A Dissertation Entitled Orthometallated Acetophenone Imines As Ligands

Home , Acetophenone, Gilman reagent, Pi interaction, Salt metathesis reaction

A Dissertation

entitled

orthoMetallated Acetophenone Imines as Ligands for Transition and Main Group Metals: Synthesis and Organometallic Reactivity and the Hydroamination of Allenes using a Palladium Allyl Triflate 3-Iminophosphine Precatalyst

John Frederick Beck

Submitted to the Graduate Faculty as partial fulfillment of the requirements for the Doctor of Philosophy Degree in Chemistry

______Dr. Joseph A.R. Schmidt, Committee Chair

______Dr. Mark R. Mason, Committee Member

______Dr. Terry P. Bigioni, Committee Member

______Dr. Maria R. Coleman, Committee Member

______Dr. Patricia R. Komuniecki, Dean College of Graduate Studies

The University of Toledo December 2011

An abstract of orthoMetallated Acetophenone Imines as Ligands for Transition and Main Group Metals: Synthesis and Organometallic Reactivity and the Hydroamination of Allenes using a Palladium Allyl Triflate 3-Iminophosphine Precatalyst

John Frederick Beck

Submitted to the Graduate Faculty as partial fulfillment of the requirements for the Doctor of Philosophy Degree in Chemistry

The University of Toledo December 2011

orthoMetallated aryl imines have been used extensively as ligands for late transition metals such as palladium and iridium. Due to the lack of a direct synthetic pathway from the imine to the orthometallated imine, there are few examples of early metals utilizing orthometallated aryl imines as ligands. Early transition metals like titanium and zirconium are unable to undergo the necessary C-H activation step to form the orthometallated complex. In order to synthesize early metal complexes utilizing orthometallated imines, a new method was developed which activates the ortho-proton, via a regiospecific lithiation, prior to metal complexation. The inclusion of a methylenedioxy moiety directs the lithiation and stabilizes the product. A series of early transition metal complexes with orthometallated imines were produced and structurally characterized, using small molecule X-ray diffraction. Multiple metal complexes were synthesized by reacting a ortholithiated imine with early transition and main group metal

t t synthons such as Ti(N Bu)Cl2py3, CpTi(N Bu)Clpy, HfCl4, EtMgBr, AlCl3, CuI, ZnCl2,

n and Bu3SnCl.

iii

The synthesis of alicyclic 3-iminophosphine ligands was extended to include a new framework incorporating a cyclopentenyl backbone with a di-tert-butyl phosphine functionality (3IPtBu). The palladium complex [(3IPtBu)Pd(allyl)]OTf displayed excellent catalytic activity in the hydroamination of 3-methyl-1,2-butadiene (1,1- dimethylallene) with primary aryl amines (anilines), selectively producing the branched allylic amine product (kinetic product) in high conversion at ambient temperature for non-halogenated substrates. Hydroamination using halogenated anilines was successful at

70 °C, providing moderate yields, with the formation of little or no linear product

(thermodynamic product). Additionally, a subsequent aromatic amino Claisen rearrangement of selected allylic amine products, employing catalytic triflic acid, proved to be an effective atom-economical method for the production of ortho-allylic anilines in a high yielding two-step, one-pot synthesis.

For Dallas Frederick and Ann Beck, my parents, Frederick Dallas and Catherina Beck, my paternal grandparents, Clarence and Doris Rutledge, my maternal grandparents,

William and Julie Rutledge, my uncle and aunt, and Bobbi Renstrom, without all of whom this would not have been possible.

Acknowledgments

I cannot express in words the thanks I owe to my parents and grandparents for shaping me into the man I am today. Without the support of my mother, Ann R. Beck, my education would not have been possible. Although my father Dallas F. Beck died when I was young, his absence showed me that nothing is guaranteed in life and that you should live your life to the fullest because you never know when it all may end. I would like to express my deepest thanks to the Kalamazoo Community Foundation and Clarence L.

Remynse for the endowment that supports the Clarence L. Remynse Scholarship. I acknowledge my advisor Dr. Joseph A.R. Schmidt and my committee members for their guidance. I also acknowledge my fellow group members Dr. Andrew Shaffer, Dr. Glenn

Kuchenbeiser, Dr. Tamam Baiz, Dr. Abdollah Neshat, Mr. Matthew Hertel, Mr. Andrew

Behrle, Mrs. Cheryl Seambos, Ms. Ksenia Kriatchkova, Mr. Aaron Jones, Mr. Nicholas

Zingales, Mr. Pascal Marillier and Ms. Danielle Samblanet. I would also like to thank Dr.

Nicholas Kingsley, Mr. Christopher Yeisley and the entire research group of Dr. Mark

Mason for their comradery. I have also been blessed by the opportunities that have been made available to me and by the many coworkers and friends who are too numerous to mention here.

Contents

Abstract iii

Acknowledgments vi

Contents vii

List of Tables x

List of Figures xi

List of Schemes xiii

Chapter 1 orthoMetallation and the Hydroamination Reaction

1.1 orthoMetallation 1

1.2 Group 4 orthoMetallation 5

1.3 orthoLithiation 6

1.4 orthoLithiation of Imines 11

1.5 Hydroamination 14

References 19

Chapter 2 Structural Characterization of Novel orthoLithiated Imines

2.1 Introduction 25

2.2 Results and Discussion 27

vii

2.3 Conclusion 42

2.4 Experimental 43

2.4.1 General Methods and Instrumentation 43

2.4.2 Ligand Synthesis 44

2.4.3 Ligand Lithiation 45

2.5 Crystallography of orthoLithiated Imines 47

References 54

Chapter 3 Isolation and Characterization of Titanium Imido Complexes using orthoMetallated Imine Ligands

3.1 Introduction 59

3.2 Results and Discussion 62

3.3 Conclusion 73

3.4 Experimental 74

3.4.1 General Methods and Instrumentation 74

3.4.2 Synthesis of Starting Materials 75

n 3.4.3 General Synthetic Procedure for complexes (L )2Ti(NR”) 76

3.5 Crystallography of 3-4a, 3-7a, 3-8a and 3-9 82

References 88

Chapter 4 Isolation and Characterization of Main Group and Late Transition Metal Complexes using orthoMetallated Imine Ligands

4.1 Introduction 97

4.2 Results and Discussion 99

4.3 Conclusion 119

4.4 Experimental 119

viii

4.4.1 General Methods and Instrumentation 119

4.4.2 Synthesis and Characterization of Reaction Products 121

4.5 Crystallography of 4-2a, 4-2b, 4-4, 4-5, 4-6, 4-7 and 4-10 132

References 137

Chapter 5 Hydroamination of 1,1-Dimethylallene with Primary Aryl Amines Under Mild Conditions: An Atom-Economical Route to N-(1,1- Dimethyl-2-Propenyl)-Anilines

5.1 Introduction 144

5.2 Results and Discussion 146

5.3 Conclusion 153

5.4 Experimental 154

5.4.1 General Methods and Instrumentation 154

5.4.2 Catalyst Synthesis 155

5.4.3 General Procedure for Catalytic Hydroamination of 1,1- 159 Dimethylallene

5.4.3.1 Characterization of Hydroamination Products 159

5.4.4 General Catalytic Procedure for Aryl Amino Claisen 162 Rearrangement

5.4.4.1 Characterization of Aryl Amino Claisen 162 Rearrangement Products

5.5 Crystallography of [(3IPtBu)Pd(allyl)]OTf (5-5) 165

References 167

List of Tables

2.1 Lithium NMR chemical shifts 33

2.2 τ values for 5-coordinate lithium centers 38

2.3 Twist angles for lithium complexes 40

2.4 Selected bond lengths and angles 41

1 2 6 2.5 Crystallographic data for compounds (Li-L )4, (Li-L )4, (Li-L )2●Et2O, 47 6 7 8 8 8 (Li-L )2, (Li-L )2, (Li-L )2, (Li-L )2●DME and H-L

3.1 Crystal data and collection parameters of 3-1a, 3-3b, 3-5a and 3-7 87

4.1 Crystallographic data for compounds 4-2, 4-4a, 4-4b, 4-5, 4-6, 4-7 and 4-10 135

5.1 Hydroamination of 1,1-dimethylallene with anilines 151

5.2 Hydroamination of 1,1-dimethylallene coupled with aryl amino Claisen 152 rearrangement

5.3 Crystallographic data for 5-5 166

List of Figures

1 2-1 ORTEP diagram of (Li-L )4 29

8 2-2 ORTEP diagram of coordination polymer of (Li-L )2 32

8 2-3 ORTEP diagram of (Li-L )2 32

6 2-4 ORTEP diagram of “donor” dimer of (Li-L )2 34

6 2-5 ORTEP diagram of coordination polymer of (Li-L )2•Et2O 36

4 2-6 ORTEP diagram of (Li-L )2●Et2O 36

8 2-7 ORTEP diagram of (Li-L )2●DME 37

8 2-8 ORTEP diagram of ((Li-L )2●DME)n 38

3-1 ORTEP diagram of 3-4b 65

3-2 ORTEP diagram of 3-7a 67

3-3 ORTEP diagram of 3-8a 68

3-4 The 1H NMR spectrum of 3-7a 69

3-5 The 1H NMR spectrum of 3-1a 71

3-6 ORTEP diagram of 3-9 73

4-1 ORTEP diagram of 4-2a 104

4-2 ORTEP diagram of 4-2b 105

4-3 ORTEP diagram of 4-4 108

4-4 ORTEP diagram of 4-5 109

4-5 ORTEP diagram of 4-6 112

4-6 ORTEP diagram of 4-7 113

4-7 ORTEP diagram of 4-10 117

5-1 ORTEP diagram of 5-5 148

xii

List of Schemes

1.1 Synthesis of cyclopentadienyl [o-(phenylazo)phenyl] nickel 2

1.2 C-H activation of a triphenylphosphine ligand of IrCl(PPh3)3 3

1.3 Insertion of a cyano group into a metal-benzyne 5

1.4 The isolation of a titanium-benzyne via the use of trimethyl phosphine 6

1.5 The reaction of anisole with n-butyl lithium and an electrophile 7

1.6 An early mechanism for the ortholithiation of anisole via n-butyllithium 8

1.7 A proposed mechanism for the lithiation of anisole 9

1.8 The solvent dependent reaction of an aryl carbamate and n-butyl lithium 11

1.9 The regiospecific lithiation of piperonal cyclohexylimine 11

1.10 The nucleophilic attack of n-butyl lithium on an imine 12

1.11 The regiospecific lithiation of an aryl imine using LiTMP 13

1.12 The zirconium catalyzed hydroamination of an alkyne and primary amine 14

1.13 The intramolecular hydroamination of an aminoalkene via a lanthanide 16 catalyst

1.14 A mechanism for the hydroamination of dienes via a palladium catalyst 17

2.1 Synthesis of lithiated imines from corresponding ketones or aldehydes 27

3.1 Synthesis of imines (H-Ln) and lithiated imines (Li-Ln) 63

xiii

3.2 Synthesis of orthometallated arylimine titanium imido complexes 63

3.3 Complex 3-1a exists as an equilibrium mixture of cis and trans isomers 70

3.4 Synthesis of 3-8b 72

3.5 Synthesis of 3-9 72

4.1 The synthesis of ortholithiated imines via Schiff base condensation 100

4.2 Synthesis of 4-1 101

4.3 Synthesis of 4-2a, 4-2b and 4-3 103

4.4 Synthesis of 4-4 and 4-5 106

4.5 Synthesis of 4-6 and 4-7 114

4.6 Synthesis of 4-8 and 4-9 115

4.7 Synthesis of 4-10 116

4.8 Synthesis of 4-13 and 4-14 118

5.1 Synthesis of 5-3 147

5.2 Metallation of 5-3 yielding the palladium complexes 5-4 and 5-5 147

xiv

Chapter 1 orthoMetallation and the Hydroamination Reaction

1.1 orthoMetallation

Over the past century, organometallic chemistry has grown from a specialized field utilizing late transition and main group metals to an area encompassing virtually all of the periodic table. Chemists originally believed that stable organometallic alkyls, like diethyl zinc, were an exception and that only a minority of metals were capable of forming stable alkyl and aryl complexes.1, 2 This was a persistent and common viewpoint even as recently as 1955, when Cotton proclaimed, “It will be apparent from this overall picture of alkyls and aryls of the transition metals that the often heard generalization that they are much less stable and accessible than those of non transition metals was quite true.”3 Time has proven this statement to be premature; many stable complexes of main group and transition metals have since been isolated. An increase in the understanding of the carbon-metal bond and the degradation pathways that lead to its destruction has made the synthesis of stable alkyl and aryl complexes much more straightforward, leading to numerous examples of stable complexes with alkyl and aryl ligands.4 The most widespread use of organometallic complexes is for catalytic transformations. Catalysts

1 are used in the polymer, fine chemical, and pharmaceutical industries, as well as natural product synthesis. One class of organometallic compounds that are of particular interest are orthometallated transition metal complexes.

Since their discovery in the 1960’s, there has been a great deal of interest in the synthesis and characterization of orthometallated transition metal complexes.5 The first report of an orthometallated transition metal complex was by Kleiman and Dubeck with the preparation of cyclopentadienyl [o-(phenylazo)phenyl] nickel.6 This was achieved by heating bis-cyclopentadienylnickel(II) in the presence of azobenzene (Scheme 1.1).

Although Kleiman and Dubeck were unable to determine the exact nature of the azo- nickel interaction, noting that this could only be done with X-ray crystallography, they were able to determine that C-H activation had taken place ortho to the azo group. In

N Ni Ni + N N Heat N - CpH

Scheme 1.1. Synthesis of the first characterized orthometallated transition metal

complex by Kleiman and Dubeck.

1965, Cope and Siekman reported the synthesis of similar palladium and platinum complexes, via the reaction of azobenzene with palladium(II) or platinum(II) chloride.7

By 1975, Heck was actively investigating the carbonylation reactions of an orthopalladation complex utilizing an orthometallated azobenzene ligand.8

The first examples of orthometallated triphenyl phosphine derivatives were independently discovered by three different groups: Parshall,9 Bennett,10 and Keim.11

These discoveries were made with several late transition metals and clearly established

2 that a C-H activation process was responsible for the formation of these orthometallated

5 phosphines. Keim found that when RhMe(PPh3)3 was heated in solution, methane was eliminated and an orange orthometallated complex was formed.11 The C-H activation of phosphine ligands had previously been noted by Chatt and Davidson.12 For

RuHCl(PPh3)3, C-H activation is reversible and in the presence of a deuterium source, results in deuteration of the ortho position of triphenyl phosphine. In contrast, the C-H

13 activation product of IrCl(PPh3)3 is readily isolable (Scheme 1.2).

H Ph PCl Ph PCl Ph P 3 Ir 3 Ir 3 Ir Ph P PPh 3 3 Ph3P - HCl Ph3P P Ph P Ph 2 2

Scheme 1.2. The isolable C-H activated iridium complex is readily formed from

IrCl(PPh3)3 via the C-H activation of an orthoproton of a triphenyl phosphine ligand.

There are four primary methods used to generate orthometallated complexes: carbon-hydrogen bond activation adjacent to the metal center, salt metathesis, ligand exchange and insertion reactions. The C-H activation of a proton ortho to the heteroatom donor to a metal center is achieved through the oxidative addition of a C-H bond across the metal, increasing the oxidation state of the metal and forming two new bonds to the metal center.5, 13 This begins with a weak agostic interaction between the metal and the

C-H bond, which has been observed crystallographically.14 The metal hydride formed by this reaction can be observed in some systems; however, in many cases a further reductive elimination reaction will result in a return to the original oxidation state of the metal and the formation of a new metal complex. For example, when [RhMe(PPh3)3] is heated in solution, the release of methane is due to the reductive elimination of a methyl

3 group and hydride from the metal center.6 It should be noted that other carbon heteroatom bonds can be activated, including C-X bonds (X = halogen).15 Oxidative addition of a C-

H or C-X bond across a metal center can be thermally or photolytically catalyzed.

A second method of generating orthometallated compounds is through ligand exchange.16 In this case, an orthometallated complex is synthesized and reacted with a new metal synthon; the ligand exchange from one metal to another generates a new metal complex.7 A subclass of this type of reaction is lithium halide exchange, where an orthohalide compound is reacted with a lithium source, such as n-butyl lithium, and lithium replaces the halide while a haloalkane is released. The lithium reagent can then be used to synthesize new orthometallated complexes that would not be accessible via C-H bond activation with a transition metal.17 This has allowed for the synthesis of many new metal complexes; however, most orthometallated complexes are still synthesized using late transition metal precursors. The reason for this is all in the oxidation state. Early transition metals are generally found in their highest oxidation state and therefore cannot undergo oxidative addition. Additionally, many metals, such as titanium for which oxidation states other than (+4) are common, undergo a reductive process instead of orthometallation. It should be noted that some group(IV) orthometallated complexes have been synthesized through alternative means (see Section 1.2).

orthoMetallated transition metal complexes showing catalytic activity have been studied, including complexes that catalyze cyclopropanation of diazoketones,18

19 20 21 hydrogenation, hydroamination, and the generation of H2 from formic acid. Lai and co-workers reported the use of orthometallated imine iridium complexes as catalysts for the hydroamination of alkenes and alkynes. Lai believed that orthometallated C~N

4 ligands may be useful alternatives to other widely used ligands, such as P~N ligands, for hydroamination.20

1.2 Group 4 orthoMetallation

Despite their use as ligands for late transition metals, orthometallated aryl imines are seldom used as ligands for early transition metals due to the lack of a direct synthetic path from the imine to the orthometallated imine. One method of synthesizing early transition metal orthometallated imines is the insertion of a cyano group into a metal- benzyne, followed by the addition of a weak acid to generate a monoanionic orthometallated aryl imine (Scheme 1.3).22-24 Although effective, there are some disadvantages to this method. First, the inability to tune the steric bulk of the imine

Zr H Zr i N + ( Pr)2P N - C6H6 i P( Pr)2 Cp Zr H 2 N

i P( Pr)2

Scheme 1.3. Insertion of a cyano group into a metal-benzyne and reaction with phenyl

acetylene, generating the group(IV) orthometallated imine. substituent makes this method unfavorable. A second disadvantage is that initially a doubly anionic ligand is produced and must be protonated to generate the monoanionic version. That said, there are several thermal routes available to produce the doubly anionic complex, utilizing a number of different starting materials. For example, group(IV)-benzyne complexes can be readily synthesized from bisaryltitanocene or bisarylzirconocene complexes. More complex organometallic reagents, such as aryl(methyl)titanocene, have also been used to generate the benzyne complexes.

Generally, the benzyne complexes are transient and not well characterized; however,

Buchwald and coworkers have been able to isolate the titanocene-benzyne complex,

2 24, 25 Cp2Ti(ƞ -C6H3-2-OMe)(PMe3), and conduct further reactivity studies (Scheme 1.4)

P O

Ti + Me3P Ti O - CH4

Scheme 1.4. The isolation of a titanium-benzyne via the use of trimethyl phosphine.

Usually the benzyne complexes used are generated in situ and converted to the more stable insertion products without isolation. Although this chemistry is useful in the synthesis of substituted benzene derivatives, there are numerous organometallic transformations required to reach the final product,26 making this a rather cumbersome method of generating early transition metal orthometallated imines. A more straightforward and shorter synthesis would be extremely beneficial for the expansion of this field of chemistry.

1.3 orthoLithiation

orthoLithiation is the activation of a carbon-hydrogen bond ortho to another functional group. The functional group that is ortho to this site of lithiation is termed the directed metallation group (DMG).27 There are numerous examples of groups that can direct the site of lithiation on arenes. These groups include, but are not limited to,

28-31 CONEt2, CH2NMe2, OCH3 and F. This list has expanded significantly over the years and continues to grow with the improved mechanistic understanding of this reaction.

The first examples of the ortholithiation of hetero-substituted arenes were noted by Gilman32, 33 and Wittig34 in the late 1930’s. Independently, both chemists discovered the ortholithiation of anisole with n-butyl lithium (Scheme 1.5).34, 35 Although neither chemist isolated the lithium salt formed from this reaction, both did react the intermediate product with a number of electrophiles. It has been noted in a number of reviews that at the time, it was a remarkably selective reaction; the selectively for this reaction, even by modern standards, is quite good.27 Before modern synthetic reactions like Heck, Negishi,

Stille and Suzuki coupling, lithium reagents were one of the few methods for

O O O nBuLi Li EX E -nBuH - LiX

Scheme 1.5. The reaction of anisole with n-butyl lithium and quenching with an

electrophile discovered independently by Gilman and Wittig. regioselectively creating new carbon-carbon or carbon-heteroatom bonds. Even today, many industrial processes continue to use lithium reagents.36

Initially, it was believed that the directed metallation group only increased the acidity of the orthocarbon, making it possible for the lithium reagent to remove the proton and form the lithium salt. The directed metallation group does indeed increase the acidity of the proton to be removed, but it also acts as a coordination site for lithium, further facilitating the deprotonation of the ortho position.37 Recent studies have questioned the assertion that the DMG acts as a coordination site for lithium during deprotonation.38 Computational and experimental studies have shown that the mechanism for ortholithation is far more complex, depending on both the substrate and the clustering of the lithium reagent in solution.39, 40

A directed metallation group must possess some key characteristics. The group must act as a good coordination site for the alkyl lithium reagents, although this may not be as important as previously believed. The group must additionally be a poor electrophile to ensure that no side reactivity with the basic lithium reagent takes place.

