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6-1-2001 Transition-metal-promoted hydroboration of : a unique reversal of regioselectivity Christopher D'Souza

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Recommended Citation D'Souza, Christopher, "Transition-metal-promoted hydroboration of alkenes: a unique reversal of regioselectivity" (2001). Thesis. Rochester Institute of Technology. Accessed from

This Thesis is brought to you for free and open access by the Thesis/Dissertation Collections at RIT Scholar Works. It has been accepted for inclusion in Theses by an authorized administrator of RIT Scholar Works. For more information, please contact [email protected]. TRANSITION-METAL-PROMOTED HYDROBORATION OF ALKENES: A UNIQUE REVERSAL OF REGIOSELECTIVITY

Christopher A. D'Souza

June 2001

A thesis submitted in partial fulfillment of the requirements for the degree of Master of Science in Chemistry

Approved: T_er_en_ce_C_.M_or_ril_1__ Thesis Advisor

Terence C. Morrill , Department Head

Department of Chemistry Rochester Institute of Technology Rochester, NY 14623-5603 Copyright Release Form

Transition-Metal-Promoted Hydroboration of Alkenes: A Unique Reversal of Regioselectivity

I, Christopher A. D'Souza, hereby grant permission to Wallace Memorial

Library of the Rochester Institute of Technology, to reproduce my thesis in whole or in part. Any reproduction will not be for commercial use or profit.

Date: 06· "2.'1.2.001 Signature: _ " lja man will begin with certainties, he shallendin doubts; but ifhe willbe content to begin with doubts, " he shallendin certainties.

- Sir Francis (Bacon. ABSTRACT

A unique reversal of regioselectivity was observed during the RhCb-nHbO catalyzed hydroboration/oxidation of 1-. While 4-octanol and 3-octanol were the major products, small amounts of octane and octanones were also obtained. Our experiments with isomeric alkenes revealed that the ratio of the isomeric was independent of the starting isomeric . Under identical experimental conditions a similar reversal of regioselectivity was also observed with allylbenzene, but not with styrene and 3,3-dimethyl-1-.

A highly efficient isomerization catalyst (Morrill's catalyst) generated in situ by the addition of catalytic amounts of a hydroborating reagent into a solution of

RhCl3-nH20 in a suitable solvent like THF, has been found to be responsible for these novel results. Deuterium labeling experiments reveal very fast, reversible, addition-elimination steps, involving a rhodium-hydride species. It was found that ruthenium and iridium compounds also bring about a similar reversal of regioselectivity. Monitoring the isomerization of 1- reveals the stepwise movement of the double bond towards the interior of the alkyl chain, accompanied by cis-trans transformations. A rhodium dihydride species has been implicated for the formation of alkanes; while the formation of ketones is a consequence of alkene insertion into the Rh-B bond, followed by p-hydride elimination. Two very valuable methodologies emerge from this research work.

The first being the capability of converting a terminal alkene into internal organoboranes, while the second involves a very economical and highly efficient method for the isomerization of compounds containing double bonds. To Christ, my Lord and Saviour, with love and gratitude, for the most precious gift of Life, through my wonderful parents. Acknowledgements

One of the greatest gifts that we have received from God is Life. A bonus is the privilege to be born in an excellent family. I thank God for my wonderful parents, extraordinary grandparents, loving aunts, uncles, cousins, nephews, and nieces, and for the numerous blessings He has showered on me throughout my life.

For being there whenever I needed them most and also for years of love, support, and encouragement, I owe thanks to my parents Richard & Marie D'Souza, as well as to my sisters Caroline and Rosita, and my brother Gerard.

I'am very grateful to my advisor, Dr. Terence C. Morrill, for giving me the opportunity to pursue my studies at R.I.T., and also for his advice and counsel, motivation and support.

Sincere thanks are overdue to my in-laws, Kamala & Dr. K. S. V. Santhanam and Shalini & Manish Damani, for their love & affection, and for making my stay in Rochester so very comfortable.

My sincere thanks also goes out to my teachers: Dr. Kay Turner, Dr. Gerard Takacs, Dr. James Worman, Dr. John Neenan, Dr. Matt Miri, Dr. Marvin lllingsworth, Dr. Paul Craig, Dr. Tom Gennett, Dr. Paul Rosenberg, and Dr. Henry Gysling, for their help and encouragement.

For hospitality, humor, and inspiration, I'm indebted to many wonderful people that I met at R.I.T. They include Paul and Liz Conrow, Kerman Bharucha, Laurie Norton, Laith Ali, Laurie Seifert, Mark Pecak, Kimberly Bliss, Anthony Sampognaro, Yanira Villarrubia, Dana DiDonato, Ryan Donnelly, Dawn Lee, Ahmad Al-Dheiby, Xuan Mai, Anvar Buranov, and Wei Cheng.

In a very special way, I would like to thank:

Dr. Andreas Langner, for the very valuable discussions that guided my initial approaches to this research.

Tom Allston, who bore with patience and good humor some of my more tedious requests.

Leena & Ladi Rasquinha, my guardian angels, who made it possible for me to attend Mass every Sunday.

My friends in the department - Brenda Mastrangelo, Joe Starling, Mark Stoddard, Gary Judge, Glenn Robinson, Cindy Drake, Brian Gallagher, David Lake and Paul Allen, who were always willing to help.

in Rev. Fr. Joe Dias, Principal, and Dr. Hoshang Master, Head, Department of Chemistry, St. Xavier's College, Bombay, India, for granting me leave of absence to pursue my studies in the U.S.

The Rochester Institute of Technology, Chemistry Department, for funding my research.

My sister-in-law, Maryann D'Souza and my brothers-in-law, Gerard Lobo and Ravi Menezes, for enriching our family.

A very special couple, Dr. Madhukant & Dr. Nalini Sanghavi, whose cool wit and generous heart really inspired me.

My darling wife, Rohini, for buoying me with her high spirits and confidence, and for making sure that I did not spend too much time "dancing with the olefins".

IV TABLE OF CONTENTS

List of Schemes vii

List of Tables viii

List of Figures xi

List of Experiments xiii

1 . Introduction 1

1.1 : Advent 1

1 .2 : Hydroboration 2

1 .3 : Isomerization and Displacement 8

1 .4 : Rhodium Catalyzed Isomerization of Alkenes 12

1.5: Rhodium Catalyzed of Alkenes 18

1.6 : Rhodium Catalyzed Hydroboration 25

2. Objective 34

3. Experimental 35

4. Results and Discussion 47

4.1 : Reproducibility Studies 49

4.2 : Solvent Effect on Regioselectivty 51

4.3 : Effect of Temperature on the Regioselectivity 52

4.4 : RhCI3-/7H20 Promoted Hydroboration of Isomeric . 53

4.5 : Hydroboration of Styrene and 3,3-Dimethyl-1-butene 55

4.6 : Hydroboration of 1-Heptene and Allylbenzene 56

4.7 : Effect of Transition-Metal-Compound on Regioselectivity... 57

4.8 : Effect of Varying Experimental Conditions 58

4.9 : Isomerization of Isomeric Octenes 61 4. 1 0: Effect of Catalyst on the Isomerization of 1 -Octene 65 4.11: Deuterium Labeling Studies 66 4.12: Proposed Mechanism 71

4.13: Dehydration of Isomeric Octanols 73

4.14: Isomerization Studies 75

4.15: Role and Fate of the Catalyst 84

5. Conclusions 86

6. References 88

VI List of Schemes

Scheme 1.1 Hurd's Mechanism for the Hydroboration of Alkenes 3

Scheme 1.2 H. C. Brown's Mechanism for the Hydroboration of Alkenes 4

Scheme 1 .3 Lipscomb's Mechanism for the Hydroboration of Alkenes. . . 7

Scheme 1 .4 Isomerization of 2- 8

Scheme 1 .5 Mechanism for the Hydroboration Rearrangement 9

Scheme 1.6 Displacement 10

Scheme 1 .7 Contra-thermodynamic Isomerization 10

Scheme 1.8 Relative Rate Constants for the Isomerization of 1 -Butene with HCI and Rh(acac)(C2H4)2 at 0C 15

Scheme 1 .9 Relative Rate Constants for the Interconversion of Linear Buteneswith Li2PdCI4-CF3C00H Catalyst 25C 16

Scheme 1.10 Mechanism for the Hydrogenation of Alkenes using RhH(PPh3)3(C0) 20

Scheme 1.11 Mechanism Proposed by Mannig and Noth 26

Scheme 1.12 Reaction of RhCI(PPh3)3 with Catecholborane 30

Scheme 4.1 Proposed Mechanism for the Isomerization of Octenes 71

Scheme 4.2 Proposed Mechanism for the RhCI3-nH20 Promoted Hydroboration of 1-Octene 72

Scheme 4.3 Isomerization Equilibria 77

Vll List of Tables

Table 1 .1 Classical Hydroboration of Terminal Alkenes 5

Table 1 .2 Effect of Substituents on the Hydroboration of Alkenes 6

Table 1 .3 PdCI2 Catalyzed Isomerization of 1 -Octene 16

Table 1.4 Isomerization of Octenes using Palladium and Rhodium Catalysts 17

Table 1.5 Hydrogenation of Aromatic Compounds with NaBH4-RhCI3 in Ethanol 21

Table 1.6 Hydrogenation of Aromatic Compounds in the Presence of RhCI3andAliquat336 22

Table 1.7 Hydrogenation of Some Unsaturated Nitro-compounds in the

336 Presence of RhCI3-Aliquat 23

Table 1.8 Hydrogenation of Nitrobenzene in the Presence of RhCI3-Aliquat 336 24

Table 1.9 RhCI(PPh3)3 Catalyzed Hydroboration of Styrene 28

Table 1.10 Product Ratios for the Hydroboration of frans-4-Octene 31

Table 1.11 Product Ratios for the Hydroboration of frans-2-Octene 31

Table 1.12 Product Ratios for the Hydroboration of Allylbenzene 33

Table 4.1 RhCI3-/iH20 Promoted Hydroboration of 1 -Octene with BH3-THF in THF. Reproducibility Studies 49

Table 4.2 Effect of Solvent on the Regioselectivity of RhCI3-nH20 Promoted Hydroboration of 1 -Octene with BH3-THF in THF... 51

Table 4.3 Effect of Temperature on the Regioselectivity of RhCI3-nH20

-Octene Catalyzed Hydroboration of 1 with BH3-THF in THF. .. 52

Table 4.4 RhCI3-nH20 Promoted Hydroboration of Isomeric Octenes with BH3-THF in THF 53

Vlll Table 4.5 Hydroboration of Isomeric Octenes with BH3-THF in THF 54

Table 4.6 Classical and RhCI3-nH20 Promoted Hydroboration of Styrene 55

Table 4.7 Classical and RhCI3-nH20 Promoted Hydroboration of 1-Heptene 56

Table 4.8 Classical and RhCI3-nH20 Promoted Hydroboration of Allylbenzene 56

Table 4.9 Classical Hydroboration of frans-1 -Phenyl-1- 56

Table 4.10 Effect of the Transition-Metal-Compound on the

Hydroboration of 1 -Octene with BH3-THF in THF 57

Table 4.1 1 Effect of Varying Experimental Conditions on the Regioselectivity of RhCI3-nH20 Promoted Hydroboration of 1-Octene with BH3-THF in THF 59

Table 4.12 Isomerization of Octenes using RhCI3-nH20/BH3-THF in THF. "Starved" Hydroboration 62

Table 4.13 Isomerization of 1-Heptene and Allylbenzene using RhCI3-nH20/BH3-THF in THF. "Starved" Hydroboration 63

Table 4.14 Effect of Catalyst on the Isomerization of 1-Octene in THF 65

Table 4.1 5 Enthalpies of Hydrogenation of Isomeric Octenes 73

Table 4.16 Dehydration of Isomeric Octanols 74

Table 4.17 Isomerization of 1-Heptene using RhCI3-nH20/BH3-THF in THF. Isomerization Studies 75

Table 4.18 Calculated Product Distribution Based on Enthalpies of Formation of Liquid 77

Table 4.19 Isomerization of 1-Octene using RhCI3-nH20/BH3-THF in THF. Isomerization Studies 78

Table 4.20 Isomerization of frans-4-Octene using RhCI3-nH20/BH3-THF in THF. Isomerization Studies 78

IX Table 4.21 Isomerization of frans-2-Octene using RhCI3-nH20/BH3-THF.. 80

Table 4.22 Isomerization of rrans-3-Octene using RhCI3-nH20/BH3-THF.. 80

Table 4.23 Isomerization of Allylbenzene using RhCI3-nH20/BH3-THF in THF. Isomerization Studies 81

Table 4.24 Effect of Temperature on the Isomerization of 1-Octene in THF 82

Table 4.25 Determination of Catalytic Activity 83

Table 4.26 Effect of Concentration of 1 -Octene on the Isomerization 83 List of Figures

Figure 3.1 Gas Chromatographic Separation of a Mixture of Octenes and Octane using Hewlett Packard 6890-5973 GC-MS System 35

Figure 3.2 Gas Chromatographic Separation of a Mixture of Octanones and Octanols using Hewlett Packard 6890-5973 GC-MS System 36

Figure 4.1 Gas Chromatographic Separation of the Product Mixture of the RhCI3-nH20 Promoted Hydroboration of 1-Octene at 21C 48

Figure 4.2 Gas Chromatographic Separation of the Product Mixture of the RhCI3-nH20 Promoted Hydroboration of 1-Octene and frans-4-Octene at 23C 54

Figure 4.3 Gas Chromatographic Separation of the Product Mixture of the RhCI3-nH20 Promoted Hydroboration of Styrene at 26C. 55

Figure 4.4 Gas Chromatographic Separation of the Product Mixture of the RhCI3-nH20 Promoted Hydroboration of 1-Octene at 25C in the Presence of Water 60

Figure 4.5 Gas Chromatographic Separation of a Product Mixture of

"Starved" the RhCI3-nH20 Catalyzed Hydroboration of 1-Octene at 23C 61

Figure 4.6 Gas Chromatographic Separation of a Product Mixture of

"Starved" the RhCI3-nH20 Catalyzed Hydroboration of 1-Heptene at 23C 64

Figure 4.7 Gas Chromatographic Separation of a Product Mixture of "Starved" the RhCI3-nH20 Catalyzed Hydroboration of Allylbenzene at 23C 64

Figure 4.8 Isomerization-Deuteration of Cyclohexene with RhCls/BHs in D20. Peak Purity Profile 67

Figure 4.9 Isomerization-Deuteration of Cyclohexene with RhCls/BH3 in D20. High Resolution Mass Spectroscopy 68

XI Figure 4.10 Isomerization-Deuteration of Styrene with RhCl3/BH3 in D20. High Resolution Mass Spectroscopy 69

Figure 4.1 1 76 Isomerization of 1 -Heptene using RhCI3-nH20/BH3-THF

Figure 4.12 Isomerization of frans-4-Octene using RhCI3-A7H20/BH3-THF. 79

Figure 4.13 Isomerization of Allylbenzene using RhCI3-nH20/BH3-THF.... 81

Figure 4.14 Gas Chromatographic Separation of a Product Mixture of

"Starved" the RhCI3-nH20 Catalyzed Hydroboration of a

mixture of 1-Heptene and 1 -Octene at 28C 84

Xll List of Experiments

3.1 Hydroboration of 1 -Octene with BH3-THF in THF [Classical] 37

3.2 RhCI3-nH20 Promoted Hydroboration of 1 -Octene with BH3-THF in THF 38

3.3 RhCI3-nH20 Promoted Hydroboration of 1 -Octene with BH3-THF in Different Solvents 38

3.4 RhCI3-nH20 Promoted Hydroboration of 1-Octene with BH3-THF in Varying Temperatures 39

3.5 RhCI3-nH20 Promoted Hydroboration of 1-Octene with BH3-THF in THF by Varying the Order in which the Reactants are Mixed 40

3.6 RhCI3-nH20 Promoted Hydroboration of 1-Octene with BH3-THF in THF by Varying the Rate of Addition of BH3-THF 41

3.7 RhCI3-nH20 Promoted Hydroboration of 1-Octene with BH3-THF in THF in the Presence of Water 41

3.8 Hydroboration of 1-Octene with with BH3-THF in THF using Different Transition-Metal Compounds 42

"Starved" 3.9 RhCI3-nH20 Catalyzed Hydroboration of 1-Octene with BH3-THFinTHF 43

"Starved" 3.10 RhCI3-nH20 Catalyzed Hydroboration of 1-Octene with BH3-THF in THF in the Presence of Traces of D20 43

3.11 Isomerization Studies 44

3.12 Catalytic Activity 45

3.13 Catalytic Efficiency 45

3.14 Dehydration of Isomeric Octanols 46

Xlll 1. INTRODUCTION

1.1 ADVENT

There is seldom a major organic synthesis accomplished today without

Frankland1 the use of the hydrides of boron as a reagent. (1859) was the first to synthesize organoboranes by the reaction of dialkylzinc compounds with triethoxyborane (eq. 1).

