar. The resulting solution was stirred for 30 min, and then DMAP (28 mg, 0.25 mmol) was added. The solution was cooled to 0 oC and acetic anhydride (0.85 mL, 918 mg, 9.00 mmol) was added dropwise. The solution was then allowed to warm up to ambient temperature, after which it was stirred an additional 6 h. The reaction mixture was diluted with Et 2O (15 mL), the organic layer was washed with saturated NaHCO 3 (2 x 10 mL), brine (10 mL), dried over MgSO 4, and concentrated. The crude product was then purified by column chromatography on silica gel (2% EtOAc/hexanes) to afford

59% of the product (711 mg, 2.63 mmol) as a yellow oil.

FTIR (film, cm -1): 2956, 2877, 1738, 1461, 1367, 1231, 1017, 966, 733; 1H NMR

(CDCl 3, 400 MHz): δ 5.47-5.45 (m, 2H), 5.28-5.27 (m, 1H), 2.05 (s, 3H), 2.04-2.00 (m,

181

2H), 1.34-1.25 (m, 4H), 0.98-0.94 (m, 10H), 0.88 (t, J = 7.2 Hz, 3H), 0.63-0.53 (m, 6H);

13 C NMR (CDCl 3, 100 MHz): δ 170.7, 129.4, 126.7, 68.6, 32.1, 31.6, 22.2, 21.2, 13.9,

+ 7.2, 1.7; HRMS (ESI) calcd for C 15 H30 O2Si [M+Na] : 293.1907, found 293.1908.

Reaction procedure for rearrangement of linear allylic acetate: To a small borosilicate glass vial equipped with a stir bar was added (E)-1-(triethylsilyl)hept-2-en-1- yl acetate (23.0 mg, 0.090 mmol), Pd(OAc) 2 (0.400 mg, 0.002 mmol), benzoquinone

(39.0 mg, 0.180 mmol), and acetic acid (0.1 mL). The vial was then placed in an oil bath at 90 °C and stirred for 10 h. The reaction was then diluted with hexanes (10 mL), washed with sat. aq. NaHSO 3 (2 x 10 mL), brine (10 mL), dried over MgSO 4 and concentrated. The reaction yielded 5 in 65% yield based upon 1H NMR using trimethoxybenzene as an internal standard.

182

5.3 Chapter 3: Experimental Details

(Z)-1-Fluorotridec-1-ene (3.18): Following a previously reported literature procedure.

CFCl 3 (6.00 mL, 65.0 mmol, 1.25 equiv) was added to a stirring solution of P nBu 3 (42.0 mL, 160 mmol, 3.08 equiv) in CH 2Cl 2 (80 mL) and the solution stirred for 1 h at 0 °C and then 3 h at 23 °C. 1-Dodecanal (11.4 mL, 52.0 mmol) was added and the solution stirred for an additional 18 h before acidifying with HCl (10% aq). The acidified solution was extracted with CH 2Cl 2 and dried over Na 2SO 4. The solvent was removed under vacuum and the product was distilled by Kugelrohr distillation. A small impurity remained which could be removed by column chromatography using silica gel (hexanes) to give pure ( Z)-

1-fluorotridec-1-ene (2.48 g, XX mmol, 24%) as a clear colorless oil.

-1 1 FTIR (film, cm ): 2922, 2853, 1671, 1465, 1378, 1034; H NMR (CDCl 3, 400 MHz): δ

6.54 (dd, J = 86, 4.8 Hz, 1H), 4.71 (dtd, J = 43.6, 7.6, 4.8 Hz, 1H), 2.13-2.08 (m, 2H),

13 1.38-1.26 (m, 18H), 0.89-0.86 (m, 3H); C NMR (CDCl 3, 100 MHz): δ 147.7 (d, J =

1016 Hz), 111.3 (d, J = 21.2 Hz), 32.2, 29.9 (2), 29.8, 29.6 (2), 29.5, 29.4, 22.9 (2), 14.3.

183

General Procedure for the Synthesis of Enol Ethers: KOtBu (1.3 equiv) in THF was slowly added to a rapidly stirring solution of (methoxymethyl)triphenylphosphonium chloride (1.3 equiv) in THF. The deep red solution was allowed to stir at 23 °C for 45 min before slowly adding a solution of the aldehyde (1 equiv) in THF. The solution turned from deep red to orange and was allowed to stir for an additional 4 h. The solvent was reduced under vacuum and diluted with hexanes. The organic layer was washed with water and brine followed by drying the organic layer over MgSO 4. The organic layer was removed under vacuum and the resulting oil purified by Kugelrohr distillation under reduced pressure.

1-Methoxyltridec-1-ene (3.29): The above general procedure was followed using 1- dodecanal (1.7 mL, 7.85 mmol) and (2-methoxyethyl)triphenylphosphonium chloride

(2.69 g, 7.85 mmol, 1.02 equiv) with potassium tert -butoxide (0.99 g, 8.88 mmol, 1.16 equiv). The resulting oil was purified by Kugelrohr distillation under reduced pressure to give 1-methoxytridec-1-ene (1.35 g, 7.66 mmol, 83%) as a clear, colorless oil. The product was isolated as a 1.6:1 mixture of E and Z isomers. Spectral data of the product matched reported literature values.

184

(4-methoxybut-3-en-1-yl)benzene (3.9): The above general procedure was followed using 3-phenylpropanal (2.94 mL, 21.9 mmol) and (2- methoxymethyl)triphenylphosphonium chloride (10.2 g, 29.7 mmol, 1.35 equiv) with potassium tert -butoxide (3.33 g, 29.7 mmol, 1.35 equiv). The crude oil was purified by

Kugelrohr distillation under reduced pressure to give (4-methoxybut-3-en-1-yl)benzene

(2.96 g, 18.2 mmol, 83%) as a clear, colorless oil. Spectral data of the product matched reported literature values.

tert -Butyl((6-methoxyhex-5-en-1-yl)oxy)dimethylsilane (3.34): The above general procedure was followed using 5-(( tert -butyldimethylsilyl)oxy)pentanal (5.45 g, 25.2 mmol) and (2-methoxyethyl)triphenylphosphonium chloride (11.2 g, 32.7 mmol, 1.3 equiv) with potassium tert -butoxide (3.68 g, 32.8 mmol, 1.3 equiv). tert -Butyl((6- methoxyhex-5-en-1-yl)oxy)dimethylsilane (4.41 g, 18.1 mmol, 72%) was isolated by

Kugelrohr distillation to give a clear, colorless oil. The product was isolated as a 1.7:1

(E:Z) mixture isomers.

-1 1 FTIR (film, cm ): 2929, 2856, 1654, 1462, 1255, 1209, 1101; H NMR (CDCl 3, 400

MHz): δ 6.27 (d, J = 12.4 Hz, 1H), 5.86 (d, J = 6.4 Hz, 0.6H), 4.72 (dt, J = 12.4, 7.2Hz,

1H), 4.33 (q, J = 7.2 Hz, 0.6H), 3.60 (t, J = 6.4 Hz, 3.2H), 3.57 (s, 1.7H), 3.49 (s, 3H),

2.07 (qd, J = 7.6, 1.2 Hz, 1.2H), 1.93 (q, J = 7.2 Hz, 2H), 1.57-1.49 (m, 3.2H), 1.41-1.34

185

13 (m, 3.2H), 0.90 (s, 14.4H), 0.46 (s, 9.5H); C NMR (CDCl 3, 100 MHz): δ 147.3, 146.3,

107.1, 103.2, 63.4, 63.3, 59.6, 56.1, 32.7, 32.4, 27.7, 27.2, 26.2, 23.8, 18.6, -5.1.

6-methoxyhex-5-en-1-yl acetate (3.36): To a stirring solution of 6-methoxyhex-5-en-1- ol (0.825 g, 6.34 mmol) and pyridine (1.60 mL, 19.8 mmol, 3 equiv) in CH 2Cl 2 (11 mL) was added acetic anhydride (1.20 mL, 12.7 mmol, 2 equiv) and 4-

(dimethylamino)pyridine (79.5 mg, 0.651 mmol, 0.1 equiv) at 0 °C. The reaction was allowed to stir for 30 min at 0 °C and an additional 15 h at 23 °C. The mixture was quenched with saturated aqueous NaHCO 3 (100 mL) and extracted with CH 2Cl 2 (3 x 100 mL). The combined organic layers were dried over Na 2SO 4, filtered, and freed of solvent under reduced pressure to afford a yellow oil, which was purified by flash chromatography on silica gel (15% EtOAc/hexanes) to give 6-methoxyhex-5-en-1-yl acetate (0.994 g, 5.77 mmol, 91%) as a clear, colorless oil.

1 H NMR (CDCl 3, 400 MHz): δ 6.29 (d, J = 12.4 Hz), 5.89 (dt, J = 6.0, 1.2 Hz, 0.5H),

4.70 (dt, J = 12.4, 7.2 Hz, 1H), 4.33-4.29 (m, 0.5H), 4.06 (t, J = 6.8 Hz, 3.1H), 3.57 (s,

1.4H), 3.50 (s, 3H), 2.12-2.06 (m, 5.6 H), 1.99-1.93 (m, 2H), 1.67-1.60 (m, 3.1H), 1.44-

13 1.37 (m, 3.1H); C NMR (CDCl 3, 100 MHz): δ 171.3, 147.6, 146.7, 106.4, 102.6, 64.7,

64.6, 59.6, 56.1, 28.3, 28.1, 27.5, 27.2, 26.2, 23.6, 21.2.

186

Triethyl((1 Z)-7-methoxyhepta-1,6-dien-1-yl)silane (3.38): The above general procedure was followed using (Z)-6-(triethylsilyl)hex-5-enal (2.00 g, 11.5 mmol) and (2- methoxyethyl)triphenylphosphonium chloride (4.62 g, 13.7 mmol, 1.5 equiv) with potassium tert -butoxide (1.54 g, 13.7 mmol, 1.5 equiv). The resulting oil was purified by flash chromatography on silica gel (hexanes) to give triethyl((1 Z)-7-methoxyhepta-1,6- dien-1-yl)silane (1.15 g, 4.78 mmol, 51%) as a clear, colorless oil. The product was isolated as a 2:1 mixture of E and Z isomers.

-1 1 FTIR (film, cm ): 2952, 2873, 1728, 1605, 1461, 1016; H NMR (CDCl 3, 400 MHz): δ

6.36 (m, 3.4H), 6.29 (d, J = 12.4 Hz, 2H), 5.88 (dd, J = 6.4, 1.2 Hz, 1H), 5.43-5.37 (m,

3.4H), 4.72 (dt, J = 12.4, 7.2 Hz, 2H), 4.34-4.30 (m, 1H), 3.57 (s, 3H), 3.50 (s, 6H), 2.14-

2.07 (m, 9.3H), 1.94 (q, J = 7.2 Hz, 4H), 1.46-1.39 (m, 6.6H), 0.94 (s, 32H), 0.61 (q, J =

13 8.0 Hz, 21H); C NMR (CDCl 3, 100 MHz): δ 150.4, 150.1, 147.5, 146.5, 125.5, 125.3,

106.8, 102.9, 59.6, 56.0, 33.9, 33.7, 31.1, 30.2, 27.7, 23.9, 7.7, 4.9.

OMe

(4-(Methoxymethylene)cyclohexyl)benzene (3.30): The above general procedure was followed using 4-phenylcyclohexanone (707 mg, 4.05 mmol) and (2- methoxymethyl)triphenylphosphonium chloride (1.90 g, 5.54 mmol, 1.35 equiv) with potassium tert -butoxide (614 mg, 5.47 mmol, 1.35 equiv). The crude oil was purified by

Kugelrohr distillation under reduced pressure to give (4-

(methoxymethylene)cyclohexyl)benzene (791 mg, 3.91 mmol, 96%) a clear, colorless oil. 187

-1 1 FTIR (film, cm ): 3024, 2924, 2834, 1716, 1686, 1215, 1125; H NMR (CDCl 3, 400

MHz): δ 7.28-7.25 (m, 2H), 7.19-7.14 (m, 3H), 5.80 (s, 1H), 3.54 (s, 3H), 2.91 (d, J =

13.6 Hz, 1H), 2.64-2.58 (m, 1H), 2.18-2.15 (m, 1H), 2.08-2.01 (m, 1H), 1.95-1.92 (m,

13 2H), 1.78 (t, J = 13.6 Hz, 1H), 1.45 (qd, J = 12.0, 3.2 Hz, 2H); C NMR (CDCl 3, 100

MHz): δ 147.4, 139.5, 128.5, 127.0, 126.1, 117.1, 59.5, 44.9, 35.9, 34.6, 30.6, 25.5.

(4-(Ethoxymethylene)cyclohexyl)benzene (3.40): The above general procedure was followed using 4-phenylcyclohexanone (2.00 g, 11.5 mmol) and (2- methoxyethyl)triphenylphosphonium chloride (5.12 g, 14.9 mmol, 1.3 equiv) with potassium tert -butoxide (1.67 g, 14.9 mmol, 1.3 equiv). The resulting oil was purified by

Kugelrohr distillation under reduced pressure to give (4-

(ethoxymethylene)cyclohexyl)benzene (1.83 g, 8.46 mmol, 74%) as a clear, colorless oil.

FTIR (film, cm -1): 3059, 2974, 2921, 2871, 1686, 1492, 1442, 1189, 1122; 1H NMR

(CDCl 3, 400 MHz): δ 7.27-7.24 (m, 2H), 7.19-7.13 (m, 3H), 5.85 (t, J = 1.6 Hz, 1H), 3.72

(q, J = 6.8 Hz, 2H), 2.94 (dt, J = 14, 2.0 Hz, 1H), 2.61 (tt, J = 12, 3.2 Hz, 1H), 2.18-2.17

(m, 1H), 2.16-2.14 (m, 1H), 2.05 (tt, J = 12.8, 2.0 Hz, 1H), 1.96-1.89 (m, 2H), 1.82-1.74

13 (m, 1H), 1.45 (qt, J = 12.4, 4.0 Hz, 2H), 1.24 (t, J = 6.8 Hz, 3H); C NMR (CDCl 3, 100

MHz): δ 147.2, 137.7, 128.3, 126.8, 125.8, 117.0, 67.2, 44.8, 35.7, 34.4, 30.5, 25.4, 15.2.