Also, the incorporation of steric bulk can help decrease the possibility of nucleophilic attack by the lithium reagents upon the directed metallation group.27 Collum

4 nBuLi L + NN Li nBu NN n Li O Bu Li L xs TMEDA n n Li n 2 Bu Bu 2 n n Bu Li - 4 L Li - 2 TMEDA Bu Bu Li nBu Li 4 L N N L

NN NN 2 anisole 2 Li Li reaggregation n n n Bu 2 Bu Bu OLi- 2 nBuH Li 2 O H

aggregation

Scheme 1.6. An early mechanism for the ortholithiation of anisole via n-butyllithium.

Note the coordination of the oxygen of anisole to lithium (L = anisole).

and coworkers performed an experimental and computational study of the ortholithiation of fluorobenzene, fluoroanisole and anisole, finding that fluorine and oxygen have very little interaction with the lithium center and inductive effects dominate (Schemes 1.6 and

1.7). Furthermore, it is believed that a triple ion mechanism is likely.38 Triple ions are a type of “ate” salt and possess both a dimer and a solvent separated ion pair; a triple ion mechanism goes through a triple ion intermediate.41, 42 Analogous to other main group

“ate” complexes, triple ions should show high basicities and nucleophilicities, as

8 suggested by Wittig in 1951.43 Collum cautioned, however, that this mechanism should not be applied universally to all systems and that there are likely mechanistic differences between substrates.

+ - + NN O Li NN n n n n - Ar-H H Bu NN Bu Bu Bu Li Li 2 Li Li Li N N N N N N nBu

-+ n O - BuH n NN Li Bu Li N N

Scheme 1.7. A proposed mechanism for the lithiation of anisole, in which inductive

forces drive the lithiation with no lithium-oxygen interaction.

The solvent used, as well as any additives such as TMEDA, can have pronounced effects on the aggregation and reactivity of lithium reagents. The aggregation state of a lithium salt is especially important in its effective basicity and for this reason the reaction being performed can also be affected by the solvent used. Addition of Lewis basic solvents (i.e. ethers or amines) causes the dissociation of the lithium clusters via a Lewis acid-base reaction. For example, THF coordination to (n-BuLi)6 leads to solvated (n-

27 BuLi)4. Furthermore, the addition of TMEDA leads to the formation of dimeric lithium complexes (Scheme 1.7). Sometimes a change in coordinating solvent can even facilitate a reaction that was otherwise ineffective. For example, the deprotonation of benzene by

[n-BuLi•(R,R)-TMCDA]2 (TMCDA = N,N,N′,N′-tetramethylcyclohexane-1,2-diamine) is

9 possible, whereas benzene shows no reactivity with n-butyl lithium alone.44 The ortholithiation of bulky aryl carbamates has also been noted in the literature. However, when less bulky substrates are used, the anionic Fries rearrangement is observed. In general, the reaction of aryl carbamates in THF with LDA favors the Fries rearrangement, which can be prevented by increasing the steric bulk of the aryl carbamate. Interestingly, the use of a less polar solvent than THF yields the ortholithiated aryl carbamate instead (Scheme 1.8).45 Without the need to modify the substrate being lithiated, it is possible to control the product that is isolated. This is perhaps one of the most remarkable examples of solvent dependent lithiation known. Although the exact mechanism remains unclear, there is a zero-order dependence on the concentration of

THF for the Fries rearrangement, but as the concentration of THF is decreased and another solvent, such as BuOMe, is increased the amount of Fries rearrangement product decreases.45 NMR and computational evidence imply that a different clustering of the lithium reagent is responsible for the lack of Fries rearrangement observed.

Me N 2 H O NMe O O 2 Li O NMe F 2 LDA/THF F O O

Me2N F O O n LDA/ BuOMe Li

isolable

Scheme 1.8. The solvent dependent reaction of an aryl carbamate with n-butyl lithium.

1.4 orthoLithiation of Imines

There are a number of examples of ortholithiation of imines in the literature.46, 47

A notable example is that of Ziegler and Fowler who were, by the judicious choice of imine, able to ortholithiate piperonal cyclohexylimine, although the lithiated imine was not isolated (Scheme 1.9).46 In contrast, lithiation of acetophenone cyclohexylimine in diethyl ether led to a mixture of ortholithiated products and species that were lithiated at both the ortho position and the methyl group.46 The addition of n-butyl lithium to

N n Li N I N BuLi I2 O n H - BuH O H - LiI O H O O O

Scheme 1.9. The regiospecific lithiation of piperonal cyclohexylimine.

R' R' R' N n Li N + H N BuLi H H H + H - Li

Scheme 1.10. The nucleophilic attack of n-butyl lithium on an imine (R’ = tBu,

Adamantyl). many imines leads to nucleophilic attack on the imine carbon (Scheme 1.10). 48, 49 This makes the choice of imine exceptionally important if one is to achieve the desired ortholithiated product. In the case of Ziegler and Fowler’s work, the methylenedioxy ring seems to act as a directing group and may be partially responsible for the selectivity of the ortholithiation observed. There have been reports of the lithiation of other similar substrates incorporating this moiety.50, 51 Additionally, there are numerous other cases of ortholithiated imines besides that of Ziegler and Fowler, and these often include more traditional DMG’s such as methoxy as seen in the work of Breit and coworkers.32

Generally, these compounds were synthesized as intermediates in the synthesis of a natural product or small molecule. The work that Ziegler and Fowler detailed in their original report was the first step in a lone multistep synthesis of (±)-Steganacin, an antileukemic natural product.52 Flippin and coworkers have ortholithiated a wider range of imines employing lithium 2,2,6,6-tetramethylpiperidide (LiTMP) and isolated the products of their subsequent reactions with numerous electrophiles in high yields

(Scheme 1.11).47 Lithium 2,2,6,6-tetramethylpiperidide is a bulky amide that is often used as a lithiation agent in place of nBuLi, tBuLi or MeLi. The sterically bulky nature of

LiTMP makes it much less likely to attack the carbon of the imine than traditional lithium

12 alkyls.52 Overall, the regiospecificity offered by ortholithiation makes it an appealing methodology for the synthesis of substituted benzene derivatives.

N Li N I N LiTMP I2 O H - HTMP O H - LiI O H

Scheme 1.11. The regiospecific lithiation of an aryl imine using lithium 2,2,6,6-

tetramethylpiperidide (LiTMP).

In all cases of lithiation discussed above the lithium salts were not isolated, and there were no reports of an isolated ortholithiated imine until the work of Schmidt and

Baiz.53 Using a backbone similar to that of Ziegler and Fowler while increasing steric bulk by incorporation of a 2,6-Et2C6H3 group bound to the nitrogen of the imine, they were able to isolate the ortholithiated imine. Replacement of THF with pentane also aided in the isolation due to the precipitation of the ortholithiated imine from pentane.

Ziegler and Fowler had previously noted that the ortholithiated imine was unstable at ambient temperature in THF, and that this could be due to the deprotonation of THF by the ortholithiated imine.46 The isolated ortholithiated imine was then subsequently used by Schmidt to synthesize a number of titanium and zirconium complexes.53 More recently, Mu and coworkers were able to ortholithiate an imine via lithium halide exchange and isolate the producy of their reaction with titanium synthons; however, once again the ortholithiated imine was not isolated.54 In summary, although ortholithiated imines have found a place in synthetic chemistry, their true potential as ligand precursors and synthetic intermediates in organic synthesis is far from being completely realized.

1.5 Hydroamination

Hydroamination is an economical way of producing new amines and imines via addition of an N-H bond across a carbon-carbon unsaturated bond. Hydroamination allows for the synthesis of new amines with 100% atom economy in high yields from cheap and easily accessible carbon sources including alkenes, dienes, alkynes, and allenes, making it a highly desirable transformation.55, 56 There are numerous examples of hydroamination catalysts in the literature. Main group hydroamination has continued to grow as a field of study with recent discoveries of active calcium, magnesium,57 and aluminum catalysts.58 Additionally, group(IV) hydroamination is of particular interest due to its proven effectiveness in the synthesis of imines and aminoalkenes from alkynes.

Cp2Zr(NHAr)2

NAr -H NAr R 2 R

Ar N R ZrCp2 R NHAr

RAr Ar N R N R ZrCp2 ZrCp2 N Ar H R

R Ar N

ZrCp2 R

H2NAr

Scheme 1.12. The zirconium catalyzed hydroamination of an alkyne and primary

amine.

Neutral group(IV) hydroamination of alkynes is believed to go through a metallacyclic intermediate (Scheme 1.12). A group(IV) imido is believed to be the active catalyst; during catalysis the alkyne binds to the metal center and undergoes a [2+2] cycloaddition with the imido moiety forming the metallacyclobutene intermediate. Coordination of a second equivalent of amine and protonation regenerates the active imido catalyst and releases the product aminoalkene, which isomerizes to the more thermodynamically stable imine in most cases.56

Lanthanide, magnesium, and cationic group(IV) hydroamination is believed to proceed via a sigma bond metathesis route. Lanthanide and magnesium hydroamination catalysts are excellent at performing intramolecular hydroamination starting with an aminoalkene and yielding a cyclized product (Scheme 1.13).59 The amine of the aminoalkene protonates one of the ligands bound to the metal center forming a new metal nitrogen bond. Next, the alkene coordinates to the metal center. Then, the rate-limiting step of insertion of the alkene into the metal nitrogen bond occurs. This is followed by the coordination of another equivalent of aminoalkene and protonation to produce the product, regenerating the active catalyst. Lanthanide hydroamination catalysts are not limited to aminoalkenes.59 There are also cases of aminoalkyne60 and conjugated aminodiene61 substrates. In general, lanthanide hydroamination catalysts are excellent catalysts for the formation of heterocycles.

L2LnN(TMS)2 + H2NR

HN(TMS)2

L2Ln N H N R R H

L2Ln N

H2NR

HN L2Ln R

Scheme 1.13. The intramolecular hydroamination of an aminoalkene via a lanthanide

catalyst.

Palladium is another metal that has shown excellent utility as a catalyst for a number of transformations, including hydroamination and aryl amination. Numerous palladium systems exist for the hydroamination of alkenes, dienes, allenes and alkynes.55

More than one operable mechanism has been proposed for these systems and many have been documented in review articles.55, 62 One of particular interest is the allylic base mechanism, which is commonly invoked for the hydroamination of dienes and allenes via a palladium catalyst.63

+ L M H L H+

L L M

H+

+ L L M M L L

HNR2 L + H + L M R2N

+ R2N H

Scheme 1.14. One mechanism for the hydroamination of dienes via a palladium

catalyst.

The allylic mechanism is based upon a palladium hydride species (Scheme 1.14).

Following coordination of the diene (or allene), insertion into the palladium-hydride bond takes place, yielding an allylic palladium complex. This is followed by coordination and insertion of the amine, creating a cationic aminoalkene, which is then released from the metal center. This results in the hydroamination product and a proton that can then be

17 used to regenerate the palladium hydride precatalyst. This is distinctly different from other palladium based mechanisms in which the Lewis acidic metal center simply activates the alkene for attack by the nucleophilic amine.

There are numerous transition and main group metals that can be used as catalysts for the hydroamination of a myriad of substrates, all of which have specific advantages and disadvantages. While palladium catalysts have superior functional group tolerance compared to group(IV) catalysts, the cost associated with palladium cannot be ignored.

There is no one ideal catalyst for all applications and further investigation of metal complexes for hydroamination is needed in order to grow the toolbox available for this versatile and important application of organometallic chemistry.

References

1. Miessler, G. L.; Tarr, D. A., Inorganic Chemistry. 3rd ed.; Pearson Education: Upper Sadddle River, NJ, 2004.

2. Wilkinson, G., The long search for stable transition metal alkyls. Science 1974, 185, 109-112.

3. Cotton, F. A., Alkyls and aryls of transition metals. Chemical Reviews 1955, 55 (3), 551-594.

4. Crabtree, R. H., The Organometallic Chemistry of the Transition Metals. John Wiley & Sons: New York, 2001.

5. Mohr, F.; Priver, S. H.; Bhargava, S. K.; Bennett, M. A., Ortho-metallated transition metal complexes derived from tertiary phosphine and arsine ligands. Coordination Chemistry Reviews 2006, 250 (15-16), 1851-1888.

6. Kleiman, J. P.; Dubeck, M., The preparation of cyclopentadienyl [o- ([phenylazo)phenyl]nickel. Journal of the American Chemical Society 1963, 85 (10), 1544-1545.

7. Cope, A. C.; Siekman, R. W., Formation of covalent bonds from platinum or palladium to carbon by direct substitution. Journal of the American Chemical Society 1965, 87 (14), 3272-3273.

8. Thompson, J. M.; Heck, R. F., Carbonylation reactions of ortho-palladation products of D-arylnitrogen derivatives. Journal of Organic Chemistry 1975, 40 (18), 2667-2674.

9. Parshall, G. W., Hydrogen deuterium exchange in a cobalt nitrogen complex. Journal of the American Chemical Society 1968, 90 (6), 1669-1670.

10. Bennett, M. A.; Milner, D. L., Chlorotris(triphenylphosphine)iridium(I): An example of hydrogen transfer to a metal from a coordinated ligand. Chemical Communications 1967, (12), 581-583.

11. Keim, W., New sigma bonded rhodium(I) complexes containing a metal-carbon bond. Journal of Organometallic Chemistry 1968, 14 (1), 179-184.

12. Chatt, J.; Davidson, J. M., 154. The tautomerism of arene and ditertiary phosphine complexes of ruthenium(0), and the preparation of new types of hydrido- complexes of ruthenium(II). Journal of the Chemical Society 1965, 843-855.

13. Cotton, F. A.; Murillo, C. A.; Bochmann, M.; Grimes, R. N., Advanced Inorganic Chemistry, 6th Edition. Wiley-Interscience: New York, 1999.

14. Brookhart, M.; Green, M. L. H.; Parkin, G., Agostic interactions in transition metal compounds. Proceedings of the National Academy of Sciences of the United States of America 2007, 104 (17), 6908-6914.

15. Chen, S.; Li, Y.; Zhao, J.; Li, X., Chelation assisted carbon-halogen bond activation by a rhodium(I) complex. Inorganic Chemistry 2008, 48 (3), 1198- 1206.

16. Ryabov, A. D., Thermodynamics, kinetics, and mechanism of exchange of cyclopalladated ligands. Inorganic Chemistry 1987, 26 (8), 1252-1260.

17. Omae, I., Organometallic intramolecular-coordination compounds containing a phosphorus donor ligand. Coordination Chemistry Reviews 1980, 32 (3), 235-271.

18. Barberis, M.; Parez-Prieto, J.; Stiriba, S.-E.; Lahuerta, P., High enantiocontrol in the intramolecular cyclopropanation of diazo ketones catalyzed by dirhodium(II) complexes with ortho-metalated aryl phosphine ligands. Organic Letters 2001, 3 (21), 3317-3319.

19. Stolzenberg, A. M.; Muetterties, E. L., Rapid, reversible orthometalation in RuHCl[P(C6H5)3]3 and its role in the catalytic-hydrogenation of alkynes. Organometallics 1985, 4 (10), 1739-1742.

20. Lai, R.; Surekha, K.; Hayashi, A.; Ozawa, F.; Liu, Y.; Peng, S.; Liu, S., Intra- and intermolecular hydroamination of alkynes catalyzed by ortho-metalated iridium complexes. Organometallics 2007, 26 (4), 1062-1068.

21. Boddien, A.; Gartner, F.; Jackstell, R.; Junge, H.; Spannenberg, A.; Baumann, W.; Ludwig, R.; Beller, M., ortho-Metalation of iron(0) tribenzylphosphine complexes: Homogeneous catalysts for the generation of hydrogen from formic acid. Angewandte Chemie-International Edition 2010, 49 (47), 8993-8996.

22. Hsu, D. P.; Lucas, E. A.; Buchwald, S. L., Synthesis and reactions of a zirconocene-benzdiyne equivalent. Tetrahedron Letters 1990, 31 (39), 5563-5566.

23. Kropp, K.; Erker, G., Stereospecific formation of 5-membered metallacycles. Zirconaindans from thermally generated (K2- dehydrobenzene)dicyclopentadienylzirconium(II) and cis-stilbene and trans- stilbene. Organometallics 1982, 1 (9), 1246-1247.

24. Cadierno, V.; Zablocka, M.; Donnadieu, B.; Igau, A.; Majoral, J. P.; Skowronska, A., X-H (X = C, N, O, P, S) bond activations induced by beta-heterosubstituted zirconaindenes. Chemistry-a European Journal 2001, 7 (1), 221-229.

25. Barr, K. J.; Watson, B. T.; Buchwald, S. L., Zirconocene(iso-butyl)chloride in situ generation of a zirconocene(methyl) chloride equivalent for use in organic synthesis. Tetrahedron Letters 1991, 32 (40), 5465-5468.

26. Campora, J.; Buchwald, S. L., Synthesis and reactivity of a titanocene benzyne complex. Organometallics 1993, 12 (10), 4182-4187.

27. Snieckus, V., Directed orthometalation: Tertiary amide and o-carbamate directors in synthetic strategies for polysubstituted aromatics. Chemical Reviews 1990, 90 (6), 879-933.

28. Bauer, W.; Schleyer, P. V., Mechanistic evidence for ortho-directed lithiations from one- and two-dimensional NMR spectroscopy and MNDO calculations. Journal of the American Chemical Society 1989, 111 (18), 7191-7198.

29. Smith, K.; El-Hiti, G. A., Regioselective control of electrophilic aromatic substitution reactions. Current Organic Synthesis 2004, 1 (3), 253-274.

30. Beak, P.; Brown, R. A., orthoMetalations. Advantage of the amide functions. Journal of Organic Chemistry 1979, 44 (24), 4463-4464.

31. Beak, P.; Brown, R. A., The tertiary amide as an effective director of ortholithiation. Journal of Organic Chemistry 1982, 47 (1), 34-46.

32. Reichert, S.; Breit, B., Development of an axial chirality switch. Organic Letters 2007, 9 (5), 899-902.

33. Gilman, H.; Webb, J. F., Lateral metalation of methyl phenyl sulfide. Journal of the American Chemical Society 1940, 62, 987-988.

34. Wittig, G.; Fuhrmann, G., Über das verhalten der halogenierten anisole gegen phenyl lithium. Chemische Berichte 1940, 73, 1197-1218.

35. Gilman, H.; Bebb, R. L., Relative reactivities of organometallic compounds. Journal of the American Chemical Society 1939, 61, 109-112.

36. Wu, G.; Huang, M., Organolithium reagents in pharmaceutical asymmetric processes. Chemical Reviews 2006, 106 (7), 2596-2616.

37. Hommes, N.; Schleyer, P. V., Mechanisms of aromatic lithiation: Influence of aggregation and directing groups. Tetrahedron 1994, 50 (20), 5903-5916.

38. Chadwick, S. T.; Rennels, R. A.; Rutherford, J. L.; Collum, D. B., Are n- BuLi/TMEDA-mediated arene ortholithiations directed? Substituent-dependent rates, substituent-independent mechanisms. Journal of the American Chemical Society 2000, 122 (36), 8640-8647.

39. Chadwick, S. T.; Ramirez, A.; Gupta, L.; Collum, D. B., n- Butyllithium/N,N,N',N'-tetramethylethylenediamine-mediated ortholithiations of aryl oxazolines: Substrate-dependent mechanisms. Journal of the American Chemical Society 2007, 129 (8), 2259-2268.

40. Collum, D. B., Is N,N,N’,N’-tetramethylethylenediamine a good ligand for lithium? Accounts of Chemical Research 1992, 25 (10), 448-454.

41. Lucht, B. L.; Bernstein, M. P.; Remenar, J. F.; Collum, D. B., Polydentate amine and ether solvates of lithium hexamethyldisilazide (LiHMDS): Relationship of ligand structure, relative solvation energy, and aggregation state. Journal of the American Chemical Society 1996, 118 (44), 10707-10718.

42. Reich, H. J.; Sikorski, W. H.; Gudmundsson, B. A.; Dykstra, R. R., Triple ion formation in localized organolithium reagents. Journal of the American Chemical Society 1998, 120 (16), 4035-4036.

43. Wittig, G.; Meyer, F. J.; Lange, G., Über das verhalten von diphenylmetallen als komplexbildner. Justus Liebigs Annalen der Chemie 1951, 571 (3), 167-201.