3(C2H5)2Zn + 2(C2H50)3B^ 2 (C2H5)3B + 3 Zn(OC2H5)2 (1)

Stock2 However, it was Alfred (1912) who was the first to isolate and characterize , B2H6.

Burg3 In 1931, H. I. Schlesinger and Anton B. developed an efficient method for the preparation of diborane, which involved passing hydrogen and boron trichloride through a silent electric arc. As part of his Ph.D. research under

Brown4 the guidance of H. I. Schlesinger, H. C. studied the reaction of diborane with carbonyl compounds. They observed that aldehydes and ketones reacted rapidly with diborane at 0C to give alkoxyboranes. Hydrolysis produced the corresponding alcohols (eq. 2).

2 RCHO + 1/2 (BH3)2 -> (RCH20)2BH + H20 -> 2 RCH2OH + (HO)3B + H2 (2)

During the period 1940-1945 (World War n), H. C. Brown and

co-workers5 H. I. Schlesinger along with a number of developed new procedures for the preparation of diborane (B2H6) and sodium borohydride (NaBH4), as part of the National Defense Project, initiated at the University of Chicago (eq.3,4,5). 25C + * 2 + 3NaBH44 4BF33 B?Hfi2 6 3 NaBF44 (3) diglyme

6 LiH 25C +8 BF3 > B2H6 + 6 LiBF4 (4)

^ou9ROoP 4 NaH + B(0CH3)3 > NaBH4 + 3 Na0CH3 (5)

BH3-THF,6 The most popular amongst the boron hydrides are

catecholborane7 and NaBH4. However, with asymmetric synthesis gaining considerable importance, the emphasis has now shifted towards the synthesis and use of chiral boron hydrides.

1.2 HYDROBORATION

In the course of their studies (1956) of selective reduction, H. C. Brown

Rao6 and B. C. Subba observed that diborane, in ether solvents, adds with remarkable ease to alkenes, in an anti-Markovnikov fashion, forming organoboranes. Protonolysis of organoboranes using acetic acid yields alkanes, while oxidation of the organoboranes with alkaline H202 gives alcohols. It was also observed that heating the substituted organoborane in refluxing diglyme

.9 (160C) prior to oxidation gives essentially the pure primary The hydroboration reaction and the chemistry of organoboranes have been

others.10 thoroughly reviewed by Brown and many In another simple, yet interesting in situ hydroboration procedure, organoboranes were obtained when a mixture of an alkene and NaBH4 in THF was treated with glacial acetic acid.

alcohol.11 Alkaline peroxide oxidation yields the corresponding Hurd12 In the earliest qualitative description suggested that BH3 reacts with

B hydride the ethylenic double bond to form a Ci bond followed by a transfer of to C2 to yield the organoborane.

SCHEME 1.1

H H H H

\ C2 R RC= B C H + H H / alkene hydroborating H B< reagent

hydride transfer

H H

R-f-?7H

H B<

organoborane Zweifel13 Brown and suggested a four-center transition state in a

concerted mechanism, in which the boron-hydrogen bond was presumably

polarized with hydrogen having some hydridic character, to account for cis

addition, the rapidity of reaction and the anti-Markovnikov (AM) addition to an

unsaturated hydrocarbon.

SCHEME 1.2

H H H H \ RC=C RC2C H + BE H /

alkene H- hydroborating -B< reagent 4-center transition state

H H

r-62c1-h

H B<

organoborane In Hurd's and Brown's descriptions, the positive charge develops at the carbon that receives the incipient hydride and the AM addition results from the stabilization of this intermediate by alkyl or aryl substituents.

Alkyl Alkyl - - -CH CH=CH2 -CH2 5+ 5-

-CH: :CH- -CH ;CH. ' 5+ 5- At that stage this mechanism proved to be consistent with the experimental results. Detailed experimental studies were limited by, the rapidity of most hydroboration reactions, complexity of the kinetics, and the uncertain

role of the -complexed reagents.

13 Table 1.1 : Classical Hydroboration of Terminal Alkenes

Alkene Anti-Markovnikov Markovnikov

1-octanol 2-octanol 1 -octene OH 94% 6%

CH0 CH3 CH3

CCH R C=CK R OH R C CHa

H OH

99% 1%

/j CHCH \\ // -CH=CK OH OH Styrene 80% 20%

OH HO J \

Allylbenzene 90% 10% Both steric and electronic factors are involved in these selectivities, but the above examples indicate a major role for electronic effects in the preferred pathway.

In spite of steric disadvantages, Markovnikov (M) addition is known to occur when electron-withdrawing, or partially positive, substituents exist on the

14 olefin

13,14 TABLE 1.2 : Effect of Substituents on the Hydroboration of Alkenes

Alkene Anti-Markovnikov Markovnikov

F F H F H H 3 i1 i2 C C C F C C=CH C CH2 -OH CH3

F H F OH

1,1,1 -trifluoro propene 26% 74%

OH OH

~Si(CH 3'3 *Si(CH3)3 ~Si(CH3)3'3 87-92%

OH Cl Cl \\ // \\ //

p-Chloro styrene 35% 65%

OH

H,C- \\ // H3C^\ //

p-Methyl styrene 18% 82% A detailed study on the effect of substituents in hydroboration was carried

al.14 out by Lipscomb et They suggested that the rc-complex that is first formed between the reactants subsequently deforms through an asymmetric four-center transition state, to yield the organoborane product, in a donation-back-donation mechanism.

SCHEME 1.3

BK H K H Br H " CH2=CHR B H H H

H--C-- -C---H C C / \ H R H R

H (M) .H H XB' \i 2/ H--C C H H* i h \ 1 ' 2 / \ c=c H R / \ H R (M) Hv H^ H:B H HNB -H

H H H C--^C H C C H R

(AM) Hs

H B H \l 2/ H--C C H / \ H R

(AM) 1.3 ISOMERIZATION AND DISPLACEMENT

Another important aspect of hydroboration is the isomerization and displacement reactions of organoboranes. At elevated temperatures (>100C) organoboranes undergo isomerization, which results in the placement of the

group.15 boron at the least hindered position of the alkyl In 1959, Brown and

Rao16 Subba showed that the hydroboration of 2-hexene yields an organoborane which, when oxidized with NaOH/H202, yields 2- and 3- hexanol in equimolar amounts. However, if this organoborane is heated in refluxing diglyme

[CH30(CH2CH20)2CH3, diethyleneglycol dimethyl ether] to 160C for 4 hours, prior to oxidation, the product obtained was exclusively 1 -hexanol. This gives us an important route to convert internal olefins into primary alcohols.

SCHEME 1.4 16 Isomerization of 2-Hexene

BH3-THF

+ NaOH / H202 OH

3- 2-hexene 2-hexanol (50%) hexanol (50%)

BH3-THF

'B- diglyme/ 160C

2-hexene 4 hours NaOH / H202

^OH

1 -hexanol (100%) H. C. Brown proposed that the hydroboration rearrangement proceeds by a series of reversible borane addition/elimination

(i.e., hydroboration/dehydroboration) steps involving an intermediate alkene. This mechanism suggests that the organoborane proceeds through a sequence of eliminations to form the olefin and dialkylborane, followed by readditions, until

trialkylborane.17 the borane has been completely converted into the more stable

SCHEME 1.5 17 Mechanism for the Hydroboration Rearrangement

H H H H H H

C R( : H R C=C H H H .B^ H H

.B. tertiary alkyl borane

H H H

R( ;h H H H

H R R

H H ,B. h h h y

primary alkyl RC C=C H borane H H

.B, Addition of a higher boiling (higher molecular weight) alkene to the

reaction mixture gives a new organoborane with the displacement of the more

alkene.18 volatile This combination of hydroboration, isomerization and

displacement, allows for the contra-thermodynamic isomerization of alkenes.

SCHEME 1.6 Displacement

B-H 1- C6H13 [C6H13-CH2-CH2-]3B C6H13 CH CH2 CH=CH2 heat 1 -octene 1 -octene

QH LB'31" CH, CH. 2

B-H 1-decene > heat

SCHEME 1.7

lsomerization1f Contra-thermodynamic

\ EB H /

hydroboration

3-ethyl-2-

1 60C isomerization

1-decene

^ heat displacement

3-ethyl-1-pentene

10 with an excess of When 1 ,2-dimethylcyclopentene (1) was treated

alcohol BH3-THF (1 .2 equivalents) at 25C, for 5 minutes, the expected tertiary

(2) was obtained, after oxidative workup. If, however, the reaction mixture is left to stand for several days at room temperature, or heated to 50C for 2 hours, a single product (3) resulting from the stereospecific migration of boron into the five-membered ring (eq. 6) was obtained in high yield (> 90%).

(i) BH3.THF

(ii) 50C (6) #. --OH (iii) Hp^NaOH

11 1 .4 RHODIUM CATALYZED ISOMERIZATION OF ALKENES

Olefin isomerization has been observed in the presence of many transition

compounds.20 metal Most of these isomerizations are accomplished by metal

hydrides or in the presence of substances (alcohols, hydrogen or protonic acids)

hydride.21 which convert the metal into its metal Two distinct general

mechanisms have been proposed depending on the type of catalyst employed.

complexes22 (A) addition/elimination reactions of metal hydride - the metal

hydride being present initially as catalyst or generated in situ; and

(B) rearrangement through a transitory 71-allyl complex - this proceeds by the

coordination of the metal with the alkene, followed by a reversible hydrogen

transfer generating the 71-allyl metal hydride intermediate. Since the latter

involves a formal increase in oxidation state, catalysts operating by this

mechanism are frequently initially in their lower oxidation states. In mechanism A

the oxidation state remains constant since the M-H a bond, is replaced by a M-C

a bond. While most isomerizations appear to proceed via the addition/elimination

mechanism,23 24 iron carbonyl and some palladium catalyzed isomerizations are

complex.25 believed to proceed via the xc-allyl

Mechanism A: Addition and elimination of a kinetically long-lived metal hydride.

RCH2 CH2 R CH R =CH CH==CH2 , CH3 . CH CH3 M M-H M-H

Mechanism B: Rearrangement through a transitory 7t-allyl hydride.

RCH2 R RCH=CH CH=pCH2 , Cr+-r->CH2 - CH, : m h : M m

12 One of the most widely used catalyst for alkene isomerization was

(RhCI3-nH20).26 rhodium (m) chloride However, the reaction required the use of a protic solvent and high temperature (eq. 7,8,9). The role of the solvent was to generate the rhodium hydride, which then brings about the isomerization by mechanism A. Use of deuterated alcohols has been shown to yield deuterated alkenes, clearly indicating that the solvent plays a major role in these reactions.

Reversible oxidation of metal by a solvent proton serves as the means of exchanging olefinic hydrogen with a solvent proton. Isomerization leads to an equilibrium mixture of isomers, initial products being kinetically controlled; a fact that permits wide variation in product composition. Results can be rationalized in terms of a reaction mechanism involving a rapid, reversible addition of hydride to the coordinated olefin.

Alkenes26e'gc RhCI3-3H20 Catalyzed Isomerization of

HO

RhCI3-3H20

EtOH (7)

RhCI3-3H20 (8) EtOH

H// /"'Me O Me

RhCI3-3H20 (9) EtOH, 100C sealed tube

13 Frequently, the products obtained vary with the catalyst used. Birch and 27 Subba Rao found out that the use of Wilkinson's catalyst as an isomerization

catalyst gave an entirely different product to that obtained when a strong base

was used (eq. 10).

OMe OMe OMe

RhCI(PPh3) 3'3 Base (10) CHCI3 reflux

1,3-diene 1,4-diene 1,3-diene

In many of these reactions double bond migration is accompanied by cis 28 to trans isomerization (eq. 11,12,13)

28b,c,d Rhodium-Catalyzed Isomerization of Allylbenzene

RhCI3-3H20 ^^CH 1 ^CH=CH (11) CH=CH2 Aliquat 336 CH3

80C. : cis = allylbenzene toluene, trans 84: 16 3 hrs. 1-phenyl-2-propene

(3 mol%) catecholborane (/ \CH^CH= CH CH, ()-CH= CH, (12) (1 mol%) Rh2(0Ac)4 trans : cis = 81: 19 80C 22 hrs

immobilized ion pair RhCI3-3H20 y \ i CH=CH (f CH^CH=CH, ft CH3 (13) Dowex 92% aq. EtOH. 0.3% unreacted 20 minutes trans : cis = 92 : 7.7 reflux

14 It would be misleading however, to have the impression that it is the stability of the alkenes that must inevitably determine the outcome of such rearrangements. Often the thermodynamically most stable alkene is not the major product. This brings home the point that the reactivity properties of intermediate complexes can have a profound influence on the selectivity of these reactions.

During their studies on the isomerization of terminal alkenes, Harrod and

25 Chalk found that the migration from the 2- to the 3-position was much slower than migration from 1- to the 2-position, a phenomenon permitting formation of a

Lindsey22 single positional isomer in high yield. Cramer and found that the relative rate constants for the isomerization of the individual at 25C, was the reason for the initial accumulation of the c/s-2-isomer. One should not lose sight of the fact that these rate constants are highly dependent on temperature and also on the catalyst that is employed.

SCHEME 1.8 Relative Rate Constants for the Isomerization of 1-Butene with HCI and Rh(acac)(C2H4)2at 0C22

X 5.6

frans-2-butene c/s-2-butene

15 SCHEME 1.9

Relative Rate Constants for the Interconversion of Linear Butenes with

25C22 Li2PdCI4-CF3COOH Catalyst at

1 -butene

frans-2-butene c/s-2-butene

Isomerization experiments with 1 -octene yielded varying ratios of isomeric

Davies23 octenes depending on the reaction conditions and the catalysts used. used a 0.02 inch 200 foot long copper tubing with a dinonylphthalate stationary phase to separate the isomeric alkenes. Unfortunately with this column the retention times of 1 -octene and frans-4-octene were identical. Infrared spectra

confirmed the rapid disappearance of 1 -octene (eq. 14).

PdCI2 + NaCI 1,2,3 &4-octenes. (14) CH3COOH

1 -octene

1-Octene23 Table 1.3: PdCI 2 Catalyzed Isomerization of Temperature 25C 25C 25C 65C 65C 65C 65C Time (hours) 4 20 24 1 2 4 27 1 -octene and 52 12 17 13 16 15 14 frans-4-octene frans-3-octene 15 34 35 38 37 37 37 frans-2-octene 20 31 31 34 30 30 33 c/s-2-octene 13 23 17 15 18 18 16

16 Abley29 McQuillin and obtained cis and frans-2-octenes when 1 -octene was refluxed for 12 hours in a benzene-methanol (3:2) mixture with catalytic

amounts of RhCI(PPh3)3 (eq. 15).

RhCI(PPh3)3'3 frans-2-octene

benzene - methanol + (15)

1 -octene reflux, 12 hours

c/s-2-octene

Asinger et al. obtained varying ratios of isomeric octenes when 1 -octene

was refluxed in a benzene-ethanol mixture in the presence of RhCI3. They also

found that the isomerization of 1 -octene and rrans-4-octene (Table 1.4) using

PdCI2 yielded the same product ratios of isomeric octenes.

Catalysts30 Table 1.4 : Isomerization of Octenes using Palladium and Rhodium

1 -octene frans-4-octene Catalyst RhCI3 RhCI3 PdCI2 aPdCI2 PdCI2 aPdCI2 mol % D10 c1 1 1 1 1 Temperature 50C 50C 60C 60C 60C 60C Time (hours) 15 3 1.5 1.5 1.5 1.5

1 -octene 2 1 29 1 1 1 c/s-2-octene 13 L 14 16 11 10 9 fAans-2-octene 42 48 25 31 29 32 c/s-3-octene 6 5 6 6 7 6 frans-3-octene 23 21 15 28 28 29

c/s-4-octene 3 3 3 5 5 4 fra/is-4-octene 11 9 7 18 20 20 Ocn l

17 1 .5 RHODIUM CATALYZED HYDROGENATION OF ALKENES

In the days gone by, the first choice for the reduction of a double bond was heterogeneous catalysis, using metals like nickel, platinum and palladium.

These catalysts were efficient, convenient to handle and could be removed by

Brown31 filtration at the end of the reaction. In 1962, H. C. found that the treatment of platinum metal salts (platinum, rhodium, ruthenium) with aqueous

NaBH4 resulted in the formation of a finely divided black precipitate, which proved to be a highly active catalyst for the hydrogenation of alkenes. The black powder obtained by treating chloroplatinic acid with NaBH4 was found to be essentially pure platinum. In the presence of platinum black as catalyst, 1 -octene undergoes hydrogenation within ten minutes.