188

8-(methoxymethylene)-1,4-dioxaspiro[4.5]decane (3.41): The above general procedure was followed using 1,4-dioxaspiro[4.5]decan-8-one (2.04 g, 13.0 mmol) and (2- methoxyethyl)triphenylphosphonium chloride (5.81 g, 16.9 mmol, 1.30 equiv) with potassium tert -butoxide (1.90 g, 16.9 mmol, 1.30 equiv). The resulting oil was purified by flash chromatography on silica gel (10% EtOAc/hexanes) to give 8-

(methoxymethylene)-1,4-dioxaspiro[4.5]decane (1.65 g, 8.96 mmol, 69%) as a clear colorless oil.

-1 1 FTIR (film, cm ): 2952, 2885, 1718, 1127, 1099; H NMR (CDCl3, 400 MHz): δ 5.78 (s,

1H), 3.94 (s, 4H), 3.53 (s, 3H), 2.31 (t, J = 6.8 Hz, 2H), 2.09 (t, J = 6.8 Hz, 4H), 1.64-

13 1.59 (m, 4H); C NMR (CDCl 3, 100 MHz): δ 139.4, 114.9, 108.9, 64.0, 58.9, 35.9, 34.6,

27.1, 21.9.

1-(tert -butyl)-4-(methoxymethylene)cyclohexane (3.43): The above general procedure was followed using 4-(tert -butyl)cyclohexanone (2.07 g, 13.4 mmol) and (2- methoxyethyl)triphenylphosphonium chloride (5.97 g, 17.4 mmol, 1.3 equiv) with potassium tert -butoxide (1.95 g, 17.4 mmol, 1.3 equiv). The resulting oil was purified by

189

Kugelrohr distillation under reduced pressure to give 1-(tert -butyl)-4-

(methoxymethylene)cyclohexane (2.11 g, 11.6 mmol, 87%) as a clear, colorless oil.

-1 1 FTIR (film, cm ): ; H NMR (CDCl 3, 400 MHz): δ 5.73 (s, 1H), 3.52 (s, 3H), 2.83-2.80

(m, 1H), 2.10-2.07 (m, 1H), 1.90-1.79 (m, 3H), 1.62-1.54 (m, 1H), 1.10 (tt, J = 12.0, 2.8

13 Hz, 1H), 1.01-0.91 (m, 2H), 0.84 (s, 9H); C NMR (CDCl 3, 100 MHz): δ 138.4, 118.3,

59.2, 48.5, 32.5, 30.6, 29.1, 27.7, 27.6, 25.4.

2-(6-methoxyhex-5-en-1-yl)isoindoline-1,3-dione (3.45): To a stirring solution of 6- methoxyhex-5-en-1-ol (1.30 g, 9.98 mmol), phthalimide (1.62 g, 11.0 mmol), and PPh 3

(2.89 g, 11.0 mmol) in THF (20 mL) was added diisopropyl azodicarboxylate (2.25 g,

11.1 mmol) over 40 min at 23 °C. The reaction was allowed to stir for 48 h. The reaction was reduced under vacuum and diethyl ether added before filtering over Celite.

The filtrate was then reduced under vacuum and the yellow-orange oil purified by flash chromatography on silica gel (20% EtOAc/hexanes) to give 2-(6-methoxyhex-5-en-1- yl)isoindoline-1,3-dione (2.18 g, 8.41 mmol, 84%) as a yellow oil. Isolated as a 1.8:1 mixture of E and Z isomers.

-1 1 FTIR (film, cm ): 3032, 2936, 2856, 1770, 1713, 1395, 1208, 1106; H NMR (CDCl 3,

400 MHz): δ 7.83-7.80 (m, 5.7H), 7.70-7.68 (m, 5.7H), 6.26 (d, J = 12.4 Hz, 1.8H), 5.85

(d, J = 6.0 Hz, 1H), 4.67 (m, 1.8H), 4.29 (q, J = 7.2 Hz, 1H), 3.67 (t, J = 7.2 Hz, 5.9H),

3.54 (s, 3H), 3.47 (s, 5.4H) 2.08 (q, J = 7.2 Hz, 2H), 1.95 (q, J = 7.2 Hz, 3.8H), 1.72-1.63 190

13 (m, 5.8H), 1.42-1.34 (m, 5.8H); C NMR (CDCl 3, 100 MHz): δ 168.3, 147.3, 146.4,

133.8, 133.7, 123.0 (2C), 106.0, 102.2, 59.4, 55.8, 37.9, 37.8, 28.0, 27.8, 27.1, 26.9, 23.2.

1-(6-methoxyhex-5-en-1-yl)pyrrolidine-2,5-dione (3.47): To a stirring solution of 6- methoxyhex-5-en-1-ol (497 mg, 3.82 mmol), succinimide (421 mg, 4.25 mmol, 1.1 equiv), and PPh 3 (1.10 g, 4.20 mmol, 1.1 equiv) in THF (6.5 mL) was added diisopropyl azodicarboxylate (0.90 mL, 4.6 mmol, 1.2 equiv) over 40 min at 23 °C. The reaction was allowed to stir for 5 h. The reaction was reduced under vacuum and the yellow-orange oil purified by flash chromatography on silica gel (40% EtOAc/hexanes) to give 1-(6- methoxyhex-5-en-1-yl)pyrrolidine-2,5-dione (753 mg, 3.56 mmol, 93%) as a yellow oil.

Isolated as a 2.6:1 ( E:Z) mixture of isomers.

1 H NMR (CDCl 3, 400 MHz): δ 6.27 (dt, J = 12.4 Hz, 1H), 5.87 (dt, J = 6.0, 1.6 Hz, 0.4

H), 4.68 (dt, J = 12.8, 7.2 Hz, 1H), 4.29 (dt, J = 6.0Hz, 0.4H), 3.57 (s, 1.2 H), 3.50 (t, J =

7.2 Hz, 2.8H), 3.49 (s, 3 H), 2.70 (s, 4H), 2.69 (s, 1.6H), 2.07 (dq, J = 7.4, 1.2 Hz, 0.8H),

1.94 (dq, J = 7.2 Hz, 0.8 Hz, 2H), 1.62-1.53 (m, 2.8H), 1.38-130 (m, 2.8H); 13 C NMR

(CDCl 3, 100 MHz): δ 177.4, 147.6, 146.7, 106.2, 102.5, 59.7, 56.1, 39.0, 38.9, 28.4, 28.1,

27.4 (2 C), 27.2 (2 C), 23.5.

191

5-(methoxymethylene)-6,7,8,9-tetrahydro-5H-benzo[7]annulene (3.49): The above general procedure was followed using 1-benzosuberone (3.2 mL, 21.4 mmol) and (2- methoxyethyl)triphenylphosphonium chloride (8.98 g, 26.2 mmol, 1.22 equiv) with potassium tert -butoxide (2.93 g, 26.1 mmol, 1.22 equiv). The resulting oil was purified by flash chromatography on silica gel (hexanes) to give (3.04 g, 16.1 mmol, 75%) as a clear, colorless oil. The product was isolated as a mixture of E and Z isomers.

-1 1 FTIR (film, cm ): 3057, 3012, 2927, 2849, 1658, 1443, 1221, 1130; H NMR (CDCl 3,

400 MHz): δ 7.26-7.24 (m, 1H), 7.15-7.06 (m, 11H), 6.06 (s, 1H), 6.02 (s, 1.9H), 3.66 (s,

6H), 3.54 (s, 3H), 2.74-2.71 (m, 6H), 2.38 (s, 4H), 2.13-2.10 (m, 2H), 1.80-1.64 (m,

13 12H); C NMR (CDCl 3, 100 MHz): δ 144.7, 143.2, 141.8 (2), 141.4, 139.5, 130.3, 129.6,

129.2, 128.2, 126.8 (2), 126.3, 125.8, 122.1, 120.4, 59.95, 37.15, 35.78, 35.75, 32.75,

28.50, 27.92, 27.79, 26.96.

(1-cyclohexyl-2-methoxyvinyl)benzene (3.51): The above general procedure was followed using cyclohexyl phenyl ketone (1.96 g, 10.4 mmol) and (2- methoxyethyl)triphenylphosphonium chloride (4.63 g, 13.5 mmol, 1.3 equiv) with potassium tert -butoxide (1.52 g, 13.5 mmol, 1.3 equiv). The resulting oil was purified by 192 flash chromatography on silica gel (hexanes) to give ( Z)-(1-cyclohexyl-2- methoxyvinyl)benzene (0.70 g, 3.25 mmol, 31%) and ( E)-(1-cyclohexyl-2- methoxyvinyl)benzene (1.30 g, 6.01 mmol, 58%) as a clear, colorless oil. The product was isolated as a mixture of E and Z isomers.

(Z)-(1-cyclohexyl-2-methoxyvinyl)benzene: FTIR (film, cm -1): 3027, 2923, 2850, 1650,

1 1493, 1447, 1219, 1130, 1072; H NMR (CDCl 3, 400 MHz): δ 7.28-7.24 (m, 2H), 7.22-

7.17 (m, 3H), 5.91 (s, 5.91), 3.63 (s, 3H), 2.64 (tt, J = 12.4, 3.2 Hz, 1H), 1.75-1.61 (m,

5H), (qd, J = 13.6, 5.6 Hz, 2H), 1.30 (qt, J = 12.8, 3.2 Hz, 2H), 1.18-1.10 (m, 2H); 13C

NMR (CDCl 3, 100 MHz): δ 145.2, 140.5, 128.9, 127.9, 126.3, 126.0, 59.9, 39.5, 31.7,

27.2, 26.4.

(E)-(1-cyclohexyl-2-methoxyvinyl)benzene: FTIR (film, cm -1): 3053, 3018, 2925, 2850,

1 1657, 1448, 1249, 1204, 1147; H NMR (CDCl 3, 400 MHz): δ 7.23-7.24 (m, 4H), 7.21-

7.17 (1H), 5.95 (s, 1H), 3.55 (s, 3H), 2.24-2.17 (m, 1H), 1.79-1.71 (m, 4H), 1.69-1.64 (m,

13 1H), 1.31-1.21 (m, 2H), 1.17-1.10 (m, 3H); C NMR (CDCl 3, 100 MHz): δ 145.2, 140.5,

128.9, 127.9, 126.3, 126.0, 59.9, 39.5, 31.7, 27.2, 26.4.

General Procedure for the Synthesis of α,β-Unsaturated Aldehydes: To 4 mL borosilicate glass vial containing the alkyl enol ether (1.00 mmol), 1,4-benzoquinone

(130 mg, 1.2 mmol, 1.20 equiv), water (20.0 µL, 1.11 mmol, 1.11 equiv), AcOH (240

193

µL, 4.19 mmol, 4.19 equiv) was added Pd(OAc)2 followed by CH 2Cl 2 (1.00 mL). The reaction was stirred at 23 °C until completion as indicated by GC analysis. The reaction mixture was then diluted with CH 2Cl 2 (50.0 mL) and washed with water (50 mL). The organic layer was dried over Na 2SO 4, reduced under vacuum and the resulting oil purified by flash chromatography on silica gel.

(E)-tridec-2-enal (3.21): The above general procedure was followed using 1- methoxytridec-1-ene (212 mg, 1.00 mmol) and 2 mol % Pd(OAc) 2 (4.6 mg, 0.02 mmol).

The crude product was purified by flash chromatography on silica gel (2 %

EtOAc/hexanes) to give ( E)-tridec-1-enal (131 mg, 0.67 mmol, 67%) as a clear, colorless oil. Spectral data of the product matched reported literature values.

(E)-4-phenylbut-2-enal (3.10): The above general procedure was followed using (4- mehoxybut-3-en-1-yl)benzene (162 mg, 1.00 mmol) and 1 mol % Pd(OAc) 2 (2.3 mg,

0.02 mmol). The crude product was purified by flash chromatography on silica gel (1:1

CH 2Cl 2/hexanes) to give ( E)-4-phenylbut-2-enal (110 mg, 0.75 mmol, 75%) as a clear, colorless oil. Spectral data of the product matched reported literature values.

194

(E)-6-(( tert -butyldimethylsilyl)oxy)hex-2-enal (3.35): The above general procedure was followed using tert-butyl((6-methoxyhex-5-en-1-yl)oxy)dimethylsilane (244 mg,

1.00 mmol) and 2.5 mol % Pd(OAc) 2 (5.6 mg, 0.02 mmol). The crude product was purified by flash chromatography on silica gel using a solvent gradient (0-4%

EtOAc/hexanes) to give ( E)-6-(( tert -butyldimethylsilyl)oxy)hex-2-enal (160 mg, 0.70 mmol, 70%) as a clear, colorless oil. Spectral data of the product matched reported literature values.

(E)-6-oxohex-4-en-1-yl acetate (3.37): The above general procedure was followed using 6-methoxyhex-5-en-1-yl acetate (172 mg, 1.00 mmol) and 1 mol % Pd(OAc) 2 (2.4 mg, 0.02 mmol). The crude product was purified by flash chromatography on silica gel using a solvent gradient (10% EtOAc/hexanes) to give (E)-6-oxohex-4-en-1-yl acetate

(125 mg, 0.80 mmol, 80%) as a clear, colorless oil.