44. Strohmann, C.; Gessner, V. H., Crystal structures of n-BuLi adducts with (R,R)- TMCDA and the consequences for the deprotonation of benzene. Journal of the American Chemical Society 2008, 130 (35), 11719-11725.

45. Singh, K. J.; Collum, D. B., Lithium diisopropylamide-mediated ortholithiation and anionic Fries rearrangement of aryl carbamates: Role of aggregates and mixed aggregates. Journal of the American Chemical Society 2006, 128 (42), 13753-13760.

46. Ziegler, F. E.; Fowler, K. W., Substitution reactions of specifically ortho-metalted piperonal cyclohexylimine. Journal of Organic Chemistry 1975, 41 (9), 1564- 1566.

47. Flippin, L. A.; Muchowski, J. M.; Carter, D. S., Directed metalation of aromatic aldimines with lithium 2,2,6,6-tetramethylpiperidide. Journal of Organic Chemistry 1993, 58 (9), 2463-2467.

48. Cliffe, I. A.; Crossley, R.; Shepherd, R. G., Sterically hindered lithium dialkylamides: A novel synthesis of lithium dialkylamides from n-tert-alkyl-n- benzylideneamines and the isolation of highly hindered s-alkyl-tert-alkylamines. Synthesis-Stuttgart 1985, (12), 1138-1140.

49. Qu, B.; Collum, D. B., Structure of n-butyllithium in mixtures of ethers and diamines: Influence of mixed solvation on 1,2-additions to imines. Journal of the American Chemical Society 2006, 128 (29), 9355-9360.

50. Khaldi, M.; Chretien, F.; Chapleur, Y., Synthesis of pentasubstituted benzamides via orthometallation: Base and substituent effects. Bulletin de la Societe Chimique de France 1996, 133 (1), 7-13.

51. Pfeffer, M.; Urriolabeitia, E. P.; Decian, A.; Fischer, J., Synthesis and characterization of asymmetric c,n-cyclometalated complexes of Mo(II). X-ray 5 crystal structures of [(ƞ -C5H5)Mo(C6H2-(OCH2O)-2,3-CH2NMe26)(I)(NO)] and

5 [(ƞ -C5H5)Mo(s-C6H4CH(Me)NMe2)(I)(NO)]. Journal of Organometallic Chemistry 1995, 494 (1-2), 187-193.

52. Ziegler, F. E.; Chliwner, I.; Fowler, K. W.; Kanfer, S. J.; Kuo, S. J.; Sinha, N. D., Ambient temperature Ullmann reaction and its application to the total synthesis of (+/-)-steganacin. Journal of the American Chemical Society 1980, 102 (2), 790- 798.

53. Baiz, T. I.; Schmidt, J. A. R., A discrete ortho-lithiated acetophenone imine derivative: Isolation, characterization, and synthesis of group IV metal complexes. Organometallics 2007, 26, 4094-4097.

54. Zhao, D. P.; Gao, B.; Gao, W.; Luo, X. Y.; Tang, D. H.; Mu, Y.; Ye, L., New titanium complexes with symmetric or asymmetric cis-9,10- dihydrophenanthrenediamide ligands formed through sequential intramolecular C- C bond forming reactions. Inorganic Chemistry 2011, 50 (1), 30-36.

55. Muller, T. E.; Hultzsch, K. C.; Yus, M.; Foubelo, F.; Tada, M., Hydroamination: Direct addition of amines to alkenes and alkynes. Chemical Reviews 2008, 108 (9), 3795-3892.

56. Muller, T. E.; Beller, M., Metal initiated amination of alkenes and alkynes Chemical Reviews 1998, 98 (2), 675-704.

57. Crimmin, M. R.; Arrowsmith, M.; Barrett, A. G. M.; Casely, I. J.; Hill, M. S.; Procopiou, P. A., Intramolecular hydroamination of aminoalkenes by calcium and magnesium complexes: A synthetic and mechanistic study. Journal of the American Chemical Society 2009, 131 (28), 9670-9685.

58. Koller, J.; Bergman, R. G., Aluminium-catalyzed intramolecular hydroamination of aminoalkenes. Chemical Communications 2010, 46 (25), 4577-4579.

59. Hong, S.; Marks, T. J., Organolanthanide catalyzed hydroamination. Accounts of Chemical Research 2004, 37 (9), 673-686.

60. Pohlki, F.; Doye, S., The catalytic hydroamination of alkynes. Chemical Society Reviews 2003, 32 (2), 104-114.

61. Tobisch, S., Mechanistic investigation of organolanthanide mediated hydroamination of conjugated aminodienes: A comprehensive computational assessment of various routes for diene activation. Chemistry-a European Journal 16 (46), 13814-13823.

62. Hultzsch, K. C., Transition metal catalyzed asymmetric hydroamination of alkenes. Advanced Synthesis & Catalysis 2005, 347 (2-3), 367-391.

63. Johns, A. M.; Liu, Z. J.; Hartwig, J. F., Primary tert- and sec-allylamines via palladium-catalyzed hydroamination and allylic substitution with hydrazine and

23 hydroxylamine derivatives. Angewandte Chemie-International Edition 2007, 46 (38), 7259-7261.

Chapter 2

Structural Characterization of Novel orthoLithiated Imines

2.1 Introduction

Since the early works of Gilman1 and Wittig2 many functional groups have been identified as good ortho-directing moieties and the general magnitude of their effect on

3-6 ortholithiation has been determined as CONEt2 > CH2NMe2 > OCH3 > F. Absent from this list is the imine functionality due to its generally poor ortho-directing ability and the usual formation of undesirable side products upon its use.7, 8 There are some examples of ortholithiated imines as synthetic intermediates in organic synthesis,9-12 but isolation and structural characterization of these compounds remains notably absent from the literature.

A search of the Cambridge Structural Database shows no examples of structurally characterized ortholithiated imines, but does yield a few examples of the closely related ortholithiated phenyl oxazolines.13-16 These include species with either one or two oxazoline groups located ortho to the lithiated phenyl carbon atom.

In 1975, Ziegler and Fowler successfully ortholithiated piperonal cyclohexylimine using n-butyl lithium (nBuLi) and isolated the subsequent product of its reaction with iodine.17 This compound and others prepared via more traditional lithium

25 halide exchange reactions have been used in the total synthesis of (±)-Steganacin, an antileukemic natural product.18 Flippin and coworkers have ortholithiated a wider range of imines employing lithium 2,2,6,6-tetramethylpiperidide (LiTMP) and isolated the products of their subsequent reactions with numerous electrophiles in high yields.10 Many of the known ortholithiated imines incorporate the more conventional ortho-directing groups, such as the methoxy group. Given its electronic similarities to the methoxy group, the methylenedioxy functionality pioneered by Ziegler and Fowler undoubtedly has an ortho-directing effect. Indeed, several ortholithiated compounds have been isolated incorporating the methylenedioxy group, including amides,19 amines20 and thioethers.21 Thus, it seemed likely that the methylenedioxy group could be used as an ortho-directing moiety to assist in the synthesis and isolation of these elusive ortholithiated imines.

In our recent work, we have shown that 3,4-methylenedioxyphenyl imines can be readily synthesized via Schiff-base condensation reactions of the related aldehydes and ketones. orthoLithiation of these imines proceeds readily to yield the deprotonated species, where regiospecific lithiation occurs at the position mutually ortho to both the methylenedioxy and imine groups.22, 23 To date, we have investigated the use of these anionic units as ancillary ligands in the early-transition metal chemistry of titanium, zirconium, niobium and tantalum.22-24 Due to the interesting NMR spectroscopic features observed for these ortholithiated imines and the general lack of structurally characterized examples of this class of molecules, we embarked on a study of the molecular structure of these ortholithiated imines, crystallized from a wide variety of non-polar solvents. In this chapter, we show the results of crystallization of these species from both coordinating

26 and non-coordinating solvents, the impact of steric bulk in the imine substituent, and the overall clustering observed in a series of eight ortholithiated imines.

2.2 Results and Discussion

A series of eight imines was prepared via the Schiff base condensation reactions of either 3’,4’-methylenedioxyacetophenone or piperonal with various primary amines in refluxing toluene along with a catalytic amount of para-toluenesulfonic acid. The only exception was H-L2 which, because of the low boiling point of tert-butylamine, was

t synthesized via an imido/oxo exchange reaction between Ti(N Bu)Cl2py3 and 3’,4’- methylenedioxyacetophenone.22 The subsequent lithiation of H-L1-8 was performed in pentane at reduced temperature (Scheme 2.1), although for the imines with very sterically

i bulky groups bound to the nitrogen atom, such as 2,6- Pr2C6H3, lithiation was effective at room temperature with no reduction in yield or purity. Of this series of eight ortholithiated imines, Li-L3 was found to be comparatively unstable, decomposing into

R' O N H2NR' O + O n R cat. H R BuLi 1-8 Li-L O Toluene O Pentane n - H2O - BuH

3 R' O Li-L : R = H; R' = 2,6-Me2C6H3 Li N 4 Li-L : R = Me; R' = 2,6-Me2C6H3 R O O L 5 R R' Li-L : R = H; R' = 2,6-Et2C6H3 N Li Li N 6 O R' L Li-L : R = Me; R' = 2,6-Et2C6H3 4 O 7 i 1 R Li-L : R = H; R' = 2,6- Pr C H Li-L : R = H; R' = Cy 2 6 3 8 i Li-L2: R = Me; R' = tBu O Li-L : R = Me; R' = 2,6- Pr2C6H3 L = Et2O, DME, or oxygen atom of a dimer complex

Scheme 2.1. Synthesis of lithiated imines from corresponding ketones or aldehydes.

27 unidentifiable products even at low temperature. The simple inclusion of a methyl group on the imine carbon to produce the related ketimine (Li-L4) dramatically increased its stability in organic solvents. This seems to indicate a significant steric contribution to the overall stability of these lithium complexes in solution. In contrast, no ortholithiated ketimines could be isolated from attempts to lithiate the related imines bearing phenyl or

4-MeC6H4 substituents on the imine nitrogen atom. Each of the successfully lithiated imines exhibited low solubility in pentane, precipitating from the reaction mixture as a powder soon after the addition of nBuLi in good yields with a high degree of purity.

Lithiation can also be successfully carried out in toluene and ethereal solvents, but due to the acidic nature of the α-proton of THF, it cannot be used as a solvent at room temperature due to protonation of the lithiated imine, although it did perform well at -78

°C.

In an effort to more deeply understand the clustering of these ortholithiated imines, we undertook a project to crystallographically characterize the different structural motifs displayed by these complexes. Specifically, we wanted to understand the effects caused by changes in ligand substituents (group bound to nitrogen of imine, aldimine versus ketimine) and the impact of crystallization from donor and non-donor solvents.

The structure of Li-L1 was determined to be a tetramer in the solid state when recrystallized from toluene/pentane. Its four lithium atoms were found to be in a pseudo- tetrahedral arrangement, where each lithium in the tetramer is four-coordinate, bound to a nitrogen atom of one ligand, two bridging aryl carbons from two different ligands and the oxygen of a fourth ligand (Figure 2-1).25 Li-L2 was crystallized from diethyl ether and its

1 26 X-ray structure was found to be nearly identical to that of (Li-L )4. These two

28 analogous structures show that one methylene proton of the methylenedioxy ring is oriented towards the imine alkyl group, while the other points toward the aryl backbone.

1 1 Because of this dissymmetry, in the H NMR spectrum of (Li-L )4, the two methylene protons of the five-membered ring are observed as singlets at 5.47 and 4.74 ppm. HMQC

NMR spectroscopy confirmed that both singlets couple to the same carbon atom. The pronounced upfield chemical shift of one of these singlets can be attributed to ring current effects due to the close proximity of the proton to the centroid of the adjacent aryl

1 Figure 2-1. ORTEP diagram of (Li-L )4 with thermal ellipsoids drawn at 50%

probability. Hydrogen atoms and toluene solvent molecule have been removed for

clarity. Li1 displays pseudo-tetrahedral geometry, bonding to C1, O3, N1 and C43.

29 backbone (~3.96 Å in the solid state).27-29 This is in remarkable contrast to the 1H NMR observed for the lithiated aryl imines (Li-L3-8). For the lithiated aryl imines, in all cases the two protons of the methylenedioxy unit were found to be equivalent on the solution

NMR timescale. Also, spectra of these ortholithiated aryl imines all showed reasonably upfield shifted methylenedioxy protons. For the initial imine, these protons appeared at approximately 5.2 ppm, while they shifted to approximately 4.9 ppm in the lithium complexes. These methylene protons were observed to be chemically equivalent, although they do appear slightly broadened in the 1H NMR spectra. We attribute this broadening to motion of the flexible methylenedioxy ring and this broadness is not observed for other protons in the lithium complexes. The effect of this motion is to average the chemical environment of these two protons about the mirror plane of the

1 2 ligand. This averaging is not possible for the tetrameric (Li-L )4 and (Li-L )4 structures as the two faces of the planar ligand are not equivalent in these structures. Thus, based on the differences in NMR spectra, a different clustering motif must be present in solution for the ortholithiated aryl imines.

Because the various ortholithiated aryl imines all displayed similar 1H NMR spectra in C6D6, we crystallized a representative collection of these species from various coordinating and non-coordinating solvents. Three ortholithiated aryl imine complexes

(Li-L6, Li-L7, and Li-L8) were crystallized from non-coordinating solvents. These three compounds displayed similar solid state structures, forming long polymeric chains of dimeric units. In each dimer within the chain, two lithium centers are bound to the bridging orthocarbon atoms of two ligands, as well as a nitrogen atom from one ligand and an oxygen atom from the methylenedioxy ring of the other ligand. The

30 methylenedioxy oxygen atom not involved in bonding within the dimer forms a dative bond to a lithium center on an adjacent dimer to link the chain. Thus, two different types of dimers exist within the polymeric chain: “donor” dimers that provide electron density from the oxygen donor atom and “acceptor” dimers with lithium atoms coordinated by this oxygen donation. Overall, an alternating linkage of “donor” and “acceptor” dimers forms the polymeric chains (Figure 2-2). The two types of dimers give rise to two chemically inequivalent lithium centers in the solid state. The lithium centers of the

“donor” dimer are square planar and the lithium centers of the “acceptor” dimer are

7 square pyramidal (Figure 2-3). However, Li NMR spectroscopy in C6D6 shows only one resonance in solution at room temperature (Table 2.1). Variable temperature NMR

o o experiments (C7D8) showed no changes between 80 C and -30 C, although significant precipitate was observed in the NMR tube upon cooling. We believe the observation of a single lithium signal is due to the dissolution of the polymeric chains to form discrete dimers, rather than higher order clusters, in solution. The high degree of solubility of these ortholithiated imines in toluene, benzene and ethers also supports the likelihood of a smaller cluster in solution. Within each dimer, there is a time-averaged mirror plane of symmetry and an inversion center relating each of the four methylene protons and accounting for the single resonance observed for these methylene protons in the spectra of the ortholithiated imines. Once again, this upfield chemical shift can be attributed to a

π interaction between the methylene protons and the aromatic system of the second ligand in the dimer.28 For example, the methylenedioxy protons are located an average of

8 Figure 2-2. ORTEP diagram of coordination polymer of (Li-L )2 with thermal ellipsoids drawn at 50% probability; hydrogen atoms, isopropyl groups and benzene solvent molecule removed for clarity.

8 Figure 2-3. ORTEP diagram of (Li-L )2 with thermal ellipsoids drawn at 50% probability; hydrogen atoms and benzene solvent molecule removed for clarity. Note the presence of the square planar lithium Li1 in “donor” dimer and square pyramidal lithium Li2 in “acceptor” dimer. Atoms labeled with “i” and “ii” are generated by the following symmetry operators: -x+1, -y, -z; -x+1, -y, -z+1.

6 (~3.3 Å) from the centroid of the aryl ring of the imine in (Li-L )2 (Figure 2-4). Thus, as

1-2 in (Li-L )4 the ring current of the aromatic group is shielding the methylene protons and shifting them upfield in the observed NMR spectra.

Table 2.1. Lithium NMR chemical shifts

Compound 7Li{1H} (ppm)

1 (Li-L )4 2.91

2 (Li-L )4 2.82

4 (Li-L )2 3.67

5 (Li-L )2 2.68

6 (Li-L )2 4.08

7 (Li-L )2 3.90

8 (Li-L )2 4.12

8 (Li-L )2●DME 3.84

6 Figure 2-4. ORTEP diagram of (Li-L )2 with thermal ellipsoids drawn at 50% probability; hydrogen atoms, disordered ethyl groups and benzene solvent molecule removed for clarity. Atoms labeled with an “ii” are generated by the following symmetry operator: -x+1, -y, -z+1.

Unlike the alkyl imine Li-L2, crystallization of the aryl imines from donor solvents resulted in materials in which ethereal solvent molecules were retained in the cluster by dative bonding to the lithium centers. In no case was the dimeric core structure disrupted, but disruption of the polymeric chains or additional coordination to the lithium centers was observed. For example, when Li-L4 was crystallized from diethyl ether, a

26 4 non-polymeric, but dimeric structure was observed in the solid state: (Li-L ●Et2O)2.

The crystallographically equivalent lithium centers displayed distorted square pyramidal geometry (τ = 0.105) with each lithium atom bearing one diethyl ether ligand arranged on opposing faces of a dimer similar to those discussed above. Interestingly, when larger

6 2,6-disubstituted aryl groups were incorporated as imine substituent (2,6-Et2C6H3 (Li-L )

4 instead of 2,6-Me2C6H3 (Li-L )), the polymeric nature of the complex in the solid state is

6 preserved giving (Li-L )2●Et2O (Figures 2-5 and 2-6). In fact, within this polymeric chain, there is little or no change to the “acceptor” dimer units, being nearly isostructural

6 to the “acceptor” dimer in (Li-L )2. However, the lithium centers of the “donor” dimers are now found to be five-coordinate square pyramidal (τ = 0.282) with diethyl ether

4 ligands coordinated on opposing faces in a very similar manner to (Li-L ●Et2O)2.

6 Figure 2-5. ORTEP diagram of “donor” dimer of (Li-L )2•Et2O with thermal ellipsoids drawn at 50% probability; hydrogen atoms and ethyl groups removed for clarity. Atoms labeled with “i” are generated by the following symmetry operator: -x+1, -y, -z

6 Figure 2-6. ORTEP diagram of (Li-L )2•Et2O with thermal ellipsoids drawn at 50% probability; hydrogen atoms and ethyl groups removed for clarity. Note the coordination of diethyl ether to the lithium centers of the “donor” dimer.

When dimethoxyethane (DME) was used as a component of the reaction solvent for the imine ortholithiation, NMR spectroscopy showed 1 eq. of DME remaining for every two lithiated ligands. This was subsequently confirmed by elemental analysis. The structure in the solid state once again shows a dimeric complex (Figure 2-7), which in this case is very similar to that observed when Li-L4 was crystallized from ether. Each lithium center has a square pyramidal geometry (τ = 0.018) with one DME oxygen atom coordinated on opposing faces of the dimer. Two separate DME molecules coordinate to this core dimeric structure. The second oxygen atom from each of these DME ligands then coordinates to another dimer unit to create a coordination polymer made up of alternating lithium dimers and bridging DME ligands (Figure 2-8). This bridging binding mode was previously observed by Jones and Nixon,30 and is related to the chelating and bridging modes commonly observed with TMEDA ligands.31, 32 Furthermore, the

8 4 complex (Li-L )2●DME retains DME after exposure to vacuum, unlike (Li-L ●Et2O)2 which loses ether readily under vacuum.

8 Figure 2-7. ORTEP diagram of (Li-L )2●DME with thermal ellipsoids drawn at 50% probability; hydrogen atoms removed for clarity. Atoms labeled with “i” are generated by the following symmetry operator: -x+1, -y+1, -z+1.

Li1 O3i

Li1i O3

Li1i

8 Figure 2-8. ORTEP diagram of ((Li-Li )2•DME)n with thermal ellipsoids drawn at 50% probability; hydrogen atoms and isopropyl groups removed for clarity. The DME molecule bridges the lithium centers of two dimers in a similar fashion to the “donor”

7 8 dimers in (Li-Li )2 and (Li-Li )2.