In contrast, homogeneous catalysts, though they offer a high degree of selectivity, are sensitive to impurities, like oxygen, are difficult to recover, since they are soluble and have a tendency to cause alkene isomerization and other side reactions. Homogeneous hydrogenation catalysts are divided into two general classes - monohydrides and dihydrides. They not only react by different mechanisms, but also have different specificities.

catalyst32 The year 1 965 saw the discovery of a new - Wilkinson's catalyst

- which was prepared by the reaction of an excess of triphenylphosphine with rhodium(m)chloride hydrate in ethanol. The dihydride [RhH2CI(PPh3)2] derived from tris(triphenylphosphine) rhodium chloride [RhCI(PPh3)3], is a versatile reagent for the reduction of alkenes and . While, hydrogenation is

18 stereochemical^ a syn process, kinetic studies indicated that the formation of

16).33 the alkene-RhH2CI(PPh3)2 complex was the rate-determining step (eq.

RhCI(PPh3)3 + H2 ; RhH2CI(PPh3)2

RhH2CI(PPh3)2 + alkene .. RhH2CI(alkene)(PPh3)2 (16)

RhCI(PPh3)2 + alkane All these reactions have typical sequences involving a combination of ligand dissociation, oxidative addition, alkyl migration and reductive elimination.

However, if p-hydride elimination precedes reductive elimination, then isomerization of the alkene occurs.

RhH(PPh3)3(CO)34 Among the monohydride catalysts, is the most popular.

It is specific for terminal alkenes and will tolerate internal alkenes, nitriles, esters and aldehydes elsewhere in the molecule. Its major drawback is that alkene isomerization predominates over hydrogenation, and this isomerization is

Osborn35 irreversible. Schrock and have shown that isomerization is a competing reaction during the hydrogenation of alkenes using cationic rhodium complexes.

Today, a field that is gaining considerable attention is asymmetric homogeneous hydrogenation. In this case, the catalyst is combined with an appropriate optically active ligand to achieve chiral functionality. Many cationic rhodium (I) complexes of optically active diphosphines, such as DIOP, DIPAMP,

CHIRAPHOS and BPPM have been used to achieve products with high

excess.36 enantiomeric

19 SCHEME 1.10 34 Mechanism for the Hydrogenation of Alkenes using RhH(PPh3)3(CO)

H

I", Rh-

CO

dissociation - L = PPh,

RhL2H(CO)

alkene

H association

reductive :Rh elimination L R CO

beta- alkene hydride insertion elimination

L- CO

:Rh^

L' oxidative

addition

H'

beta- hydride elimination

RhLH(CO) + r^

20 al.37 In 1982, Satoh et (Japan) showed that under mild conditions, a combination of sodium borohydride and rhodium trichloride in a hydroxylic solvent, proved to be very useful for the reduction of aromatic nuclei to the

corresponding saturated cyclic compounds (Table 1 .5).

Table 1.5 : Hydrogenation of Aromatic Compounds with NaBH4-RhCI3 in Ethanol

Substrate C Product % yield

ft yCHCHCOOH 30 / VcHCH-COOH 94

NH-COCH3 NH-COCH3

o 40 ^J^CH2-CH2-^) quantitative -o

40 60 N \-COOC2H5 H-N \-COOC2H5

c 22 \_J h2 h2 \_y 5 OV-rO OH

21

H

21 al.38 In 1983, Blum et (Israel) found that a combination of RhCI3-A7H20 and

336 Aliquat (methyltrioctylammonium chloride) in dichloromethane (phase transfer catalysis) catalyzed the hydrogenation of a variety of unsaturated

compounds. Aromatic compounds were reduced to cyclohexane derivatives

under exceedingly mild conditions (Table 1.6).

Table 1.6 : Hydrogenation of Aromatic Compounds in the Presence of

336 RhCI3 and Aliquat

Conversion

Substrate Products (% yield)

51

Benzene cyclohexane (100)

CH, CH,

16

Toluene methylcyclohexane (100)

<^V-CH -CH ( CH=CK 2 "CH0 W // 100 CH3

Styrene ethylbenzene (94) ethylcyclohexane (6)

OH OH

56

cyclohexanol cyclohexanone cyclohexane Phenol (27) (67) (6)

22 Israel39 In 1987, the same laboratory in reported that the ion pair formed

336 from aqueous rhodium trichloride and Aliquat catalyzed the selective

hydrogenation of olefinic C=C bonds of a variety of nitro compounds, in a two

phase system, at 30C (Table 1 .7).

Table 1.7 : Hydrogenation of Some Unsaturated Nitro-Compounds in the

336 Presence of RhCI3- Aliquat

Time Substrate Solvent Products Conversion (hrs) %

rv-cH,-

O II CH C CH CH2 C CH3 II CHCL 78 CH CH

*NO vNO

C OMe CH C OMe II CH2 CH CH3N02 5.5 CH 55

^N0o ~NO,

23 In contrast to the reduction of nitro compounds with olefinic double bonds, hydrogenation of nitrobenzene was found to give a mixture of aniline and

nitrocyclohexane (Table 1.8).

Table 1.8 : Hydrogenation of Nitrobenzene in the Presence

336 of RhCI3- Aliquat

Substrate Solvent Time Products Conversion hrs %

CH2 CH N02 N02 CH2CI2 22 17 CH CH2 6

NH2

l^ N02 J^ \^ CH2CI2 6 Aniline N02 70 (90%) \^

Nitrocyclohexane (5%)

24 1.6 RHODIUM CATALYZED HYDROBORATION

Transition metal catalyzed hydroborations have been studied extensively

utility.47 because of their synthetic While metals like Ni, Ru, La and Ir have been used with varying degrees of success, Rh(I) has remained the metal of choice

Ito40 for catalyzed hydroborations. In 1975, Kono and showed that Wilkinson's

hydrogenation32 catalyst, RhCI(PPh3)3, which was known to catalyze and the

hydrosilylation41 of alkenes, undergoes oxidative addition when treated with catecholborane. However, the real impetus to the use of rhodium compounds to catalyze hydroborations was given by an interesting experiment by Mannig and

Noth42 in 1985. They showed that catalysis could alter the chemoselectivity of reactions of multifunctional substrates. Without the catalyst, catecholborane (CB) adds to the carbonyl group of 5-hexe-2-one, whereas the hydroboration of the alkene takes place preferentially in the presence of less than 1 mol% of

Wilkinson's catalyst (eq. 17).

B-H no catalyst

25C benzene

catecholborane

0.5 mol% RhCI(PPh3)3

0C

5-hexe-2-one

25 SCHEME 1.11

Noth42 Mechanism Proposed by Mannig and

RhL3CI

16e\d8

dissociation -L

B-H RhL2CI

e" 1 d8 4 , catecholborane L=PPh, reductive oxidative elimination addition

H >

-O \ BRh 1 0 L Cl Nl

16e',d6

olefin

hydride olefin binding migration insertion

H L oN \m/ c BRh-

-OXCI

18e',d6 H -O ID or | BRh

.0 cA

16e\d6

The mechanism proposed (Scheme 1.1 1) for these reactions involves the oxidative addition of B-H bond to the Rh(I) species, followed by alkene insertion into the Rh-H bond and subsequent C-B bond coupling.

26 .43 Burgess was the first to report that enantioselective hydroboration was

al.44 possible with chiral rhodium catalysts. In 1989, Hayashi et (Japan) obtained a very high enantioselectivity with reversed regiochemistry when styrene was treated CB in the presence of cationic rhodium complexes and tertiary phosphine ligands (eq. 18). However, the same reaction employing Wilkinson's catalyst afforded the anti-Markovnikov (AM) product (10:90). They observed that high regioselectivity was obtainable only with rhodium complexes that have tertiary

al.47c phosphine ligands and a positive charge on the rhodium. Hayashi et suggested that the high regioselectivity giving 1 -phenylethanol may be caused by an Tj3-benzylrhodium intermediate formed by the addition of a cationic rhodium hydride species to styrene.

o OH 1) B-H O (18) [Rh(C0D)2]BF4 V^ ^^ (+) BINAP -phenylethanol ou. rtu/nn 2-phenylethanol 1 2 2 (AM) 1% (M) 99%

They also observed that under the same conditions, 1 -octene gave

1-octanol (AM) as the major product (eq. 19).

1) B-H O 1-octanol (AM) [Rh(C0D)2]BF4 92% (19) 1 -octene (+) BINAP + 2) NaOH / H202

2-octanol (M) 8%

27 Fu)45 The following year, two groups, one from the U.S. (Evans and and

al.)46 the other from China (Dai et reported that they observed a reversal of regioselectivity during the hydroboration of styrene with catecholborane, in the presence of Wilkinson's catalyst.

1)CB-H(D) RhCI(PPh3)3

2) NaOH / l\^J H202 ^^ (AM) (M) styrene 2-phenylethanol 1 -phenylethanol

1 2

Table 1.9 : RhCI(PPh3)3 Catalyzed Hydroboration of Styrene Mol. ratio Reference Styrene CB-H RhCI(PPh3)3 Product ratio 1 : 2 4/(c> Hayashi 1.1 0.01 90 : 10 4& Evans 2 0.01 1 : 99

Dai40 2 0.02 14 : 86 4a Burgess 1 0.02 80 : 20 4B(C) Evans 2 0.01 40 : 60

Uncatalyzed 1 - 80 : 20

However, they observed that the RhCI(PPh3)3 catalyzed hydroboration of

selectivities47 regio- stereo- 1 -decene proceeded with and complementary to the uncatalyzed reaction. In order to understand these differences in regioselectivity

Evans48 Burgess.49 deuterium labeling studies were undertaken by and Minor discrepancies in the results of the two groups made things even more complicated. Deuterium labeling experiments using 0.1 equivalents of catecholborane-d, revealed the presence of the label in the recovered starting material, indicating the reversibility of the migratory insertion of alkenes into

Rh-H(D) bonds (eq. 20). The loss of regiocontrol that is observed during the

28 "aged" hydroboration of styrene employing oxygen-treated RhCI(PPh3)3 or samples of RhCI(PPh3)3, revealed the dramatic effect on the outcome of the reaction, as a consequence of catalyst oxidation. When catalytic amount of

Burgess49 deuterated catecholborane was employed, reported extensive deuterium scrambling among all positions along the decyl chain of 1-decanol and majority (95%) of the unreacted alkene was made up of randomly labeled

Fu48 internally isomerized decene isomers (eq. 21). Evans and have been able to effect olefin isomerization by using either oxygen-treated Wilkinson's catalyst or undistilled 1-decene. They suggested that the presence of allylic hydroperoxides in the undistilled solvents and reactants maybe responsible for the oxidation of the catalyst.

50%

1) 0.002 RhCI(PPh3)3 50%'o/^^Octyl <^^Octyl + (20) O B 1-decene 0.1 D 86% O HO, "Octyl THF 14% 2) NaOH / H202

HO, 'Octyl 1) 0.002 RhCI(PPh3)3 ^^Octyl (21) 1-decene o-i CC:b-d R ^^Octyl + "^^v THF R 2 3 2) NaOH / H202 5% 95%

Deuterium was observed in all possible positions in 1, 2 and 3.

29 In 1992, new evidence was found which provides additional mechanistic

hydroborations.50 insight into catalyzed alkene The catecholborane/RhCI(PPh3)3 hydroborating system is complex, affording several phosphinorhodium and

boron-containing products arising from rhodium-mediated degradation of catecholborane. It was found that 50% of the rhodium forms RhH2CI(PPh3)3, with

traces of RhH(PPh3)3. These hydrido complexes are probably not directly

involved in the catalytic cycle for hydroboration, but would be capable of double-

bond isomerization reactions, and distributing deuterium labels.

Scheme 1.12

Catecholborane3.50 Reaction of RhCI(PPh3)3 with CB RhCI(PPh3)3 * PPh3 + B2(02C6H4)3 + RhH2CI(PPh3)3 +

1

RhHCI(B02C6H.)(PPh3)'3'2 CB BH3' CIBK

+ 2^2^6' BH,.PPh, BJ09CfiHJ4/3 PPhc RhH(PPh3)3

HB(02C6H4) = CB = catecholborane. RhCI(B02C6H4)2(PPh3)'3'2 1 + 3

+ B2(02C6H4)3

.48 The label distributions reported by Evans and Fu are reproducible when the

catalyst system is prepared and manipulated under anaerobic conditions, while

Donk50 the deuterium label distributions reported by Burgess and are attributed

to partial oxidation of the catalyst. The oxidized catalyst was also found to be a

esters more active catalyst for alkene hydrogenation. Vinylboronate have been

the rhodium catalyzed obtained along with hydrogenation products during

30 alkenes.51 hydroboration of Formation of vinylboronate esters may be due to insertion of the alkene into the Rh-B bond instead of the Rh-H bond, followed by

elimination.52 [3 -hydride

al.48c Evans et found that treating rrans-4-octene with CB in the presence

RhCI(PPh3)3 followed by basic oxidative workup gave exclusively 4-octanol.

However, small quantities of isomeric octanols were detected when the reaction was catalyzed by [Rh(nbd)(diphos-4)]BF4 (eq. 22). Isomeric octanols were also obtained during the [Rh(nbd)(diphos-4)]BF4 catalyzed hydroboration of

rrans-2-octene.

1)CB-H

2.5% catalyst x-octanol. (22) 2) NaOH / H20, x= 1,2,3,4. rrans-4-octene

48c Table 1.10 : Product Ratios for the Hydroboration of frans-4-Octene

4-octanol 3-octanol 2-octanol 1 -octanol

RhCI(PPh3)3 100 - - - [Rh(nbd)(diphos-4)]BF4 87 7 2 4

48c Table 1.11 : Product Ratios for the Hydroboration of frans-2-Octene

4-octanol 3-octanol 2-octanol 1 -octanol

[Rh(nbd)(diphos-4)lBF4 - 12 20 68

= = nbd norbornadk3ne; diphos-4 1 ,4-bis(diphenylp iosphino)butane

31 In order to overcome the intrinsic side reactions associated with the use of

Pereira53 catecholborane (CB), Srebnik and used pinacolborane (PBH) as a hydroborating reagent. The pinacolboronates unlike catecholboronates are insensitive to moisture, making isolation and purification much easier. They found that the reaction of PBH with 1 -octene or frans-4-octene in CH2CI2 in the presence of 0.2 mol% RhCI(PPh3)3 at 25C gave 100% terminal octyl pinacolboronate (eq. 23), a result analogous to that obtained during the

24).54 hydrozirconation of alkenes (eq. However, the reaction of pinacol-4-octylboronate with RhCI(PPh3)3 or RhCKPPh^s/PBH did not provide the terminal octyl pinacolboronate. Reaction of frans-4-octene with PBH in the presence RhCI(CO)(PPh3)2 of gave 97% pinacol-4-octylboronate and

3% terminal octylpinacolboronate.

1)CB-H

RhCI(PPh) 2)[0] 3'3 (23)

PBH CH2CI2 *B' 0 rrans-4-octene t O

pinacol-1 -octylboronate

(C2H5)2Zr(CI)H

Benzene, 25C (C2H5)2" '5/2

octane

32 al.47d Westcott et have also observed similar reversals in regioselectivity during the rhodium catalyzed hydroboration of allylbenzene (eq. 25). However, hydroboration of 1 -octene with [Rh(COD){(Ph2PCH2CH2)2)}]BF4 and RhCI(PPh3)3 proceeds with high selectivity forming terminal boronate ester in nearly quantitative yield.

Beat HBcat

25C, THF (25) 2 mol% catalyst Beat allylbenzene

or 1-phenylprop-2-ene Beat

Allylbenzene47d Table 1.12 : Product Ratios for the Hydroboration of Catalyst 1 2 3 RhCI(PPh3)3 70 9 21 [Rh(COD){(Ph2PCH2CH2)2)}]BF4 75 16 9 Rh(n3-2-Me-allyl)(DPPB) 65 33 2 Uncatalyzed 90 10 0

= = COD cyclooctadiene, DPPB 1 ,4-bis(diphenylphosphino)butane

Although, most of the rhodium catalyzed hydroborations have used Rh(l) as the catalyst, most recently Rh(n) catalyzed hydroborations have been

28c,55 investigated and have shown to bring about a reversal of regioselectivity combination of NaBH4, 02 and rhodium (in) porphyrin has also been used to

alkenes.56 bring about hydroboration-oxidation of

Due to the enormous costs involved in rhodium catalysis, efforts are underway to develop efficient, long-lived and recyclable forms of the catalyst.

polymer-supported58entrapped59 Many silica-bound57, and sol-gel rhodium catalysts have been tested and commercialized.

33 2. OBJECTIVE

During the RhCI3-nH20 catalyzed hydroboration of 1 -octene we noticed a unique reversal of regioselectivity. Instead of the getting 1-octanol as the major product, we got a mixture of 4-octanol (40.8%); 3-octanol (34.9%); 2-octanol

(16.4%) and 1-octanol (2.2%), along with octane (5.0%) and isomeric octanones

(0.8%). The objective of this study has been to elucidate the mechanism to account for this unique reversal of regioselectivity. The other issue that we needed to investigate was the formation of octane and octanones. When the reaction was carried out using catalytic amounts of the hydroborating reagent

("starved" hydroboration) we obtained a mixture of isomeric alkenes. Our other goal was to find out the nature and structure of the species responsible for this rapid isomerization. In order to determine the optimum conditions required for obtaining the desired results, the reaction was carried out under varying temperatures, solvents, and catalysts.