-1 1 FTIR (film, cm ):; H NMR (CDCl 3, 400 MHz): δ 9.52 (d, J = 8.0 Hz, 1H), 6.87 (dt, J =

15.6, 6.8 Hz, 1H), (qt, J = 7.6, 1.6 Hz, 1H), 4.12 (t, J = 6.4 Hz, 2H), 2.47-2.41 (m, 2H),

13 2.06 (s, 1H), 1.87 (quin, J = 6.4 Hz, 2H); C NMR (CDCl 3, 100 MHz): δ 193.7, 170.9,

156.9, 133.3, 63.2, 29.1, 26.8, 20.8.

195

(2 E, 6 Z)-7-(triethylsilyl)hepta-2,6-dienal (3.39): The above general procedure was followed using triethyl((1 Z)-7-methoxyhepta-1,6-dienal (246 mg, 1.03 mmol) and 4 mol

% Pd(OAc) 2 (8.9 mg, 0.04 mmol). The crude product was purified by flash chromatography on silica gel (2 % EtOAc/hexanes) to give (2 E, 6Z)-7-

(triethylsilyl)hepta-2,6-dienal (159 mg, 0.69 mmol, 69%) as a clear, colorless oil.

FTIR (film, cm -1): 2954, 2909, 2874, 2819, 1686, 1605, 1458, 1123, 1015; 1H NMR

(CDCl 3, 400 MHz): δ 9.51 (d, J = 7.6 Hz, 1H), 6.85 (dt, J = 15.6, 6.8 Hz, 1H), 6.38-6.31

(m, 1H), 6.17-6.11 (m, 1H), 5.52 (d, J = 14.4 Hz, 1H), 2.43 (q, J = 6.8 Hz, 2H), 2.33 (q,

13 J = 7.2 Hz, 2H), 0.95 (t, J = 7.6 Hz, 9H), 0.62 (q, J = 8.0 Hz, 6H); C NMR (CDCl 3, 100

MHz): δ 193.7, 157.3, 147.2, 133.2, 127.4, 32.6, 32.0, 7.4, 4.6.

1,2,3,6-tetrahydro-[1,1’-biphenyl]-4-carbaldehyde from (4-

(methoxymethylene)cyclohexyl)benzene (3.31): The above general procedure was followed using (4-(methoxymethylene)cyclohexyl)benzene (206 mg, 1.02 mmol) and 2 mol % Pd(OAc) 2 (4.4 mg, 0.02 mmol). The crude product was purified by flash chromatography on silica gel (5 % EtOAc/hexanes) to give 1,2,3,6-tetrahydro-[1,1’- biphenyl]-4-carbaldehyde (160 mg, 0.84 mmol, 84%) as a clear, colorless oil.

196

1,2,3,6-tetrahydro-[1,1’-biphenyl]-4-carbaldehyde from (4-

(ethoxymethylene)cyclohexyl)benzene (3.31): The above general procedure was followed using 4-(ethoxymethylene)cyclohexyl)benzene (220 mg, 1.02 mmol) and 2 mol

% Pd(OAc) 2 (4.4 mg, 0.02 mmol). The crude product was purified by flash chromatography on silica gel (5 % EtOAc/hexanes) to give 1,2,3,6-tetrahydro-[1,1’- biphenyl]-4-carbaldehyde (163 mg, 0.86 mmol, 86%) as a clear, colorless oil.

1 H NMR (CDCl 3, 400 MHz): δ 9.47 (s, 1H), 7.33-7.19 (m, 5H), 6.85 (s, 1H), 2.86-2.81

(m, 1H), 2.66-2.61 (m, 1H), 2.52-2.38 (m, 2H), 2.25-2.18 (m, 1H), 2.05-2.02 (m, 1H),

13 1.71 (qd, J = 12.4, 5.2 Hz, 1H); C NMR (CDCl 3, 100 MHz): δ 193.6, 150.2, 145.4,

141.1, 128.4, 126.6, 126.3, 39.6, 34.2, 28.5, 21.7.

1,4-dioxaspiro[4.5]dec-7-ene-8-carbaldehyde (3.42): The above general procedure was followed using 8-(methoxymethylene)-1,4-dioxaspiro[4.5]decane (183 mg, 1.00 mmol) and 2.5 mol % Pd(OAc) 2 (5.6 mg, 0.02 mmol). The crude product was purified by flash chromatography on silica gel (10% EtOAc/hexanes) to give 1,4-dioxaspiro[4.5]dec-7- ene-8-carbaldehyde (129 mg, 0.77 mmol, 77%) as a clear, colorless oil.

-1 1 FTIR (film, cm ): 2958, 2887, 2821, 1683, 1117, 1061; H NMR (CDCl 3, 400 MHz): δ

9.39 (s, 1H), 6.63 (t, J = 2.0 Hz), 3.94 (s, 4H), 2.52 (t, J = 0.8 Hz, 2H), 2.38 (td, J = 5.2,

197

13 2.8 Hz, 2H), 1.73 (t, J = 6.4 Hz, 2H); C NMR (CDCl 3, 100 MHz): δ 193.2, 147.4, 140.8,

107.6, 64.7, 37.0, 30.2, 20.5.

4-(tert -butyl)cyclohex-1-enecarbaldehyde (3.44): The above general procedure was followed using 1-(tert -butyl)-4-(methoxymethylene)cyclohexane (182 mg, 1.00 mmol) and 2 mol % Pd(OAc) 2 (4.5 mg, 0.02 mmol). The crude product was purified by flash chromatography on silica gel using a solvent gradient (5% EtOAc/hexanes) to give 4-

(tert -butyl)cyclohex-1-enecarbaldehyde (153 mg, 0.92 mmol, 92%) as a clear, colorless oil.

-1 1 FTIR (film, cm ): 2961, 2869, 2819, 1678, 1645, 1396, 1365, 1159; H NMR (CDCl 3,

400 MHz): δ 9.43 (s, 1H), 6.82 (d, J = 2.4 Hz, 1H), 2.52-2.39 (m, 2H), 2.11-1.94 (m, 2H),

13 1.37-1.31 (m, 1H), 1.17-1.09 (m, 1H), 0.91 (s, 9H); C NMR (CDCl 3, 100 MHz): δ193.7,

151.6, 141.4, 43.9, 32.1, 28.2, 26.9, 22.7, 22.4.

(E)-6-(1,3-dioxoisoindolin-2-yl)hex-2-enal (3.46): The above general procedure was followed using 2-(6-methoxyhex-5-en-1-yl)isoindoline-1,3-dione (262 mg, 1.01 mmol) and 2.5 mol % Pd(OAc) 2 (5.6 mg, 0.025 mmol). The crude product was purified by flash 198 chromatography on silica gel (25 % EtOAc/hexanes) to give ( E)-6-(1,3-dioxoisoindolin-

2-yl)hex-2-enal (180 mg, 0.73 mmol, 73%) as a white solid.

-1 1 FTIR (film, cm ): 3032, 2936, 2856, 1770, 1713, 1395, 1208, 1106; H NMR (CDCl 3,

400 MHz): δ 9.48 (d, J = 7.6 Hz, 1H), 7.88-7.83 (m, 2H), 7.76-7.71 (m, 2H), 6.85 (dt, J =

16.0, 6.4 Hz, 1H), 6.18-6.12 (m, 1H), 3.76 (t, J = 7.2 Hz, 2H), 2.45-2.39 (m, 2H), 1.97-

13 1.89 (m, 2H); C NMR (CDCl 3, 100 MHz): δ 193.6, 168.2, 156.5, 134.0, 133.4, 131.9,

123.2, 37.1, 29.9, 26.7.

6-(2,5-dioxopyrrolidin-1-yl)hexanal (3.48): The above general procedure was followed using using 1-(6-methoxyhex-5-en-1-yl)pyrrolidine-2,5-dione (210 mg, 1.00 mmol) and

2.5 mol % Pd(OAc) 2 (5.6 mg, 0.025 mmol). The crude product was purified by flash chromatography on silica gel (30-40% EtOAc/hexanes) to give (E)-6-(2,5- dioxopyrrolidin-1-yl)hex-2-enal (145 mg, 0.74 mmol, 74%) as a pale yellow oil.

-1 1 FTIR (film, cm ): 2944, 2829, 1693, 1440, 1402, 1163, 1137; H NMR (CDCl 3, 400

MHz): δ 9.51-9.48 (m, 1H), 6.88-6.79 (m, 1H), 6.17-6.09 (m, 1H), 3.58-3.53 (m, 2H),

13 2.73-2.71 (m, 4H), 2.39-2.34 (m, 2H), 1.85-1.77 (m, 2H); C NMR (CDCl 3, 100 MHz): δ

193.8, 177.3, 156.6, 133.4, 38.0, 29.9, 28.2, 25.9.

199

6,7-dihydro-5H-benzo[7]annulene-9-carbaldehyde (3.50): A slight modification to the above general procedure was followed. To 4 mL borosilicate glass vial containing the 5-

(methoxymethylene)-6,7,8,9-tetrahydro-5H-benzo[7]annulene (188 mg, 1.00 mmol), 1,4- benzoquinone (129 mg, 1.2 mmol, 1.2 equiv), and water (20.0 µL, 1.11 mmol, 1.11 equiv) was added 5 mol % Pd(OAc) 2 (11.2 mg, 0.05 mmol) followed by AcOH (1.00 mL). The reaction was stirred at 40 °C until completion as indicated by GC analysis. The reaction mixture was then diluted with CH 2Cl 2 (50.0 mL) and washed with water (50 mL). The organic layer was dried over Na 2SO 4, reduced under vacuum and the crude product purified by flash chromatography on silica gel using a solvent gradient (5%

EtOAc/hexanes) to give ( E)-6-(benzyloxy)hex-2-enal (85 mg, 0.42 mmol, 42%) as a clear, pale orange oil.

1 H NMR (CDCl 3, 400 MHz): δ 9.66 (s, 1H), 7.44-7.14 (m, 5H), 2.55-2.52 (m, 2H), 2.23-

13 2.22 (m, 4H); C NMR (CDCl 3, 100 MHz): δ 192.6, 154.9, 143.6, 141.2, 132.7, 129.2,

129.1, 128.3, 126.1, 33.9, 32.1, 26.3.

2-cyclohexylidene-2-phenylacetaldehyde (3.52): A slight modification to the above general procedure was followed. To 4 mL borosilicate glass vial containing (1- 200 cyclohexyl-2-methoxyvinyl)benzene (216 mg, 1.00 mmol), 1,4-benzoquinone (130 mg,

1.20 mmol, 1.2 equiv), and water (20.0 µL, 1.11 mmol, 1.11 equiv) was added 10 mol %

Pd(OAc) 2 (22.4 mg, 0.10 mmol, 0.10 equiv) followed by AcOH (1.00 mL). The reaction was stirred at 23 °C for 4 d. The reaction mixture was then diluted with CH 2Cl 2 (50.0 mL) and washed with water (50 mL). The organic layer was dried over Na 2SO 4, reduced under vacuum and the crude product purified by flash chromatography on silica gel (1%

EtOAc/hexanes) to give 2-cyclohexylidene-2-phenylacetaldehyde (115 mg, 0.58 mmol,

58%) as a light brown oil.

-1 1 FTIR (film, cm ): 2935, 2857, 1683, 1448, 1274, 1149; H NMR (CDCl 3, 400 MHz): δ

10.3 (s, 1H), 7.38-7.26 (m, 3H), 7.05-7.03 (m, 2H), 2.90-2.87 (m, 2H), 2.21-2.18 (m,

13 2H), 1.84-1.81 (m, 2H), 1.84-1.62 (m, 4H); C NMR (CDCl 3, 100 MHz): δ 189.7, 164.1,

136.6, 135.9, 129.9, 128.2, 127.2 34.6, 29.6, 28.9, 28.6, 26.4.

201

5.4 Chapter 4: Experimental Details

[(P tBu 3)Pd(CH 2C(CH 3)2PtBu 2)(OAc)]HOAc (4.1) : Tri-tert -butylphosphine (PtBu 3)

(230 mg, 1.14 mmol) was added to a stirring solution of Pd(OAc) 2 (116 mg, 0.517 mmol) in THF (1 mL) at 23 °C. The solution was stirred for 2 h. The solvent was removed under reduced pressure and the resulting pale yellow solid dissolved in a minimal amount of pentane before filtering over Celite. The resulting solution was reduced in vacuum until solid formation began and then placed at -30 °C overnight to promote crystal formation. The product was isolated by vacuum filtration, washing with cold pentane to give [(P tBu 3)Pd(CH 2C(CH 3)2PtBu 2)(OAc)]HOAc (263 mg, 0.418 mmol, 81%) as pale yellow needles. FTIR (film, cm -1): 2900, 2478, 1736, 1707, 1570, 1410, 1271, 1172,

1 1021, 806; H NMR (C 7D8, 400 MHz): δ 13.85 (s, 1H), 2.05 (s, 6H), 1.47-1.12 (m, 53H);

31 31 P NMR (C 7D8, 162 MHz, 23 °C): δ 67.3, 67.2, 62.9, 6.9, 8.9; P NMR (C 7D8, 162

MHz, -20 °C): δ 66.3 (d, J = 354 Hz), -8.7 (d, J = 354 Hz); Anal. Calcd. for

C28 H60 O4P2Pd: C, 53.45; H, 9.61. Found: C, 53.53; H, 9.52.

202

[(C4H9NO)Pd(CH 2C(CH 3)2PtBu 2)(OAc)]HOAc (4.3) Method A : To a 4 mL borosilicate glass vial charged with Pd(OAc) 2 (92 mg, 0.40 mmol), tri-tert - butylphosphine (83 mg, 0.41 mmol, 1.0 equiv), and morpholine (36 µL, 0.41 mmol, 1.0 equiv) was added THF (2 mL). The reaction mixture was stirred at ambient temperature for 2 h. The solvent was removed under reduced pressure and the yellow solid dissolved in a minimal amount of pentane. The solution was then filtered through a pad of Celite, and placed at -30 °C for 12 h. The product was isolated by vacuum filtration, washing with cold pentane to give [(C4H9NO)Pd(CH 2C(CH 3)2PtBu 2)(OAc)]HOAc (44 mg, 0.086 mmol, 21%) as an off-white crystalline solid.