Table 2.2. τ values for 5-coordinate lithium centers

Compound τ

4 (Li-L ●Et2O)2 0.105

6 (Li-L )2 0.105

6 a (Li-L )2●Et2O 0.087, 0.282

7 (Li-L )2 0.245

8 (Li-L )2 0.131

8 (Li-L )2●DME 0.018

adonor dimer with ether bond

For five coordinate complexes, the τ value is often used as a measure to quantify the degree to which the coordination geometry relates to that of an idealized square pyramidal (τ = 0) or trigonal bipyramidal (τ = 1) arrangement.33 In the various five coordinate lithium centers reported herein, the τ value is close to zero in all cases (Table

2.2), indicating a minimal distortion around the metal center from that of the idealized square pyramidal geometry. The degree of intermolecular versus intramolecular lithium solvation can be expressed via a parameter known as the twist angle.34 The twist angle is given as the angle between the plane defined by the two lithium centers and the bridging donor carbon atom and the plane of the aryl ring of the ligand. If these two planes are coplanar the twist angle is 0° (indicating strong intramolecular solvation), while a perpendicular arrangement gives a twist angle of 90° (intermolecular solvation).16, 34-37

The twist angles for the “donor” dimers range from 0.8 - 5.9° as expected for square planar metal complexes, while the twist angles for the “acceptor” dimers are larger (16.0

- 29.6°), indicating much higher degrees of intermolecular solvation from the “donor” dimers to the lithium ions (Table 2.3). Additionally, the five-coordinate complexes incorporating ethereal ligands, rather than “donor” dimers, have slightly larger twist angles, although this difference in most likely a reflection of the significant difference in steric bulk between the donor dimer and diethyl ether or DME, rather than a difference in oxygen donor character. Sterics also play an important role in maintaining the planarity of the “donor” dimer. As steric bulk increases, a decrease in the twist angle of the

”donor” dimers occurs, probably due to minimization of the steric interactions between the bulky groups at the 2 and 6 positions of the aromatic rings. For example, the ketimine

“donor” dimer (Li-L8) has the most planar character with a twist angle of only 0.8°;

39 however, the structurally analogous aldimine (Li-L7) has a twist angle of 5.2°. Thus, inclusion of the methyl group on the imine carbon atom seems to impact the solvation of the lithium center.

An examination of the metrical parameters from the crystal structures shows that the carbon-lithium bond lengths are similar for all the lithium complexes (Table 2.4).

This bridging binding motif is observed in many lithium complexes.13, 38, 39 There is a slight elongation of the carbon-lithium bond trans to the nitrogen donor in both the square planar and square pyramidal structures in comparison to the carbon-lithium bond trans to the oxygen donor. This is due to the stronger trans effect of nitrogen compared to that of oxygen. The additional elongation observed in the carbon-lithium bond trans to nitrogen for the square pyramidal lithium centers is also due to movement of the lithium out of the basal plane, in order to form the square pyramidal geometry. This distortion causes a

Table 2.3. Twist angles for lithium complexes

Compound Twist Angle (°)

4 (Li-L ●Et2O)2 30.8(1)

6 a (Li-L )2 5.9(1), 29.6(1)

6 a (Li-L )2●Et2O 35.0(2), 27.2(2)

7 a (Li-L )2 5.2(1), 21.5(1)

8 a (Li-L )2 0.8(2), 16.0(2)

8 (Li-L )2●DME 28.6(2)

aacceptor dimer

40 lengthening of the carbon-lithium bonds compared to those with square planar geometry.

4 This is especially pronounced in (Li-L ●Et2O)2, where the carbon-lithium bonds range from 2.153(2) Å trans to oxygen to 2.640(2) Å trans to nitrogen. Note that this complex also shows the largest twist angle (30.8(1)°).

Table 2.4. Selected bond lengths and anglesa

Compound Li1-Cb Li1-Cc Li1-N1 C2-C1-C6 C1-Li1-N1

1 (Li-L )4 2.215(6) _ 2.051(6) 109.7(3) 85.0(2)

2 (Li-L )4 2.202(6) _ 2.061(6) 110.2(3) 85.0(2)

4 (Li-L ●Et2O)2 2.153(2) 2.640(2) 2.108(2) 109.9(1) 80.99(8)

6 (Li-L )2 2.247(5) 2.447(5) 2.059(5) 109.5(2) 83.8(2)

6 (Li-L )2●Et2O 2.259(4) 2.323(4) 2.079(4) 109.7(2) 79.6(1)

7 (Li-L )2 2.132(5) 2.464(6) 2.038(5) 109.2(2) 85.7(2)

8 (Li-L )2 2.146(3) 2.475(3) 2.025(3) 109.6(1) 83.6(1)

8 (Li-L )2●DME 2.178(4) 2.538(4) 2.137(4) 110.1(2) 80.4(1) aFor Li-L6-8, values shown are for the “donor” dimers. bLithium-carbon bond trans to oxygen for aryl imines cLithium-carbon bond trans to nitrogen for aryl imines

For comparison, we include the crystal structure of H-L8, noting that the ligand itself undergoes various substantial changes upon deprotonation. The protic ligand (H-

L8) has a bond angle (C2-C1-C6) around C1 of 117.4(1)°. This is a slight deviation from the expected value of 120°. It is coupling to an elongation of the C1-C6 bond in the aromatic system and is caused by resonance effects between the conjugated imine and the aromatic system. Upon deprotonation, C1 undergoes significant changes; the C2-C1-C6

41 bond angle decreases from 117.4(1)° (H-L8) to 109.5(1)° (Li-L8). This decrease in bond angle indicates an increase in the p-character of the carbon bond to the metal.34, 37, 40-44

Concurrently, the planarity of the aromatic ring is maintained by corresponding increases in other carbon-carbon bond lengths and angles. This decrease of the C2-C1-C6 bond angle upon lithiation is commonly observed, although an angle of 109° is among the smallest reported. Additional stabilizing effects are likely provided by contributions from the lone pair on oxygen and resonance with the imine, leading to the excellent stability observed in the complexes reported herein.

2.3 Conclusion

Several ortholithiated alkyl and aryl imines were synthesized and structurally characterized. To our knowledge, these are the first examples of isolated and structurally characterized ortholithiated imines, although some ortholithiated phenyl oxazolines have been previously reported.16 In general, the clustering in the solid state was dependent upon both the crystallization solvent used and the substituent on the imine nitrogen atom.

Recrystallization from non-coordinating solvents led to the formation of coordination polymers for the ortholithiated aryl imines, where individual dimeric units were linked coordinatively to form infinite chains, giving rise to two types of lithium centers - square planar and square pyramidal. Crystallization from ethereal solvents, such as diethyl ether, led to the formation of discrete dimeric lithium complexes with square pyramidal lithium centers when the nitrogen substituent was 2,6-Me2C6H3. When more sterically bulky nitrogen substituents were used, such as 2,6-Et2C6H3, the dimers formed polymeric chains

6 even in the presence of diethyl ether. In the case of (Li-L )2●Et2O the same dimers are

42 observed as in the polymer derived from crystallization from non-coordinating solvents, but the remaining open coordination sites of the square planar lithium atoms were filled by diethyl ether ligands. The tert-butyl and cyclohexyl derivatives both formed tetramers

1 2 in the solid state; (Li-L )4 and (Li-L )4 were crystallized from toluene/pentane and diethyl ether, respectively. Lithium NMR showed only one resonance in the solution state for each complex, indicating disruption of the polymeric chains in the solution state. All aryl imine complexes likely exist as dimers in solution and the alkyl imines as tetramers.

Overall, we have shown that ortholithiated imines can be readily synthesized and isolated, and their rich structural chemistry, dependent on recrystallization solvent and ligand substituent, corresponded well to the steric and electronic features of the various isolated complexes.

2.4 Experimental

2.4.1 General Methods and Instrumentation

All manipulations involving lithium reagents were performed under an inert N2 atmosphere using standard glove box and Schlenk techniques. Solvents were predried before use; pentane and toluene were passed through columns of 4Å molecular sieves and sparged with nitrogen. Diethyl ether was passed through columns of activated alumina and 4 Å molecular sieves and sparged with nitrogen. Dimethoxyethane (DME) was dried over sodium metal, freeze-pump-thawed three times, and vacuum distilled. Benzene-d6 was dried over sodium metal, freeze-pump-thawed three times, and vacuum distilled. tert-Butylamine was dried over calcium hydride, freeze-pump-thawed three times, and distilled under reduced pressure. Piperonal, 3’,4’-methylenedioxyacetophenone, and p-

43 toluenesulfonic acid were purchased from Acros and used as received. 1H and 13C{1H}

NMR data were obtained on a 600 MHz Inova NMR spectrometer at ambient temperature at 599.9 MHz for 1H NMR and 150.8 MHz for 13C{1H} NMR. All spectra

1 were taken using C6D6 as NMR solvent. H NMR shifts are given relative to C6D5H (7.16

13 ppm) and C NMR shifts are given relative to C6D6 (128.1 ppm). Unless otherwise

3 7 noted, all coupling constants are JHH. All Li NMR spectra are given relative to an external LiCl (3.00 M in D2O) standard (0.00 ppm) and were obtained on a 400 MHz

VXRS NMR spectrometer at 155.4 MHz. IR samples were prepared as Nujol mulls and taken between KBr plates on a Perkin-Elmer XTL FTIR spectrophotometer. Melting points were observed on a capillary melting point (Uni-Melt) apparatus in sealed capillary tubes and are uncorrected. X-ray structure determinations were performed at the

Ohio Crystallographic Consortium housed at The University of Toledo. Elemental analyses were determined by Desert Analytics, Tucson, AZ or Galbraith Laboratories,

Inc., Knoxville, TN.

2.4.2 Ligand Synthesis

The appropriate amount of a primary amine (1-2 eq.) was added to a solution of either

3’,4’-methylenedioxyacetophenone or piperonal (1 eq.) in toluene. A catalytic amount of p-toluenesulfonic acid was added and the reaction was refluxed for 2 days (piperonal) or

3 days (3’,4’-methylenedioxyacetophenone). A Dean-Stark trap was used to collect water generated during the course of the reaction. The progress of the reaction was monitored via the volume of water collected in the Dean-Stark trap. The reaction was allowed to cool and neutralized with a saturated aqueous NaHCO3 solution and washed twice with

44 deionized water. The solvent was then removed via reduced pressure and the residue distilled to yield the final product. The only exception (H-L2) was prepared via imido/oxo exchange of Ti(NtBu)Cl2py3 and 3’,4’-methylenedioxyacetophenone due to the volatility of tert-butylamine. Compounds H-L1-2, H-L4, and H-L6-8 were prepared via previously published methods.17, 22, 23

2.4.3 Ligand Lithiation

The imine (1 eq.) was dissolved in pentane, cooled to -78 °C, and nBuLi (0.99 eq.) slowly added. As the reaction proceeded, the lithiated product precipitated as a powder, which was subsequently washed with pentane to yield the final lithiated imine. The use of 3:1 pentane/DME as a reaction solvent under identical conditions yielded the DME adduct

8 1 (Li-L )2●DME, which also precipitated from the reaction solvent. Compounds H-L , Li-

L1-2, Li-L4, and Li-L6-8 were prepared via previously published methods.17, 22, 23

H-L3: thick red oil (14 g, 80%); 1H NMR: δ 7.73 (s, 1H, CH=N), 7.70 (s, 1H, Ar-H), 7.04

(d, 2H, 7 Hz, m-2,6-Me2C6H3), 6.97 (t, 1H, 7 Hz, p-2,6-Me2C6H3), 6.91 (d, 1H, 7 Hz, Ar-

13 1 H), 6.57 (d, 1H, 7 Hz, Ar-H), 5.21 (s, 2H, OCH2O), 2.12 (s, 6H, Me). C{ H} NMR: δ

161.6, 152.2, 151.9, 149.1, 131.9, 128.6, 127.5, 125.7, 124.1, 108.4, 107.1, 101.7, 18.7.

IR: 3059 (m), 3013 (m), 2899 (m), 2786 (w), 2041 (w), 1853 (w), 1687 (m), 1636 (s),

1586 (s), 1487 (s), 1447 (s), 1377 (m), 1344 (m), 1251 (s), 1202 (s), 1086 (s), 1038 (s),

932 (s), 851 (m), 809 (s), 767 (s). Anal. for C16H15NO2 (253.30): calcd. C 75.87, H 5.97,

N, 5.53; found C 75.47, H 5.74, N 5.61.

H-L5: thick yellow oil (19 g, 87%); 1H NMR: δ 7.90 (s, 1H, CH=N), 7.80 (s, 1H, Ar-H),

7.17-7.12 (m, 3H, 2,6-Et2C6H3), 7.02 (d, 1H, 8 Hz, Ar-H), 6.66 (d, 1H, 8 Hz, Ar-H), 5.33

13 1 (s, 2H, OCH2O), 2.62 (q, 4H, 8 Hz, CH2CH3), 1.22 (t, 6H, 8 Hz, CH2CH3). C{ H}

NMR: δ 161.4, 151.6, 151.2, 149.3, 133.7, 131.9, 127.0, 125.9, 124.5, 108.6, 107.2,

101.8, 25.6, 15.3. IR: 3256 (w), 3224 (w), 3064 (s), 3012 (s), 2967 (s), 2872 (s), 2781

(m), 2698 (w), 2635 (w), 2597 (w), 2551 (w), 2046 (w), 1919 (w), 1858 (w), 1713 (m),

1691 (m), 1643 (s), 1607 (s), 1591 (s), 1552 (m), 1499 (s), 1456 (s), 1385 (s), 1372 (s),

1346 (s), 1263 (s), 1199 (s), 1180 (s), 1123 (s), 1099 (s), 1036 (s), 978 (m), 935 (s), 878

(s), 856 (s), 812 (s), 793 (s), 755 (s), 725 (m), 696 (m). Anal. for C18H19NO2 (281.35): calcd. C 76.84, H 6.81, N 4.98; found C 76.44, H 6.92, N, 5.06.

Li-L3: tan solid decomposes readily during preparation under similar reaction conditions to (Li-L1-2,4-8) (2.7 g, 67%); 1H NMR: δ 7.80 (s, 1H, CH=N), 6.92-6.83 (m, 4H, Ar-H),

6.53 (d, 1H, 8 Hz, Ar-H), 4.96 (s, 2H, OCH2O), 1.93 (s, 6H, Me).

Li-L5: tan solid (2.9 g, 70%); 1H NMR: δ 7.91 (s, 1H, CH=N), 6.96-6.93 (m, 3H, 2,6-

Et2C6H3), 6.88 (d, 1H, 8 Hz, Ar-H), 6.61 (d, 1H, 8 Hz, Ar-H), 4.96 (s, 2H, OCH2O), 2.33

13 1 (q, 4H, 7 Hz, CH2CH3), 0.94 (t, 6H, 7 Hz, CH2CH3). C{ H} NMR: δ 175.2, 157.0,

154.9, 150.4, 145.1, 142.9, 135.3, 130.6, 127.0, 125.3, 106.2, 98.8, 25.5, 15.5. 7Li{1H}

NMR: δ 2.68. IR: 1627 (s), 1589 (w), 1552 (s), 1455 (s), 1366 (s), 1322 (m), 1236 (s),

1173 (m), 1113 (w), 1095 (m), 1046 (m), 933 (m), 861(w), 800 (m), 756 (w). mp 135-

136 °C (dec.). Anal. for C18H18LiNO2 (287.28): calcd. C 75.25, H 6.32, N 4.88; found C

71.94, H 6.12, N 4.81.

8 1 (Li-L )2●DME: tan solid (1.05 g, 67%); H NMR: δ 7.26 (d, 2H, 8 Hz, Ar-H), 7.05-6.99

(m, 6H, 2,6-iPr2C6H3), 6.66 (d, 2H, 8 Hz, Ar-H), 4.81 (s, 4H, OCH2O), 3.27 (s, 4H,

MeOCH2), 3.08 (s, 6H, OMe), 2.79 (sept, 4H, 7 Hz, CHMe2), 1.92 (s, 6H, N=CMe), 0.99

13 1 (d, 12H, 7 Hz, CHMe2), 0.90 (d, 12H, 7 Hz, CHMe2). C{ H} NMR: δ 177.4, 155.7,

146.6, 144.2, 143.5, 138.4, 125.0, 124.5, 123.6, 104.8, 97.8, 71.8, 58.6, 28.5, 23.7, 23.3,

18.4 (one aromatic carbon not observed). 7Li{1H} NMR: δ 3.84. IR: 1604 (s), 1556 (s),

1456 (s), 1375 (s), 1322 (m), 1276 (m), 1243 (s), 1185 (m), 1071 (s), 1038 (s), 931 (m),

819 (w), 776 (m). Anal. for C46H58Li2N2O6 (748.84): C 73.78, H 7.81, N 3.74; found C

73.23, H 7.76, N 3.85. mp 73 °C (dec.).

2.5 Crystallography of ortholithiated Imines

1 A summary of crystal data and collection parameters for crystal structures of (Li-L )4,

2 6 6 7 8 8 8 (Li-L )4, (Li-L )2●Et2O, (Li-L )2, (Li-L )2, (Li-L )2, (Li-L )2●DME and H-L are provided in Table 2.5. Detailed descriptions of data collection, as well as data solution, are provided below. ORTEP diagrams were generated with the ORTEP-3 software package.45 For each sample, a suitable crystal was mounted on a glass fiber using

Paratone-N hydrocarbon oil. The crystal was transferred to a Siemens SMART46 diffractometer with a CCD area detector, centered in the X-ray beam, and cooled to 140

K using a nitrogen-flow low-temperature apparatus that had been previously calibrated by a thermocouple placed at the same position as the crystal. An arbitrary hemisphere of data was collected using 0.3° ω scans, and the data were integrated by the program

SAINT.47 The final unit cell parameters were determined by a least-squares refinement of the reflections with I > 2σ(I). Data analysis using Siemens XPREP48 and the

47 successful solution and refinement of the structure determined the space group.

1 2 6 Empirical absorption corrections were applied for (Li-L )4, (Li-L )4, (Li-L )2●Et2O, (Li-

6 7 8 8 8 49 L )2, (Li-L )2, (Li-L )2, (Li-L )2●DME and H-L using the program SADABS.

Equivalent reflections were averaged, and the structures were solved by direct methods using the SHELXTL software package.50 Unless otherwise noted, all non-hydrogen atoms were refined anisotropically.

1 2 6 Table 2.5. Crystallographic data for compounds (Li-L )4, (Li-L )4, (Li-L )2●Et2O, (Li-

6 7 8 8 8 L )2, (Li-L )2, (Li-L )2, (Li-L )2●DME and H-L

1 2 6 Compound (Li-L )4 (Li-L )4 (Li-L )2●Et2O

Formula C56H64Li4N4O8●1/4(C7H8) C13H16LiNO2 C42H50Li2N2O5

Formula weight 971.91 225.21 676.72

Space group C2/c P-421c P21/n

Temperature (K) 140 140 140

a (Å) 39.324(1) 14.671(2) 13.129(3)

b (Å) 13.3815(4) 14.671(2) 19.984(4)

c (Å) 21.1315(7) 11.476(2) 15.547(3)

α (°) 90.00 90.00 90.00

β (°) 91.277(2) 90.00 112.816(3)

γ (°) 90.00 90.00 90.00

V (Å3) 11116.9(6) 2470.1(5) 3760.(1)

Z 8 8 4

3 Densitycalc (g/cm ) 1.161 1.211 1.195

Diffractometer Siemens SMART Siemens SMART Siemens SMART

Radiation Mo-Kα (λ = 0.71073 Å) Mo-Kα (λ = 0.71073 Å) Mo-Kα (λ = 0.71073 Å)

Monochromator Graphite Graphite Graphite

Detector CCD area detector CCD area detector CCD area detector

Scan type, width ω, 0.3° ω, 0.3° ω, 0.3°

Scan speed (s) 60 40 30

Reflections measured Hemisphere Hemisphere Hemisphere

2θ range (°) 2.08 – 46.60 3.92 – 56.04 3.46 – 57.00

Crystal dimensions (mm) 0.26 x 0.19 x 0.09 0.10 x 0.08 x 0.05 0.10 x 0.07 x 0.06

Reflections measured 44139 26764 37100

Unique reflections 8015 2979 8793

Observations (I > 2σ(I)) 4814 1529 5559

Rint 0.0861 0.1469 0.0712

Parameters 685 155 479

R, Rw, Rall 0.0545, 0.1742, 0.0893 0.0612, 0.1744, 0.1438 0.0621, 0.1758, 0.1078

GoF 1.000 1.001 1.083

Table 2.5. cont.

6 7 8 Compound (Li-L )2 (Li-L )2 (Li-L )2

Formula C38H40Li2N2O4●C6H6 C80H88Li4N4O8●C6H6 C42H48Li2N2O4●1/2(C7H8)

Formula weight 680.71 1339.41 704.77

Space group P21/c Pna21 P-1

Temperature (K) 140 140 140

a (Å) 15.106(4) 26.831(1) 11.9324(9)

b (Å) 13.206(3) 23.069(1) 12.7291(9)

c (Å) 22.163(6) 12.4740(8) 14.312(1)

α (°) 90.00 90.00 91.001(2)

β (°) 109.515(5) 90.00 92.430(2)

γ (°) 90.00 90.00 112.044(2)

V (Å3) 4167(2) 7720.9(8) 2011.8(3)

Z 4 4 2

3 Densitycalc (g/cm ) 1.085 1.152 1.163

Diffractometer Siemens SMART Siemens SMART Siemens SMART

Radiation Mo-Kα (λ = 0.71073 Å) Mo-Kα (λ = 0.71073 Å) Mo-Kα (λ = 0.71073 Å)

Monochromator Graphite Graphite Graphite

Detector CCD area detector CCD area detector CCD area detector

Scan type, width ω, 0.3° ω, 0.3° ω, 0.3°

Scan speed 30 30 30

Reflections measured Hemisphere Hemisphere Hemisphere

2θ range (°) 3.64 – 58.46 2.32 – 56.64 3.46 – 56.60

Crystal dimensions (mm) 0.20 x 0.05 x 0.05 0.20 x 0.05 x 0.05 0.10 x 0.10 x 0.05

Reflections measured 31766 81349 22547

Unique reflections 10443 19208 9954

Observations (I > 2σ(I)) 7566 11406 8315

Rint 0.0464 0.0624 0.0345

Parameters 506 967 492

R, Rw, Rall 0.0974, 0.2803, 0.1179 0.0562, 0.1382, 0.1125 0.0575, 0.1652, 0.0668

GoF 1.069 1.004 1.049

Table 2.5. cont.