34 3. EXPERIMENTAL

General

GC analysis was performed using Hewlett Packard 6890-5973 GC-MS system.

Column: - HP-1MS Crosslinked Methyl Siloxane, (HP 19091S-936) 60 m,

250 urn diameter, 0.25 urn thickness, He carrier, 15.6 psi initial pressure,

min"1 1 .0 mL flow, MS detector.

Oven Ramp C/min Next C Hold (min) Run time Initial 35 5.00 5.00 Ramp 1 5.00 40 5.00 11.00 Ramp 2 5.00 50 4.00 17.00 Ramp 3 10.00 100 8.00 30.00 Post run 10.00 250 3.00 33.00 Solvent delay: 14.20 minutes.

Figure 3.1 Gas Chromatographic Separation of a Mixture of Octenes and Octane using Hewlett Packard 6890-5973 GC-MS System Abundance TIC: OCTENES.D 1.2e+07 16.04 1$36

1.1O+07

1O+07 15.03 16.97

9000000

8000000

7000000

6000000

5000000

4000000

3000000

2000000

1000000

,L nme-> 14^20 'U'M ultJOISlOO 15120 15^40 15.60 15180 16l00 16120 16.40 16160 16180 17l00 17120 jgij 'l7l60

Retention time (minutes): 1 -octene = 15.03; frans-4-octene = 15.52; frans-3-octene = 15.77; octane = 16.04; frans-2-octene = 16.36; c/s-2-octene = 16.97.

35 Figure 3.2 : Gas Chromatographic Separation of a Mixture of Octanones and Octanols using Hewlett Packard 6890-5973 GC-MS System Abundance TIC: OCTANONE.D 24 UI7225l01 1.16+07 25.27

1e+07

9000000

8000000 25.45 |

7000000 28.80

6000000

5000000 | 4000000 I

3000000

2000000

1000000 23.96

- V v_ A. ^ ( ' ' ' ' I nme-> 23I06 23l50 24I00 24l50 25lo6 25l50 26lO0 26l50 27l00 27l50 28.00 28l50 29loo 29156

Retention time (minutes): 4-octanone = 23.96; 3-octanone = 24.55; 2-octanone = 24.72; 4-octanol = 25.01 ; 3-octanol = 25.27; 2-octanol = 25.45; 1-octanol = 28.80.

Materials

1 -octene, rrans-2-octene, rrans-3-octene, frans-4-octene, styrene, allylbenzene,

3,3-dimethyl-1-butene, 1-heptene, RhCI3-nH20, RhBr3-nH20, RhCI(PPh3)3,

[RhCI(COD)]2 and BH3 -THF were obtained from Aldrich Chemical Co.; c/s-2-octene from TCI America; THF and diethyl ether from Fisher Chemicals; lrCI3-/iH20 and RuCI3-nH20 from Strem Chemicals.

36 General Procedure for Alkaline Peroxide Oxidation, Extraction, and

Purification

Once the hydroboration was completed, the reaction mixture was cooled in an ice-bath and quenched with one drop of NaOH solution. The flow of nitrogen was stopped when the effervescence ceased. After the addition of 3M aqueous NaOH (3 mL) and 30% aqueous H202 (4 mL), the flask was removed from the ice-bath and stirred at room temperature for 2-3 hrs. The solution was saturated with solid NaCI and the products were extracted with diethyl ether. The ether extract was washed with NaCI solution, dried over anhydrous MgS04, filtered and the ether from the filtrate was removed by vacuum distillation. Yields and product ratios were determined using GC-MS. For the GC-MS analysis two drops of the concentrated ether extract were taken in 3 mL of pentane, and 1 fxL of this solution was injected onto the column.

3.1 Hydroboration of 1-Octene with BH3-THF [Classical Hydroboration]

A mixture of 1 -octene (0.5 mL, 3.19 mmol) and THF (10 mL) was stirred in a three-necked round bottom flask, at room temperature (24C) for 5 minutes, in an atmosphere of dry nitrogen. Using a syringe, BH3-THF (2 mL, 2 mmol) was slowly injected into the reaction flask. The reaction was allowed to continue for total period of 2 hours, followed by alkaline peroxide oxidation, extraction and purification. A similar procedure was adopted for the hydroboration of styrene, frans-2-octene, rrans-3-octene, frans-4-octene, 1-heptene, allylbenzene, and

3,3-dimethyl-1 -butene.

37 3.2 RhCI3 nH20 Promoted Hydroboration of 1-Octene with BH3-THF in THF

A mixture of RhCI3-nH20 (10 mg, 0.048 mmol), 1 -octene (0.5 mL, 3.19 mmol) and THF (10 mL) was stirred in a three-necked round bottom flask, at room temperature (24C) for 15 minutes, in an atmosphere of dry nitrogen.

RhCI3.nH20 was partially soluble in the THF imparting a reddish color to the solution. Using a syringe, BH3 -THF (3 mL, 3 mmol) was injected into the reaction flask. During the initial stages (first half-hour) BH3-THF was added at a very slow rate. Within a few minutes the RhCI3-nH20 dissolved completely resulting in a pale yellow solution, which slowly turned brown and ultimately a fine black suspension was observed. Addition of the BH3 -THF was completed within one hour and the reaction was allowed to continue for an additional hour.

This was followed by, alkaline peroxide oxidation, extraction, and purification.

The above procedure was adopted for the RhCI3-nH20 promoted hydroboration of frans-2-octene, frans-3-octene, frans-4-octene, 1-heptene, allylbenzene, styrene and 3,3-dimethyl-1-butene.

3.3 RhCI3nH20 Promoted Hydroboration of 1-Octene with BH3-THF in

Different Solvents

A mixture of RhCI3-/7H20 (10 mg, 0.048 mmol), 1 -octene (0.5 mL, 3.19 mmol) and 10 mL of the solvent [diethyl ether, methylene chloride, or dioxane] was stirred in a three-necked round bottom flask, at room temperature for

15 minutes, in an atmosphere of dry nitrogen. While a good portion of the

RhCI3-A7H20 dissolved in the diethyl ether, its solubility in methylene chloride and

38 dioxane was considerably low. Using a syringe, BH3 -THF (3 mL, 3 mmol) was

injected into the reaction flask. During the initial stages (first half-hour) BH3-THF

was added at a very slow rate. The solution was initially reddish in color, turned

pale yellow, brown and finally a fine black suspension was observed. Addition of

the BH3 -THF was completed within one hour and the reaction was allowed to

continue for an additional hour, followed by alkaline peroxide oxidation,

extraction and purification.

3.4 RhCI3nH20 Promoted Hydroboration of 1-Octene with BH3-THF in THF

at Varying Temperatures

A mixture of RhCI3-nH20 (10 mg, 0.048 mmol), 1 -octene (0.5 mL, 3.19

mmol) and THF (10 mL) was stirred in a three-necked round bottom flask, at

different temperatures [0, 24 and 60C] for 15 minutes, in an atmosphere of dry

nitrogen. The RhCI3-nH20 was partially soluble in the THF, imparting a reddish

color to the solution. With the temperatures maintained at the desired level,

using a syringe, BH3 -THF (3 mL, 3 mmol) was injected into the reaction flask.

During the initial stages (first half-hour) BH3-THF was added at a very slow rate.

Within a few minutes the RhCI3-nH20 dissolved completely resulting in a pale

yellow solution, which slowly turned brown and ultimately a fine black suspension was observed. Addition of the BH3-THF was completed within one hour and the

reaction was allowed to continue for an additional hour, followed by alkaline

peroxide oxidation, extraction, and purification.

39 3.5 RhCI3nH20 Promoted Hydroboration of 1-Octene with BH3-THF in THF

by Varying the Order in which the Reactants are Mixed [Reverse- 1 & 2]

3.5.1 A mixture of RhCI3-nH20 (10 mg, 0.048 mmol) and THF (10 mL) was stirred in a three-necked round bottom flask, at room temperature for 15 minutes, in an atmosphere of dry nitrogen. RhCI3-nH20 was partially soluble in the THF, imparting a reddish color to the solution. Using a syringe, BH3 -THF (3 mL, 3 mmol) was injected into the reaction flask. During the initial stages (first half- hour) BH3 -THF was added at a very slow rate. Within a few minutes the

RhCI3-nH20 dissolved completely resulting in a pale yellow solution, which slowly turned brown and ultimately a fine black suspension was observed. Addition of the BH3-THF was completed within 15 minutes. Next, 1-octene (0.5 mL, 3.19 mmol) was added to the flask and the reaction mixture was stirred for 2 hours.

This was followed by alkaline peroxide oxidation, extraction, and purification.

3.5.2 A mixture of 1-octene (0.5 mL, 3.19 mmol) and THF (10 mL) was stirred in a three-necked round bottom flask, at room temperature for 5 minutes, in an atmosphere of dry nitrogen. Using a syringe, BH3 -THF (3 mL, 3 mmol) was slowly injected into the reaction flask, over a period of 30 minutes. After the addition of BH3 -THF was completed RhCI3-A7H20 (10 mg, 0.048 mmol) was added to the flask. A fine black precipitate appeared in the solution within a few minutes. Two hours later, the mixture was subjected to alkaline peroxide oxidation, extraction, and purification.

40 3.6 RhCI3 nH20 Promoted Hydroboration of 1-Octene with BH3-THF in THF

by Varying the Rate of Addition of BH3-THF [FAST]

A mixture of RhCI3-nH20 (10 mg, 0.048 mmol), 1-octene (0.5 mL, 3.19 mmol) and THF (10 mL) was stirred in a three-necked round bottom flask, at room temperature for 15 minutes, in an atmosphere of dry nitrogen. RhCI3-nH20 was partially soluble in the THF, imparting a reddish color to the solution. Using a syringe, BH3-THF (3 mL, 3 mmol) was injected into the reaction flask, at a fast rate so as to complete the addition within 10 minutes. Within a few seconds a fine black precipitate appeared in the flask. After the addition of the BH3 -THF was completed the reaction was allowed to continue for 2 hours. This was followed by alkaline peroxide oxidation, extraction, and purification.

3.7 RhCI3nH20 Promoted Hydroboration of 1-Octene with BH3-THF in THF

in the Presence of Water

A mixture of RhCI3-nH20 (10 mg, 0.048 mmol), 1-octene (0.5 mL, 3.19

three- mmol), water (0.08 mL, 4.4 mmol) and THF (10 mL) was stirred in a necked round bottom flask, at room temperature (24C) for 15 minutes, in an atmosphere of dry nitrogen. The RhCI3-nH20 was partially soluble in the THF, imparting a reddish color to the solution. Using a syringe, BH3 -THF

(3 mL, 3 mmol) was injected into the reaction flask. During the initial stages

at a slow rate. Within a few (first half-hour) BH3 -THF was added very minutes the RhCI3-nH20 dissolved completely resulting in a pale yellow solution, which

fine black suspension was observed. slowly turned brown and ultimately a

41 Addition of the BH3 -THF was completed within one hour and the reaction was

allowed to continue for an additional hour. This was followed by alkaline peroxide

oxidation, extraction, and purification. A similar experiment was performed using

D20 (4.4 mmol) instead of H20.

3.8 Hydroboration of 1-Octene with BH3-THF in THF using Different

Transition-Metal Compounds

A mixture containing 10 mg of the transition-metal-compound under

investigation [RhCI3-nH20 (0.048 mmol), RhBr3-nH20 (0.029 mmol), RhCI(PPh3)3

(0.01 1 mmol), [RhCI(COD)]2 (0.020 mmol), lrCI3-nH20 (0.033 mmol), RuCI3-nH20

(0.048 mmol)], 1-octene (0.5 mL, 3.19 mmol) and THF (10 mL) was stirred in a

three-necked round bottom flask, at room temperature for 15 minutes, in an

atmosphere of dry nitrogen. While RhCI3-nH20 and RhBr3-nH20 were not

completely soluble in THF, RhCI(PPh3)3 dissolved in THF, imparting a yellowish

color to the solution. Using a syringe, BH3-THF (3 mL, 3 mmol) was injected into

the reaction flask. During the initial stages (first half-hour) BH3-THF was added

at a very slow rate. In the case of all rhodium compounds, the solution turned

from yellow to brown and finally a fine black suspension was observed. Addition

of the BH3-THF was completed within one hour and the reaction was allowed to continue for an additional hour, followed by alkaline peroxide oxidation, extraction, and purification.

42 "Starved" 3.9 RhCI3nH20 Catalyzed Hydroboration of 1-Octene with

BH3-THF in THF

A mixture of RhCI3-nH20 (10 mg, 0.048 mmol), 1-octene (0.5 mL, 3.19 mmol) and THF (10 mL) was stirred in a three-necked round bottom flask, at room temperature (24C) for 15 minutes, in an atmosphere of dry nitrogen. The

RhCI3-nH20 was partially soluble in the THF, imparting a reddish color to the solution. Using a syringe, BH3 -THF (0.3 mL, 0.3 mmol) was injected into the reaction flask at a very slow rate, over a period of 15 minutes. Within a few minutes the RhCI3-nH20 dissolved completely resulting in a pale yellow solution, which slowly turned brownish-black. The reaction was allowed to continue for an additional 2 hrs, followed by alkaline peroxide oxidation, extraction, and purification. The above procedure was adopted for the RhCI3-nH20 catalyzed

"starved" hydroboration of c/s-2-octene, frans-2-octene, frans-3-octene, frans-4-octene, 1-heptene, and allylbenzene.

"Starved" 3.10 RhCI3nH20 Catalyzed Hydroboration of 1-Octene with

BH3-THF in THF in the Presence of Traces of D20 [Labeling Studies]

A mixture of RhCI3-nH20 (10 mg, 0.048 mmol), 1-octene (0.5 mL, 3.19 mmol), D20 (0.08 mL, 4.4 mmol) and THF (10 mL) was stirred in a three-necked round bottom flask, at room temperature (24C) for 15 minutes, in an atmosphere of dry nitrogen. The RhCI3-nH20 was partially soluble in the THF, imparting a reddish color to the solution. Using a syringe, BH3-THF (0.3 mL, 0.3 mmol) was injected into the reaction flask at a very slow rate, over a period of

43 15 minutes. Within a few minutes the RhCI3-nH20 completely dissolved resulting

in a pale yellow solution, which slowly turned brownish-black. The reaction was allowed to continue for an additional 2 hrs, followed by alkaline peroxide

oxidation, extraction and purification. In yet another modification to the above

procedure BD3-THF (0.8 mL, 0.8 mmol) was used instead of BH3-THF, under

anhydrous conditions.

3.11 Isomerization Studies

A mixture of RhCI3-nH20 (10 mg, 0.048 mmol), 1-octene (2 mL, 12.76

mmol), and THF (30 mL) was stirred in a three-necked round bottom flask, at

room temperature (24C) for 15 minutes, in an atmosphere of dry nitrogen. The

RhCI3-nH20 was partially soluble in the THF, imparting a reddish color to the

solution. Using a syringe, BH3 -THF (0.3 mL, 0.3 mmol) was injected into the

reaction flask at a very slow rate. Within a few minutes the RhCI3-nH20 completely dissolved resulting in a pale yellow solution. At regular intervals

0.5 mL aliquots of the reaction mixture were extracted and quenched using a mixture of NaOH and H202. After 10 minutes the products were extracted using

3 mL of pentane and analyzed using GC-MS. A similar procedure was adopted using 1-heptene (1.5 mL), frans-4-octene (1.5 mL), frans-2-octene (0.5 mL), frans-3-octene (0.5 mL) and allylbenzene (1.5 mL). An isomerization study was also carried out using 2 mL of 1-octene at a temperature of 60C.

44 3.12 Catalytic Activity

A mixture of RhCI3-nH20 (30 mg, 0.144 mmol), 1-octene (3 mL,

19.14mmol), and THF (30 mL) was stirred in a three-necked round bottom flask, at room temperature (24C) for 15 minutes, in an atmosphere of dry nitrogen.

The RhCI3-nH20 was partially soluble in the THF, imparting a reddish color to the solution. Using a syringe, BH3 -THF (0.3 mL, 0.3 mmol) was injected into the reaction flask at a very slow rate. After 24 hours, 0.5 mL aliquot of the reaction mixture was extracted and quenched using a mixture of NaOH and H202. After

10 minutes the products were extracted using 3 mL of pentane. Next, 1 mL of

1-octene was added to the reaction flask and 0.5 mL aliquots of the reaction

mixture were extracted at desired intervals, quenched with NaOH and H202, and after 10 minutes extracted with 3 mL of pentane and analyzed using GC-MS.