[(C4H9NO)Pd(CH 2C(CH 3)2PtBu 2)(OAc)]HOAc (4.3) Method B: To a 4 mL borosilicate glass vial charged with complex 4.1 (70 mg, 0.11 mmol) was added morpholine (10 µL, 0.11 mmol, 1.1 equiv) and THF (1 mL). The reaction mixture was stirred at ambient temperature for 2 h. The solvent was removed under reduced pressure.

The resulting white solid was dissolved in pentane and the solution was placed at -30 °C for 12 h. The product was isolated by vacuum filtration, washing with cold pentane to give [(C4H9NO)Pd(CH 2C(CH 3)2PtBu 2)(OAc)]HOAc (34 mg, 0.07 mmol, 58%) as a white crystalline solid.

Additionally the morpholine complex was prepared less the coordinated acetic acid as follows. [(C4H9NO)Pd(CH 2C(CH 3)2PtBu 2)(OAc)] : To complex 4.2 (112 mg, 0.15 mmol) in THF (1 mL) was added morpholine (26.0 µL, 0.30 mmol, 2 equiv). The reaction was stirred for 2 h at ambient temperature. The solvent was removed under reduced pressure and the off-white solid dissolved in a minimal amount of pentane. The

203 crude solution was then filtered through a pad of Celite, and the solution placed at -30 °C for 12 h. The product was isolated by vacuum filtration, washing with cold pentane to give [(C4H9NO)Pd(CH 2C(CH 3)2PtBu 2)(OAc)] (61 mg, 0.13 mmol, 44%) as a white crystalline solid. FTIR (film, cm -1): 3014, 2960, 1580, 1385, 1179, 1105, 1040, 887, 662;

1 H NMR (C 6D6, 400 MHz): δ 3.46 (t, J = 4.4 Hz, 4H), 2.64 (s, 4H), 2.16 (s, 3H), 1.36 (d,

31 J = 13.6 Hz, 18H), 1.24 (d, J = 13.6 Hz, 6H), 0.55 (d, J = 0.4 Hz, 2H); P NMR (C 6D6,

162 MHz): δ -6.7; Anal. Calcd. for C 18 H38 NO3PPd: C, 47.63; H, 8.44. Found: C, 46.71;

H, 7.51.

[(PPh 3)Pd(CH 2C(CH 3)2PtBu 2)(OAc)]HOAc (4.4) Method A : To a 4 mL borosilicate glass vial charged with Pd(OAc) 2 (103 mg, 0.46 mmol), tri-tert -butylphosphine (93 mg,

0.46 mmol, 1.0 equiv), and triphenylphosphine (126 mg, 0.48 mmol, 1.0 equiv) was added THF (4 mL). The reaction mixture was stirred at ambient temperature for 2 h.

The solvent was removed under reduced pressure and the yellow solid dissolved in diethyl ether. The crude solution was then filtered through a pad of Celite, and the solvent reduced until crystal formation began. The solution was placed at -30 °C for 4 h, then pentane was added slowly to the reaction mixture and the solution cooled at -30 °C for an additional 12 h to complete crystallization. The product was isolated by vacuum filtration, washing with cold pentane to give [(PPh 3)Pd(CH 2C(CH 3)2PtBu 2)(OAc)]HOAc

(268 mg, 0.389 mmol, 85%) as an off-white crystalline solid.

204

[(PPh 3)Pd(CH 2C(CH 3)2PtBu 2)(OAc)]HOAc (4.4) Method B: To a 4 mL borosilicate glass vial charged with complex 4.1 (74.0 mg, 0.12 mmol) was added triphenylphosphine

(35 mg, 0.13 mmol, 1.1 equiv) and THF (2 mL). The reaction mixture was stirred at ambient temperature for 2 h. The solvent was removed under reduced pressure and the white solid dissolved in diethyl ether. The crude solution was then filtered through a pad of Celite, and the solvent reduced until crystal formation began. The solution was placed at -30 °C for 4 h, then pentane was added slowly to the reaction mixture and the solution cooled at -30 °C for an additional 12 h to complete crystallization. The product was isolated by vacuum filtration, washing with cold pentane to give

[(PPh 3)Pd(CH 2C(CH 3)2PtBu 2)(OAc)]HOAc (75 mg, 0.11 mmol, 93%) as a white crystalline solid. FTIR (film, cm -1): 2963, 2904, 1712, 1602, 1552, 1434, 1255, 1094,

1 755, 697; H NMR (C 6D6, 400 MHz): δ 14.21 (s, 1H), 7.86 (t, J = 8.8 Hz, 6H), 7.17-7.14

(m, 6H), 7.08-7.05 (m, 3H), 1.98 (s, 6H), 1.45 (d, J = 13.2 Hz, 18H), 1.22 (d, J = 12.8

31 Hz, 6H), 0.70 (t, J = 6.8 Hz, 2H); P NMR (C 6D6, 162 MHz): δ 23.2 (d, J = 402 Hz), 6.0

(d, J = 402 Hz); Anal. Calcd for C 34 H48 O4P2Pd: C, 59.26; H, 7.02. Found: C, 58.98; H,

7.01.

[(PPh 2CH 2)2Pd(CH 2C(CH 3)2PtBu 2)(OAc)]HOAc (4.5) : To a round bottomed flask charged with complex 4.1 (92 mg, 0.15 mmol) was added (1,2- bis(diphenylphosphino)ethane) (dppe) (60 mg, 0.15 mmol, 1.0 equiv) and THF (1 mL).

The reaction was stirred at ambient temperature for 2 h. After 2 h the solvent was 205 removed under vacuum and the resulting clear residue was taken up in a minimum amount of toluene, layered with pentane, and placed at -30 °C for 12 h. The off-white crystals were washed with pentane and dried under reduced pressure to give

[(Ph 2PCH2)2Pd(CH 2C(CH 3)2PtBu 2)(OAc)]HOAc (118 mg, 0.143 mmol, 98%) as off- white crystals. FTIR (film, cm -1): 3054, 2966, 2911, 1670, 1436, 1367, 1101, 748, 699,

1 647; H NMR (CD 2Cl 2, 400 MHz): δ 7.57-7.39 (m, 20H), 2.50-2.38 (m, 2H), 2.23-2.13

31 (m, 2H), 1.789 (s, 6H), 1.44 (d, J = 13.2), 1.21-1.12 (m, 20H); P NMR (CD 2Cl 2, 162

MHz): δ 47.1 (dd, J = 360 Hz, J = 26 Hz), 41.6 (d, J = 26 Hz), -0.5 (d, J = 360 Hz); Anal.

Calcd. for C 42 H57 O4P3Pd: C, 61.13; H, 6.96. Found: C, 61.25; H, 6.84.

Pd(PtBu 2Me) 2(OAc) 2 (4.6) : Di-tert -butylmethylphosphine (PtBu 2Me) (82 mg, 0.51 mmol, 2.3 equiv) was added to a stirring solution of Pd(OAc) 2 (50 mg, 0.22 mmol) in

THF (1 mL) at 23 °C. The solution was stirred for 2 h. The solvent was removed under reduced pressure and the resulting yellow solid dissolved in a minimal amount of diethyl ether, layered with pentane and placed at -30 °C overnight to promote crystal formation.

The product was isolated by vacuum filtration, washing with cold pentane to give

Pd(P tBu 2Me) 2(OAc) 2 (102 mg, 0.153 mmol, 69%) as a yellow crystalline solid. FTIR

-1 1 (film, cm ): 2966, 2900, 1628, 1370, 1311, 1020, 884, 690; H NMR (C 6D6, 400 MHz): δ

31 2.05 (s, 6H), 1.32 (t, J = 6.8 Hz, 32H), 0.89 (t, J = 3.2 Hz, 6H); P NMR (C 6D6, 162

206

MHz): δ 28.1; Anal. Calcd. for C 22 H48 O4P2Pd: C, 48.49; H, 8.88. Found: C, 48.45; H,

8.66.

General procedure for the reduction of [(P tBu 3)Pd(CH 2C(CH 3)2PtBu 2)(OAc)]HOAc using H 2: In a 4 mL borosilicate vial with septum cap, complex 4.1 (10 mg, 0.16 mmol) was dissolved in toluene-d8 (1 mL). The reaction mixture was placed under an H 2 atmosphere via a balloon of H 2 and allowed to purge for 5 min. After the 5 min purge was complete the reaction mixture, under a balloon of H 2, was stirred at 23 °C for 12 h.

1 31 The formation of Pd(P tBu 3)3 was confirmed by H NMR and P NMR.

General procedure for the thermal reduction of

[(P tBu 3)Pd(CH 2C(CH 3)2PtBu 2)(OAc)]HOAc : In a 4 mL borosilicate vial with septum cap, complex 4.1 (10 mg, 0.16 mmol) was dissolved in toluene-d8 (1 mL). The reaction mixture, was stirred at 90 °C for 12 h. The formation of Pd(P tBu 3)3 was confirmed by

1H NMR and 31 P NMR.

207

General procedure for the amination of 2-bromotoluene: N,N -Dibutyl-o-toluidine was prepared according to a slightly modified literature procedure as follows. 1 To a 4 mL vial with septum cap containing 2-bromotoluene (120 µL, 1.00 mmol), dibutylamine (168 µL,

1.00 mmol), sodium acetate (144 mg, 1.50 mmol), 1,3,5-trimethoxybenzene (16.8 mg,

0.100 mmol) and catalyst (0.02 mmol) was added toluene (1 mL). The solution was stirred for 15 min to 6 h at 23 °C, 70 °C or 110 °C as specifiied. The reaction solution was then filtered over Celite and the toluene was removed in vacuum. The resulting

1 residue was taken up in CDCl 3 and analyzed by H NMR.

General procedure for the reduction of complexes using NaO tBu and HNBu 2: A 4 mL borosilicate vial was charged with either complex 4.1 (10 mg, 0.16 mmol), complex

4.2 (5.0 mg, 0.014 mmol Pd), or a combination of Pd(OAc) 2 (10 mg, 0.44 mmol) and

PtBu 3 (7.2 mg, 0.36 mmol). Sodium tert -butoxide (5 equiv) or sodium tert -butoxide (5 equiv) and dibutylamine (5 equiv) was added followed by toluene (1 mL). The resulting mixture was stirred for 1 h before being analyzed by 31 P NMR.

208

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209

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215

Appendix A: 1H NMR and 13 C NMR for Selected Compounds

216

217

e M O S S e : methyl(3-((methylsulfinyl)methyl)benzyl)sulfane M 2.8 H NMR of NMR of H 1

218

e M O S S : methyl(3-((methylsulfinyl)methyl)benzyl)sulfane e 2.8 M C NMR of 13

219

n B O S : 1,3-bis((benzylsulfinyl)methyl)benzeme : 1,3-bis((benzylsulfinyl)methyl)benzeme 2.9

O S n B H NMR of NMR of H 1

220

n B O S

O S n B : 1,3-bis((benzylsulfinyl)methyl)benzeme : 1,3-bis((benzylsulfinyl)methyl)benzeme 2.9 C NMR of 13

221

n B O S N

O S n B : 2,6-bis((benzylsulfinyl)methyl)pyridine : 2,6-bis((benzylsulfinyl)methyl)pyridine 2.10 H NMR of NMR of H 1

222

n B O S N

O S n B : 2,6-bis((benzylsulfinyl)methyl)pyridine : 2,6-bis((benzylsulfinyl)methyl)pyridine 2.10 H NMR of NMR of H 1

223

e M O S N

O S e : 2,6-bis((methylsulfinyl)methyl)pyridine M 2.11 H NMR of NMR of H 1

224

e M : 2,6-bis((methylsulfinyl)methyl)pyridine : 2,6-bis((methylsulfinyl)methyl)pyridine O S 2.11 N C NMR of

O S 13 e M

225

t E O S N

O S t E : 2,6-bis((ethylsulfinyl)methyl)pyridine : 2,6-bis((ethylsulfinyl)methyl)pyridine 2.12 H NMR of NMR of H 1

226

t E O S N : 2,6-bis((ethylsulfinyl)methyl)pyridine : 2,6-bis((ethylsulfinyl)methyl)pyridine

O S t 2.12 E C NMR of 13

227

O S t E : 2-((ethylsulfinyl)methyl)pyridine 2.13 H NMR of NMR of H 1

228

O S t E : 2-((ethylsulfinyl)methyl)pyridine : 2-((ethylsulfinyl)methyl)pyridine 2.13 C NMR of 13

229

O S e M : 2-((methylsulfinyl)methyl)pyridine : 2-((methylsulfinyl)methyl)pyridine 2.14 H NMR of NMR of H 1

230

O S e M : 2-((methylsulfinyl)methyl)pyridine : 2-((methylsulfinyl)methyl)pyridine 2.14 C NMR of 13

231

O S n B : 2-((bnezylsulfinyl)methyl)pyridine : 2-((bnezylsulfinyl)methyl)pyridine 2.15 H NMR of NMR of H 1

232

O S n B : 2-((bnezylsulfinyl)methyl)pyridine : 2-((bnezylsulfinyl)methyl)pyridine 2.15 C NMR of 13

233

n S B O

O S : 1,2-((bnezylsulfinyl)methyl)benzene : 1,2-((bnezylsulfinyl)methyl)benzene Bn 2.16 H NMR of NMR of H 1

234

n S B O

O S Bn : 1,2-((bnezylsulfinyl)methyl)benzene : 1,2-((bnezylsulfinyl)methyl)benzene 2.16 C NMR of 13

235

n B S S n B : 1,3-bis((bnezylthio)methyl)benzene : 1,3-bis((bnezylthio)methyl)benzene 2.21 H NMR of NMR of H 1

236

n B S S n B : 1,3-bis((bnezylthio)methyl)benzene : 1,3-bis((bnezylthio)methyl)benzene 2.21 C NMR of 13