8 8 Compound (Li-L )2●DME H-L

Formula C23H29LiNO3 C21H25NO2

Formula weight 374.41 323.42

Space group P-1 P21

Temperature (K) 140 140

a (Å) 9.0416(9) 6.983(2)

b (Å) 9.380(1) 24.325(7)

c (Å) 12.648(1) 10.799(3)

α (°) 75.385(2) 90.00

β (°) 86.376(3) 90.296(7)

γ (°) 80.736(3) 90.00

V (Å3) 1024.2(2) 1834.3(9)

Z 2 4

3 Densitycalc (g/cm ) 1.214 1.171

Diffractometer Siemens SMART Siemens SMART

Radiation Mo-Kα (λ = 0.71073 Å) Mo-Kα (λ = 0.71073 Å)

Monochromator Graphite Graphite

Detector CCD area detector CCD area detector

Scan type, width ω, 0.3° ω, 0.3°

Scan speed (s) 30 30

Reflections measured Hemisphere Hemisphere

2θ range (°) 4.54 – 56.64 3.34 – 57.10

Crystal dimensions (mm) 0.10 x 0.06 x 0.05 0.30 x 0.20 x 0.10

Reflections measured 9904 20833

Unique reflections 4641 8322

Observations (I > 2σ(I)) 2565 7336

Rint 0.0772 0.0238

Parameters 262 433

R, Rw, Rall 0.0614, 0.1839, 0.1193 0.0408, 0.1045, 0.0476

GoF 0.988 1.033

1 (Li-L )4: X-ray quality crystals were grown from a 1:1 toluene/pentane solution at

-20°C. One quarter molecule of toluene was also present in the asymmetric unit. Carbon atoms of the solvent were refined anisotropically and its hydrogen atoms were not modeled. The final cycle of full-matrix least-squares refinement was based on 4814 observed reflections and 685 variable parameters and converged yielding final residuals:

R = 0.0545, Rall = 0.0893, and GOF = 1.000.

2 (Li-L )4: X-ray quality crystals were grown from a saturated ether solution at -

25°C. The final cycle of full-matrix least-squares refinement was based on 1529 observed reflections and 155 variable parameters and converged yielding final residuals:

R = 0.0612, Rall = 0.1438, and GOF = 1.001.

6 (Li-L )2●Et2O: X-ray quality crystals were grown from a saturated ether solution at -25°C. The final cycle of full-matrix least-squares refinement was based on 5559 observed reflections and 479 variable parameters and converged yielding final residuals:

R = 0.0621, Rall = 0.1078, and GOF = 1.083.

6 (Li-L )2: X-ray quality crystals were grown from a saturated benzene solution at room temperature. One molecule of benzene also crystallized in the asymmetric unit.

The final cycle of full-matrix least-squares refinement was based on 7566 observed reflections and 506 variable parameters and converged yielding final residuals: R =

0.0974, Rall = 0.1179, and GOF = 1.069.

7 (Li-L )2: X-ray quality crystals were grown from a saturated benzene solution at room temperature. One benzene molecule cocrystallized; all solvent carbon atoms were modeled anisotropically with hydrogens attached. The final cycle of full-matrix least-

52 squares refinement was based on 11406 observed reflections and 967 variable parameters and converged yielding final residuals: R = 0.0562, Rall = 0.1125, and GOF = 1.004.

8 (Li-L )2: X-ray quality crystals were grown from a toluene solution layered with pentane. One half of a disordered toluene cocrystallized in the asymmetric unit and its carbon atoms were modeled anisotropically and hydrogen atoms were not modeled. The final cycle of full-matrix least-squares refinement was based on 8315 observed reflections and 492 variable parameters and converged yielding final residuals: R =

0.0575, Rall = 0.0668, and GOF = 1.049.

8 (Li-L )2●DME: X-ray quality crystals were grown from a pentane/DME solution at -25 °C. The final cycle of full-matrix least-squares refinement was based on 2565 observed reflections and 262 variable parameters and converged yielding final residuals:

R = 0.0614, Rall = 0.1193, and GOF = 0.988.

H-L8: X-ray quality crystals were grown from a methanol solution. The final cycle of full-matrix least-squares refinement was based on 7336 observed reflections and

433 variable parameters and converged yielding final residuals: R = 0.0408, Rall =

0.0476, and GOF = 1.033.

References

1. Gilman, H.; Webb, J. F., Lateral metalation of methyl phenyl sulfide. Journal of the American Chemical Society 1940, 62, 987-988.

2. Wittig, G.; Fuhrmann, G., Über das verhalten der halogenierten anisole gegen phenyl lithium. Chemische Berichte 1940, 73, 1197-1218.

3. Bauer, W.; Schleyer, P. V., Mechanistic evidence for ortho-directed lithiations from one- and two-dimensional NMR spectroscopy and MNDO calculations. Journal of the American Chemical Society 1989, 111 (18), 7191-7198.

4. Smith, K.; El-Hiti, G. A., Regioselective control of electrophilic aromatic substitution reactions. Current Organic Synthesis 2004, 1 (3), 253-274.

5. Beak, P.; Brown, R. A., orthoMetalations. Advantage of the amide functions. Journal of Organic Chemistry 1979, 44 (24), 4463-4464.

6. Beak, P.; Brown, R. A., The tertiary amide as an effective director of ortholithiation. Journal of Organic Chemistry 1982, 47 (1), 34-46.

7. Comins, D. L.; Brown, J. D., orthoMetalation directed by alpha-amino alkoxides. Journal of Organic Chemistry 1984, 49 (6), 1078-1083.

8. Tomioka, K.; Shioya, Y.; Nagaoka, Y.; Yamada, K., Electronic and steric control in regioselective addition reactions of organolithium reagents with enaldimines. Journal of Organic Chemistry 2001, 66 (21), 7051-7054.

9. Flippin, L. A.; Berger, J.; Parnes, J. S.; Gudiksen, M. S., Effect of the substitution pattern on reactions of methoxylated araldehyde 2,4-dimethylpent-3-ylimines with organolithium reagents. Journal of Organic Chemistry 1996, 61 (14), 4812- 4815.

10. Flippin, L. A.; Muchowski, J. M.; Carter, D. S., Directed metalation of aromatic aldimines with lithium 2,2,6,6-tetramethylpiperidide. Journal of Organic Chemistry 1993, 58 (9), 2463-2467.

11. Forth, M. A.; Mitchell, M. B.; Smith, S. A. C.; Gombatz, K.; Snyder, L., Imine directed metalation of o-tolualdehyde: The use of catalytic amine base a route to 2-(8-phenyloctyl)benzaldehyde. Journal of Organic Chemistry 1994, 59 (9), 2616-2619.

12. Kovalskiy, D. A.; Perevalov, V. P., Synthesis of 3-(3-piperidyl)-isoquinoline and 3-(4-piperidyl)-isoquinoline. Chemistry of Heterocyclic Compounds 2009, 45 (8), 957-964.

13. Stol, M.; Snelders, D. J. M.; de Pater, J. J. M.; van Klink, G. P. M.; Kooijman, H.; Spek, A. L.; van Koten, G., Synthesis and structural characterization of lithium

and trimethyltin complexes of 2,6-bis(oxazolinyl)phenyl. Organometallics 2005, 24 (4), 743-749.

14. Evans, P. A.; Nelson, J. D.; Stanley, A. L., Directed lithiation transmetalation approach to palladium-catalyzed cross-coupling acylation reactions. Journal of Organic Chemistry 1995, 60 (7), 2298-2301.

15. Chadwick, S. T.; Ramirez, A.; Gupta, L.; Collum, D. B., n- Butyllithium/N,N,N',N'-tetramethylethylenediamine-mediated ortholithiations of aryl oxazolines: Substrate-dependent mechanisms. Journal of the American Chemical Society 2007, 129 (8), 2259-2268.

16. Jantzi, K. L.; Guzei, I. A.; Reich, H. J., Solution and solid-state structures of lithiated phenyloxazolines. Organometallics 2006, 25 (22), 5390-5395.

17. Ziegler, F. E.; Fowler, K. W., Substitution reactions of specifically orthometalated piperonal cyclohexylimine. Journal of Organic Chemistry 1976, 41 (9), 1564-1566.

18. Ziegler, F. E.; Chliwner, I.; Fowler, K. W.; Kanfer, S. J.; Kuo, S. J.; Sinha, N. D., Ambient temperature Ullmann reaction and its application to the total synthesis of (+/-)-steganacin. Journal of the American Chemical Society 1980, 102 (2), 790- 798.

19. Khaldi, M.; Chretien, F.; Chapleur, Y., Synthesis of pentasubstituted benzamides via orthometallation: Base and substituent effects. Bulletin de la Societe Chimique de France 1996, 133 (1), 7-13.

20. Pfeffer, M.; Urriolabeitia, E. P.; Decian, A.; Fischer, J., Synthesis and characterization of asymmetric C,N-cyclometalated complexes of Mo(II). X-ray 5 crystal structures of [(ƞ -C5H5)Mo(C6H2-(OCH2O)-2,3-CH2NMe2-(6))(I)(NO)] 5 and [(ƞ -C5H5)Mo(s-C6H4CH(Me)NMe2)(I)(NO)]. Journal of Organometallic Chemistry 1995, 494 (1-2), 187-193.

21. Trost, B. M.; Reiffen, M.; Crimmin, M., Thionium ions as reactive carbonyl equivalents in cyclization reactions. Journal of the American Chemical Society 1979, 101 (1), 257-259.

22. Neshat, A.; Seambos, C. L.; Beck, J. F.; Schmidt, J. A. R., Mono-anionic acetophenone imine ligands: Synthesis, ortho-lithiation and first examples of group (V) metal complexes. Dalton Transactions 2009, (25), 4987-5000.

23. Baiz, T. I.; Schmidt, J. A. R., A discrete ortho-lithiated acetophenone imine derivative: Isolation, characterization, and synthesis of group IV metal complexes. Organometallics 2007, 26, 4094-4097.

24. Beck, J. F.; Baiz, T. I.; Neshat, A.; Schmidt, J. A. R., Titanium imido complexes utilizing orthometallated derivatized acetophenone and piperonal imine ligands:

Synthesis, isolation, and characterization. Dalton Transactions 2009, (25), 5001- 5008.

25. Baiz, T. I. M.S. Thesis, Synthesis of group IV metal complexes employing a newly developed orthometallated imine ligand system. University of Toledo, Toledo, OH, 2007.

26. Neshat, A. Ph.D. Dissertation, Group V imido complexes bearing mono-anionic acetophenone imine ligands. University of Toledo, Toledo, OH, 2011.

27. Lambert, J. B.; Mazzola, E. P., Nuclear Magnetic Resonance Spectroscopy. Pearson Education Inc.: Upper Saddle River, NJ, 2004.

28. Pavia, D. L.; Lampman, G. M.; Kriz, G. S., Introduction to Spectroscopy. 3rd ed.; Thomson Learning, Inc.: Belmont, CA, 2001.

29. Martin, N. H.; Floyd, R. M.; Woodcock, H. L.; Huffman, S.; Lee, C. K., Computation of through-space NMR shielding effects in aromatic ring pi-stacked complexes. Journal of Molecular Graphics and Modelling 2008, 26 (7), 1125- 1130.

30. Skowronskaptasinska, M.; Verboom, W.; Reinhoudt, D. N., Effect of different dialkylamino groups on the regioselectivity of lithiation of o-protected 3- (dialkylamino)phenols. Journal of Organic Chemistry 1985, 50 (15), 2690-2698.

31. Nichols, M. A.; Williard, P. G., Solid-state structures of n-butyllithium-tmeda, n- butyllithium-THF, and n-butyllithium-DME complexes. Journal of the American Chemical Society 1993, 115 (4), 1568-1572.

32. Collum, D. B., Is N,N,N',N'-tetramethylethylenediamine a good ligand for lithium? Accounts of Chemical Research 1992, 25 (10), 448-454.

33. Addison, A. W.; Rao, T. N.; Reedijk, J.; Vanrijn, J.; Verschoor, G. C., Synthesis, structure, and spectroscopic properties of copper(II) compounds containing nitrogen sulphur donor ligands: The crystal and molecular structure of aqua[1,7- bis(N-methylbenzimidazol-2'-yl)-2,6-dithiaheptane]copper(II) perchlorate. Dalton Transactions 1984, (7), 1349-1356.

34. Betz, J.; Hampel, F.; Bauer, W., The solution and solid state structure of [1- (dimethylamino)-8-naphthyl]lithium•THF]2. Dalton Transactions 2001, (12), 1876-1879.

35. Fernandez, I.; Ona-Burgos, P.; Oliva, J. M.; Lopez-Ortiz, F., Solution and computed structure of o-lithium N,N-diisopropyl-P,P-diphenylphosphinic amide unprecedented Li-O-Li-O self-assembly of an aryllithium. Journal of the American Chemical Society 2010, 132 (14), 5193-5204.

36. Gaul, C.; Arvidsson, P. I.; Bauer, W.; Gawley, R. E.; Seebach, D., Computational, React-IR, and NMR-spectroscopic investigations on the chiral formyl anion equivalent N-(D-lithiomethylthiomethyl)-4-isopropyl-5,5-diphenyloxazolidin-2- one and related compounds. Chemistry - A European Journal 2001, 7 (19), 4117- 4125.

37. Betz, J.; Bauer, W., NMR and calculational studies on the regioselective lithiation of 1-methoxynaphthalene. Journal of the American Chemical Society 2002, 124 (29), 8699-8706.

38. Dinnebier, R. E.; Behrens, U.; Olbrich, F., Lewis base-free phenyllithium: Determination of the solid-state structure by synchrotron powder diffraction. Journal of the American Chemical Society 1998, 120 (7), 1430-1433.

39. Jastrzebski, J.; van Koten, G.; Goubitz, K.; Arlen, C.; Pfeffer, M., Synthesis of 8- (dimethylamino)-1-naphthyllithium etherate - its structure in the solid (X-ray) and in solution (7Li and 1H NMR). Journal of Organometallic Chemistry 1983, 246 (3), C75-C79.

40. Harder, S.; Ekhart, P. F.; Brandsma, L.; Kanters, J. A.; Duisenberg, A. J. M.; Schleyer, P. v. R., Crystal structure of [2-(dimethylamino)-6-tert- butoxyphenyl]lithium. Organometallics 1992, 11 (7), 2623-2627.

41. Linnert, M.; Bruhn, C.; Ruffer, T.; Schmidt, H.; Steinborn, D., Ortho versus D- metalation of ethyl phenyl sulfide by n-butyllithium/N,N,N',N'- tetramethylethylenediamine: Synthesis, reactivity, and crystal structures of (2- (ethylthio)phenyl)- and (1-(phenylthio)ethyl)lithium. Organometallics 2004, 23 (15), 3668-3673.

42. Domenicano, A.; Vaciago, A.; Coulson, C. A., Molecular geometry of substituted benzene derivatives II: A bond angle versus electronegativity correlation for the phenyl derivatives of second-row elements. Acta Crystallographica, Section B: Structural Science 1975, 31 (JUN15), 1630-1641.

43. Betz, J.; Hampel, F.; Bauer, W., Solution and solid-state structure of (1-methoxy- 8-naphthyllithium•THF)2. Organic Letters 2000, 2 (24), 3805-3807.

44. Bent, H. A., An appraisal of valence-bond structures and hybridization in compounds of the first-row elements. Chemical Reviews 1961, 61 (3), 275-311.

45. Barnes, C. L., ORTEP-3 for windows - a version of ORTEP-III with a graphical user interface. Journal of Applied Crystallography 1997, 30 (1), 568-568.

46. SMART: Area-Detector Software Package, 5.625; Bruker AXS, Inc.: Madison, WI, 1997-2001.

47. SAINT: SAX Area-Detector Integration Program, 6.22; Bruker AXS, Inc.: Madison, WI, 1997-2001.

48. XPREP: Reciprocal Space Exploration Program, 6.12; Bruker AXS, Inc.: Madison, WI, 2001.

49. SADABS: Bruker/Siemens Area Detector Absorption Program, 2.03; Bruker AXS, Inc.: Madison, WI, 2001.

50. SHELXTL-97, Structure Solution Program, 6.10; Bruker AXS, Inc.: Madison, WI, 2000.

Chapter 3

Isolation and Characterization of Titanium Imido Complexes using orthoMetallated Imine Ligands

3.1 Introduction

Over the past two decades, significant effort has been devoted to the synthesis and characterization of metal imido complexes.1-7 The versatile dianionic imido ligand (R-N2-

) has been utilized with uranium,8 early1, 9 and late transition metals.10-12 Notably, the

Schrock alkene metathesis13 catalyst and Bergman’s hydroamination14, 15 and imine metathesis16-18 catalysts contain the imido moiety. The first structurally authenticated terminal titanium imido complexes were reported in 1990,19, 20 and several examples of bridging imidos were characterized prior to 1990.21-24 Subsequent reports have shown that titanium imido complexes participate in a number of catalytic and stoichiometric reactions with unsaturated molecules. Catalysts based on titanium imido complexes have been used for olefin polymerization4 and the hydroamination of alkynes.14, 25-36

Stochiometric reactions with isocyanates,37, 38 alkynes,38, 39 carbon disulfide1, 37 and carbon dioxide37 have also been reported, in addition to imine metathesis reactions.40, 41

Methods to access titanium imido complexes range from the oxidation of titanium(II)

42 complexes to the more commonly used reaction of TiCl4 with multiple equivalents of

43 tert-butyl amine in the presence of pyridine to yield Ti(NC(CH3)3)Cl2py3. Aryl imido titanium complexes can be easily synthesized from this reactant via arylamine/tert- butylimido exchange.43 Titanium imido complexes have been reported utilizing many different ancillary ligands including triazacyclic,44, 45 pyrrolyl,46 cyclopentadienyl,39 anionic chelating amines,2, 47 amidate,27, 48 guanidinate,40 and amidinate ligands.37

Several reports describe the use of orthometallated imines as ligands for late transition metals,46, 49-53 whereas examples of relevant early transition metal complexes are rare. When using early transition metal starting materials the oxidative addition step necessary for the formation of the orthometallated complex is typically not favored due to the high oxidation state of the metal center. A few examples of early transition metal orthometallated imines have been synthesized by the insertion of a nitrile into a metal- benzyne, followed by the addition of a weak acid to generate a monoanionic orthometallated arylimine.54-56 This synthetic methodology limits the steric and electronic tunability on the nitrogen substituent which is a significant disadvantage of this route. A more desirable method involves deprotonation of an imine prior to reaction with an early transition metal synthon. This would reduce the number of steps needed to synthesize the final imine complex while allowing for variation of the electronic and steric properties of these ligands.

orthoMetallated N,N-dimethylbenzylamines have been used extensively as ligands for main group57, 58 and early transition metals.59, 60 Activation of the amine is achieved through a regiospecific ortholithiation.59 Complexation with a transition or main group metal proceeds by means of a salt metathesis reaction between the ortholithiated amine and the corresponding metal halide. Unfortunately, the ortholithiation of imines is not as readily achieved. For example, lithiation of acetophenone cyclohexylimine in diethyl ether leads to a combination of species including the desired ortholithiated product and a dilithiated product that has been deprotonated at both the methyl group and ortho position.61 Addition of n-butyllithium to an imine can also lead to nucleophilic attack on the imine carbon.62 The choice of imine and the reaction conditions employed are critical in synthesizing an exclusively ortholithiated product.

In 1975, Ziegler and Fowler were able to regioselectively ortholithiate piperonal cyclohexylimine, although the lithiated imine was not isolated.61 The ortholithiation was confirmed by subsequent reactions with bromine, carbon dioxide and methyl iodide.61

We previously reported the isolation of the lithium salt of piperonal cyclohexylimine, as well the synthesis of a related piperonal arylimine.63, 64 Furthermore, we synthesized and lithiated several 3',4'-methylenedioxyacetophenone arylimines using a similar synthetic method to that of the piperonal arylimine.63 The ortholithiated imines were subsequently employed to produce several group 4 metal complexes. The bis-orthometallated imine zirconium(IV) dichloride complex yielded alkyl complexes upon reaction with lithium reagents.65 Herein, the use of orthometallated aryl and alkyl imines as ligands for titanium imido complexes is described.