3.13 Catalytic Efficiency

A mixture of RhCI3-nH20 (10 mg, 0.048 mmol), 1-octene (1 mL, 6.38

mmol), and THF (15 mL) was stirred in a three-necked round bottom flask, at

room temperature (24C) for 15 minutes, in an atmosphere of dry nitrogen. The

RhCI3-A7H20 was partially soluble in the THF, imparting a reddish color to the

solution. Using a syringe, 3 to 4 drops of BH3 -THF were injected into the

reaction flask at a very slow rate. When the RhCI3-/?H20 had completely

dissolved, 50 mL of 1-octene was added dropwise into the reaction flask,

followed by the slow addition of BH3 -THF (0.3 mL, 0.3 mmol). At the desired time intervals, 0.5 mL aliquots of the reaction mixture were extracted and

45 quenched using a mixture of NaOH and H202. After 10 minutes the products were extracted using 3 mL of pentane and analyzed using GC-MS.

3.14 Dehydration of Isomeric Octanols

3 mL of the octanol and 1 mL of 85% phosphoric acid (H3P04) were taken

in a 5 mL conical vial. The vial was fitted with a Hickman stillhead and a

water-cooled condenser. The mixture was heated while being stirred on a hot

plate for 2 hours. As the vapors condensed in the stillhead, droplets started

collecting in the cup. The liquid in the cup was withdrawn using a Pasteur pipet

and subjected to GC-MS analysis.

46 4. RESULTS AND DISCUSSION

Transition-metal catalyzed hydroborations have been studied in great

chemists.47 detail by numerous well known In most of these studies catecholborane (CB) was used in the presence of catalytic amounts of a Rh(I) compound. While, the rhodium-catalyzed hydroboration of styrene gave very interesting results (Table 1.9), those with unsubstituted terminal alkenes

al.38,39 proceeded in the reported anti-Markovnikov (AM) fashion. Blum et used

336 rhodium trichloride-Aliquat under phase transfer conditions to reduce olefins, and arenes at room temperature. Motivated by these two very interesting reactions, experiments were undertaken in our research group to study the RhCI3-nH20 catalyzed hydroboration of 1-octene in methylene chloride

using catecholborane (CB) in the presence of methyltrioctylammonium chloride

(Aliquat 336). Initial results (Lu Yang, RIT, MS thesis 1996) revealed a reversal of regioselectivity with the 2-octanol (M) being the major product. The goal of my

research was to study the RhCI3-nH20 catalyzed hydroboration of 1-octene in

THF using BH3-THF instead of CB in the presence of Aliquat 336. Initial results

revealed a reversal of regioselectivity similar to that obtained by Lu Yang.

Capillary gas chromatography of the product mixture was performed using

GOW-MAC GC Series 350, 4 ft x Va in. packed column, thermal conductivity detector [2-octanol: 1-octanol = 96 : 4]. Further experimentation revealed that a

similar result could be obtained even in the absence of Aliquat 336. Yields of the crude octanols as determined using GOW-MAC GC, ranged between

65-75%. To our utmost surprise the analysis of the same product mixture using a

47 Hewlett Packard 6890-5873 GC-MS system, revealed the presence of 4-octanol,

3-octanol, 2-octanol, 1-octanol, octanones and octane (Figure 4.1). Before

on embarking an in-depth study of the reaction mechanism, we carried out selected experiments designed to optimize this unique reversal of regioselectivity, study the reproducibility of these experiments and improve product yields. Rhodium chloride is a costly compound and so our first goal was to determine the minimum amount of RhCI3-nH20 that was required to obtain the desired results. Initial reactions were conducted using 50 mg of RhCI3-nH20, but it was soon determined that 10 mg of RhCI3-nH20 would suffice.

Figure 4.1 : Gas Chromatographic Separation of the Product Mixture of the

RhCI3-nH20 Promoted Hydroboration of 1 -Octene at 21C Abundance TIC:OCT1.D 2SL2S 1.4O+07

1.36+07 24.SII 1.26+07 | 1.16+07 !5.43 16+07

9000000

8000000

7000000

6000000

5000000

4000000 15.81

3000000

2000000 28.65 1000000

,T ' ' |[ rime-> isloo ielob iVlob ielob 19I00 '20I00 21 100 22l00 23l00 24.'00 25.00 26l00 27l00 28.00 29.00

Retention time (minutes): octane = 15.81 ; 4-octanone = 23.93; 3-octanone = 24.45; 4-octanone = 24.60; 4-octanol = 24.99; 3-octanol = 25.26; 2-octanol = 25.43; 1 -octanol = 28.65.

48 4.1 Reproducibility Studies

The RhCI3-nH20 promoted hydroboration of 1-octene was carried out

under identical conditions, to verify if the experiment gave reproducible results

(Table 4.1). While, the product ratios of the isomeric octanols were in agreement,

there was one experiment (#4) in which, neither octane nor octanones were

formed. In this experiment great care was taken to ensure that anhydrous

conditions were maintained. This suggests that the presence of moisture in the

reaction mixture may be responsible for the formation of octane. In all these

experiments, the RhCI3-nH20, which was initially partially soluble in THF, slowly

dissolved when the BH3-THF was added. As the addition of BH3-THF was

continued, the solution, which was initially reddish, turns yellow, then brown and

finally a very fine black suspension was visible.

Table 4.1 : RhCI3-nH20 Promoted Hydroboration of 1 -Octene with Bh13-THF

THFa in [Reproducibility Studies] \. Expt. c#1 #2 #3 #4 #5 #6

b(%)\ Products \.

Octane 6.73 7.05 7.48 0 6.65 4.99 Octanones 1.15 0.84 0.56 0 0 0.77 4-Octanol 37.40 38.82 38.73 42.81 40.74 40.82 (41.3) (42.1) (42.3) (42.8) (43.6) (43.3) 3-Octanol 33.77 33.41 33.42 37.2 34.79 34.78 (37.3) (36.3) (36.5) (37.2) (37.3) (36.9) 2-Octanol 16.33 16.45 15.80 17.71 16.21 16.42 (18.1) (17.9) (17.2) (17.7) (17.4) (17.4)

1 -Octanol 2.98 3.43 3.63 2.29 1.61 2.22 (3.3) (3.7) (4) (2.3) (1.7) (2.4) aHydroboration was carried out at room temperature for 2 he>urs by the si 3w addition o BH3-THF (3 mmol) into a mixture of 1-octene (3.19 mmol) and RhCU-n^O (0.048 mmol) in THF. Oxidation of the alkylboranes was achieved using alkaline peroxide. Product distributions were determined by GC. Numbers in parentheses indicate ratio of the isomeric octanols. 2-ethyl-1 -hexanol (1.64%) was also obtained.

49 Four questions that emerge from these results: (i) Does the boron migrate from the terminal carbon to the interior of the carbon chain? (ii) What causes the hydrogenation of the alkene? (iii) How can we account for the formation of octanones in the product mixture? (iv) What is the black suspension? A closer look at the results would tempt us to assume that the boron somehow migrates from the terminus to the interior of the carbon chain. This is contrary to the

al.16 observations made by Brown et wherein the boron always prefers to reside on the least substituted or the terminal carbon. If this assumption of ours is false, then how did the boron migrate down the chain? The only other pathway that could lead to these unexpected octanols was through the initial isomerization of

1 -octene and subsequent hydroboration of these isomeric octenes. This sounds possible, but it raises numerous other questions. What causes the alkene isomerization? Is it RhCI3-nH20? Is it the black suspension? Is it some in situ generated catalyst? RhCI3.nH20 in protic solvents and at elevated temperatures

been shown (eq. to be an excellent catalyst for (Table 1 .4) has 7,8,9) isomerizing alkenes.26,30 However, isomerization studies conducted by RIT MS student

Anthony Sampognaro, with RhCI3-nH20 and 1-octene in THF at room temperature, revealed that only 27% of 1-octene was isomerized after 24 hours.

Simple alkene isomerization did not occur rapidly enough to account for the array of isomeric alcohols. We soon began to speculate on the possibility of the black suspension being capable of alkene isomerization. We had enough evidence to

rhodium.31,506,59 indicate that the black suspension was elemental Experiments

50 with rhodium black and 1-octene in THF, proved that it was ineffective as an

isomerization catalyst.

4.2 Solvent Effect on Regioselectivity

The data in Table 4.2 reveals that of the three ethers that were

investigated, THF seemed to be the best solvent to bring about the desired

reversal of regioselectivity. Of the three ethers RhCI3-nH20 was most soluble in

THF and least in dioxane. Methylene chloride proved to be an effective solvent

336 only when used in the presence of Aliquat as phase transfer catalyst. This

drives home the point that catalyst solubilization plays an important role in this

336 reaction. 1 -Chlorooctane (5.27%) was one of the products when Aliquat

was used.

Table 4.2 : Effect of Solvenl on the Regioselectivity of RhCI3-nH20 Promoted THFa Hydroboration of 1-Octene with BH3-THF in \. Solvent THF Ether CH2CI2 CCH2CI2 + Dioxane A 336 b<%>\. Products \.

Octane 4.99 0.31 1.08 2.00 0 Octanones 0.77 0 0.79 0 0 4-Octanol 40.82 37.60 3.0 37.70 2.45 (43.3) (37.7) (3.2) (40.6) (2.4) 3-Octanol 34.78 38.99 48.45 35.23 31.99 (36.9) (39.1) (49.4) (38.0) (32.0) 2-Octanol 16.42 21.63 35.56 17.33 27.56 (17.4) (21.7) (36.2) (18.7) (27.6)

1 -Octanol 2.22 1.48 11.02 2.47 38.01 (2.4) (1.5) (11.2) (2.7) (38) aHydroboration was carried out at room temperature by the slow addition of BH3 -THF (3 mmol) into a mixture of 1-octene (3.19 mmol) and RhCI3-nH20 (0.048 mmol) in the appropriate solvent. Alkylboranes were oxidized to the alcohols using alkaline peroxide. "Product distributions were determined by GC. cAlong with octane and octanols, 1 -chlorooctane (5.27%) was also obtained. Numbers in parentheses indicate ratio of the isomeric octanols.

51 4.3 Effect of Temperature on the Regioselectivity

At low temperature, 0C, 4-octanol was not the major product (Table 4.3) clearly revealing that isomerization does not proceed very effectively at low temperatures. Raising the temperature to 60C decreases the amount of

4-octanol and 3-octanol, while percentage of 2-octanol is slightly increased. This

may be attributed to the slow migration of boron towards the terminus; the

al.16'18 so-called contra-thermodynamic isomerization observed by Brown et

Probably, 1-octanol would have been the major product had we performed the

experiment in boiling diglyme. Another interesting observation is the decreasing

amount of octane that is produced as we move from low to high temperature.

Table 4.3 : Effect of Temperature on the Regioselectivity of RhCI3-nH20 THFa Promoted Hydroboration of 1-Octene with BH3-THF in "\. Temp. 0C 21 C 60C

b(%)^\ Products^\^ Octane 10.35 4.99 4.48 Octanones 0 0.77 0.84 4-Octanol 13.36 40.82 38.43 (14.9) (43.3) (40.8) 3-Octanol 41.93 34.78 30.99 (46.8) (36.9) (32.9) 2-Octanol 26.73 16.42 22.90 (29.8) (17.4) (24.3)

1 -Octanol 7.63 2.22 1.83 (8.5) (2.4) (1.9) aHydroboration was carried out at different temperatures for 2 hours by the slow addition of BH3-THF (3 mmol) into a mixture of 1-octene (3.19 mmol) and RhCI3-nH20 (0.048 mmol) in THF. Oxidation of the alkylboranes was achieved using alkaline peroxide. "Product distributions were determined by GC. Numbers in parentheses indicate ratio of the isomeric octanols.

52 4.4 RhCI3nH20 Promoted Hydroboration of Isomeric Octenes

Our laboratory soon acquired a whole set of isomeric octenes, which we

required for the determination of their retention times (tr) using the GC-MS. To

our surprise hydroborating frans-4-octene in the presence of RhCI3-nH20 gave

us a result similar to that obtained with 1-octene. This made us really curious,

and we soon carried out the RhCI3-nH20 promoted hydroboration of all the

isomeric octenes that we had acquired. The RhCI3-nH20 promoted hydroboration

of isomeric octenes (Table 4.4) reveals that no matter which isomeric octene one

starts out with, the ratio of the isomeric octanols are almost identical. The

RhCI3-/?H20 promoted hydroboration of a mixture of 1-octene and rra/is-4-octene

gave the same product ratio of isomeric octanols (Figure 4.2). These results

were very significant and deserved a thorough and careful investigation.

Table 4.4 : RhCI3-nH20 Promoted Hydroboration of 1 someric Octenes with

BH3-THFa

cf-4- ^XReactant 1 -octene f-2-octene f-3-octene cf-4-octene 1 + octene b(%)\ Products \.

Octane 4.99 0 2.01 0 4.81 Octanaones 0.77 0 0 0 0.47 4-Octanol 40.82 42.33 49.88 46.20 43.08 (43.3) (42.3) (50.9) (46.2) (45.5) 3-Octanol 34.78 37.06 42.53 35.19 33.76 (36.9) (37.1) (43.4) (35.2) (35.6) 2-Octanol 16.42 18.78 5.59 16.27 15.67 (17.4) (18.8) (5.7) (16.3) (16.6)

1 -Octanol 2.22 1.83 0 2.35 2.2 (2.4) (1.8) (0) (2.4) (2.3) aHydroboration was carried out at room temperature for 2 hours by the slow addition of BH3-THF (3 mmol) into a mixture of the isomeric octene (3.19 mmol) and RhCI3-nH20 (0.048 mmol) in THF. Oxidation of the alkylboranes was achieved using alkaline peroxide. "Product distributions were determined by GC. CGC analysis of frans-4-octene revealed the presence of frans-3-octene. Numbers in parentheses indicate ratio of the isomeric octanols.

53 Figure 4.2 : Gas Chromatographic Separation of the Product Mixture of the

RhCI3-nH20 Promoted Hydroboration of 1-Octene and frans-4-Octene at 23C Abundance TIC: OCT1&4.D 29.32 1.4e+07

1.3e+07 25.

1.26+07 ft

1.16+07 35.48

16+07

9000000

8000000

7000000

6000000

5000000 15.85 4000000

3000000

28.67 2000000 | 1000000 23.944.46

' ' 28.00 I29.00 Tlme-> islob ielob 17I00 ielob 1blob 20I00 21I00 22I00 23I00 24l00 25100 26l00 27lob

Retention time (minutes): octane = 15.85; 4-octanone = 23.94; 3-octanone = 24.46; 4-octanol = 25.06; 3-octanol = 25.32; 2-octanol = 25.48; 1-octanol = 28.67.

Uncatalyzed [Classical] hydroboration of the isomeric octenes (Table 4.5)

was carried out to enable us to appreciate the extent to which the reversal of

regioselectivity was occurring.

[Classical]3 Table 4.5 : Hydroboration of someric Octenes with BH 3-THF in THF %-t- "\Reactant 1 -Octene 2-f-Octene 3-f-Octene D4-f-Octene 1 + Octene b(%N^ Products \.

4-Octanol 52 95.4 53.1

3-Octanol 0.1 51.3 48 4.6 3.1

2-Octanol 7.1 48.7 3.1

1 -Octanol 92.8 40.7 aHydroboration was carried out at room temperature for 2 hours by the slow addition of BH3-THF (3 mmol) into the isomeric octene (3.19 mmol) in THF, followed by alkaline peroxide oxidation. "Product distributions were determined by GC. CGC analysis of frans-4-octene revealed the presence of frans-3-octene.

54 4.5 Hydroboration of Styrene and 3,3-Dimethyl-1-butene

In order to prove that alkene isomerization was the key to obtain isomeric alcohols, we performed experiments using styrene and 3,3-dimethyl-1-butene, knowing fully well that they were not capable of undergoing any isomerization.

Our hypothesis was proved right when we found that the regioselectivties of the

RhCI3-nH20 promoted hydroborations of 3,3-dimethyl-1-butene and styrene

(Table 4.6) compare favorably with those of the uncatalyzed variants.

Styrene3 Table 4.6 : Classical and R hCI3-nH20 Promoted Hydrobora tion of

Reported113 DProducts (%) Classical cRh-catalyzed Ethylbenzene 3.07 5.24

1 -Phenylethanol 20 17.25(18) 16.20(17) 2-Phenylethanol 80 79.69 (82) 79.69 (83) Hydroboration was carried out at room temperature for 2 hours by the slow addition of BH3-THF (3 mmol) into styrene (4.36 mmol) in THF. RhCI3-nH20 (0.048 mmol) was used for the catalyzed reaction. Organoboranes were oxidized to the alcohols using alkaline peroxide. "Product distributions were determined by GC. Numbers in parentheses indicate ratio of the isomeric phenylethanols.

Figure 4.3 : Gas Chromatographic Separation of the Product Mixture of the RhCI3-nH20 Promoted Hydroboration of Styrene at 26C Abundance TIC:STY11.D 1C145

1.86+07

1.66+07

1.46+07

1.26+07

9.00

16+07

8000000

6000000 5.56

4000000

2000000

\ - rU ' , I 10.00 1 11 nme-> 5.50 6.00 6.50 7.00 7.50 8.00 8.50 9.00 9.50 0l50 lob nlsb

Retention time (minutes): Ethylbenzene = 5.56; 1 -phenylethanol = 9.00; 2-phenylethanol = 10.45.