237

t E S : 1,3-bis((ethylthio)methyl)benzene 2.22 S t E H NMR of NMR of H 1

238

t E S S t E : 1,3-bis((ethylthio)methyl)benzene 2.22 C NMR of 13

239

n B S : 1,3-bis((benzylthio)methyl)benzene : 1,3-bis((benzylthio)methyl)benzene 2.23 S n B H NMR of NMR of H 1

240

n B S S n B : 1,3-bis((benzylthio)methyl)benzene : 1,3-bis((benzylthio)methyl)benzene 2.23 C NMR of 13

241

e M S N S e M : 1,3-bis((methylthio)methyl)pyridine 2.24 H NMR of NMR of H 1

242

e M S N S e M : 1,3-bis((methylthio)methyl)pyridine : 1,3-bis((methylthio)methyl)pyridine 2.24 C NMR of 13

243

t E S : 1,3-bis((ethylthio)methyl)pyridine N 2.25 S t E H NMR of NMR of H 1

244

t E S N S t E : 1,3-bis((ethylthio)methyl)pyridine : 1,3-bis((ethylthio)methyl)pyridine 2.25 C NMR of 13

245

u B t S N S -butylthio)methyl)pyridine -butylthio)methyl)pyridine u B t tert : 1,3-bis(( 2.26 H NMR of NMR of H 1

246

u B t S -butylthio)methyl)pyridine -butylthio)methyl)pyridine N tert S u B : 1,3-bis(( t 2.26 C NMR of 13

247

n B S N S n B : 1,3-bis((benzylthio)methyl)pyridine : 1,3-bis((benzylthio)methyl)pyridine 2.27 H NMR of NMR of H 1

248

n B S N S n B : 1,3-bis((benzylthio)methyl)pyridine : 1,3-bis((benzylthio)methyl)pyridine 2.27 C NMR of 13

249

n B S : 2-((benzylthio)methyl)pyridine : 2-((benzylthio)methyl)pyridine N 2.28 H NMR of NMR of H 1

250

n B S N : 2-((benzylthio)methyl)pyridine : 2-((benzylthio)methyl)pyridine 2.28 C NMR of 13

251

t S E : 1,2-bis((ethylthio)methyl)pyridine S 2.29 Et H NMR of NMR of H 1

252

t S E S Et : 1,2-bis((ethylthio)methyl)pyridine : 1,2-bis((ethylthio)methyl)pyridine 2.29 C NMR of 13

253

n S B S : 1,2-bis((benzylthio)methyl)pyridine : 1,2-bis((benzylthio)methyl)pyridine Bn 2.30 H NMR of NMR of H 1

254

n S B S Bn : 1,2-bis((benzylthio)methyl)pyridine : 1,2-bis((benzylthio)methyl)pyridine 2.30 C NMR of 13

255

: 1,2-bis(naphthalene-1-ylthio)ethane 2.37 H NMR of NMR of H 1

256

: 1,2-bis(naphthalene-1-ylthio)ethane 2.37 C NMR of 13

257

: 1,2-bis((4-fluorophenyl)thio)ethane 2.38 H NMR of NMR of H 1

258

: 1,2-bis((4-fluorophenyl)thio)ethane 2.38 C NMR of 13

259

: 1,2-bis((4-methoxyphenyl)thio)ethane 2.39 H NMR of NMR of H 1

260

: 1,2-bis((4-methoxyphenyl)thio)ethane 2.39 C NMR of 13

261

2.46 H NMR of ComplexNMR of H 1

262

2.46 C ComplexNMR of 13

263

-tolyloxy)ethyl)sulfane p O phenyl(2-( S 2.49: H NMR of NMR of H 1

264

-tolyloxy)ethyl)sulfane p O phenyl(2-( S 2.49: H NMR of NMR of H 1

265

OAc )-3-phenylprop-2-en-1-yl )-3-phenylprop-2-en-1-yl E : (2 2.55 H NMR of NMR of H 1

266

OAc )-3-phenylprop-2-en-1-yl )-3-phenylprop-2-en-1-yl E : (2 2.55 C NMR of 13

267

OAc )-3-(4-methoxyphenyl)prop-2-en-1-yl )-3-(4-methoxyphenyl)prop-2-en-1-yl E : (2 O 2.57 H NMR of NMR of H 1

268

OAc )-3-(4-methoxyphenyl)prop-2-en-1-yl )-3-(4-methoxyphenyl)prop-2-en-1-yl E O : (2 2.57 C NMR of 3 1

269

yl - 1 - en - 2 - OAc fluorophenyl)prop - (4 - 3 - ) F E (2 : 9 2.5 of of

NMR H H 1

270

OAc F )-3-(4-fluorophenyl)prop-2-en-1-yl )-3-(4-fluorophenyl)prop-2-en-1-yl E : (2 2.59 C NMR of 13

271

OAc )-4-phenylbut-2-en-1-yl )-4-phenylbut-2-en-1-yl E : (2 2.51 H NMR of NMR of H 1

272

OAc )-4-phenylbut-2-en-1-yl )-4-phenylbut-2-en-1-yl E : (2 2.51 C NMR of 3 1

273

OAc )-dodec-2-en-1-yl )-dodec-2-en-1-yl E 2 ( : 2.60 H NMR of NMR of H 1

274

OAc )-dodec-2-en-1-yl acetate )-dodec-2-en-1-yl E : (2 2.60 C NMR of 3 1

275

OAc O N H )-5-oxo-5-(phenylamino)pent-2-enyl )-5-oxo-5-(phenylamino)pent-2-enyl E ( Ph : 2.62 H NMR of NMR of H 1

276

OAc O N H Ph )-5-oxo-5-(phenylamino)pent-2-enyl )-5-oxo-5-(phenylamino)pent-2-enyl E ( : 2.62 C NMR of 13

277

OAc O O H NMR of (2E)-pent-2-ene-1,5-diyl diacetate (2E)-pent-2-ene-1,5-diyl NMR of H 1

278

c A O O O )-pent-2-ene-1,5-diyl diacetate )-pent-2-ene-1,5-diyl E : (2 2.64 C NMR of 13

279

N O O AcO )-6-[(diethylcarbamoyl)oxy]hex-2-en-1-yl acetate)-6-[(diethylcarbamoyl)oxy]hex-2-en-1-yl E : (2 2.66 H NMR of NMR of H 1

280

N O O AcO )-6-[(diethylcarbamoyl)oxy]hex-2-en-1-yl acetate )-6-[(diethylcarbamoyl)oxy]hex-2-en-1-yl E 2 ( : 2.66 C NMR of 3 1

281

OMe )-4-methoxybenzyl-5-(acetyloxy)pent-3-enoate E O O : (3 2.68 AcO H NMR of NMR of H 1

282

OMe O O AcO )-4-methoxybenzyl-5-(acetyloxy)pent-3-enoate )-4-methoxybenzyl-5-(acetyloxy)pent-3-enoate E 3 ( : 2.68 C NMR of 3 1

283

OAc )-5-(benzyloxy)pent-2-en-1-yl acetate )-5-(benzyloxy)pent-2-en-1-yl acetate E O : (2 2.70 H NMR of NMR of H 1

284

)-5-(benzyloxy)pent-2-en-1-yl acetate )-5-(benzyloxy)pent-2-en-1-yl E : (2 2.70 C NMR of 13

285

-butyldiphenylsilyl)oxy Si tert O AcO )-6-(acetyloxy)hex-4-en-1-( E : (4 2.72 H NMR of NMR of H 1

286

- Si tert O AcO )-6-(acetyloxy)hex-4-en-1-( E 4 ( : 2.72 C NMR of 3 1

287

O O AcO )-4-(2-methyl-1,3-dioxolan-2-yl)but-2-en-1-yl acetate E : (2 2.74 H NMR of NMR of H 1

288

O O AcO )-4-(2-methyl-1,3-dioxolan-2-yl)but-2-en-1-yl acetate )-4-(2-methyl-1,3-dioxolan-2-yl)but-2-en-1-yl E : (2 2.74 C NMR of 3 1

289

O S -tolyloxy)ethyl)sulfane)palladium(II) p Cl Cl Pd S O : dichlorobis(phenyl(2-( 2.82 H NMR of NMR of H 1

290

O O S : 1-methyl-4-(2-(phenylsulfinyl)ethoxy)benzene 2.88 H NMR of NMR of H 1

291

O O S : 1-methyl-4-(2-(phenylsulfinyl)ethoxy)benzene 2.88 C NMR of 3 1

292

19 2 H 9 C Pd(OAc)/ : bis[acetate(1,2,3-trihapto-1-dodecene)palladium :bis[acetate(1,2,3-trihapto-1-dodecene)palladium 2.90 H NMR of NMR of H 1

293

S O : ((3-phenylpropyl)sulfinyl)benzene : ((3-phenylpropyl)sulfinyl)benzene 2.94 H NMR of NMR of H 1

294

S O : ((3-phenylpropyl)sulfinyl)benzene : ((3-phenylpropyl)sulfinyl)benzene 2.94 C NMR of 13

295

: iodide 1-ethyl-4-(ethylthio)pyridin-1-ium 2.97 H NMR of NMR of H 1

296

: iodide 1-ethyl-4-(ethylthio)pyridin-1-ium 2.97 C NMR of 13

297

)-triphenyl(hept-1-en-1-yl)silane )-triphenyl(hept-1-en-1-yl)silane Z : ( 2.121 H NMR of NMR of H 1

298

)-triphenyl(hept-1-en-1-yl)silane )-triphenyl(hept-1-en-1-yl)silane Z : ( 2.121 C NMR of 13

299

-butyl(hept-1-en-1-yl)dimethylsilane tert )- Z : ( 2.123 H NMR of NMR of H 1

300

-butyl(hept-1-en-1-yl)dimethylsilane tert )- Z : ( 2.123 C NMR of 13

301

)-benzyl(hept-1-en-1-yl)dimethylsilane )-benzyl(hept-1-en-1-yl)dimethylsilane Z : ( 2.125 H NMR of NMR of H 1

302

)-benzyl(hept-1-en-1-yl)dimethylsilane )-benzyl(hept-1-en-1-yl)dimethylsilane Z : ( 2.125 C NMR of 13

303

-butyldimethyl((6-(triethylsilyl)hex-5-en-1-yl)oxy)silane tert )- Z :( 2.131 H NMR of NMR of H 1

304

-butyldimethyl((6-(triethylsilyl)hex-5-en-1-yl)oxy)silane tert )- Z : ( 2.131 C NMR of 13

305

-butyldimethyl((4-(triethylsilyl)but-3-en-1-yl)oxy)silane tert )- Z : ( 2.133 H NMR of NMR of H 1

306

-butyldimethyl((4-(triethylsilyl)but-3-en-1-yl)oxy)silane tert )- Z : ( 2.133 C NMR of 13

307

)-triethyl(5-phenylpent-1-en-1-yl)silane )-triethyl(5-phenylpent-1-en-1-yl)silane Z : ( 2.138 H NMR of NMR of H 1

308

)-triethyl(5-phenylpent-1-en-1-yl)silane )-triethyl(5-phenylpent-1-en-1-yl)silane Z : ( 2.138 H NMR of NMR of H 1

309

)-tert-butyldimethyl(3-phenylprop-1-en-1-yl)silane )-tert-butyldimethyl(3-phenylprop-1-en-1-yl)silane Z : ( 2.140 H NMR of NMR of H 1

310

-butyldimethyl(3-phenylprop-1-en-1-yl)silane -butyldimethyl(3-phenylprop-1-en-1-yl)silane tert )- Z : ( 2.140 C NMR of 13

311

)-triethyl (4-methylpent-1-en-1-yl)silane)-triethyl Z : ( 2.144 H NMR of NMR of H 1

312

)-triethyl (4-methylpent-1-en-1-yl)silane (4-methylpent-1-en-1-yl)silane )-triethyl Z : ( 2.144 C NMR of 13

313

)-6-(triethyl silyl)hex-5-en-1-ol silyl)hex-5-en-1-ol )-6-(triethyl Z H NMR of ( NMR of H 1

314

)-6-(triethyl silyl)hex-5-en-1-ol silyl)hex-5-en-1-ol )-6-(triethyl Z C ( NMR of 13

315

)-6-(triethyl silyl)hex-5-en-1-yl acetate)-6-(triethyl Z : ( 2.146 H NMR of NMR of H 1

316

)-6-(triethyl silyl)hex-5-en-1-yl acetate silyl)hex-5-en-1-yl )-6-(triethyl Z : ( 2.146 C NMR of 13

317

)-6-(triethyl silyl)hex-5-en-1-yl)isoindoline-1,3-dione )-6-(triethyl Z : ( 2.148 H NMR of NMR of H 1

318

)-6-(triethyl silyl)hex-5-en-1-yl)isoindoline-1,3-dione )-6-(triethyl Z : ( 2.148 C NMR of 13

319

)-1-(triethylsilyl)hept-1-en-3-yl acetate E : ( 2.118 H NMR of NMR of H 1

320

)-1-(triethylsilyl)hept-1-en-3-yl acetate )-1-(triethylsilyl)hept-1-en-3-yl E : ( 2.118 C NMR of 13

321

322

)-1-(trimethylsilyl)hept-1-en-3-yl acetate E : ( 2.120 H NMR of NMR of H 1

323

)-1-(trimethylsilyl)hept-1-en-3-yl acetate )-1-(trimethylsilyl)hept-1-en-3-yl E : ( 2.120 C NMR of 13

324

)-1-(triphenylsilyl)hept-1-en-3-yl acetate)-1-(triphenylsilyl)hept-1-en-3-yl E : ( 2.122 H NMR of NMR of H 1

325

)-1-(triphenylsilyl)hept-1-en-3-yl acetate )-1-(triphenylsilyl)hept-1-en-3-yl E : ( 2.122 C NMR of 13