3.2 Results and Discussion

Synthesis of the imines H-Ln (n = 1,4,6,7,8) was achieved through the high yield

(>80%) Schiff-base condensation of piperonal or 3’,4’-methylenedioxyacetophenone with a primary amine (Scheme 3.1). The 1H NMR spectra of H-L1,4,6,7,8 each show a singlet in the region of 5.2 to 6.3 ppm representing the methylene carbons of the -

OCH2O- moiety. The aromatic proton located ortho to both the imine and -OCH2O- groups is observed at approximately 7.9 ppm as a singlet or finely split doublet (due to

4 JHH coupling). The proton signals for the methylene moiety act as excellent diagnostic peaks during lithiation and transition metal complexation. Upon lithiation with n- butyllithium (70-90% yield), there is an upfield shift for the methylene resonance to < 5 ppm in addition to the disappearance of the resonance associated with the ortho proton.

Regiospecific lithiation was confirmed by quenching of the lithiated imine with D2O and

n I2. The lithiated imines (Li-L ; n = 1,4,6,7,8) are stable for at least a year under a nitrogen atmosphere, but are extremely moisture sensitive and smolder immediately upon exposure to air. For the lithiated arylimines (Li-Ln; n = 4,6,7,8) the methylene resonances are shifted upfield in the 1H NMR spectra, but appear to be chemically equivalent in each case, indicating that the mirror plane of the imine is preserved. The upfield shift of the methylene resonance is very likely indicative of close proximity of these protons to the π system of another imine in a clustered superstructure.66-68 In contrast, the lithiated alkylimine Li-L1 exhibited a distinct splitting of the methylene protons, observed as two singlets at 5.47 and 4.74 ppm. This reduction in symmetry leads us to conclude that a different clustering motif is preferred for the lithiated alkylimine as compared to the arylimine (see Chapter 2). The smaller size of the alkyl groups compared to the aryl

62 groups may account for this difference in the solution structure of the lithiated alkylimine.

O O R' O R' O N Li N H2NR' nBuLi O - H O O -nBuH O R 2 R R H-Ln Li-Ln

Scheme 3.1. Synthesis of imines (H-Ln) and lithiated imines (Li-Ln); n = 1: R = H;

R’ = Cy; n = 4: R = Me; R’ = 2,6-Me2C6H3; n = 6: R = Me, R’ = 2,6-Et2C6H3; n =7: R

i i = H, R’ = 2,6- Pr2C6H3; n = 8: R = Me, R’ = 2,6- Pr2C6H3;.

The lithiated arylimines (Li-Ln; n = 4, 6-8) were reacted with titanium imido complexes of the form Ti(NR”)Cl2py3 (R" = C(CH3)3, 2,6-Me2C6H3, 2,6-Et2C6H3, and

i 2,6- Pr2C6H3). In all cases, following filtration and purification, a monomeric pyridine- free titanium imido complex was isolated with two chelating C~N ligands coordinated to

O R'' O R' 2 Li-Ln N N R_ + Ti - 2 LiCl RN Ti(NR")Cl py - 3 py 2 3 R' O O

Scheme 3.2. Synthesis of orthometallated arylimine titanium imido complexes; R =

Me, R’ = 2,6-Me2C6H3, R” = C(CH3)3 (3-4a; 31%); R = Me, R’ = 2,6-Me2C6H3, R” =

2,6-Me2C6H3 (3-4b; 62%); R = Me, R’ = 2,6-Et2C6H3, R” = C(CH3)3 (3-6a; 81%); R =

i i H, R’ = 2,6- Pr2C6H3, R” = C(CH3)3 (3-7a; 48%); R = H, R’ = 2,6- Pr2C6H3, R” = 2,6-

i Me2C6H3 (3-7b; 43%); R = H, R’ = 2,6- Pr2C6H3, R” = 2,6-Et2C6H3 (3-7c; 59%); R =

i i i H, R’ = 2,6- Pr2C6H3, R” = 2,6- Pr2C6H3 (3-7d; 24%); R = Me, R’ = 2,6- Pr2C6H3, R” =

C(CH3)3 (3-8a; 82%).

63 the metal center in yields varying from 24-82% (Scheme 3.2). The isolated complexes displayed remarkable thermal stability, up to 195 °C for 3-7d, as well as solubility in nonpolar solvents such as benzene, toluene, and pentane. Each of these complexes (3-4 through 3-8) was highly symmetric with a C2 rotation axis aligned with the titanium

4 imido bond, as is readily noted upon spectroscopic characterization. (L )2Ti(N-2,6-

Me2C6H3) was crystallized from a toluene/pentane solution, and the solid-state structure was determined by X-ray diffraction (3-4b, Figure 3-1). The complex is distorted square pyramidal in geometry with two chelating C~N ligands in which the carbon donor atoms are approximately trans to each other. The aryl groups bonded to the nitrogen in the individual ligands are nearly perpendicular to the ligand backbone, and the two ligands are related by a C2 rotation axis collinear with the titanium imido bond. This distorted square pyramidal structure is typical of the many five coordinate titanium imido complexes observed recently.2, 3, 35, 69-81 The two ligands fold away from the metal center and this, combined with the trans influence of the imido group, prevents the byproduct

Figure 3-1. ORTEP diagram (50% thermal ellipsoids) of 3-4b; hydrogen atoms and

½ molecule of toluene solvate omitted for clarity. Bond lengths (in Å): Ti1-N1 =

1.713(2), Ti1-N2 = 2.186(2), Ti1-N3 = 2.198(2), Ti1-C9 = 2.202(3), Ti1-C26 =

2.200(3); angles (in °): Ti1-N1-C1 = 174.8(2), N2-Ti1-C9 = 75.9(1), N3-Ti1-C26 =

75.1(1), C9-Ti1-C26 = 156.4(1).

pyridine from coordinating to the titanium center. The imido titanium bond is nearly linear with a Ti-N-C bond angle of 174.8(2)° and a titanium imido bond length of

1.713(2) Å. The 1H NMR spectrum of 3-4b shows weak splitting of the methylene

2 protons into two doublets ( JHH = 1.2 Hz), consistent with germinal coupling between the

65 two protons of this methylene carbon. There is a substantial upfield shift for one of the methylene resonances to 4.98 ppm (a change of 0.32 ppm compared to free ligand) and a much smaller downfield shift for the other methylene resonance, shifting only 0.02 ppm.

The shielding of the upfield methylene proton can be attributed to the interaction of the methylene proton with the π system of the adjacent aromatic ring of the second ligand.67,

68 The centroid of the neighboring aromatic ring is 3.919 Å from the methylene carbon

7 8 atom. (L )2Ti(NC(CH3)3) (3-7a; Figure 3-2) and (L )2Ti(NC(CH3)3) (3-8a; Figure 3-3) were also characterized by X-ray diffraction. Each of these complexes has the same distorted square pyramidal structure as was observed with 3-4b. The titanium imido bond lengths are longer for the aryl imido species 3-4b than the tert-butyl imido derivatives

(1.678(2) Å for 3-7a and 1.690(2) Å for 3-8a) due to the smaller steric bulk of 3-7a and

3-8a compared to 3-4b, as well as the greater basicity of the tert-butyl imido group. The imido bonds are nearly linear in all cases (176.5(2)° for 3-7a and 171.1(2)° for 3-8a), representative of the triple bond character of the titanium imido bond. The planes formed by the five membered chelate ring of each ligand form an angle of 121.0° for 3-4b,

124.4° for 3-7a, and127.5° for 3-8a. The folding of the ligand pushes the titanium center away from the plane formed by the carbon and nitrogen donors of the two ligands for 3-

8a. This forces the metal center 0.691 Å above the plane of the carbon and nitrogen donors (0.734 Å for 3-4b and 0.723 Å for 3-7a).

Figure 3-2. ORTEP diagram (50% thermal ellipsoids) of 3-7a; hydrogen atoms omitted for clarity. Bond lengths (in Å): Ti1-N1 = 1.678(2), Ti1-N2 = 2.223(2), Ti-N3

= 2.217(2), Ti1-C11 = 2.200(2), Ti1-C27 = 2.207(2); angles (in °) Ti1-N1-C1 =

176.5(2), N2-Ti1-C11 = 76.22(7), N3-Ti1-C27 = 76.28(7), C11-Ti1-C27 = 155.90(8).

Figure 3-3. ORTEP diagram (50% thermal ellipsoids) of 3-8a; hydrogen atoms omitted for clarity. Bond lengths (in Å): Ti1-N1 = 1.690(2), Ti1-N2 = 2.239(2),

Ti1-N3 = 2.258(2), Ti1-C5 = 2.198(2), Ti1-C26 = 2.194(2); angles (in °): Ti1-

N1-C1 = 171.1(2), N2-Ti1-C5 = 74.84(7), N3-Ti1-C26 = 75.30(7), C5-Ti1-C26

= 159.06(8).

Figure 3-4. The 1H NMR spectrum of 3-7a showing the upfield chemical shift of the -

OCH2O- protons, due to an interaction with an adjacent aryl ring.

The synthesis of each complex was performed in toluene with optimized reaction temperatures ranging from 0 °C (3-4a, 3-4b, 3-6a, 3-7a, 3-8a) to ambient temperature (3-

1a, 3-7d) to 50 °C (3-7b, 3-7c). All reactions were complete within 2 h at these reaction temperatures. At low temperature, compounds 3-7b and 3-7c yielded mixtures composed primarily of the desired product, but with significant amounts of inseparable impurities present. A possible explanation is the stochiometric metathesis between the metal imido group and the imine moiety of the ligand used, although we were not able to observe this

40, 41 spectroscopically. The metathesis of imido complexes such as Ti(NC(CH3)3)Cl2py3 with α-diimine ligands has been noted previously.82 Alternatively, synthesis of complexes

3-7b and 3-7c at elevated temperature (50 °C) eliminated the formation of impurities.

The use of alkylimine ligands was investigated following the successful synthesis

1 of 3-4 and 3-6 through 3-8. Lithiated alkylimine Li-L reacted with Ti(NC(CH3)3)Cl2py3

69 to yield an equilibrium mixture of two isomers in solution (cis/trans 3-1a; Scheme 3.3).

One equivalent of pyridine remained coordinated to the titanium center. The 1H NMR spectrum indicated two highly symmetrical species in solution, as evidenced by four resonances in a 1:1:1:1 ratio corresponding to the methylene protons of the two different isomers. Variable temperature NMR experiments were conducted in an effort to determine the individual spectra of the two complexes. Surprisingly, there was no change in the relative proportion of the two complexes at temperatures as low as -60 °C, while at elevated temperatures (~ 60 °C), the four peaks coalesced into one large singlet, indicating the formation of a fluxional species in solution. NOESY experiments confirmed the rapid interchange between isomers, even at room temperature, and therefore, we were not able to separate the NMR spectra of the two isomers (cis/trans 3-

1a; Figure 3-5). The upfield shift of the methylene proton typically observed with the aryl imines (Ln; n = 4,6,7,8) was not observed, due to the absence of the imine aromatic group in L1. Broad resonances at 9.18, 6.74 and 6.65 ppm are consistent with fluxional pyridine coordinated trans to the imido moiety. This was further supported by NOESY experiments showing throughspace interactions between the ortho protons of the pyridine moiety and the backbone protons of the imine. Quenching of the complexes with H2O yielded the protic imine H-L1, confirming the absence of ligand-based side reactions.

O O O O Cy O O N N N H Ti Ti HN HN N H_ Cy N O Cy N Cy O cis/trans 3-1a

Scheme 3.3. Complex 3-1a exists as an equilibrium mixture of cis and trans isomers.

Figure 3-5. The 1H NMR spectrum of 3-1a which exists as an equilibrium mixture of

cis and trans isomers in solution.

It has been difficult to synthesize a mono-ligated titanium imido complex. For all the reaction conditions attempted and ortholithiated imines used, no mono-ligated titanium imido complexes were isolated. In order to synthesize a mono-ligated titanium imido complex, an alternative titanium imido precursor, CpTi(NtBu)Clpy, was employed.

t Synthesized from the reaction of NaCp and Ti(N Bu)Cl2py3, it was believed that it would be possible to synthesize a metal complex with only one orthometallated imine ligand.

The metal complex isolated [(L8)TiCp(NtBu) (3-8b)] has a 1H NMR spectrum consistent with a mono-ligated imido complex (Scheme 3.4). The two protons of the

2 methylenedioxy ring are diastereotopic ( JHH = 1.2 Hz) and both are shifted slightly upfield compared to free ligand. A singlet at 6.39 ppm corresponds to the protons of a spinning Cp ligand and the singlet for the tert-butyl group of the imido moiety is clearly present.

O O Ti N N + O Li N Ti Cl Toluene, RT N O - LiCl N - py Ar

Scheme 3.4. The synthesis of (L8)TiCp(NtBu) (3-8b) using CpTi(NtBu)Clpy as a

precursor.

8 The reaction of Li-L with HfCl4 in toluene/DME yielded the “ate” salt

8 [Li(DME)3][(L )HfCl4] (3-9) in low yield (Scheme 3.5). It was believed that “ate” salt formation could be responsible for some of the low solubility observed for previously synthesized titanium and zirconium complexes. The isolation of this “ate” salt confirms that this ligand system can support the formation of anionic early transition metal complexes and furthermore, the judicious choice of solvent allows for the isolation of group(IV) “ate” salts using this ligand system. 3-9 was crystallized from a toluene/pentane solution, and the solid-state structure was determined by X-ray diffraction (Figure 3-6.). The hafnium center is 6-coordinate with four chloride ligands one anionic carbon donor and a neutral nitrogen donor. The lithium cation is also 6- coordinate with 3 chelating DME molecules bound to the lithium center.

Cl Li N Cl N + Hf [Li(DME)3] HfCl4 Cl Cl O Toluene/DME O 70 °C O O

Scheme 3.5. The synthesis of a hafnium “ate” salt (3-9).

8 - Figure 3-6. ORTEP diagram (50% thermal ellipsoids) of [(L )HfCl4] ; hydrogen

atoms and Li(DME)3 cation removed for clarity.

3.3 Conclusion

A series of aryl and alkyl imines were deprotonated using n-butyllithium and subsequently utilized as ligands for titanium imido complexes. The resultant complexes displayed a distorted square pyramidal geometry utilizing two monoanionic chelating imine ligands (C~N), with the imido moiety collinear with the C2 rotation axis for all arylimine ligated complexes. X-ray crystallography confirmed the connectivity that was deduced from the 1H and 13C NMR data. The short Ti-N bond length of the imido group denotes a high degree of sp character in the bond and participation of the nitrogen lone

73 pair in bonding to the metal center. These compounds were quite thermally robust and soluble in standard nonpolar solvents. When an alkylimine ligand was used, deviation from the coordination geometry observed for all arylimine complexes was observed.

Compound 3-1a exists as a 1:1 mixture of cis and trans isomers (cis/trans 3-1a), with one equivalent of pyridine coordinated to the metal center. The coordination of pyridine and fluxionality of the C~N ligands lead us to postulate that this compound (3-1a) may function as an effective precatalyst for imine metathesis or hydroamination reactions because the labile pyridine moiety could decoordinate to open a reactive coordination site on the metal center. This and other catalytic reactions are areas of active investigation in our research laboratory. Thus far no catalytic activity has been observed with phenylacetylene and anilines.

3.4 Experimental

3.4.1 General Methods and Instrumentation

All manipulations involving titanium or lithium were performed under an inert N2 atmosphere using standard glove box and Schlenk techniques. Solvents were predried before use; methylene chloride, pentane and toluene were passed through columns of 4Å molecular sieves and sparged with nitrogen. Ether was passed through a column of activated alumina and sparged with nitrogen. Benzene-d6 was dried over sodium metal, freeze-pump-thawed three times, and vacuum distilled. 2,6-Dimethylaniline, 2,6- diethylaniline, and 2,6-diisopropylaniline were dried over calcium hydride, freeze-pump- thawed three times, distilled under reduced pressure and stored in the dark. tert-

Butylamine was dried over calcium hydride, freeze-pump-thawed three times, and

74 distilled under reduced pressure. Dimethoxyethane (DME) was dried over sodium metal, freeze-pump-thawed three times, and vacuum distilled. Piperonal, 3’,4’- methylenedioxyacetophenone, TiCl4, n-butyllithium (1.6 M in hexanes), and p- toluenesulfonic acid were purchased from Acros and used as received. HfCl4 was purchased from Strem Chemicals, Inc., and used as received. 1H and 13C{1H} NMR data were obtained on a 600 MHz Inova NMR spectrometer at ambient temperature at 599.9

MHz and 150.8 MHz, respectively. All spectra were taken using C6D6 as NMR solvent.

1 13 H NMR shifts are given relative to C6D5H (7.16 ppm) and C NMR shifts are given

3 relative to C6D6 (128.1 ppm). Unless otherwise noted, all coupling constants are JHH. All

7 Li NMR spectra are given relative to an external LiCl (3.00 M in D2O) standard (0.00 ppm) and were obtained on a 400 MHz VXRS NMR spectrometer at 155.4 MHz. IR samples were prepared as Nujol mulls and taken between KBr plates on a Perkin-Elmer

XTL FTIR spectrophotometer. Melting points were observed on a capillary melting point

(Uni-Melt) apparatus in sealed capillary tubes and are uncorrected. X-ray structure determinations were performed at the Ohio Crystallographic Consortium housed at The

University of Toledo. Elemental analyses were determined by Desert Analytics, Tucson,

AZ or Galbraith Laboratories, Inc., Knoxville, TN. Several titanium complexes analyzed as low in carbon due to carbide formation, as noted parenthetically in the characterization section.

3.4.2 Synthesis of Starting Materials

t All titanium imido precursors CpTi(N Bu)Clpy, Ti(NC(CH3)3)Cl2py3 and Ti(NAr)Cl2py3;

i Ar = 2,6-Me2C6H3, 2,6-Et2C6H3, or 2,6- Pr2C6H3) were prepared according to previously

43, 83 published reports. Ti(NAr)Cl2py3 was crystallized from a methylene chloride/pentane solution. Compounds H-Ln, (n = 1,4,6,7,8),61, 63, 65 Li-Ln (n = 1,4,6,7,8),63, 65, 84 and

6 65 (L )2Ti(NC(CH3)3) (3-6a) were prepared according to previously published literature preparations.

n 3.4.3 General Synthetic Procedure for Complexes (L )2Ti(NR”)

The lithiated ligand Li-Ln (n = 1,4,6,7,8; 2 eq.; 1.4-6.6 mmol) was dissolved in toluene

(30-40 ml). The appropriate Ti(NR”)Cl2py3 (1 eq.), where R” = C(CH3)3, 2,6-Me2C6H3,

i 2,6-Et2C6H3, or 2,6- Pr2C6H3, was dissolved in toluene (30-40 ml). The lithiated ligand was added via cannula to the rapidly stirring solution of Ti(NR”)Cl2py3 at 0 °C (3-4a, 3-

4b, 3-4a, 3-7a, 3-8a), ambient temperature (3-1a, 3-7d), or 50 °C (3-7b, 3-7c). The reaction was allowed to stir for 2 hours at this temperature as a bright red color developed. After returning to ambient temperature, the solution was filtered to remove lithium chloride, and the volatiles were removed by reduced pressure. Isolation was accomplished as noted below.

1 (L )2Ti(NC(CH3)3)py (cis/trans 3-1a): tan solid following trituration of crude material with pentane, washing with pentane (30 ml x 3), and removal of volatiles using reduced pressure; 1:1 ratio of cis and trans isomers (1.34 g, 62%); 1H NMR: δ 9.18 (br s, 4H),

7.99 (s, 2H), 7.98 (s, 2H), 7.00 (d, 2H, 7.2 Hz), 6.89 (d, 2H, 7.2 Hz), 6.83 (d, 4H, 7.2 Hz),

6.74 (br s, 2H), 6.65 (br s, 4H), 5.77 (s, 2H), 5.71 (s, 2H), 5.59 (s, 2H), 5.50 (s, 2H), 3.22-

3.18 (m, 2H), 3.00-2.95 (m, 2H), 2.51-2.50 (m, 2H), 1.73-1.46 (m, 14H), 1.43 (s, 18H),

1.40-0.76 (m, 24H); 13C{1H} NMR: 173.5, 169.4, 166.2, 165.5, 153.9, 153.7, 152.1,

147.7, 146.1, 140.7, 139.1, 137.4, 125.7, 124.8, 122.5, 106.1, 104.2, 99.3, 98.7, 65.8,

65.3, 64.5, 34.2, 33.7, 33.6, 33.2, 32.5, 26.5, 26.3, 26.2, 26.1, 26.0; IR: 1618 (m), 1557

(m), 1446 (m), 1386 (m), 1249 (s), 1100 (m), 1054 (m), 938 (w), 793 (w), 695 (w); Anal.