55 4.6 Hydroboration of 1-Heptene and Allylbenzene

To get a better understanding of this unique reversal of regioselectivity, experiments were performed using 1-heptene and allylbenzene. Table 4.7 and

Table 4.8 indicate that the internal alcohols are the major products, once again confirming our assumption that alkene isomerization is indeed responsible for the reversed regioselectivity.

1-Heotenea Table 4.7 : Classical and RhCI3-nH20 Promoted Hydroboration of Reported" DProducts (%) Classical cRh-catalyzed Heptane 1.39 2.84 Heptanal/Heptanones 0 4-Heptanol 13.30(13.7) 3-Heptanol 0.31(0.3) 50.63(52.1) 2-Heptanol 6 7.75 (7.9) 31.05(32.0) 1 -Heptanol 94 90.56(91.8) 2.18(2.2) Hydroboration was carried out at room temperature for 2 hours by the slow addition of BH3-THF (3 mmol) into 1-heptene (3.55 mmol) in THF. cRhCI3-nH20 (0.048 mmol) was used for the catalyzed reaction. Alkylboranes were oxidized to the alcohols using alkaline peroxide. "Product distributions were determined by GC. Numbers in parentheses indicate ratio of the isomeric heptanols.

Allylbenzene3 Table 4.8 : Classical and RhCI3.nH20 Promoted Hydroboration of

Reported" "^Products (%) Classical cRh-catalyzed Propylbenzene 9.92 Phenylpropanones 3.01

3-Phenyl-1 -propanol 90 89.97 (90) 1.55(1.8) 1 -Phenyl-2-propanol 10 10.03(10) 13.20(15.3) 1-Phenyl-1 -propanol 71.70(82.9) aHydroboration was carried out at room temperature for 2 hours by the slow addition of BH3-THF (3 mmol) into allylbenzene (3.77 mmol) in THF. cRhCI3-nH20 (0.048 mmol) was used for the catalyzed reaction. Organoboranes were oxidized to the alcohols using alkaline peroxide. "Product

ctrans- -phenyl- distributions were determined by GC. 1 1-propene (0.613%) was also obtained. Numbers in parentheses indicate ratio of the isomeric phenylpropanols.

frans-1-Phenyl-1- Table 4.9 : Classical Hydroboration of propene Reported" Catalyzed4' DProducts (%) aClassical

3-Phenyl-1 -propanol 0 0 0

1 -Phenyl-2-propanol 15 14 2

1 -Phenyl- 1 -propanol 85 86 98 aHydroboration was carried out at room temperature for 2 hours by the slow addition of BH3-THF

-propene in THF. (2 mmol) into frans-1 -phenyl-1 (3.77 mmol) Organoboranes were oxidized to the alcohols using alkaline peroxide. "Product distributions were determined by GC.

56 4.7 Effect of Transition-Metal-Compound on the Regioselectivity

It now became necessary to investigate if other transition metal

compounds could also bring about a reversal of regioselectivity (Table 4.10)

similar to that brought about by RhCI3-nH20. We first started experimenting with

RhBr3-nH20 and found that it worked quite well. We had samples of RhCI(PPh3)3

("aged") lying around in the laboratory and decided to try the same. It worked

documented48"50 too, though not as effectively as RhCI3-nH20. It is well that

"aged" RhCI(PPh3)3 contains traces of Rh(n) and Rh(JU) which may be

responsible for the observed result. Experiments conducted with [RhCI(COD)]2,

RuCI3-nH20 and lrCI3-nH20 did not give the dramatic results that we obtained

with RhCI3-nH20. This was expected considering the fact that the catalyst has a

al.30 profound effect on the isomerization, as shown by Asinger et during the

isomerization of 1-octene (Table 1.4).

Table 4.10 : Effect of the Transition-Metal-Compound on the Hydroboration

THF3 of 1 -Octene with BH3-THF in \jCatalyst RhCI(PPh3)3 [RhCI(COD)]2 RhCI3 RhBr3 lrCI3 RuCI3 "(%)N\ Products \.

Octane 4.99 0.17 1.74 5.79 6.19 7.07 Octanones 0.77 1.71 0.42 1.24 0 0.95 4-Octanol 40.82 26.24 16.07 5.03 3.73 8.67 (43.3) (26.7) (16.4) (5.4) (4.0) (9.4) 3-Octanol 34.78 40.87 38.56 26.06 9.21 25.58 (36.9) (41.7) (39.4) (28.1) (9.8) (27.8) 2-Octanol 16.42 23.74 26.7 19.76 10.02 18.57 (17.4) (24.2) (27.3) (21.3) (10.7) (20.2)

1 -Octanol 2.22 7.27 16.42 41.93 70.85 39.15 (2.4) (7.4) (16.9) (45.2) (75.5) (42.6) aHydroboration was carried out in THF at room temperature for 2 hours by the slow addition of BH3-THF (3 mmol) into 1-octene (3.19 mmol) and 10 mg of the transition-metal compound in THF. Alkylboranes were oxidized to the alcohols using alkaline peroxide. "Product distributions were determined by GC. Numbers in parentheses indicate ratio of the isomeric octanols.

57 4.8 Effect of Varying Experimental Conditions

A set of carefully designed experiments gave us very valuable information

regarding this unique reversal of regioselectivity (Table 4.11). In the first

experiment (Reverse-1), BH3-THF was added to a solution of RhCI3-nH20 in

THF. Into the fine black suspension that was obtained, 1-octene was added and

the hydroboration was allowed to proceed for 2 hours. The results reveal that the

reaction proceeded in a manner similar to the uncatalyzed reaction, indicating

that the black suspension was indeed incapable of alkene isomerization.

In Reverse-2, 1-octene was first hydroborated using BH3-THF and into this

mixture of organoboranes, RhCI3-nH20 was added. Once again there is no

reversal of regioselectivity, very clearly indicating that the order in which the

reactants are mixed is of prime importance. In yet another modification (Fast) to

our usual procedure, BH3-THF was added fast, within 10 minutes, into a solution

of RhCI3-A7H20 and 1-octene in THF. In this case, although there is a slight

reversal of regioselectivity, it was not as dramatic as it was when BH3-THF was

added slowly. This drives home the point that the slow addition of BH3-THF was the most critical factor in achieving the unique reversal of regioselectivity. It soon dawned on us that the combination of RhCI3-nH20 and catalytic amounts of

BH3-THF was somehow responsible for the in situ generation of a highly efficient isomerization catalyst.

58 Table 4.11 : Effect of Varying Experimental Conditions on the Regioselectivity of

RhCI3-nH20 Promoted Hydroboration of 1 -Octene with BH3-THF in THF

\. Expt. aReverse-1 DReverse-2 cFast aNo water eWater

"(%)\. Products^\

Octenes 0 0 0 20.38 19.11 Octane 0 2.75 8.19 8.84 13.99 Octanones 0 0 0 0 0.47 4-Octanol 0 0 0.60 27.27 26.10 (0) (0) (0.7) (38.5) (39.3) 3-Octanol 0 0 5.86 26.81 26.59 (0) (0) (6.4) (37.9) (40.0) 2-Octanol 6.24 6.67 8.92 13.54 13.30 (6.2) (6.9) (9.7) (19.1) (20.0)

1 -Octanol 93.76 90.58 76.43 3.16 0.44 (93.8) (93.1) (83.2) (4.5) (0.7)

BH3-THF/1 -octene/ RhCI3.nH20 = 3 / 3.19 / 0.048 (mmol). aBH3-THF was added to a solution of RhCI3-nH20 in THF followed by the addition of 1-octene into the resultant solution. bBH3-THF was added to 1-octene in THF followed by the addition of RhCI3-nH20 into the resultant solution. CBH3-THF was added very fast, within 10 minutes, into a mixture of RhCI3-r?H20 and 1-octene in THF. dBH3 -THF (4 mmol) was added slowly into a mixture of 1-octene (6.37 mmol) and RhCI3-nH20 (0.048 mmol) in THF under anhydrous conditions. eBH3-THF (4 mmol) was added slowly into a mixture of 1-octene (6.37 mmol) and RhCI3-nH20 (0.048 mmol) in THF in the presence of water (4.4 mmol). Numbers in parentheses indicate ratio of the isomeric octanols.

Our speculations were put to rest when we were studying the effect of water on the regioselectivity of the reaction. Two experiments were performed simultaneously; one employing anhydrous conditions and the other with a small amount of water deliberately added into the reaction mixture. We were aware of the fact that water and BH3-THF were not compatible, but had to go ahead with this experiment in order to verify if it was the presence of water, that was in some way, responsible for alkene hydrogenation. Fortunately, the BH3-THF used in both these experiments was old and probably less than 1 M in BH3-THF, leading to incomplete hydroboration. This proved to be advantageous, since the analysis of the product mixture (Figure 4.4) revealed the presence of isomeric octenes

59 (20%) along with the octane and isomeric octanols. The other interesting observation was the increased percentage of octane obtained in the reaction that was adulterated with water, clearly indicating that the presence of water is partly

responsible for alkene hydrogenation. It was now clear that an in situ catalyst was responsible for alkene isomerization and that it was the hydroboration of these isomeric alkenes that resulted in the formation of the isomeric alcohols.

With this very valuable information, it was time to surge ahead. Numerous experiments were conducted to determine the optimum conditions required to obtained the reversed regioselectivity.

Figure 4.4 : Gas Chromatographic Separation of the Product Mixture of the

RhCI3-nH20 Promoted Hydroboration of 1 -Octene at 25C in the Presence of Water Abundance TIC: 7500000 25L22 7000000 i 24.9i 6500000 15.91 6000000

5500000

5000000 1 5.40

4500000

4000000

3500000

3000000

2500000

J6.17 2000000 15 1500000

1000000

16.81 500000 23.9S i I 28.69 A: rime-> 15100 16.00 17.00 18.00 19.00 20.00 21.00 22.00 23.00 24.00 25.00 26.00 27.00 28.00 29.00

Retention time (minutes): rrans-4-octene = 15.42; frans-3-octene = 15.65; octane = 15.91; frans-2-octene = 16.17; os-2-octene = 16.81 ; 4-octanone = 23.95; 3-octanone = 24.47; 2-octanone = 24.60; 4-octanol = 24.95; 3-octanol = 25.22; 2-octanol = 25.40; 1-octanol = 28.69.

60 4.9 ["Starved" Isomerization of Isomeric Octenes Hydroboration]

One of our experiments (Table 4.11) in which the hydroboration was

conducted in the presence of water, deliberately added to the reaction mixture,

was the real eye opener. The GC-MS analysis revealed (Figure 4.4) that along

with the isomeric alcohols and octane, isomeric octenes were also obtained.

At this point, we can say with a certain degree of confidence that the high

percentage of octane may be due to the presence of water in the reaction

mixture.

An experiment in which the ratio of the reactants was

1-octene / = RhCI3-nH20 / BH3-THF 3.19 / 0.048 / 0.3 (mmol) gave us 87.6% of

isomerized octenes (Figure 4.5).

Figure 4.5 : Gas Chromatographic Separation of the Product Mixture of the

"Starved" RhCI3-nH20 Catalyzed Hydroboration

of 1 -Octene at 23C Abundance TIC:ISOOC1.D 15,836,37

1.66+07

1.46+07 15.!

1.2e+07

S.9I 16+07 16.92

.B9

8000000

6000000

4000000

2000000

14.96

L'-' 'JJ.L' 'J_L-' '.'LL nme-> 15.00 16.00 17.00 18l00 19100 20.00 21.00 22.00 23.00 24.00 25.00 26.00 27.00 28.00 29.00

Retention time (minutes): 1-octene = 14.96; frans-4-octene = 15.53; frans-3-octene = 15.83; c/s-4-octene = 15.89; octane = 15.98; frans-2-octene = 16.37; c/s-2-octene = 16.92; 4-octanol = 24.86; 3-octanol = 25.13; 2-octanol = 25.32.

61 We soon devised a new methodology, currently referred to in our research

"starved" group as the hydroboration, in which an alkene is treated with

RhCI3-nH20 in the presence of catalytic amounts of BH3-THF. This incomplete hydroboration/oxidation gives us small quantities of the isomeric alcohols, but

large amounts of the isomeric alkenes. Soon the other isomeric octenes were put to the test and as expected they gave results (Table 4.12) similar to those obtained with 1-octene.

Table 4.12 : Isomerization of Isomeric Octenes using RhCI3-nH20/BH3-THF in THF

"Starved" Hydroboration3

\. Reactant 1 -Octene o2-Octene f-2-Octene f-3-Octene cf-4-Octene

b(%)\. Products^\

1 -Octene 0.50 0.52 0.73 0.36 0.40 (0.6) (0.7) (0.8) (0.4) (0.5) frans-4-Octene 20.16 11.25 21.05 16.00 17.44 (23.0) (15.3) (21.9) (19.8) (21.5) frans-3-Octene 29.29 22.56 31.6 35.69 27.08 (33.4) (30.7) (32.5) (44.0) (33.3) c/s-4-Octene 3.24 3.13 3.79 4.49 3.72 (3.7) (4.2) (3.9) (5.5) (4.6) Octane 6.62 14.61 3.04 9.44 4.76 frans-2-Octene 26.63 28.21 26.70 18.86 25.47 (30.4) (38.3) (30.8) (23.3) (31.3) c/s-2-Octene 7.76 7.93 9.67 5.63 7.16 (8.9) (10.8) (10.1) (7.0) (8.8) Octanones 0 3.43 0 1.06 0.44 4-Octanol 1.62 1.17 0 4.08 5.22 3-Octanol 2.30 4.06 0 3.77 5.39 2-Octanol 1.88 3.13 0 0.62 2.90

1 -Octanol 0 0 0 0 0 isomerization was carried out at room temperature for 2 hours by the very slow addition of BH3-THF (0.3 mmol) into a mixture of the isomeric octene (3.19 mmol) and RhCI3-nH20 (0.048 mmol) in THF, followed by oxidation with alkaline peroxide. "Product distributions were determined by GC. CGC analysis of fra/7s-4-octene revealed the presence of frans-3-octene. Numbers in parentheses indicate ratio of the isomeric octenes.

62 These experiments confirmed our assumption that alkene isomerization

"starved" was indeed the key factor for the reversed regioselectivity. The

hydroboration of 1-heptene (Figure 4.6) and allylbenzene (Figure 4.7) also gave

us isomerized alkenes (Table 4.13).

Table 4.13 : Isomerization of 1-Heptene and Allylbenzene using RhCI3-nH20/BH3-THF in THF

"Starved" Hydroboration3

\. Reactant C1-Heptene ^-v. Reactant aAllylbenzene

(1 -Phenyl-2-propene) b(%)^\ Products ^\ Products ^^

1-Heptene 0.61 Allylbenzene 0

(0.8) (1 -Phenyl-2-propene) (0) rrans-3-Heptene 28.01 c/s-1-Phenyl-1- 8.37 (38.7) propene (9.6) c/s-3-Heptene 4.76 frans-1 -Phenyl-1- 79.02 (6.6) propene (90.4) Heptane 5.93 Propylbenzene 7.72

rrans-2-Heptene 29.48 Phenylpropanols 4.88 (40.7) c/s-2-Heptene 9.57 (13.2) 4-Heptanol 4.01 3-Heptanol 10.70 2-Heptanol 6.96 1-Heptanol 0 isomerization was carried out at room temperature for 2 hours by the very slow addition of BH3-THF into a mixture of the alkene and RhCI3-nH20 in THF, followed by oxidation with alkaline peroxide. "Product distributions were determined by GC. Numbers in parentheses indicate ratio of the isomeric alkenes. 1-heptene / RhCI3-nH20 / BH3-THF = 3.55 / 0.048 / 0.3 (mmol). "Allylbenzene / RhCI3-nH20 / BH3-THF = 3.77 / 0.048 / 0.3 (mmol).

63 Figure 4.6 : Gas Chromatographic Separation of the Product Mixture of the

"Starved" RhCI3-nH2Q Catalyzed Hydroboration of 1-Heptene at 23C

ISOHEPXT~ SBuhdance TIC:

1.56+07

Retention time (minutes): 1-heptene = 8.88; frans-3-heptene = 9.36; ; heptane = 9.44; c/s-3-heptene = 9.49; frans-2-heptene = 9.71; c/s-2-heptene = 10.10.

Figure 4.7 : Gas Chromatographic Separation of the Product Mixture of the

"Starved" RhCI3-nH20 Catalyzed Hydroboration of Allylbenzene at 23C

Abundance TIC: ISOAB.D 2 3.68 1.56+07

1.4e+07

1.36+07

1.26+07

1.16+07

16+07

9000000 I 8000000 18.26 7000000 20.59

6000000 ;

5000000 j

4000000 29.15 3000000 I

2000000 28.29 I 32.92 1000000 I I I rime-> 17'b0 1800 19'ob 20'00 21100 22l00 23l00 24l00 25l00 26l00 27l00 28l00 29l00 30.00 31.00 32.00 33.00 34.00 35l00 36l00

c/s- -phenyl- Retention time (minutes): propyl benzene = 18.26; 1 1 -propene = 20.59;

= = frans-1-phenyl-1 -propene = 23.68; 1 -phenyl-2-propanol 28.29; 1-phenyl-1 -propanol 29.15; 3-phenyl-1 -propanol = 32.92.