326

-butyldimethylsilyl)hept-1-en-3-yl acetate-butyldimethylsilyl)hept-1-en-3-yl tert )-1-( E : ( 2.124 H NMR of NMR of H 1

327

-butyldimethylsilyl)hept-1-en-3-yl acetate-butyldimethylsilyl)hept-1-en-3-yl tert )-1-( E : ( 2.124 C NMR of 13

328

)-1-(benzyldimethylsilyl)hept-1-en-3-yl )-1-(benzyldimethylsilyl)hept-1-en-3-yl acetate E : ( 2.126 H NMR of NMR of H 1

329

)-1-(benzyldimethylsilyl)hept-1-en-3-yl acetate )-1-(benzyldimethylsilyl)hept-1-en-3-yl E : ( 2.126 C NMR of 13

330

)-1-(triethylsilyl)dec-1-en-3-yl acetate E : ( 2.130 H NMR of NMR of H 1

331

)-1-(triethylsilyl)dec-1-en-3-yl acetate )-1-(triethylsilyl)dec-1-en-3-yl E : ( 2.130 C NMR of 13

332

-butyldimethylsilyl)oxy)-1-(triethylsilyl)hex-1-en-3-yl acetate-butyldimethylsilyl)oxy)-1-(triethylsilyl)hex-1-en-3-yl tert )-6-(( E : ( 2.132 H NMR of NMR of H 1

333

-butyldimethylsilyl)oxy)-1-(triethylsilyl)hex-1-en-3-yl acetate tert )-6-(( E : ( 2.132 C NMR of 13

334

-butyldimethylsilyl)oxy)-1-(triethylsilyl)but-3-en-2-yl acetate-butyldimethylsilyl)oxy)-1-(triethylsilyl)but-3-en-2-yl tert )-6-(( E : ( 2.134 H NMR of NMR of H 1

335

-butyldimethylsilyl)oxy)-1-(triethylsilyl)but-3-en-2-yl acetate tert )-6-(( E : ( 2.134 C NMR of 13

336

2.137 and and 2.136 H NMR of NMR of H 1

337

2.137 and and 2.136 C NMR of 13

338

)-5-phenyl-1-(triethylsilyl)pent-1-en-3-yl acetate E : ( 2.139 H NMR of NMR of H 1

339

)-5-phenyl-1-(triethylsilyl)pent-1-en-3-yl acetate )-5-phenyl-1-(triethylsilyl)pent-1-en-3-yl E : ( 2.139 C NMR of 13

340

)-4-methyl-1-(triethylsilyl)pent-1-en-3-yl acetate)-4-methyl-1-(triethylsilyl)pent-1-en-3-yl E : ( 2.145 H NMR of NMR of H 1

341

)-4-methyl-1-(triethylsilyl)pent-1-en-3-yl acetate )-4-methyl-1-(triethylsilyl)pent-1-en-3-yl E : ( 2.145 C NMR of 13

342

)-6-(triethylsilyl)hex-5-ene-1,4-diyl diacetate E : ( 2.147 H NMR of NMR of H 1

343

)-6-(triethylsilyl)hex-5-ene-1,4-diyl diacetate diacetate )-6-(triethylsilyl)hex-5-ene-1,4-diyl E : ( 2.147 C NMR of 13

344

)-6-(1,3-dioxoisoindolin-2-yl)-1-(triethylsilyl)hex-1-en-3-yl acetate)-6-(1,3-dioxoisoindolin-2-yl)-1-(triethylsilyl)hex-1-en-3-yl E

: (

2.149

H NMR of NMR of H

345

)-6-(1,3-dioxoisoindolin-2-yl)-1-(triethylsilyl)hex-1-en-3-yl acetate )-6-(1,3-dioxoisoindolin-2-yl)-1-(triethylsilyl)hex-1-en-3-yl E : ( 2.149 C NMR of 13

346

)-1-(triethylsilyl)hept-2-en-1-yl acetate)-1-(triethylsilyl)hept-2-en-1-yl E : ( 2.156 H NMR of NMR of H 1

347

)-1-(triethylsilyl)hept-2-en-1-yl acetate)-1-(triethylsilyl)hept-2-en-1-yl E : ( 2.156 C NMR of 13

348

)-fluorotridec-1-ene )-fluorotridec-1-ene Z : ( 3.18 H NMR of NMR of H 1

349

)-fluorotridec-1-ene )-fluorotridec-1-ene Z : ( 3.18 C NMR of 13

350

-butyl((6-methoxyhex-5-en-1-yl)oxy)dimethylsilane tert : 3.34 H NMR of NMR of H 1

351

-butyl((6-methoxyhex-5-en-1-yl)oxy)dimethylsilane tert : 3.34 C NMR of 13

352

: 6-methoxyhex-5-en-1-yl acetate : 6-methoxyhex-5-en-1-yl 3.36 H NMR of NMR of H 1

353

: 6-methoxyhex-5-en-1-yl acetate : 6-methoxyhex-5-en-1-yl 3.36 C NMR of 13

354

)-7-methoxyhepta-1,6-dien-1-yl)sialne )-7-methoxyhepta-1,6-dien-1-yl)sialne Z : triethyl((1 3.38 H NMR of NMR of H 1

355

)-7-methoxyhepta-1,6-dien-1-yl)sialne )-7-methoxyhepta-1,6-dien-1-yl)sialne Z : triethyl((1 3..38 C NMR of 13

356

: (4-(methoxymethylene)cyclohexyl)benzene 3.30 H NMR of NMR of H 1

357

: (4-(methoxymethylene)cyclohexyl)benzene : (4-(methoxymethylene)cyclohexyl)benzene 3.30 C NMR of 13

358

: (4-(ethoxymethylene)cyclohexyl)benzene 3.40 H NMR of NMR of H 1

359

: (4-(ethoxymethylene)cyclohexyl)benzene : (4-(ethoxymethylene)cyclohexyl)benzene 3.40 C NMR of 13

360

: 8-(methoxymethylene)-1,4-dioxaspiro[4.5]decane : 8-(methoxymethylene)-1,4-dioxaspiro[4.5]decane 3.41 H NMR of NMR of H 1

361

: 8-(methoxymethylene)-1,4-dioxaspiro[4.5]decane : 8-(methoxymethylene)-1,4-dioxaspiro[4.5]decane 3.41 C NMR of 13

362

-butyl)-4-(methoxymethylene)cyclohexane tert : 1-( 3.43 H NMR of NMR of H 1

363

-butyl)-4-(methoxymethylene)cyclohexane tert : 1-( 3.43 C NMR of 13

364

: 2-(6-methoxyhex-5-en-1-yl)isoindoline-1,3-dione 3.45 H NMR of NMR of H 1

365

: 2-(6-methoxyhex-5-en-1-yl)isoindoline-1,3-dione 3.45 C NMR of 13

366

: 1-(6-methoxyhex-5-en-1-yl)pyrrolidine-2,5-dione 3.47 H NMR of NMR of H 1

367

: 1-(6-methoxyhex-5-en-1-yl)pyrrolidine-2,5-dione : 1-(6-methoxyhex-5-en-1-yl)pyrrolidine-2,5-dione 3.47 C NMR of 13

368

-benzo[7]annulene H : 5-(methoxymethylene)-6,7,8,9-tetrahydro-5 3.49 H NMR of NMR of H 1

369

-benzo[7]annulene H : 5-(methoxymethylene)-6,7,8,9-tetrahydro-5 3.49 C NMR of 13

370

: (1-cyclohexyl-2-methoxyvinyl)benzene 3.51 A H NMR of NMR of H 1

371

: (1-cyclohexyl-2-methoxyvinyl)benzene : (1-cyclohexyl-2-methoxyvinyl)benzene 3.51 A C NMR of 13

372

: (1-cyclohexyl-2-methoxyvinyl)benzene : (1-cyclohexyl-2-methoxyvinyl)benzene 3.51 B H NMR of NMR of H 1

373

: (1-cyclohexyl-2-methoxyvinyl)benzene : (1-cyclohexyl-2-methoxyvinyl)benzene 3.51 B C NMR of 13

374

)-6-oxohex-4-en-1-yl acetate )-6-oxohex-4-en-1-yl E : ( 3.37 H NMR of NMR of H 1

375

)-6-oxohex-4-en-1-yl acetate )-6-oxohex-4-en-1-yl E : ( 3.37 C NMR of 13

376

)-7-(triethylsilyl)hepta-2,6-dienal )-7-(triethylsilyl)hepta-2,6-dienal Z , 6 E : (2 3.39 H NMR of NMR of H 1

377

)-7-(triethylsilyl)hepta-2,6-dienal )-7-(triethylsilyl)hepta-2,6-dienal Z , 6 E : (2 3.39 C NMR of 13

378

: 1,2,3,6-tetrahydro[1.1’-biphenyl]-4-carbaldehyde 3.31 H NMR of NMR of H 1

379

: 1,2,3,6-tetrahydro[1.1’-biphenyl]-4-carbaldehyde : 1,2,3,6-tetrahydro[1.1’-biphenyl]-4-carbaldehyde 3.31 C NMR of 13

380

: 1,4-dioxaspiro[4.5]dec-7-ene-8-carbaldehyde 3.42 H NMR of NMR of H 1

381

: 1,4-dioxaspiro[4.5]dec-7-ene-8-carbaldehyde : 1,4-dioxaspiro[4.5]dec-7-ene-8-carbaldehyde 3.42 C NMR of 13

382

-butyl)cyclohex-1-enecarbaldehyde tert : 4-( 3.44 H NMR of NMR of H 1

383

-butyl)cyclohex-1-enecarbaldehyde -butyl)cyclohex-1-enecarbaldehyde tert : 4-( 3.44 C NMR of 13

384

: 6-(1,3-dioxoisoindolein-2-yl)hex-2-enal : 6-(1,3-dioxoisoindolein-2-yl)hex-2-enal 3.46 H NMR of NMR of H 1

385

: 6-(1,3-dioxoisoindolein-2-yl)hex-2-enal : 6-(1,3-dioxoisoindolein-2-yl)hex-2-enal 3.46 C NMR of 13

386

: 6-(2,5)-dioxopyrrolidin-1-yl)hexanal : 6-(2,5)-dioxopyrrolidin-1-yl)hexanal 3.48 H NMR of NMR of H 1

387

: 6-(2,5)-dioxopyrrolidin-1-yl)hexanal : 6-(2,5)-dioxopyrrolidin-1-yl)hexanal 3.48 C NMR of 13

388

-benzo[7]annulene-9-carbaldehyde H : 6,7-dihydro-5 3.50 H NMR of NMR of H 1

389

-benzo[7]annulene-9-carbaldehyde H : 6,7-dihydro-5 3.50 C NMR of 13

390

: 2-cyclohexylidene-2-phenylacetaldehyde : 2-cyclohexylidene-2-phenylacetaldehyde 3.52 H NMR of NMR of H 1

391

: 2-cyclohexylidene-2-phenylacetaldehyde : 2-cyclohexylidene-2-phenylacetaldehyde 3.52 C NMR of 13

392

) 4.1 )(OAc)]HOAc ( )(OAc)]HOAc 2 Bu t P 2 ) 3 C(CH 2 )Pd(CH 3 Bu t H NMR [(P H 1

393

) 4.1 )(OAc)]HOAc ( )(OAc)]HOAc 2 Bu t P 2 ) 3 C(CH 2 )Pd(CH 3 Bu t PNMR [(P 1 3

394

) ) -20 at 4.1 )(OAc)]HOAc ( )(OAc)]HOAc 2 Bu t P 2 ) 3 C(CH 2 )Pd(CH 3 Bu t PNMR [(P 1 3

395

) 4.3 )(OAc)] ( )(OAc)] 2 Bu t P 2 ) 3 C(CH 2 NO)Pd(CH 9 H 4 H NMR [(C H 1

396

) 4.3 )(OAc)] ( )(OAc)] 2 Bu t P 2 ) 3 C(CH 2 NO)Pd(CH 9 H 4 PNMR [(C 1 3

397

) 4.4 )(OAc)]HOAc ( )(OAc)]HOAc 2 Bu t P 2 ) 3 C(CH 2 )Pd(CH 3 H NMR [(PPh H 1

398

) 4.4 )(OAc)]HOAc ( )(OAc)]HOAc 2 Bu t P 2 ) 3 C(CH 2 )Pd(CH 3 PNMR [(PPh 1 3

399

) 4.5 )(OAc)]HOAc ( )(OAc)]HOAc 2 Bu t P 2 ) 3 C(CH 2 Pd(CH 2 ) 2 PCH 2 H NMR [(Ph H 1

400

)(OAc)]HOAc )(OAc)]HOAc 2 Bu t P 2 ) 3 C(CH 2 Pd(CH 2 ) 2 PCH 2 PNMR [(Ph 1 3

401

) 4.6 ( 2 (OAc) 2 Me) 2 Bu t H NMR Pd(P H 1

402

) 4.6 ( 2 (OAc) 2 Me) 2 Bu t PNMR Pd(P 31

403

Appendix B: X-Ray Crystallographic Information

404

Crystallographic Data for Complex 2.82

______

Molecular formula C30 H32 Cl2 O2 Pd1 S2 Formula weight 665.98 Temperature 150(2) K Wavelength 0.71073 Å Crystal system monoclinic Space group C2/c Unit cell dimensions a = 34.5537(4) Å b = 10.9542(1) Å c = 7.9173(1) Å β= 95.489(1)° Volume 2983.03(6) Å 3 Z 4 Density (calculated) 1.483 Mg/m 3 Absorption coefficient 0.967 mm -1 F(000) 1360 Theta range for data collection 2.57 to 27.48° Index ranges -44 ≤ h ≤ 44, -13 ≤ k ≤ 14, -10 ≤ l ≤ 10 Reflections collected 35882 Independent reflections 3425 [R(int) = 0.052] Completeness to theta = 27.47° 99.7 % Refinement method Full-matrix least-squares on F 2 Goodness-of-fit on F 2 1.039 Final R indices [I>2sigma(I)] R1 = 0.0257, wR2 = 0.0529 R indices (all data) R1 = 0.0468, wR2 = 0.0578 Largest diff. peak and hole 1.028 and -0.609 e/Å 3