54 53 calcd. for C32H41N3O4Ti: C, 66.31 (62.17); H, 7.25; N, 7.25. Found: C, 62.82; H, 6.64;

N, 7.41; mp 165 °C (dec.).

4 (L )2Ti(NC(CH3)3) (3-4a): bright red solid after washing crude material with pentane and crystallization from 1:1 toluene/pentane (0.20 g, 31%); 1H NMR δ 6.96 (d, 2H, 7.2

Hz), 6.87 (d, 2H, 8.4 Hz), 6.83 (t, 2H, 7.2 Hz), 6.62 (d, 2H, 7.2 Hz), 6.51 (d, 2H, 8.4 Hz),

2 2 5.50 (d, 2H, JHH = 1.7 Hz), 5.07 (d, 2H, JHH = 1.7 Hz), 2.59 (s, 6H), 2.48 (s, 6H), 1.50 (s,

6H), 1.41 (s, 9H); 13C{1H} NMR: δ 185.9, 167.9, 153.8, 148.7, 146.9, 138.5, 132.7,

130.1, 128.0, 125.6, 123.7, 105.4, 100.2, 71.7, 33.7, 19.6, 18.6, 17.2 (backbone carbon is obscured by C6D6); IR: 1539 (s), 1461 (m), 1406 (s), 1348 (m), 1305 (m), 1250 (s), 1201

(m), 1114 (m), 1090 (m), 1048 (m), 936 (w), 861 (w), 793 (m); Anal. calcd. for

53 C38H41N3O4Ti • ½ C7H8: C, 71.44 (68.00); H, 6.50; N, 6.02. Found: C, 67.94; H, 6.32;

N, 5.94; mp 119 ºC (dec.).

4 (L )2Ti(N-2,6-Me2C6H3) (3-4b): solid was washed with pentane and analytically pure dark red solid was isolated after crystallization from 1:1 toluene/pentane (0.75 g, 62%);

1H NMR: δ 6.95 (d, 2H, 7.2 Hz), 6.85-6.84 (m, 4H), 6.80 (t, 1H, 7.2 Hz), 6.66 (t, 2H, 7.2

2 Hz), 6.62 (d, 2H, 7.8 Hz), 6.52 (d, 2H, 7.8 Hz), 5.32 (d, 2H, JHH = 1.2 Hz), 4.98 (d, 2H,

2 13 1 JHH = 1.2 Hz), 2.70 (s, 6H), 2.32 (s, 6H), 1.58 (s, 6H), 1.55 (s, 6H); C{ H} NMR: δ

186.4, 168.5, 162.6, 152.8, 149.0, 146.3, 138.1, 133.1, 132.6, 130.0, 128.6, 127.6, 127.2,

125.6, 123.7, 119.7, 105.4, 100.2, 20.0, 19.2, 17.9, 16.9; IR: 2360 (m), 1597 (m), 1531

(s), 1460 (s), 1407 (s), 1377 (m), 1310 (s), 1247 (s), 1197 (m), 1142 (m), 1115 (m), 1088

(m), 1039 (m), 926 (w), 862 (w), 791 (m), 767 (w), 735 (w); Anal. calcd. for

53 C42H41N3O4Ti • ½ C7H8: C, 73.28 (70.06); H, 6.08; N, 5.63. Found: C, 70.59; H, 5.76;

N, 5.43; mp 136 ºC (dec.).

7 (L )2Ti(NC(CH3)3) (3-7a): red solid folowing recrystallization from 1:2 toluene/pentane

1 (0.38 g, 48%); H NMR: δ 7.80 (s, 2H), 7.09 (d, 2H, 6.6 Hz), 7.01 (t, 2H, 6.6 Hz), 6.81

2 (d, 2H, 6.6 Hz), 6.60 (d, 2H, 8.8 Hz), 6.43 (d, 2H, 8.8 Hz), 5.36 (d, 2H, JHH = 1.7 Hz),

2 4.68 (d, 2H, JHH = 1.7 Hz), 4.09 (sept, 2H, 6.6 Hz), 2.33 (sept, 2H, 6.6 Hz), 1.52 (d, 6H,

6.6 Hz), 1.35 (s, 9H), 1.21 (d, 6H, 6.6 Hz), 0.93 (d, 6H, 6.6 Hz), 0.46 (d, 6H, 6.6 Hz);

13C{1H} NMR: δ 179.5, 166.7, 153.9, 149.7, 147.6, 143.1, 140.9, 136.2, 127.5, 126.3,

122.9, 122.6, 105.9, 94.8, 72.4, 33.0, 22.8, 22.7, 21.5; IR: 1927 (w), 1863 (w), 1596 (m),

1542 (s), 1459 (s), 1409 (s), 1251 (s), 1174 (m), 1105 (s), 1061 (m), 974 (w), 937 (m),

53 885 (w), 856 (w); Anal. calcd. for C44H53N3O4Ti • ½ C7H8: C, 72.97 (69.89); H, 7.36;

N, 5.37. Found: C, 69.81; H, 7.27; N, 5.42; mp 198 °C (dec.).

7 (L )2Ti(N-2,6-Me2C6H3) (3-7b): Solid was washed with pentane (3 x 30 ml) to give a dark orange solid (0.25g, 43%) ; 1H NMR: δ 7.80 (s, 2H), 6.99-6.95 (m, 4H), 6.85 (d, 2H,

3 4 7.2 Hz), 6.81 (dd, 2H, JHH = 6.9 Hz, JHH = 1.8 Hz), 6.64 (t, 1H, 7.2 Hz), 6.60 (d, 2H, 7.8

2 2 Hz), 6.47 (d, 2H, 7.8 Hz), 5.25 (d, 2H, JHH = 1.2 Hz), 4.68 (d, 2H, JHH = 1.2 Hz), 3.89

(sept, 2H, 6.6 Hz), 2.59 (s, 6H), 2.52 (sept, 2H, 6.6 Hz), 1.18 (d, 6H, 6.6 Hz), 1.16 (d, 6H,

6.6 Hz), 0.97 (d, 6H, 6.6 Hz), 0.54 (d, 6H, 6.6 Hz); 13C{1H} NMR: δ 179.7, 167.4, 162.9,

153.5, 150.2, 147.2, 143.5, 140.7, 136.2, 132.6, 127.9, 126.9, 126.6, 123.3, 122.6, 120.2,

106.2, 100.1, 30.4, 28.6, 25.7, 24.6, 22.6, 21.4, 19.8; IR: 1606 (m), 1547 (m), 1463 (s),

1370 (s), 1311 (s), 1252 (s), 1100 (s), 1066 (s), 973 (w), 940 (m), 889 (w), 855 (w), 813

(m), 762 (m), 703 (m), 644 (w); mp 151 °C (dec.).

7 (L )2Ti(N-2,6-Et2C6H3) (3-7c): brown solid upon filtration and trituration with pentane; analytically pure sample was crystallized from 2:1 pentane/toluene (0.51 g, 59%); 1H

3 4 NMR: δ 7.79 (s, 2H), 7.00 (dd, 2H, JHH = 5.9 Hz, JHH = 1.6 Hz), 6.95 (t, 2H, 5.9 Hz),

3 4 6.90 (d, 2H, 7.2 Hz), 6.82 (dd, 2H, JHH = 5.9 Hz, JHH = 1.6 Hz), 6.73 (t, 1H, 7.2 Hz),

2 2 6.58 (d, 2H, 7.8 Hz), 6.48 (d, 2H, 7.8 Hz), 5.31 (d, 2H, JHH = 1.2 Hz), 4.73 (d, 2H, JHH =

1.2 Hz), 3.86 (sept, 2H, 7.2 Hz), 3.26 (m, 2H), 3.10 (m, 2H), 2.52 (sept, 2H, 7.2 Hz),

1.18-1.15 (m, 18H), 0.96 (d, 6H, 7.2 Hz), 0.54 (d, 6H, 7.2 Hz); 13C{1H} NMR: δ 179.7,

167.3, 153.6, 150.2, 147.4, 143.6, 140.8, 139.1, 136.3, 127.9, 126.6, 126.5, 125.4, 123.3,

122.5, 120.9, 106.1, 100.1, 30.4, 28.6, 25.8, 25.7, 24.7, 22.5, 21.3, 15.7; IR: 2359 (m),

2337 (w), 1599 (m), 1542 (m), 1455 (m), 1408 (s), 1301 (m), 1249 (s), 1177 (m), 1111

(s), 1064 (s), 977 (m), 940 (m), 794 (s); Anal. calcd. for C50H57N3O4Ti • 2 LiCl: C, 66.97;

H, 6.41; N, 4.69. Found: C, 66.83; H, 6.63; N, 4.79; mp: 165 ºC (dec.).

7 i (L )2Ti(N-2,6- Pr2C6H3) (3-7d): brown powder after washing with pentane (0.21 g,

24%); 1H NMR: δ 7.79 (s, 2H), 7.03 (m, 6H), 6.83 (t, 1H, 7.8 Hz), 6.81 (d, 2H, 5.9 Hz),

2 2 6.56 (d, 2H, 7.8 Hz), 6.47 (d, 2H, 7.8 Hz), 5.34 (d, 2H, JHH = 1.8 Hz), 4.76 (d, 2H, JHH =

1.8 Hz), 4.71 (sept, 2H, 6.6 Hz), 3.77 (sept, 2H, 7.2 Hz), 2.51 (sept, 2H, 7.2 Hz), 1.22 (d,

6H, 6.6 Hz), 1.18 (d, 6H, 6.6 Hz), 1.15 (d, 6H, 7.2 Hz), 1.11 (d, 6H, 7.2 Hz), 0.95 (d, 6H,

7.2 Hz), 0.54 (d, 6H, 7.2 Hz); 13C{1H} NMR: δ 179.6, 167.4, 160.5, 153.6, 150.3, 147.3,

143.6, 143.3, 140.9, 136.2, 127.8, 126.5, 123.4, 122.5, 121.5, 121.4, 106.0, 100.4, 30.6,

28.5, 27.7, 25.7, 24.7, 24.2, 23.4, 22.6, 21.2; IR: 1596 (s), 1542 (s), 1460 (s), 1333 (s),

1281 (m), 1249 (s), 1175 (m), 1104 (s), 1060 (s), 976 (m), 940 (m), 885 (w), 856 (w), 794

(m), 752 (m); Anal. calcd. for C52H61N3O4Ti: C, 74.36; H, 7.32; N, 5.00. Found: C,

73.56; H, 7.06; N, 4.80; mp 195 ºC (dec.).

8 (L )2Ti(NC(CH3)3) (3-8a) orange solid after recrystallization from 1:1 toluene/pentane

(0.47 g, 82%); 1H NMR: δ 7.08 (d, 2H, 7.6 Hz), 7.02 (t, 2H, 7.6 Hz), 6.89 (d, 2H, 7.6

Hz), 6.82 (d, 2H, 7.6 Hz), 6.49 (d, 2H, 7.6 Hz), 5.44 (s, 2H), 4.81 (s, 2H), 3.77 (sept, 2H,

7.2 Hz), 2.27 (sept, 2H, 7.2 Hz), 1.77 (s, 6H), 1.50 (d, 6H, 7.2 Hz), 1.29 (s, 9H), 1.13 (d,

6H, 7.2 Hz), 0.86 (d, 6H, 7.2 Hz), 0.40 (d, 6H, 7.2 Hz); 13C{1H} NMR: δ 186.0, 167.7,

153.4, 148.2, 144.8, 142.8, 140.4, 138.1, 126.1, 123.7, 123.4, 122.9, 105.2, 99.5, 71.9,

33.0, 30.3, 28.3, 25.1, 24.6, 24.5, 22.4, 20.1; IR: 2952 (s), 2916 (s), 2853 (s), 2725 (m),

1602 (w), 1533 (m), 1463 (s), 1407 (s), 1377 (s), 1346 (m), 1302 (s), 1249 (m), 1205 (w),

1181 (w), 1144 (w), 1110 (w), 1093 (w), 1052 (w), 943 (w), 931 (w), 896 (w), 862 (w),

804 (w), 791 (w), 782 (w), 722 (m); Anal. calcd. for C46H57N3O4Ti: C, 72.33; H, 7.52; N,

5.50. Found: C, 72.38; H, 7.85; N, 5.42.

(L8)TiCp(NtBu) (3-8b)

A Schlenk flask was charged with Li-L8 (0.28 g, 0.84 mmol) and toluene (10 ml) was added via cannula. A second Schlenk flask was charged with CpTi(NtBu)Clpy (0.25 g,

0.84 mmol) and toluene (6 ml) was added via cannula. The solution of Li-L8 was added via cannula to the stirring solution of CpTi(NtBu)Clpy. The reaction was allowed to stir

80 for 1.5 hours. The crude reaction mixture was filtered and the solvent removed via reduced pressure. The residue was dissolved in a minimal amount of diethyl ether and cooled to – 25 °C yielding crystalline material. The supernatant was removed and the crystals were dried under reduced pressure. 3-8b was isolated as a dark red crystalline solid (155 mg, 35%). 1H NMR: δ 7.10-7.08 (m, 3H), 6.97 (t, 1H, 5.9 Hz), 6.62 (d, 1H, 7.8

2 2 Hz), 6.39 (s, 5H), 5.51 (d, 1H, JHH = 1.2 Hz), 5.47 (d, 1H, JHH = 1.2 Hz), 4.21 (sept, 1H,

6.6 Hz), 2.55 (sept, 1H, 6.6 Hz), 1.80 (s, 3H), 1.29 (d, 3H, 6.6 Hz), 1.24 (s, 9H), 1.10 (d,

3H, 6.6 Hz), 1.08 (d, 3H, 6.6 Hz), 0.85 (d, 3H, 6.6 Hz); 13C{1H} NMR: δ 179.9, 174.7,

153.0, 146.7, 141.9, 141.6, 140.9, 153.4, 127.4, 125.5, 124.9, 124.5, 110.0, 105.0, 99.8,

66.8, 32.7, 27.5, 24.89, 24.86, 24.77, 24.4, 19.6.

8 8 [Li(DME)3] [(L )HfCl4] (3-9) A Schlenk flask was charged with Li-L (0.44 g, 1.3 mmol) and toluene (20 ml) was added via cannula. A second Schlenk flask was charged with HfCl4 (0.21 g, 0.66 mmol) and toluene (20 ml) was added via cannula. Next, DME

(10 ml) was added to the stirring slurry of HfCl4 in toluene, which was then heated to 70

8 °C. The solution of Li-L was added via cannula to the stirring solution of HfCl4. The reaction was allowed to stir for 1 hour at 70 °C. The crude reaction mixture was filtered warm and allowed to stand until crystals formed. The supernatant was removed and the crystals were dried under reduced pressure. 3-9 was isolated as a yellow crystalline solid

(200 mg, 33%). 1H NMR δ 7.24 (d, 2H, 8.4 Hz), 7.20 (t, 1H, 8.4 Hz), 7.00 (d, 1H, 8.4

Hz), 6.57 (d, 1H, 8.4 Hz), 5.34 (s, 2H), 3.86 (sept, 2H, 6.6 Hz), 3.09 (s, 12H), 3.07 (s,

18H), 1.94 (s, 3H), 1.71 (d, 6H, 6.6 Hz), 1.08 (d, 6H, 6.6 Hz); 13C{1H} NMR: δ 177.4,

155.8, 146.7, 144.2, 143.5, 138.5, 124.8, 124.5, 123.6, 104.7, 97.8, 71.5, 58.8, 28.5, 23.8,

23.3, 18.6 (one aromatic carbon resonance was not observed); 7Li NMR: -0.772.

3.5 Crystallography of 3-4b 3-7a, 3-8a and 3-9

Summaries of crystal data and collection parameters for crystal structures of 3-4b, 3-7a,

3-8a and 3-9 are provided in Table 3.1. Detailed descriptions of data collection, as well as data solution, are provided below. ORTEP diagrams were generated with the ORTEP-

3 software package.85

For 3-4b, X-ray quality crystals were grown from a layered solution of toluene and pentane, which was cooled to -25 °C. A red crystalline block with dimensions 0.21 x

0.20 x 0.10 mm was mounted on a pulled glass fiber using Paratone-N hydrocarbon oil.

The crystal was transferred to a Siemens SMART86 diffractometer with a CCD area detector, centered in the X-ray beam, and cooled to 140 K using a nitrogen-flow low- temperature apparatus that had been previously calibrated by a thermocouple placed at the same position as the crystal. An arbitrary hemisphere of data was collected using 0.3°

ω-scans that were counted for a total of 30 s per frame. The data was integrated by

SAINT87 to a maximum 2θ of 56.6°, and the final unit cell parameters were determined by a least-squares refinement of 3472 reflections with I > 10σ(I). Data analysis using

Siemens XPREP88 gave a primitive triclinic cell and based on the successful solution and refinement of the structure, the space group was determined to be P-1 (#2). An empirical absorption correction was applied using SADABS.89

Of the 21835 reflections that comprised the hemisphere, 9596 were unique (Rint =

0.0581), and all equivalent reflections were averaged. The structure was solved by

Patterson map using the SHELXTL90 software package. The unit cell contained one molecule of toluene located on an inversion center. All non-hydrogen atoms were refined anisotropically. Hydrogen atoms were included in fixed positions for the titanium complex, but omitted from the toluene solvate. The final cycle of full-matrix least- squares refinement was based on 6124 observed reflections and 487 variable parameters and converged yielding final residuals: R(obs) = 0.0702, R(all) = 0.1132, and GOF =

1.040.

For 3-7a, X-ray quality crystals were grown from a saturated solution of diethyl ether at -25 °C. An orange crystalline plate with dimensions 0.30 x 0.15 x 0.05 mm was mounted on a pulled glass fiber using Paratone-N hydrocarbon oil. The crystal was transferred to a Siemens SMART86 diffractometer with a CCD area detector, centered in the X-ray beam, and cooled to 200 K using a nitrogen-flow low-temperature apparatus that had been previously calibrated by a thermocouple placed at the same position as the crystal. An arbitrary hemisphere of data was collected using 0.3° ω-scans that were counted for a total of 40 s per frame. The data was integrated by SAINT87 to a maximum

2θ of 57.0°, and the final unit cell parameters were determined by a least-squares refinement of 5029 reflections with I > 10 σ(I). Data analysis using Siemens XPREP88 gave a primitive monoclinic cell and based on the successful solution and refinement of the structure, the space group was determined to be P21/n (#14). An empirical absorption correction was applied using SADABS.89

Of the 45289 reflections that comprised the hemisphere, 10246 were unique (Rint

= 0.0806), and all equivalent reflections were averaged. The structure was solved by

Patterson methods using the SHELXTL90 software package. All non-hydrogen atoms were refined anisotropically. Hydrogen atoms for all atoms were included but not refined. The final cycle of full-matrix least-squares refinement was based on 6761 observed reflections and 470 variable parameters and converged yielding final residuals:

R(obs) = 0.0564, R(all) = 0.0971, and GOF = 1.018.

For 3-8a, X-ray quality crystals were grown from a solution of toluene at -25 °C.

An orange crystalline plate with dimensions 0.29 x 0.27 x 0.14 mm was mounted on a pulled glass fiber using Paratone-N hydrocarbon oil. The crystal was transferred to a

Siemens SMART86 diffractometer with a CCD area detector, centered in the X-ray beam, and cooled to 153 K using a nitrogen-flow low-temperature apparatus that had been previously calibrated by a thermocouple placed at the same position as the crystal. An arbitrary hemisphere of data was collected using 0.3° ω-scans that were counted for a total of 30 s per frame. Due to poor crystal quality, the data was integrated by SAINT87 to a maximum 2θ of 45.5° (a resolution of 0.92Å), and the final unit cell parameters were determined by a least-squares refinement of 4737 reflections with I > 10 σ(I). Data analysis using Siemens XPREP88 gave a primitive monoclinic cell and based on the successful solution and refinement of the structure, the space group was determined to be

89 P21/c (#14). An empirical absorption correction was applied using SADABS.

Of the 29304 reflections that comprised the hemisphere, 5525 were unique (Rint =

0.0467), and all equivalent reflections were averaged. The structure was solved by direct

84 methods using the SHELXTL90 software package. All non-hydrogen atoms of the complex were refined anisotropically. Hydrogen atoms were included but not refined.

The final cycle of full-matrix least-squares refinement was based on 4486 observed reflections and 487 variable parameters and converged yielding final residuals: R(obs) =

0.0368, R(all) = 0.0492, and GOF = 1.036. Due to the reduced resolution of this structure, geometric parameters are less reliable than in the other three crystal structures presented herein.