64 4.1 0 Effect of Catalyst on the Isomerization of 1 -Octene

"Starved" hydroboration when carried out using RhBr3-nH20 and

RhCI(PPh3)3 gave results (Table 4.14) almost similar to those obtained with

RhCI3-nH20. We tried isomerizing 1-octene using RhCI3-nH20 and catecholborane instead of BH3-THF and it worked well. These results clearly indicate that, a rhodium compound in the presence of small quantities of a hydroborating agent could act as an effective alkene isomerizer.

Table 4.14 : Effect of Catalyst on the Isomerization of 1 -Octene in THF

"Starved" Hydroboration3

\Catalyst aRhCI3 aRhBr3 aRhCI(PPh3)3 RhCI3 RhCI3 eRhCI3 + + + + + + BH3-THF BH3-THF BH3-THF CB-THF BD3-THF D20 b(%)^\ + Products \. BH3-THF

1 -Octene 0.50 0.77 2.74 0.74 0 0.42 (0.6) (0.9) (3.5) (0.8) (0) (0.5) rrans-4-Octene 20.16 15.50 2.96 15.60 9.89 19.39 (23.0) (17.5) (3.8) (16.7) (25.0) (23.3) frans-3-Octene 29.29 27.71 9.86 28.31 14.90 29.28 (33.4) (31.2) (12.7) (30.4) (37.7) (35.1) c/s-4-Octene 3.24 4.17 3.1 3.80 0 0 (3.7) (4.7) (4.0) (4.1) (0) (0) Octane 6.62 2.57 3.20 4.17 15.28 16.35 frans-2-Octene 26.63 31.43 38.30 34.08 11.84 26.73 (30.4) (35.4) (49.2) (36.6) (30.0) (32.1) c/s-2-Octene 7.76 7.76 20.83 10.67 2.90 7.53 (8.9) (10.3) (26.8) (11.4) (7.3) (9.0) Octanones 0 0 0 0 0 0 4-Octanol 1.62 0 0.50 0 15.80 0 3-Octanol 2.30 1.50 4.52 0.85 16.77 0.30 2-Octanol 1.88 1.41 3.97 0.65 9.59 0

1 -Octanol 0 5.77 10.03 1.13 3.04 0 isomerization was carried out at room temperature by the very slow addition of BH3 -THF (0.3 mmol) into a mixture of 1-octene (3.19 mmol) and 10 mg of the transition-metal compound in THF. Oxidation of the alkylboranes was accomplished using alkaline peroxide. Product distributions were determined by GC. c1 -octene / RhCI3-nH20 / Catecholborane = 3.19 / 0.048 /

= 1.0 (mmol). d1 -octene / RhCI3-nH20 / BD3-THF 3.19 / 0.048 / 0.8 (mmol). e1 -octene / RhCI3-nH20 / BH3-THF / D20 = 6.37 / 0.048 / 0.5 / 4.4 (mmol). D20 was added to the reaction mixture before the addition of the BH3-THF. Numbers in parentheses indicate ratio of the isomeric octenes.

65 4.11 Deuterium Labeling Studies

"

certainties." Creativity requires the courage to let go of [assumed]

- Erich Fromm

Gratified by this success we soon embarked upon an in-depth study of the reaction mechanism. In our first experiment (Table 4.14) we conducted the

"starved" hydroboration of 1-octene using RhCI3-nH20 and BD3-THF.

As expected the GC analysis of the product mixture indicated the presence of octane, octanols and octenes. The high-resolution mass spectroscopy analysis of this product mixture revealed extensive deuterium scrambling among all positions along the octyl chain of the isomeric octanols and the isomeric octenes.

This result suggested that the isomerization catalyst was a labeled species and

activity.48,49 hence capable of this random labeling In our second experiment, a small amount of deuterated water (D20, 4.4 mmol) was added to the reaction

"starved" flask during the RhCI3-/iH20 catalyzed hydroboration of 1-octene. Our intention was to find out, if the in situ generated isomerization catalyst was capable of undergoing deuterium exchange with D20. Our results were truly exciting; the octanols, octane, and isomeric octenes in the product mixture were all randomly labeled. Even more fulfilling, were the results obtained during the

"starved" RhCI3-/7H20 catalyzed hydroboration of styrene and cyclohexene in the presence of D20. In both cases, high-resolution mass spectroscopy analysis revealed the presence of the label on the alkene, clearly indicating that our in situ generated catalyst reacted with alkenes without prejudice of whether they can undergo isomerization or not. Peak purity analysis of the peak corresponding to

66 styrene (F.W. = 104.15) shows that it was made up of six different components,

while that of = cyclohexene (F.W. 82.15) was made up of eight components

(Figure 4.8).

Figure 4.8 : Isomerization-Deuteration of Cyclohexene with RhCl3/BH3 in D20 Peak Purity Profile ldiT7iraO (69.70 to 70.30): STRVDDCY.D Ion 85.00 (84.70 to 85.30): STRVDDCY.D Ion 69.00 (68.70 tfi 69.30): STRVDDCY.D Ion 84.00 (83.70 to\B4.30): STRVDDCY.D 3200000 Ion 55.00 (54.70 to 55.30): STRVDDCY.D Ion 68.00 67.70 Jo 58.30): STRVDDCY.D Ion 83.00 82.70 to i 13.30): STRVDDCY.D Ion 67.00 (66.70 to 67.30): STRVDDCY.D 3000000

2800000

2600000

2400000

2200000

2000000'

1800000

1600000

1400000

1200000

1000000

800000:

600000

400000

200000

>.60' Time-> 7.20 'IT 7.35 7.40 7.45 '.50 7.55 7.70

Retention time (minutes): cyclohexene = 7.42. Components = 8.

67 High-resolution mass spectroscopy analysis of cyclohexene shows

(Figure the 4.9) presence of molecular ions having masses greater than 82, a

clear manifestation of deuterated cyclohexene. We now have a very versatile

procedure to label alkenes, using one of the most economical deuterated

reagents, namely D20.

Figure : 4.9 Isomerization-Deuteration of Cyclohexene with RhCls/BH3 in D20 High-Resolution Mass Spectroscopy Abundance Scan 115 (7.325 min): STRVDDCY.D 7P

9000

6000

7000

57 6000

5000 86

4000

3000 40

2000 28 1000 207 96104 119 133 147 161170179 191 223 235 249258267 2?1289298 bl ' on/z-> 2b 30 40 50 60 70 80 90 1 66 I'l6 1 20 130 140 150 166 170 180 1 90 200 jjo 220 230 240 260 270 280 300 Abundance #21207: Cyclohexene 67

9000

8000

7000 54

6000

5000 39 4000 82

3000 27 2000

1000 14

UJi fa' ' ti/z-> lb 20 30 40 50 60 70 80 90 "l66 1 120 130 140 150 166 170 180 190 266 2i6 220 2J0 240 250 260 270 280 290 300

Retention time (minutes): cyclohexene (F.W. = 82.15) = 7.42. Components = 8.

68 Figure 4.10 : Isomerization-Deuteration of Styrene with RhCla/BH3 in D20 High-Resolution Mass Spectroscopy Abundance "Scan 121 (5.866 min): STRVDDST.D 106

9000

8000

7000

6000

5000 79

4000

3000 51 2000

1000 39 63

117 133 147 163 177 191 207 223 237 249258267 281 295 0 " " " 2JL h.i'lLi" " 'iab' ite-> 20 ab "4b sb eb 7b 8b oti "job ifa 120 ifa iso ieo 170 fab 755 200 2-ib 230 afa 25b 260 27b 260 29b 366 Abundance #118937: Styrene 104

9000

8000

7000

6000

5000 78

4000 51 3000

2000

39 1000 63

' lib' ' ifa' n/z-> 2'b 3b so bb to ab 160 120 iio iso ieo 170 iso i5o 266 2-ib J220 23b 24b 250 260 27b 2eo Retention time (minutes): styrene (F.W. = 104.15) = 5.93. Components = 6.

A thorough literature search was now undertaken to figure out the

structure and nature of the in situ generated isomerization catalyst. One

significant finding of this search was that transition-metal hydrides were good

catalysts.21,22 isomerization In our system (RhCI3-nH20 + BH3-THF) there could

be more than one such rhodium-hydride (Rh-H) intermediate possible. One of them could be obtained by the exchange of a chloride with a hydride giving us a

compound.31,50,60 RhHCI2 While the other could be obtained by the

bond.42,50 well-documented insertion of rhodium into the boron-hydrogen

69 this Both these species may be responsible for isomerizing double bonds. With sizable body of data at hand, we were now in a very good position to propose a mechanism to account for this unique reversal of regioselectivity that we observed during the transition-metal-promoted hydroboration of alkenes.

70 4.12 Proposed Mechanism

While we accept the mechanism (Scheme 1.9) that was proposed by

Noth,42 Evans48 Burgess,49 Mannig and which has been supported by and we

believe that the olefin insertion (into the Rh-H bond) followed by p-hydride

elimination64 occurs at a much more rapid rate, compared to the reductive

elimination to give the C-B bond, resulting in alkene isomerization.

Scheme 4.1 Proposed Mechanism for the Isomerization of Octenes

1 -octene alkene association

Rh= h alkene B<^ insertion B-Rh-H complex |3-hydride H elimination hydride migration

H A B<^

free

BRh

alkene (3-hydride insertion elimination

frans-2-octene c/'s-2 -octene

71 Scheme 4.2

Proposed Mechanism

C.,H7-CH=CH-C3H7 4-octene bh3-thf + RhCI3-nH20

C4H9-CH=CH-CH2-CH3 ^"C6H13 3-octene

1 -octene CcH1l-CH=CH-CH3 C8H16 2-octene C6H13-CH=CH2 -octene isomerized octenes

/C6H13 alkene free octenes association B Rh H-^=/C6H13 / cis & trans H

alkene alkene dissociation alkene insertion dissociation

fast fast Q h toefa-hydride H bete-hydride Hjk^J6H13 6 13 H / elimination =\ elimination H C6H13 '^6H13 B Rh B Rh / Rh / B RhB H H

reductive alkene slow elimination insertion

H H H C6H13 C6H13 'C6H13 RhB B B reductive elimination

H H C6H13 'C6H13 B Alkene insertion, followed by befa-hydride elimination, proceeds at a much faster rate than reductive elimination, OH NaOH/Hp. resulting in the formation of isomeric alkenes. Isomerization could be brought about either by a 'B-Rh-H' "Rh-H" H or or RhHCI2 species. "classical" Isomerized octenes undergo hydroboration C6H13 to yield internal octanols. OH

72 The ratio of the alkenes formed is dependent on their kinetics and relative stabilities, and it is these isomeric alkenes that subsequently get hydroborated in the classical fashion.

Chalk25 Harrod and have shown that during the isomerization of terminal alkenes migration from 2- to the 3- position is much slower than from 1- to the

2-position, indicating that along with thermodynamic stability, reaction kinetics

also play a very important role in determining equilibrium product ratios.

Heats of hydrogenation data (Table 4.15) reveals that fra/is-2-octene,

frans-3-octene and frans-4-octene are the most stable, while 1-octene is the

least. The results in Table 4.12 indicate that the ratio of the isomeric octenes is

in agreement with their thermodynamic stabilities.

Table 4.15 : Enthalpies of Hydrogenation of Isomeric Octenes Alkene ArH (kJ/mol)62 ArH (kJ/mol)63

1 -Octene -125.61.2 -125.52

c/s-2-Octene -119.4 1.1 -117.95

frans-2-Octene -115.510.7 -113.77

c/s-3-Octene -117.810.4 -118.24

frans-3-Octene -115.010.4 -114.06

c/s-4-Octene -118.210.4 -118.24

frans-4-Octene -115.010.4 -114.06

4.13 Dehydration of Isomeric Octanols

Intrigued by these isomerization results, we decided to study the dehydration of octanols, with the intention of finding out if the ratio of the isomeric octenes obtained by carbocation rearrangement, resembled those obtained by rhodium-catalyzed isomerization. Table 4.16 indicates that under the

73 experimental conditions that we employed, the ratio of the isomeric octenes is

dependent on the starting alcohol. These results suggest that both,

thermodynamic and kinetic control play a significant role in these reactions. One

should bear in mind the fact that thermodynamic and kinetic control of product

distribution is really one of time and not of temperature control of the reaction. In

our dehydration studies, longer periods of time and slow heating may have

resulted in almost identical product ratio of the isomeric octenes.

Octanols3 Table 4.16 : Dehydra tion of Isomeric

^.Reactant 1 -Octanol 2-Octanol 3-Octanol

b(%)\^ Products\.

1 -Octene 9.7 9.3 1.5 (18.1) (9.5) (1.6) frans-4-Octene 2.4 4.5 5.0 (4.5) (4.5) (5.2) frans-3-Octene 9.6 15.8 28.7 (17.9) (16.1) (29.9) c/s-4-Octene 3.1 4.1 10.1 (5.7) (4.2) (10.6) Octane 0 0 0 frans-2-Octene 17.9 35.9 29.1 (33.3) (36.5) (30.3) c/s-2-Octene 11.0 28.7 21.6 (20.5) (29.1) (22.5) Octanones 0 0.9 0 4-Octanol 0 0 0 3-Octanol 0 0 3.9 2-Octanol 0 0.8 0

1 -Octanol 46.3 0 0

isomerization was c)arried out by refluxing the} octanol (3 mL) in 85% H 3P04 (1 mL) for 2 hours. "Product distributions were determined by GC. Numbers in parentheses indicate ratio of the isomeric octenes.

74 4.14 Isomerization Studies

In order to get a better idea of how the double bond migrates down the alkyl chain a few more isomerization studies were conducted. In these experiments the in situ catalyst was generated in the presence of the desired alkene, and aliquots of the reaction mixture were quenched using NaOH/H202.

After ten minutes the products were extracted using pentane and subjected to

GC analysis. Table 4.17 gives us some great insight into the migratory pattern adopted by 1-heptene during its isomerization. There is a clear indication that the migration of the double bond takes place in a stepwise manner.

h2o/bh3-ti- THFa Table 4.17 : Isomesrization of 1 -Heptene using RhCI3-n F in Time 1-Heptene c-2-Heptene f-2-Heptene Heptane f-3-Heptene o3-Heptene (min) 0 100 0 0 0 0 0 5 85.489 8.631 5.274 0 0.606 0 10 74.810 14.699 8.862 0.189 0.967 0.474 15 44.696 30.498 20.814 0.214 2.492 1.286 20 15.971 36.383 35.699 0.418 7.883 3.646

25 6.474 33.486 42.733 0.636 1 1 .938 4.732 40 0.754 12.174 44.224 1.357 34.699 7.330

45 0.796 12.448 42.472 1.405 35.549 j 7.601 50 0.801 12.824 41.931 1.432 35.410 7.518 60 0.792 12.547 41.881 1.427 35.834 7.518 120 0.718 12.557 42.686 1.313 35.559 7.167 alsomerizati(jn was carrieij out at room temperature by the slow addit on of BH3-TH F (0.3 mL, 0.3 mmol) into a mixture of the 1-heptene (1.5 mL, 10.65 mmol) and RhCI3-nH20 (10 mg, 0.048 mmol) in 15 mL of THF. At regular time intervals 0.5 mL aliquots of the reaction mixture were quenched using NaOH/H202. Products were extracted using 3 mL of pentane. Product distributions were determined by GC.

75 In the beginning, 1-heptene is isomerized predominantly into c/s-2-heptene, which undergoes rapid isomerization to frans-2-heptene. It is the cis and frans-2-heptene, which subsequently isomerize to give cis and frans-3-heptene. After 20 minutes, we notice that c/s-2-heptene and frans-2-heptene are present in equal proportions. As the isomerization proceeds, we see a gradual decrease in the percentage of c/s-2-heptene, with simultaneous increase in the amounts of frans-2-heptene, frans-3-heptene, and c/s-3-heptene.

Figure 4.11 : Isomerization of 1-Heptene using RhCI3-nH20/BH3-THF in THF

1 -heptene

t-3-heptene

D c-3-heptene

t-2-heptene

? c-2-heptene

Time in minutes

76 A kinetic study would be very challenging considering the numerous equilibria (Scheme 4.3) that exist in the system at any given moment.

Scheme 4.3

1-heptene

frans-2-heptene

frans-3-heptene c/s-3-heptene

In order to verify if we had achieved thermodynamic equilibrium during our isomerization studies, we did a comparison of our experimental results with

formation61 those calculated using enthalpies of of isomeric heptenes. The results in Table 4.18 are a clear indication that the isomeric heptenes in our experiment were approaching their equilibrium concentrations.