Atomic coordinates ( x 10 4) and equivalent isotropic displacement parameters (Å 2x 10 3) for 2.82 . U(eq) is defined as one third of the trace of the orthogonalized U ij tensor. ______x y z U(eq) ______

Pd 0 3431(2) 2500 17(1) S -622(14) 3384(4) 1128(6) 18(1)

405

Cl 314(14) 3422(4) 66(5) 22(1) O -1294(4) 3179(12) -1539(16) 24(1) C(1) -612(6) 3558(18) -1159(2) 20(1) C(2) -999(6) 4011(19) -1960(2) 22(1) C(3) -1669(6) 3414(18) -2186(2) 23(1) C(4) -1949(6) 2647(2) -1628(3) 31(1) C(5) -2337(6) 2798(2) -2225(3) 37(1) C(6) -2454(7) 3705(2) -3385(3) 37(1) C(7) -2169(7) 4455(2) -3925(3) 37(1) C(8) -1779(6) 4332(2) -3343(3) 30(1) C(9) -2878(7) 3866(3) -4018(3) 58(1) C(10) -743(6) 1798(17) 1283(2) 19(1) C(11) -1097(6) 1482(2) 1830(3) 29(1) C(12) -1198(6) 262(2) 1900(3) 38(1) C(13) -951(7) -627(2) 1417(3) 36(1) C(14) -596(7) -307(2) 896(3) 37(1) C(15) 489(6) 906(2) 825(3) 31(1)

______

Bond lengths [Å] and angles [°] for Complex 2.82 . ______

Pd-Cl 2.3011(4) Pd-Cl(2) 2.3011(4) Pd-S(2) 2.3149(5) Pd-S 2.3149(5) S-C(10) 1.7933(19) S-(C1) 1.8244(17) O-(C3) 1.373(2) O-C(2) 1.428(2) C(1)-C(2) 1.507(3) C(3)-C(4) 1.385(3) C(3)-C(8) 1.388(3) C(4)-C(5) 1.387(3) C(5)-C(6) 1.387(3) C(6)-C(7) 1.379(3) C(6)-C(9) 1.513(3) C(7)-C(8) 1.392(3) C(10)-C(11) 1.380(3) C(10)-C(15) 1.384(3) C(11)-C(12) 1.383(3)

406

C(12)-C(13) 1.373(3) C(13)-C(14) 1.375(3) C(14)-C(15) 1.381(3) Cl-Pd-Cl(2) 179.52(3) Cl-Pd-S 84.340(16) Cl-Pd-S(2) 95.649(16) Cl(2)-Pd-S 95.649(16) Cl(2)-Pd-S(2) 84.340(16) S-Pd-S(2) 177.42(3) C(10)-S-C(1) 101.28(9) C(10)-S-Pd 101.61(6) C(1)-S-Pd 11.02(7) C(3)-O-C(2) 117.60(14) C(2)-C(1)-S 110.59(13) O-C(2)-C(1) 108.36(15) O-C(3)-C(4) 115.60(17) O-C(3)-C(8) 124.67(18) C(4)-C(3)-C(8) 119.73(19) C(3)-C(4)-C(5) 120.0(2) C(6)-C(5)-C(4) 121.4(2) C(7)-C(6)-C(5) 117.5(2) C(7)-C(6)-C(9) 121.6(2) C(5)-C(6)-C(9) 120.9(2) C(6)-C(7)-C(8) 122.5(2) C(3)-C(8)-C(7) 118.9(2) C(11)-C(10)-C(15) 120.55(19) C(11)-C(10)-S 118.88(15) C(15)-C(10)-S 120.55(16) C(10)-C(11)-C(12) 119.2(2) C(13)-C(12)-C(11) 120.6(2) C(12)-C(13)-C(14) 119.9(2) C(13)-C(14)-C(15) 120.5(2) C(14)-C(15)-C(10) 119.3(2) ______

407

Anisotropic displacement parameters (Å 2x 10 3) for 2.82 . The anisotropic displacement factor exponent takes the form: -2π2[ h 2a* 2U11 + ... + 2 h k a* b* U 12 ] ______U11 U22 U33 U23 U13 U12 ______

Pd 21(13) 14(1) 15(1) 0 (1) 0 0 S 21(1) 16(1) 17(1) -1(1) 04(2) 1(1) Cl 25(1) 24(1) 17(1) 1(1) 07(2) 1(1) O 20(1) 25(1) 28(1) 1(1) -1(1) 2(1) C(1) 23(1) 21(1) 17(1) -1(1) 4(1) -3(1) C(2) 26(1) 19(1) 21(1) 3(1) 2(1) -3(1) C(3) 22(1) 025(1) 21(1) -2(9) 1(8) 3(1) C(4) 29(1) 33(1) 29(1) 3(10) 3(1) -3(1) C(5) 26(1) 45(2) 39(1) -1(1) 1(1) -1(1) C(6) 28(1) 46(2) 37(1) -16(1) -1 (1) 1(1) C(7) 38(1) 36(2) 35(1) -0(11) -1 (1) 14(1) C(8) 30(1) 31(1) 30(1) 1(10) 0(1) 0(1) C(9) 31(2) 76(2) 63(2) -23(15) -1(1) 15(1) C(10) 21(1) 19(1) 19(1) 0(8) 0(1) -0(1) C(11) 26(1) 30(1) 32(1) 1(10) 1(1) 0(1) C(12) 31(1) 37(2) 45(1) 12(12) 1(1) -13(1) C(13) 44(2) 27(1) 39(1) 1(10) -1(1) -10(1) C(14) 38(1) 19(1) 54(1) 0(11) 1(1) 0(1) C(15) 27(1) 22(1) 44(1) -0 (10) 11(1) -0(1) ______

Torsion angles [°] for 2.82 . ______

Cl-Pd-S-C(10) 99.74(6) Cl-Pd-S(2)-C(10) -79.78(6) Cl(2)-Pd-S-C(1) -7.29(7) Cl-Pd-S(2)-C(1) 173.19(7) C(10)-S-C(1)-C(2) 94.76(15) Pd-S-C(1)-C(2) -157.99(12) C(3)-O-C(2)-C(1) -178.45(15) S-C(1)-C(2)-O -56.50(18) C(2)-O-C(3)-C(4) -174.61(17) C(2)-O-C(3)-C(8) 6.3(3)

408

O-C(3)-C(4)-C(5) -179.12(18) C(8)-C(3)-C(4)-C(5) 0.0(3) C(3)-C(4)-C(5)-C(6) 0.2(3) C(4)-C(5)-C(6)-C(7) 0.0(3) C(4)-C(5)-C(6)-C(9) -179.6(2) C(5)-C(6)-C(7)-C(8) -0.3(3) C(9)-C(6)-C(7)-C(8) 179.2(2) O-C(3)-C(8)-C(7) 178.68(18) C(4)-C(3)-C(8)-C(7) -0.4(3) C(6)-C(7)-C(8)-C(3) 0.5(3) C(1)-S-C(10)-C(11) -113.68(16) Pd-S-C(10)-C(11) 131.84(15) C(1)-S-C(10)-C(15) 64.92(18) Pd-S-C(10)-C(15) -49.56(17) C(15)-C(10)-C(11)-C(12) -0.7(3) S-C(10)-C(11)-C(12) 177.88(16) C(10)-C(11)-C(12)-C(13) -0.5(3) C(11)-C(12)-C(13)-C(14) 1.5(3) C(12)-C(13)-C(14)-C(15) -1.2(3) C(13)-C(14)-C(15)-C(10) -0.1(3) C(11)-C(10)-C(15)-C(14) 1.0(3) S-C(10)-C(15)-C(14) -177.56(16) ______

409

Crystallographic Data for Complex 4.1

______

Molecular formula C26 H56 O2 P2 Pd + CH3COOH Formula weight 629.10 Temperature 200(2) K Wavelength 0.71073 Å Crystal system monoclinic Space group P2 1/n Unit cell dimensions a = 8.5090(1) Å b = 24.1146(2) Å c = 16.0237(2) Å β= 93.2157(4)° Volume 3282.74(6) Å 3 Z 4 Density (calculated) 1.273 Mg/m 3 Absorption coefficient 0.691 mm -1 F(000) 1344 Crystal size 0.31 x 0.15 x 0.15 mm 3 Theta range for data collection 2.12 to 27.47° Index ranges -10 ≤ h ≤ 10, -31 ≤ k ≤ 31, -20 ≤ l ≤ 20 Reflections collected 53438 Independent reflections 7487 [R(int) = 0.042] Completeness to theta = 27.47° 99.7 % Refinement method Full-matrix least-squares on F 2 Data / restraints / parameters 7487 / 0 / 315 Goodness-of-fit on F 2 1.030 Final R indices [I>2sigma(I)] R1 = 0.0373, wR2 = 0.0923 R indices (all data) R1 = 0.0570, wR2 = 0.0998 Largest diff. peak and hole 0.737 and -0.486 e/Å 3 ______

410

Atomic coordinates ( x 10 4) and equivalent isotropic displacement parameters (Å 2x 10 3) for palladacycle A. U(eq) is defined as one third of the trace of the orthogonalized Uij tensor. ______

x y z U(eq) ______

C(1) 7880(4) 9074(1) 10024(2) 55(1) C(2) 7716(4) 9387(1) 9174(2) 51(1) C(3) 9621(5) 8973(2) 10223(2) 70(1) C(4) 7219(6) 9378(2) 10772(2) 85(1) C(5) 7592(4) 7783(1) 10035(2) 47(1) C(6) 9271(4) 7683(2) 9759(2) 59(1) C(7) 6591(5) 7293(2) 9716(3) 74(1) C(8) 7606(5) 7796(2) 10993(2) 67(1) C(9) 4630(4) 8523(2) 9626(2) 64(1) C(10) 4074(5) 9106(2) 9350(3) 87(2) C(11) 4049(5) 8390(2) 10492(3) 85(2) C(12) 3836(4) 8125(2) 8979(3) 91(2) C(13) 10138(3) 9330(2) 6883(2) 53(1) C(14) 10791(4) 8756(2) 7120(3) 72(1) C(15) 10668(4) 9502(2) 6025(2) 75(1) C(16) 10898(5) 9734(2) 7531(3) 87(2) C(17) 7176(5) 10079(2) 7010(2) 59(1) C(18) 7776(5) 10454(2) 6306(3) 77(1) C(19) 7581(7) 10378(2) 7825(3) 96(2) C(20) 5351(5) 10061(2) 6922(3) 83(1) C(21) 6920(3) 8977(1) 6048(2) 45(1) C(22) 5260(4) 8785(2) 6279(2) 59(1) C(23) 7811(5) 8450(2) 5829(2) 61(1) C(24) 6741(5) 9335(2) 5254(2) 68(1) C(25) 7706(4) 7590(1) 7562(2) 51(1) C(26) 6873(6) 7065(2) 7281(3) 81(1) O(1) 6850(3) 8006(1) 7648(1) 49(1) O(2) 9156(3) 7596(1) 7680(2) 84(1) P(1) 6840(1) 8460(1) 9558(1) 39(1) P(2) 7925(1) 9325(1) 7016(1) 35(1) Pd 7437(1) 8777(1) 8273(1) 32(1) C(1A) 11682(6) 6552(2) 8082(4) 96(2) O(1A) 11499(9) 7057(3) 7779(5) 81(2)* O(2A) 10400(9) 6477(3) 8622(5) 91(3)* 411

C(2A) 12587(9) 6066(4) 7892(5) 48(2)* O(1B) 12189(12) 7051(4) 8278(6) 156(3)* O(2B) 10408(7) 6494(2) 7629(4) 89(2)* C(2B) 13132(9) 6285(3) 8290(5) 65(2)*

*These atoms belong to a disordered acetic acid molecule and were refined isotropically. The occupancy factor for O(1A), O(2A), and C(2A) refined to 0.417(6), and the occupancy factor for O(1B), O(2B) and C(2B) is 0.583(6). ______

Bond lengths [Å] and angles [°] for palladacycle A ______

C(1)-C(3) 1.516(5) C(1)-C(4) 1.539(5) C(1)-C(2) 1.556(4) C(1)-P(1) 1.860(4) C(2)-Pd 2.066(3) C(5)-C(7) 1.528(5) C(5)-C(8) 1.533(5) C(5)-C(6) 1.538(5) C(5)-P(1) 1.899(3) C(9)-C(11) 1.533(5) C(9)-C(10) 1.540(6) C(9)-C(12) 1.541(6) C(9)-P(1) 1.896(3) C(13)-C(15) 1.529(4) C(13)-C(14) 1.530(5) C(13)-C(16) 1.540(5) C(13)-P(2) 1.907(3) C(17)-C(19) 1.513(6) C(17)-C(20) 1.552(5) C(17)-C(18) 1.554(5) C(17)-P(2) 1.928(4) C(21)-C(23) 1.531(5) C(21)-C(24) 1.539(4) C(21)-C(22) 1.550(4) C(21)-P(2) 1.921(3) C(25)-O(2) 1.238(4) C(25)-O(1) 1.252(4) C(25)-C(26) 1.508(5) O(1)-Pd 2.156(2) P(1)-Pd 2.2795(7) 412