Table 4.18 : Calculated Product Distribution Based on Enthalpies of Formation of Liquid Heptenes Compound A,H AA,H B, D BfD Calc.(%) Expt.(%)

1-heptene -23.35 2.8 0.0088 2 0.0176 0.427 0.728 c-2-heptene -25.31 0.84 0.242 2 0.484 1 1 .743 12.724

f-2-heptene -26.15 0 1 2 2.000 48.525 43.254 c-3-heptene -25.00 1.15 0.143 2 0.286 6.939 7.262 f-3-heptene -25.91 0.24 0.667 2 1.334 32.366 36.032

AfH = = Enthalpies of formation of isomeric heptenes in kcal/mol. D degeneracy.

exp[-AAH = = -1 000/RT]. Calc. = [B,-D B, = Boltzmann factor Probability (%) / SB,-D] x 1 00. ZBt-D = partition function.

77 In the case of 1-octene, the lack of control over the reaction results in its rapid isomerization. Within five minutes, we notice that frans-2-octene is the major product followed by frans-3-octene. As time goes by, the percentage of frans-2-octene decreases, while that of frans-3-octene and frans-4-octene increases, until equilibrium is reached (Table 4.19).

THFa Table 4.19 : Isomerization of 1 -Octene usinq RhCI3-nH20 /BH3-THF in Time 1-Octene f-2-Octene c-2-Octene f-3-Octene Octane f-4-Octene c-4-Octene (min) 0 100 j 0 0 0 0 0 0 5 7.927 44.947 14.862 20.613 0.965 6.583 4.103 10 2.604 34.78 10.626 29.69 1.069 16.513 4.718 15 1.31 32.829 9.806 31.273 1.078 18.849 4.855 20 1.088 31.855 9.438 31.83 1.072 19.82 4.897 25 0.919 31.488 9.415 32.015 1.079 20.2 4.884 30 0.794 31.543 9.023 32.405 1.049 20.33 4.856 60 0.684 30.788 9.487 32.217 1.116 20.932 4.775 24 hrs 0.700 30.556 9.586 32.19 1.138 21.142 4.688 7 days 0.769 30.055 9.736 32.136 1.173 21.883 4.247 alsomerization was carried out at room temperature by the addition of BH3 -THF (0.3 mL, 0.3 mmol) into a mixture of the 1-octene (2 mL, 12.76 mmol) and RhCI3-nH20 (10 mg, 0.048 mmol) in 30 mL of THF. At the desired time intervals 0.5 mL aliquots of the reaction mixture were quenched using NaOH/H202. Products were extracted using 3 mL of pentane. Product distributions were determined by GC.

Table 4.20 : Isomerization of frans-4-Qctene using RhCI3-nH2Q/BH3-THF in THF

Time 1 -Octene f-2-Octene o-2-Octene f-3-Octene Octane f-4-Octene c-4-Octene (min) 0 0 16.902 0 83.093 0 0 0.37 16.933 0 82.697 0 25 0.069 1.388 0.483 21.956 0.22 75.885 0 45 0.193 7.236 2.649 29.237 0.375 56.284 4.027 60 0.316 14.788 4.712 34.103 0.663 40.494 4.924 90 0.583 27.806 8.139 33.560 1.606 23.458 4.848 120 0.668 29.704 8.898 31.390 4.718 20.074 4.547 5 hrs 0.646 29.599 8.965 31.384 4.777 20.152 4.477 72 hrs 0.717 28.753 9.642 31.159 4.799 21.568 3.361 isomerization was carried out at room temperature by the addition of BH3 -THF (0.3 mL, 0.3 frans-4-octene 9.57 and RhCI3-nH20 (10 mmol) into a mixture of the (1.5 mL, mmol) mg, 0.048 time intervals 0.5 mL aliquots of the reaction mixture mmol) in 20 mL of THF. At the desired were were extracted 3 mL of pentane. quenched using NaOH/H202. Products using Product distributions were determined by GC.

78 In order to confirm this stepwise movement of the double bond we

performed an isomerization study (Table 4.20) with rrans-4-octene.

Figure 4.12 : Isomerization of rrans-4-Octene using RhCI3-nH20/BH3-THF

120 Time in minutes

Here too, we observe the stepwise movement of the double bond from the interior of the molecule to the next position to give us frans-3-octene, followed by another migration to give frans-2-octene, accompanied by cis-trans transformations. At equilibrium, the ratio of the isomeric octenes is in good agreement with those obtained with 1-octene (Table 4.19). The above hypothesis was validated, by studying the migratory pattern adopted by frans-2-octene (Table 4.21 ) and frans-3-octene (Table 4.22).

79 RhCI3-nH2Q/Br- Table 4.21 : Isomerization of rrans-2-Qctene using

Time 1 -Octene f-2-Octene c-2-Octene Octane f-3-Octene f-4-Octene c-4-Octene Jhrs}_ 0 0 100 0 0 0 0 0 1 0.939 50.121 12.142 1.102 21.995 9.435 4.266 0.679 31.299 8.998 2.637 31.769 19.901 4.718 0.738 30.055 9.544 3.049 31.628 20.941 4.045

Table 4.22 : Isomerization of frans-3-Octene using RhCI3nH20/BH

Time 1 -Octene f-2-Octene c-2-Octene Octane f-3-Octene f-4-Octene c-4-Octene (hrs) 0 0 0 0 0 100 0 0 1 0 1.945 0.538 1.965 85.338 1.269 8.944 2 0.412 9.659 3.131 3.88 68.051 6.901 7.71

3 0.515 15.953 5.345 5.406 55.091 1 1 .706 5.984 isomerization was carried out at room temperature by the addition of 0.2 mL BH3 -THF into a mixture of the octene (0.5 mL, 3.19 mmol) and RhCI3-nH20 (10 mg, 0.048 mmol) in 10 mL of THF. Product distributions were determined by GC.

A closer look at the above results reveals that the rate of isomerization of

1-octene is much faster when compared to the other internal isomeric octenes.

Chalk25 We are once again reminded about the experiments of Harrod and during which they observed that during the isomerization of terminal alkenes,

3- 1- migration from the 2- to the position was much slower than from the to the

2- reaction kinetics position, indicating that along with thermodynamic stability, also play a very important role in determining equilibrium product ratios.

In the case of allylbenzene (Figure 4.13), the double bond has only one position into which it can migrate. However, unlike the unsubstituted straight

major product chain terminal alkenes, wherein the c/s-2-isomer is the during the

allylbenzene (Table yields a higher early stages of the isomerization, 4.23)

-phenyl- start of percentage of trans-} 1 -propene from the very the reaction.

80 Figure 4.13 : Isomerization of Allylbenzene using RhCI3-r7H20/BH3-THF

100

CD *- C

CD Q.

Time in minutes 120

THFa Table 4.23 : Isomerization of Allylbenzene using RhCI3-nH20/BH3-THF in

Time Allylbenzene Propyl benzene cis- 1 -phenyl-1- trans-1 -phenyl-1- (min) propene propene 0 100 0 0 0 5 98.954 0 0.263 0.783 10 96.182 0 0.972 2.846 15 88.952 0 2.850 8.197 25 79.936 0.171 5.178 14.715 35 67.246 0.326 8.505 23.923 45 59.555 0.366 10.612 29.467 60 50.955 0.563 12.925 35.557 90 41.422 0.706 14.663 43.209 120 9.613 2.906 18.444 69.037 5 hrs 6.272 3.340 19.123 71.265 24 hrs 6.048 3.467 17.786 72.699 isomerization was carried out at room temperature by the slow addition of BH3-THF (0.2 mL, 0.2 mmol) into a mixture of the allylbenzene (1.5 mL, 11.31 mmol) and RhCI3-nH20 (10 mg, 0.048 distributions were determined mmol) in 15 mL of THF Product by GC.

81 Table 4.24 indicates that the isomerization is very temperature sensitive.

Higher temperatures seem to favor the rapid isomerization of the alkene. This sensitive dependence on temperature may be attributed to metal-carbon bond being relatively more stable and hence not capable of undergoing rapid reaction at low temperature.

Table 4.24 : Effect of Temperature on the Isomerization of 1 25C

Time 1 -Octene f-2-Octene c-2-Octene f-3-Octene Octane f-4-Octene c-4-Octene (min) 0 100 0 0 0 0 0 0 5 7.927 44.947 14.862 20.613 0.965 6.583 4.103 15 1.31 32.829 9.806 31.273 1.078 18.849 4.855

60C

Time 1 -Octene f-2-Octene c-2-Octene f-3-Octene Octane f-4-Octene c-4-Octene (min) 0 100 0 0 0 0 0 0 0.912 30.625 10.297 31.902 0 21.031 5.232 15 0.871 30.803 9.922 32.432 0 20.417 5.555 isomerization was carried out at different temperatures (25C and 60C) by the addition of BH3-THF (0.3 mL, 0.3 mmol) into a mixture of the 1-octene (2 mL, 12.76 mmol) and RhCI3-nH20 (10 mg, 0.048 mmol) in 30 mL of THF. At regular time intervals 0.5 mL aliquots of the reaction mixture were quenched using NaOH/H202. Products were extracted using 3 mL of pentane. Product distributions were determined by GC.

In order to test catalytic activity, 1 mL of 1-octene was added into a solution containing a mixture of the catalyst and isomerized octenes. Table 4.25 shows that even after 24 hours, the catalyst although a bit slow is still active.

Table 4.26 gives us a very good insight into the efficiency of our in situ generated catalyst. As little as 10 mg (0.048 mmol) of RhCI3-/?H20 was capable of isomerizing 50 mL of 1-octene to an extent of 94% within 30 minutes at room temperature, which is really remarkable!

82 Table 4.25 : Determination of the Catalytic Activity Time 1 -Octene f-2-Octene c-2-Octene f-3-Octene Octane f-4-Octene c-4-Octene

Omin 0.731 33.412 10.368 31 .062 0 18.699 5.728 '15 min 30.512 23.973 8.263 21.124 12.691 3.438 30 min 29.975 24.390 8.853 21.040 12.368 3.373 60 min 22.538 27.841 13.880 20.828 1 1 .673 3.241 4 hrs 17.470 29.277 16.689 21.081 1 1 .975 3.508

20 hrs 7.604 31 .534 19.681 23.220 0 14.128 3.832 48 hrs 3.675 34.561 19.049 24.011 0 13.760 4.944 Isomerization was carried out at room temperature by the addition of BH3 -THF (0.3 mL, 0.3 mmol) into a mixture of the 1-octene (3 mL, 19.14 mmol) and RhCI3-nH20 (30 mg, 0.144 mmol) in 30 mL of THF. At the desired time intervals 0.5 mL aliquots of the reaction mixture were quenched using NaOH/H202. Products were extracted using 3 mL of pentane. Product distributions were determined by GC. "Product distribution after 24 hours. cProduct distributions after the addition of 1 mL 1-octene into the reaction flask in which the isomerization was going on for the past 24 hours.

Isomerization3 Table 4.26 : El feet of the Concentration of 1 -Octene on the

Time 1 -Octene f-2-Octene c-2-Octene f-3-Octene Octane f-4-Octene c-4-Octene (min) 0 100 0 0 0 0 0 0 15 10.816 41.673 42.293 3.565 0 0 1.654

30 3.837 52.953 31 .280 8.461 0 0.555 2.913 60 3.030 55.855 26.557 10.376 0 0.853 3.329 isomerization was carried out at room temperature by the addition of three drops of BH3 -THF into a mixture of the 1-octene (1 mL) and RhCI3-nH20 (10 mg, 0.048 mmol) in 15 mL of THF. When the dissolution of RhCI3-nH20 was complete, 50 mL of 1-octene was added dropwise into the flask, followed by the addition of BH3-THF (0.3 mL, 0.3 mmol). At the desired time intervals 0.5 mL aliquots of the reaction mixture were quenched using NaOH/H202. Products were extracted using 3 mL of pentane. Product distributions were determined by GC.

A desired quality of an isomerization catalyst is its capability of being nonselective in the presence of a mixture of unrelated alkenes. To test our

"starved" catalyst we performed the hydroboration of a 1:1 mixture of 1-heptene and 1-octene. Figure 4.14 indicates that both the alkenes were simultaneously isomerized into their respective internal isomers. This nonselective isomerization

can used with great success in capability of our catalyst be the chemical industry.

83 Figure 4.14 : Gas Chromatographic Separation of the Product Mixture of the "Starved" RhCI3-nH20 Catalyzed Hydroboration of

1-Heptene and 1 -Octene at 28C Sundance mcnsoHPOCTcr

9.32'

1.1e+07

1622 1e+07 15.69

9000000

8000000 15.44 7000000

6000000

5000000

10.06 4000000 16.83

3000000 !.76 16.86

2000000

1000000 8.85 14.92 JLJ rime-> 8.50 9.0b 9.50 10.00 iolso iilbb i i !sd iibb \2\s6 13'rib iilsb u'.oo 14I5015I00 is'sb iblbb 16150 i7!bb 17I50 ib!bo islso

Retention time (minutes): 1-heptene = 8.85; frans-3-heptene = 9.32; ; heptane = 9.40; c/s-3-heptene = 9.45; frans-2-heptene = 9.66; c/s-2-heptene = 10.06; 1-octene = 14.92; rrans-4-octene = 15.44; frans-3-octene = 15.69; c/s-4-octene = 15.76; octane = 15.86; frans-2-octene = 1 6.22; c/s-2-octene = 1 6.83.

4.15 Role and Fate of the Catalyst

A clear understanding of the role, efficiency, and fate of the catalyst is

now at hand. The very slow addition of BH3-THF into a mixture of the alkene and

catalyst in THF appears to be of critical importance in achieving this unique

reversal of regioselectivity. This modified procedure facilitates the generation of

the in situ catalyst, presumably a rhodium hydride species, which is responsible

"Rh-H" for alkene isomerization. This species adds reversibly across a double

bond in a Markovnikov fashion, thus facilitating the formation of internal alkenes.

In many cases, it has been observed that the hydrogen in metal hydride complexes, ionizes as a proton. A rhodium-dihydride species may be

84 hydrogenation.50 implicated to account for the alkene Excess BH3-THF reduces the catalyst into its elemental state, which appears as a fine black suspension in

mixture.60 our reaction Rhodium black is known to be a very efficient

hydrogenation catalyst.31

In situ catalyst generation via slow addition of BH3-THF allows for the

fine-tuning of the isomerization aptitude of the catalyst, resulting in a high degree

of reversal of regioselectivity in the overall reaction. Catalyst deactivation and

ultimate destruction can be achieved very easily, either by the addition of excess

BH3-THF, thus reducing the metal to its inactive elemental state, or by quenching

the reaction using Na0H/H202. It has been well established that the presence of

the octanones in the product mixture is due to the rhodium-catalyzed formation

of vinylboranes, which arise via alkene insertion into the Rh-B bond, followed by

P-hydride elimination.51

85 5. CONCLUSIONS

Unlike all the previously reported rhodium-catalyzed hydroborations of aliphatic alkenes, the results reported herein reveal a unique reversal of regioselectivity. The combination of catalytic amounts of RhCI3-nH20 and

BH3-THF (Morrill's catalyst) offers an excellent route for the one-pot synthesis of isomeric alcohols, aldehydes, ketones, amines, and halides, so far not accessible using any of the currently available procedures. Proper control of in situ catalyst generation and choice of solvent can be used with great success to enhance the yield of the desired isomeric alkenes. The rapid reversibilty of the alkene insertion/p-hydride elimination step in the mechanism, has far reaching consequences on the regioselectivity. Formation of the vinylborane via alkene insertion into the Rh-B bond followed by (3-hydride elimination can be conveniently used to explain the presence of isomeric ketones amongst the isolated products. We now have one of the most efficient catalysts for the room temperature isomerization of alkenes. This procedure can be effectively used by numerous industries that require internalized alkenes as raw materials for the manufacture of their products. Alkene isomerization using Morrill's catalyst in the presence of D20 gives us one of the most versatile procedures to label alkenes.

The almost identical product ratios of the isomeric alcohols, no matter which isomeric octene is the starting material, suggests that the reactions in all these cases proceed through a common equilibrium or transition state. This also gives us a good route to convert a mixture of alkenes into a predictable ratio of isomeric alcohols, amines or halides.

86 "aged" Wilkinson's catalyst which is can also bring about a reversal of regioselectivity probably due to its oxidation to Rh(n) and Rh(m) states. lrCI3-nH20 and RuCI3-nH20 were also effective in bringing about a similar reversal of regioselectivity. BH3 -THF is a preferred hydroborating reagent since it affords a much cleaner work-up when compared to catecholborane.

Our future goal is to synthesize, isolate and characterize this highly efficient isomerization catalyst, with the intention of making it available in a

marketable form.

If perchance, in the near furture, we invent devices that can see things at the molecular level, this isomerization experiment will definitely emerge as a classic to watch the elegant dance of the double bonds.

"The greatest friend of Truth is Time, her greatest enemy is Prejudice, Humility." and her constant compamon is Charles C. Colton.

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