P(2)-Pd 2.4637(7) C(1A)-O(2B) 1.278(7) C(1A)-O(1B) 1.311(11) C(1A)-O(1A) 1.317(9) C(1A)-C(2B) 1.415(9) C(1A)-O(2A) 1.441(9) C(1A)-C(2A) 1.445(10) C(3)-C(1)-C(4) 108.0(3) C(3)-C(1)-C(2) 107.5(3) C(4)-C(1)-C(2) 115.6(3) C(3)-C(1)-P(1) 113.2(3) C(4)-C(1)-P(1) 120.4(3) C(2)-C(1)-P(1) 91.0(2) C(1)-C(2)-Pd 105.5(2) C(7)-C(5)-C(8) 108.9(3) C(7)-C(5)-C(6) 107.0(3) C(8)-C(5)-C(6) 109.6(3) C(7)-C(5)-P(1) 111.2(2) C(8)-C(5)-P(1) 111.7(2) C(6)-C(5)-P(1) 108.4(2) C(11)-C(9)-C(10) 109.9(3) C(11)-C(9)-C(12) 109.1(4) C(10)-C(9)-C(12) 105.0(3) C(11)-C(9)-P(1) 114.0(2) C(10)-C(9)-P(1) 110.3(3) C(12)-C(9)-P(1) 108.1(3) C(15)-C(13)-C(14) 110.4(3) C(15)-C(13)-C(16) 107.5(3) C(14)-C(13)-C(16) 105.8(3) C(15)-C(13)-P(2) 116.4(2) C(14)-C(13)-P(2) 108.3(2) C(16)-C(13)-P(2) 108.0(3) C(19)-C(17)-C(20) 105.7(4) C(19)-C(17)-C(18) 106.4(3) C(20)-C(17)-C(18) 108.6(3) C(19)-C(17)-P(2) 112.7(3) C(20)-C(17)-P(2) 107.5(3) C(18)-C(17)-P(2) 115.5(3) C(23)-C(21)-C(24) 107.7(3) C(23)-C(21)-C(22) 106.1(3) C(24)-C(21)-C(22) 108.4(3) C(23)-C(21)-P(2) 110.1(2) C(24)-C(21)-P(2) 116.2(2) C(22)-C(21)-P(2) 107.9(2) 413

O(2)-C(25)-O(1) 123.7(3) O(2)-C(25)-C(26) 120.3(4) O(1)-C(25)-C(26) 116.1(3) C(25)-O(1)-Pd 128.4(2) C(1)-P(1)-C(9) 111.36(19) C(1)-P(1)-C(5) 112.35(16) C(9)-P(1)-C(5) 111.03(16) C(1)-P(1)-Pd 88.32(11) C(9)-P(1)-Pd 107.29(11) C(5)-P(1)-Pd 124.40(10) C(13)-P(2)-C(21) 108.09(15) C(13)-P(2)-C(17) 108.76(17) C(21)-P(2)-C(17) 106.05(16) C(13)-P(2)-Pd 107.88(10) C(21)-P(2)-Pd 109.75(10) C(17)-P(2)-Pd 116.07(11) C(2)-Pd-O(1) 162.35(11) C(2)-Pd-P(1) 68.31(9) O(1)-Pd-P(1) 94.17(6) C(2)-Pd-P(2) 99.87(9) O(1)-Pd-P(2) 97.34(6) P(1)-Pd-P(2) 167.01(3) O(2B)-C(1A)-O(1B) 119.6(6) O(2B)-C(1A)-C(2B) 141.7(6) O(1B)-C(1A)-C(2B) 95.2(6) O(1A)-C(1A)-O(2A) 105.0(6) O(1A)-C(1A)-C(2A) 136.7(6) O(2A)-C(1A)-C(2A) 117.0(5) ______

Anisotropic displacement parameters (Å 2x 10 3) for palladacycle A. The anisotropic displacement factor exponent takes the form: -2π2[ h 2a* 2U11 + ... + 2 h k a* b* U 12 ] ______

U11 U22 U33 U23 U13 U12 ______

C(1) 70(2) 50(2) 45(2) 2(2) 3(2) 3(2) C(2) 73(2) 41(2) 40(2) -2(1) 5(2) -4(2) C(3) 70(2) 74(3) 64(2) 3(2) -16(2) -15(2) C(4) 133(4) 76(3) 46(2) -5(2) 7(2) 17(3)

414

C(5) 50(2) 45(2) 47(2) 16(1) 5(1) 6(1) C(6) 57(2) 56(2) 66(2) 11(2) 6(2) 20(2) C(7) 90(3) 56(2) 77(3) 19(2) 11(2) -9(2) C(8) 72(2) 78(3) 50(2) 29(2) 5(2) 12(2) C(9) 36(2) 99(3) 60(2) 32(2) 15(2) 13(2) C(10) 60(2) 114(4) 89(3) 48(3) 24(2) 44(2) C(11) 56(2) 130(4) 73(3) 44(3) 34(2) 26(2) C(12) 40(2) 138(5) 94(3) 36(3) -1(2) -9(2) C(13) 29(2) 79(2) 49(2) 25(2) -1(1) -11(2) C(14) 35(2) 102(3) 79(3) 34(2) 6(2) 10(2) C(15) 36(2) 124(4) 67(2) 38(2) 13(2) -6(2) C(16) 57(2) 128(4) 73(3) 21(3) -15(2) -47(2) C(17) 77(2) 45(2) 57(2) 7(2) 7(2) 4(2) C(18) 103(3) 55(2) 75(3) 25(2) 7(2) -5(2) C(19) 176(5) 39(2) 74(3) 3(2) 4(3) 10(3) C(20) 69(3) 67(3) 117(4) 18(3) 25(2) 28(2) C(21) 41(2) 58(2) 35(2) 3(1) -5(1) -3(1) C(22) 40(2) 66(2) 70(2) 3(2) -12(2) -9(2) C(23) 70(2) 66(2) 45(2) -6(2) 6(2) 1(2) C(24) 74(2) 84(3) 44(2) 16(2) -14(2) -4(2) C(25) 67(2) 49(2) 40(2) 3(1) 12(2) 2(2) C(26) 126(4) 45(2) 74(3) -16(2) 24(3) -5(2) O(1) 57(1) 36(1) 52(1) -2(1) 3(1) -1(1) O(2) 65(2) 100(2) 88(2) -3(2) 7(2) 19(2) P(1) 35(1) 47(1) 36(1) 13(1) 8(1) 6(1) P(2) 31(1) 42(1) 32(1) 7(1) 2(1) -4(1) Pd 32(1) 31(1) 32(1) 3(1) 5(1) -1(1) C(1A) 69(3) 74(3) 140(5) 43(3) -32(3) -25(2) ______

Calculated hydrogen coordinates ( x 10 4) and isotropic displacement parameters (Å 2x 10 3) for palladacycle A. ______

x y z U(eq) ______

H(2A) 8669 9610 9088 62 H(2B) 6790 9636 9156 62 H(3A) 10068 8778 9755 105 H(3B) 9759 8747 10729 105 H(3C) 10159 9329 10312 105 415

H(4A) 6094 9450 10657 128 H(4B) 7775 9731 10862 128 H(4C) 7368 9148 11274 128 H(6A) 9954 7989 9955 89 H(6B) 9254 7663 9148 89 H(6C) 9676 7334 9998 89 H(7A) 6583 7279 9105 111 H(7B) 5512 7338 9890 111 H(7C) 7036 6948 9950 111 H(8A) 8258 8106 11204 100 H(8B) 8040 7447 11218 100 H(8C) 6529 7843 11167 100 H(10A) 4436 9186 8793 130 H(10B) 4511 9382 9749 130 H(10C) 2922 9122 9334 130 H(11A) 4548 8643 10906 128 H(11B) 4325 8007 10642 128 H(11C) 2904 8436 10482 128 H(12A) 4204 8208 8424 136 H(12B) 2691 8172 8971 136 H(12C) 4107 7741 9129 136 H(14A) 10454 8653 7674 108 H(14B) 11944 8765 7131 108 H(14C) 10394 8483 6707 108 H(15A) 10252 9872 5884 113 H(15B) 10271 9235 5603 113 H(15C) 11821 9511 6037 113 H(16A) 10579 9634 8090 130 H(16B) 10553 10113 7398 130 H(16C) 12047 9711 7519 130 H(18A) 7524 10280 5762 116 H(18B) 8918 10500 6387 116 H(18C) 7263 10817 6324 116 H(19A) 7224 10156 8291 145 H(19B) 7058 10740 7818 145 H(19C) 8723 10430 7893 145 H(20A) 5015 9869 6403 125 H(20B) 4935 10440 6909 125 H(20C) 4951 9861 7400 125 H(22A) 4636 9109 6425 88 H(22B) 5358 8532 6757 88 H(22C) 4737 8594 5800 88 H(23A) 7941 8213 6325 91 H(23B) 8849 8550 5639 91 416

H(23C) 7215 8250 5383 91 H(24A) 6169 9676 5376 102 H(24B) 6155 9128 4812 102 H(24C) 7785 9430 5068 102 H(26A) 6819 7046 6669 121 H(26B) 5805 7064 7480 121 H(26C) 7454 6743 7511 121 ______

Torsion angles [°] for palladacycle A. ______

C(3)-C(1)-C(2)-Pd 91.5(3) C(4)-C(1)-C(2)-Pd -147.9(3) P(1)-C(1)-C(2)-Pd -23.2(2) O(2)-C(25)-O(1)-Pd -15.6(5) C(26)-C(25)-O(1)-Pd 165.8(2) C(3)-C(1)-P(1)-C(9) 162.7(2) C(4)-C(1)-P(1)-C(9) 32.9(3) C(2)-C(1)-P(1)-C(9) -87.8(2) C(3)-C(1)-P(1)-C(5) 37.4(3) C(4)-C(1)-P(1)-C(5) -92.4(3) C(2)-C(1)-P(1)-C(5) 146.9(2) C(3)-C(1)-P(1)-Pd -89.4(2) C(4)-C(1)-P(1)-Pd 140.8(3) C(2)-C(1)-P(1)-Pd 20.12(19) C(11)-C(9)-P(1)-C(1) -78.1(4) C(10)-C(9)-P(1)-C(1) 46.1(3) C(12)-C(9)-P(1)-C(1) 160.4(3) C(11)-C(9)-P(1)-C(5) 47.9(4) C(10)-C(9)-P(1)-C(5) 172.1(3) C(12)-C(9)-P(1)-C(5) -73.6(3) C(11)-C(9)-P(1)-Pd -173.2(3) C(10)-C(9)-P(1)-Pd -49.0(3) C(12)-C(9)-P(1)-Pd 65.3(3) C(7)-C(5)-P(1)-C(1) 173.3(2) C(8)-C(5)-P(1)-C(1) 51.5(3) C(6)-C(5)-P(1)-C(1) -69.4(3) C(7)-C(5)-P(1)-C(9) 47.8(3) C(8)-C(5)-P(1)-C(9) -74.0(3) C(6)-C(5)-P(1)-C(9) 165.2(3) C(7)-C(5)-P(1)-Pd -82.7(3) 417

C(8)-C(5)-P(1)-Pd 155.6(2) C(6)-C(5)-P(1)-Pd 34.7(3) C(15)-C(13)-P(2)-C(21) 44.8(3) C(14)-C(13)-P(2)-C(21) -80.2(3) C(16)-C(13)-P(2)-C(21) 165.7(2) C(15)-C(13)-P(2)-C(17) -70.0(3) C(14)-C(13)-P(2)-C(17) 165.0(3) C(16)-C(13)-P(2)-C(17) 50.9(3) C(15)-C(13)-P(2)-Pd 163.4(3) C(14)-C(13)-P(2)-Pd 38.4(3) C(16)-C(13)-P(2)-Pd -75.7(3) C(23)-C(21)-P(2)-C(13) 44.9(3) C(24)-C(21)-P(2)-C(13) -77.8(3) C(22)-C(21)-P(2)-C(13) 160.3(2) C(23)-C(21)-P(2)-C(17) 161.4(2) C(24)-C(21)-P(2)-C(17) 38.7(3) C(22)-C(21)-P(2)-C(17) -83.2(3) C(23)-C(21)-P(2)-Pd -72.5(2) C(24)-C(21)-P(2)-Pd 164.8(2) C(22)-C(21)-P(2)-Pd 42.9(2) C(19)-C(17)-P(2)-C(13) -76.1(3) C(20)-C(17)-P(2)-C(13) 167.8(3) C(18)-C(17)-P(2)-C(13) 46.4(3) C(19)-C(17)-P(2)-C(21) 167.8(3) C(20)-C(17)-P(2)-C(21) 51.8(3) C(18)-C(17)-P(2)-C(21) -69.6(3) C(19)-C(17)-P(2)-Pd 45.7(3) C(20)-C(17)-P(2)-Pd -70.4(3) C(18)-C(17)-P(2)-Pd 168.2(3) C(1)-C(2)-Pd-O(1) 27.5(5) C(1)-C(2)-Pd-P(1) 20.2(2) C(1)-C(2)-Pd-P(2) -165.4(2) C(25)-O(1)-Pd-C(2) -92.8(4) C(25)-O(1)-Pd-P(1) -86.0(2) C(25)-O(1)-Pd-P(2) 100.0(2) C(1)-P(1)-Pd-C(2) -16.19(16) C(9)-P(1)-Pd-C(2) 95.67(19) C(5)-P(1)-Pd-C(2) -132.36(17) C(1)-P(1)-Pd-O(1) 166.01(13) C(9)-P(1)-Pd-O(1) -82.12(16) C(5)-P(1)-Pd-O(1) 49.84(14) C(1)-P(1)-Pd-P(2) -41.61(17) C(9)-P(1)-Pd-P(2) 70.3(2) C(5)-P(1)-Pd-P(2) -157.78(16) 418

C(13)-P(2)-Pd-C(2) 86.67(17) C(21)-P(2)-Pd-C(2) -155.78(15) C(17)-P(2)-Pd-C(2) -35.61(17) C(13)-P(2)-Pd-O(1) -97.24(14) C(21)-P(2)-Pd-O(1) 20.31(12) C(17)-P(2)-Pd-O(1) 140.48(15) C(13)-P(2)-Pd-P(1) 110.55(17) C(21)-P(2)-Pd-P(1) -131.91(15) C(17)-P(2)-Pd-P(1) -11.73(19) ______

419