For 3-9, X-ray quality crystals were grown from a saturated toluene/dimethoxyethane solution at ambient temperature. A yellow crystalline rod with dimensions 0.60 x 0.20 x 0.10 mm was mounted on a pulled glass fiber using Paratone-N hydrocarbon oil. The crystal was transferred to a Siemens SMART86 diffractometer with a CCD area detector, centered in the X-ray beam, and cooled to 140 K using a nitrogen- flow low-temperature apparatus that had been previously calibrated by a thermocouple placed at the same position as the crystal. An arbitrary hemisphere of data was collected using 0.3° ω-scans that were counted for a total of 20 s per frame. The data was integrated by SAINT87 to a maximum 2θ of 49.4°, and the final unit cell parameters were determined by a least-squares refinement of 5995 reflections with I > 10 σ(I). Data analysis using Siemens XPREP88 gave a primitive monoclinic cell and based on the successful solution and refinement of the structure, the space group was determined to be

P-1 (#2). An empirical absorption correction was applied using SADABS.89

Of the 21406 reflections that comprised the hemisphere, 6776 were unique (Rint =

0.0460), and all equivalent reflections were averaged. The structure was solved by direct

85 methods using the SHELXTL90 software package. All non-hydrogen atoms of the complex were refined anisotropically. Hydrogen atoms were included but not refined.

The DME ligands of the lithium cation were disordered; several of the methyl groups of the DME ligands were disordered over multiple positions, as well as the ethyl backbone of one DME ligand. Electron density corresponding to additional disorder found in the

DME ligands was observed, but not modeled, in the final crystallographic model. The final cycle of full-matrix least-squares refinement was based on 5995 observed reflections and 483 variable parameters and converged yielding final residuals: R =

0.0604, Rall = 0.0690, and GOF = 1.083.

Table 3.1. Crystal Data and Collection Parameters of (3-4b), (3-7a), (3-8a) and (3-9)

Compound 3-4b 3-7a 3-8a 3-9

Formula C46H57N3O4Ti C42H41N3O4Ti • ½ C7H8 C44H53N3O4Ti C33H54Cl4HfNLiO8

Formula weight 763.85 745.75 735.79 920.00

Space group P21/c P-1 P21/n P-1

Temperature (K) 153(2) 140(2) 200(2) 140 a (Å) 10.8857(8) 10.999(1) 12.288(4) 9.845(1) b (Å) 20.862(1) 12.696(1) 24.290(8) 11.200(2) c (Å) 18.346(1) 14.624(1) 13.775(4) 19.027(3)

α (°) 90 73.494(2) 90 106.657(3)

β (°) 99.708(4) 81.949(2) 97.28(1) 97.125(3)

γ (°) 90 88.826(2) 90 92.133(3)

V (Å3) 4106.7(5) 1938.4(3) 4078(2) 1988.5(5)

Z 4 2 4 2

3 Densitycalc (g/cm ) 1.235 1.278 1.198 1.537

Diffractometer Siemens SMART Siemens SMART Siemens SMART Siemens SMART

Radiation Mo-Kα (λ = 0.71073 Mo-Kα (λ = 0.71073 Å) Mo-Kα (λ = 0.71073 Å) Mo-Kα (λ = 0.71073 Å)

Monochromator Graphite Graphite Graphite Graphite

Detector CCD area detector CCD area detector CCD area detector CCD detector

Scan type, width ω, 0.3° ω, 0.3° ω, 0.3° ω, 0.3°

Scan speed 30 s / frame 30 s / frame 40 s / frame 20

Reflections measured Hemisphere Hemisphere Hemisphere Hemisphere

2θ range (°) 3.80 – 45.50 3.34-56.62 3.36-56.98 2.26-49.42

Crystal dimensions (mm) 0.29 u 0.27 u 0.14 0.21 x 0.20 x 0.10 0.30 x 0.15 x 0.05 0.60 x 0.20 x 0.10

Reflections measured 29304 21835 45289 21406

Unique reflections 5525 9596 10246 6776

Observations 4486 6124 6761 5995

(I > 2 σ (I))

Rint 0.0467 0.0581 0.0806 0.0460

Parameters 487 487 470 483

R(obs), Rw(all), R(all) 0.0368; 0.0998; 0.0492 0.0702; 0.1843; 0.1132 0.0564, 0.1420, 0.0971 0.0604, 0.1720, 0.0690

GOF 1.036 1.040 1.018 1.083

References

1. Hazari, N.; Mountford, P., Reactions and applications of titanium imido complexes. Accounts of Chemical Research 2005, 38 (11), 839-849.

2. Ketterer, N. A.; Ziller, J. W.; Rheingold, A. L.; Heyduk, A. F., Imido and organometallic-amido titanium(IV) complexes of a chelating phenanthrenediamide ligand. Organometallics 2007, 26 (22), 5330-5338.

3. Lorber, C.; Choukroun, R.; Vendier, L., A general and facile one-step synthesis of imido-titanium(IV) complexes: Application to the synthesis of compounds containing functionalized or chiral imido ligands and bimetallic diimido architectures. European Journal of Inorganic Chemistry 2006, (22), 4503-4518.

4. Owen, C. T.; Bolton, P. D.; Cowley, A. R.; Mountford, P., Cyclopentadienyl titanium imido compounds and their ethylene polymerization capability: Control of molecular weight distributions by imido N-substituents. Organometallics 2007, 26 (1), 83-92.

5. Herrmann, H.; Fillol, J. L.; Wadepohl, H.; Gade, L. H., A zirconium (1- pyridinio)imido complex: Facile N-N bond cleavage and N-C bond formation. Organometallics 2008, 27 (2), 172-174.

6. Clulow, A. J.; Selby, J. D.; Cushion, M. G.; Schwarz, A. D.; Mountford, P., Synthesis, structures and reactivity of group 4 hydrazido complexes supported by calix[4]arene ligands. Inorganic Chemistry 2008, 47 (24), 12049-12062.

7. Mountford, P., New titanium imido chemistry. Chemical Communications 1997, (22), 2127-2134.

8. Spencer, L. P.; Yang, P.; Scott, B. L.; Batista, E. R.; Boncella, J. M., Uranium(VI) bis(imido) chalcogenate complexes: Synthesis and density functional theory analysis. Inorganic Chemistry 2009, 48 (6), 2693-2700.

9. Cross, W. B.; Anderson, J. C.; Wilson, C.; Blake, A. J., Molybdenum oxo-imido aryloxide complexes: Oxo analogues of olefin metathesis catalysts. Inorganic Chemistry 2006, 45 (11), 4556-4561.

10. Takemoto, S.; Ogura, S.; Yo, H.; Hosokoshi, Y.; Kamikawa, K.; Matsuzaka, H., Diiron amido-imido complex (Cp*Fe)2(P2-NHPh)(P2-NPh) : Synthesis and a net hydrogen atom abstraction reaction to form a bis(imido) complex. Inorganic Chemistry 2006, 45 (13), 4871-4873.

11. Cowley, R. E.; Bontchev, R. P.; Sorrell, J.; Sarracino, O.; Feng, Y. H.; Wang, H. B.; Smith, J. M., Formation of a cobalt(III) imido from a cobalt(II) amido complex. Evidence for proton-coupled electron transfer. Journal of the American Chemical Society 2007, 129 (9), 2424-2425.

12. Anandhi, U.; Holbert, T.; Lueng, D.; Sharp, P. R., Platinum and palladium imido and oxo complexes with small natural bite angle diphosphine ligands. Inorganic Chemistry 2003, 42 (4), 1282-1295.

13. Cefalo, D. R.; Kiely, A. F.; Wuchrer, M.; Jamieson, J. Y.; Schrock, R. R.; Hoveyda, A. H., Enantioselective synthesis of unsaturated cyclic tertiary ethers by Mo-catalyzed olefin metathesis. Journal of the American Chemical Society 2001, 123 (13), 3139-3140.

14. Johnson, J. S.; Bergman, R. G., Imidotitanium complexes as hydroamination catalysts: Substantially enhanced reactivity from an unexpected cyclopentadienide/amide ligand exchange. Journal of the American Chemical Society 2001, 123 (12), 2923-2924.

15. Ackermann, L.; Bergman, R. G.; Loy, R. N., Use of group 4 bis(sulfonamido) complexes in the intramolecular hydroamination of alkynes and allenes. Journal of the American Chemical Society 2003, 125 (39), 11956-11963.

16. Zuckerman, R. L.; Krska, S. W.; Bergman, R. G., Zirconium-mediated metathesis of imines: A study of the scope, longevity, and mechanism of a complicated catalytic system. Journal of the American Chemical Society 2000, 122 (5), 751- 761.

17. Krska, S. W.; Zuckerman, R. L.; Bergman, R. G., Use of steric hindrance and a metallacyclobutene resting state to develop robust and kinetically characterizable zirconium-based imine metathesis catalysts. Journal of the American Chemical Society 1998, 120 (45), 11828-11829.

18. Meyer, K. E.; Walsh, P. J.; Bergman, R. G., Zirconium mediated imine metathesis - synthesis of 2,4-diaza-1-zirconiacyclobutanes and the mechanism of their reactions with imines and alkynes. Journal of the American Chemical Society 1994, 116 (6), 2669-2670.

19. Roesky, H. W.; Voelker, H.; Witt, M.; Noltemeyer, M., Synthesis and structure of Ph2P(S)N=TiCl23C5H5N, the 1st imidotitanium complex. Angewandte Chemie International Edition. 1990, 29 (6), 669-670.

20. Hill, J. E.; Profilet, R. D.; Fanwick, P. E.; Rothwell, I. P., Synthesis, structure, and reactivity of aryloxo(imido)titanium complexes. Angewandte Chemie International Edition 1990, 29 (6), 664-665.

21. Thorn, D. L.; Nugent, W. A.; Harlow, R. L., Structures of (CH3)2(tert-Bu)W2(P- tert-Bu)2 and (CH3)2N)2Ti2(P-tert-Bu)2 - a molecular orbital explanation of the existence of unsymmetrically or symmetrically bridging organoimido ligands. Journal of the American Chemical Society 1981, 103 (2), 357-363.

22. Alcock, N. W.; Pierce-Butler, M.; Willey, G. R., Planar Ti2N2 rings with 5- coordinate titanium(IV) - X-ray structure of catena-di-P-chloro-bis-P- 89

(trimethylsilylamino)-di-[chlorotitanium(IV)]. Chemical Communications 1974, (15), 627a-627a.

23. Alcock, N. W.; Pierce-Butler, M.; Willey, G. R., Catena-di-P-chloro-bis-P- (trimethylsilylamino)-di[chlorotitanium(IV)] preparation, properties, and crystal structure. Dalton Transactions 1976, (8), 707-713.

24. Vroegop, C. T.; Teuben, J. H.; Bolhuis, F.; Vanderlinden, J. G. M., New amido- titanium and imido-titanium complexes. Chemical Communications 1983, (10), 550-552.

25. Severin, R.; Doye, S., The catalytic hydroamination of alkynes. Chemistry Society Reviews 2007, 36 (9), 1407-1420.

26. Grabe, K.; Pohlki, F.; Doye, S., Neutral Ti complexes as catalysts for the hydroamination of alkynes and alkenes: Do the labile ligands change the catalytic activity? European Journal of Organic Chemistry 2008, (28), 4815-4823.

27. Zhang, Z.; Leitch, D. C.; Lu, M.; Patrick, B. O.; Schafer, L. L., An easy-to-use, regioselective, and robust bis(amidate) titanium hydroamination precatalyst: Mechanistic and synthetic investigations toward the preparation of tetrahydroisoquinolines and benzoquinolizine alkaloids. Chemistry - A European Journal 2007, 13 (7), 2012-2022.

28. Haak, E.; Bytschkov, I.; Doye, S., Intermolecular hydroamination of alkynes catalyzed by dimethyltitanocene. Angewandte Chemie International Edition 1999, 38 (22), 3389-3391.

29. Esteruelas, M. A.; Lopez, A. M.; Mateo, A. C.; Onate, E., New titanium complexes containing a cyclopentadienyl ligand with a pendant aminoalkyl substituent: Preparation, behavior of the amino group, and catalytic hydroamination of alkynes. Organometallics 2005, 24 (21), 5084-5094.

30. Buil, M. L.; Esteruelas, M. A.; Lopez, A. M.; Mateo, A. C., Preparation of half- sandwich alkyl-titanium(IV) complexes stabilized by a cyclopentadienyl ligand with a pendant phosphine tether and their use in the catalytic hydroamination of aliphatic and aromatic alkynes. Organometallics 2006, 25 (17), 4079-4089.

31. Banerjee, S.; Shi, Y. H.; Cao, C. S.; Odom, A. L., Titanium-catalyzed iminohydrazination of alkynes. Journal of Organometallic Chemistry 2005, 690 (23), 5066-5077.

32. Thomson, R. K.; Zahariev, F. E.; Zhang, Z.; Patrick, B. O.; Wang, Y. A.; Schafer, L. L., Structure, bonding, and reactivity of Ti and Zr amidate complexes: DFT and X-ray crystallographic studies. Inorganic Chemistry 2005, 44 (24), 8680- 8689.

33. Lorber, C.; Choukroun, R.; Vendier, L., Hydroamination of alkynes catalyzed by imido complexes of titanium and vanadium. Organometallics 2004, 23 (8), 1845- 1850.

34. Li, Y. H.; Shi, Y. H.; Odom, A. L., Titanium hydrazido and imido complexes: Synthesis, structure, reactivity, and relevance to alkyne hydroamination. Journal of the American Chemical Society 2004, 126 (6), 1794-1803.

35. Vujkovic, N.; Ward, B. D.; Maisse-Francois, A.; Wadepohl, H.; Mountford, P.; Gade, L. H., Imido-alkyne coupling in titanium complexes: New insights into the alkyne hydroamination reaction. Organometallics 2007, 26 (23), 5522-5534.

36. Bexrud, J. A.; Li, C. Y.; Schafer, L. L., Enhanced reactivity results in reduced catalytic performance: Unexpected ligand reactivity of a bis(N-2,6- diisopropylphenylperflourophenyl-amidate)titanium-bis(diethylamido) hydroamination precatalyst. Organometallics 2007, 26 (25), 6366-6372.

37. Guiducci, A. E.; Boyd, C. L.; Mountford, P., Reactions of cyclopentadienyl- amidinate titanium imido compounds with CS2, COS, isocyanates, and other unsaturated organic compounds. Organometallics 2006, 25 (5), 1167-1187.

38. Bolton, P. D.; Feliz, M.; Cowley, A. R.; Clot, E.; Mountford, P., Ti=NR vs Ti-R' functional group selectivity in titanium imido alkyl cations from an experimental perspective. Organometallics 2008, 27 (23), 6096-6110.

39. Polse, J. L.; Andersen, R. A.; Bergman, R. G., Reactivity of a terminal Ti(IV) imido complex toward alkenes and alkynes: Cycloaddition vs C-H activation. Journal of the American Chemical Society 1998, 120 (51), 13405-13414.

40. Ong, T. G.; Yap, G. P. A.; Richeson, D. S., Catalytic C=N bond metathesis of carbodiimides by group 4 and 5 imido complexes supported by guanidinate ligands. Chemical Communications 2003, (20), 2612-2613.

41. McInnes, J. M.; Mountford, P., Transition metal imide organic imine metathesis reactions: Unexpected observations. Chemical Communications 1998, (16), 1669-1670.

42. Duchateau, R.; Williams, A. J.; Gambarotta, S.; Chiang, M. Y., Carbon-carbon double-bond formation in the intermolecular acetonitrile reductive coupling promoted by a mononuclear Titanium(II) compound - preparation and characterization of 2 Titanium(IV) imido derivatives. Inorganic Chemistry 1991, 30 (25), 4863-4866.

43. Blake, A. J.; Collier, P. E.; Dunn, S. C.; Li, W. S.; Mountford, P.; Shishkin, O. V., Synthesis and imido-group exchange reactions of tert-butylimidotitanium complexes. Dalton Transactions 1997, (9), 1549-1558.

44. Adams, N.; Arts, H. J.; Bolton, P. D.; Cowell, D.; Dubberley, S. R.; Friederichs, N.; Grant, C. M.; Kranenburg, M.; Sealey, A. J.; Wang, B.; Wilson, P. J.; Zuideveld, M.; Blake, A. J.; Schroder, M.; Mountford, P., Imido titanium ethylene polymerization catalysts containing triazacyclic ligands. Organometallics 2006, 25 (16), 3888-3903.

45. Gardner, J. D.; Robson, D. A.; Rees, L. H.; Mountford, P., Titanium tert-butyl- and trimethylsilyl-imido complexes with monopendant arm triazacyclononane ligands. Inorganic Chemistry 2001, 40 (4), 820-824.

46. Li, H. M.; Su, J. G.; Lu, Z. L.; Fun, H. K.; Chantrapromma, S., Palladacycle complexes of (S)-4-iso-propyl-2-phenyl-2-oxazoline: Synthesis, crystal structures and catalytical methanolysis of pesticide. Inorganic Chemistry Communications 2008, 11 (3), 235-238.

47. Lloyd, J.; Vatsadze, S. Z.; Robson, D. A.; Blake, A. J.; Mountford, P., New titanium imido complexes containing piperazine-based diamido-diamine ligands. Journal of Organometallic Chemistry 1999, 591 (1-2), 114-126.

48. Thomson, R. K.; Bexrud, J. A.; Schafer, L. L., A pentagonal pyramidal zirconium imido complex for catalytic hydroamination of unactivated alkenes. Organometallics 2006, 25 (17), 4069-4071.

49. Lai, R. Y.; Surekha, K.; Hayashi, A.; Ozawa, F.; Liu, Y. H.; Peng, S. M.; Liu, S. T., Intra- and intermolecular hydroamination of alkynes catalyzed by ortho- metalated iridium complexes. Organometallics 2007, 26 (4), 1062-1068.

50. Circu, V.; Gibbs, T. J. K.; Omnes, L.; Horton, P. N.; Hursthouse, M. B.; Bruce, D. W., Orthometallated palladium(II) imine complexes as candidate materials for the biaxial nematic phase. Crystal and molecular structure of three palladium imine complexes. Journal of Materials Chemistry 2006, 16 (44), 4316-4325.

51. Marcazzan, P.; Patrick, B. O.; James, B. R., Rhodium(III)-cyclometalated-imine complexes: Solution behavior and reactivity with molecular hydrogen. Organometallics 2005, 24 (7), 1445-1451.

52. Krug, C.; Hartwig, J. F., Reactions of an arylrhodium complex with aldehydes, imines, ketones, and alkynones. New classes of insertion reactions. Organometallics 2004, 23 (20), 4594-4607.

53. Klein, H. F.; Camadanli, S.; Beck, R.; Leukel, D.; Florke, U., Cyclometalation of substrates containing imine and pyridyl anchoring groups by iron and cobalt complexes. Angewandte Chemie International Edition 2005, 44 (6), 975-977.

54. Mashima, K.; Tanaka, Y.; Nakamura, A., Synthesis, characterization, and 5 4 reactions of a mononuclear tantalum-benzyne complex, Ta(K -C5Me5)(K - 2 C4H6)(K -C6H4). Organometallics 1995, 14 (12), 5642-5651.

55. Barr, K. J.; Watson, B. T.; Buchwald, S. L., Zirconocene(iso-butyl) chloride: In situ generation of a zirconocene(methyl) chloride equivalent for use in organic synthesis. Tetrahedron Letters 1991, 32 (40), 5465-5468.

56. Hsu, D. P.; Lucas, E. A.; Buchwald, S. L., Synthesis and reactions of a zirconocene-benzdiyne equivalent. Tetrahedron Letters 1990, 31 (39), 5563-5566.

57. Lund, C. L.; Schachner, J. A.; Burgess, I. J.; Quail, J. W.; Schatte, G.; Muller, J., Synthesis and characterization of aluminum- and gallium-bridged [1.1] chromarenophanes and [1.1] molybdarenophanes. Inorganic Chemistry 2008, 47 (13), 5992-6000.

58. Padelkova, Z.; Nechaev, M. S.; Cernosek, Z.; Brus, J.; Ruzicka, A., Solvent controlled ring size in double C,N-chelated stannoxanes. Organometallics 2008, 27 (20), 5303-5308.

59. Schumann, H.; Freitag, S.; Girgsdies, F.; Hemling, H.; Kociok-Kohn, G., Homoleptic organometallic compounds of zinc, cadmium, and mercury, intramolecularly stabilized by amine ligands. European Journal of Inorganic Chemistry 1998, (2), 245-252.

60. Contel, M.; Stol, M.; Casado, M. A.; van Klink, G. P. M.; Ellis, D. D.; Spek, A. L.; van Koten, G., A bis(ortho-amine)aryl-gold(I) compound as an efficient, nontoxic, arylating reagent. Organometallics 2002, 21 (21), 4556-4559.

61. Ziegler, F. E.; Fowler, K. W., Substitution reactions of specifically ortho- metalated piperonal cyclohexylimine. Journal of Organic Chemistry 1976, 41, 1564-1566.

62. Qu, B.; Collum, D. B., Structure of n-butyllithium in mixtures of ethers and diamines: Influence of mixed solvation on 1,2-additions to imines. Journal of the American Chemical Society 2006, 128 (29), 9355-9360.

63. Neshat, A.; Seambos, C. L.; Beck, J. F.; Schmidt, J. A. R., Mono-anionic acetophenone imine ligands: Synthesis, ortho-lithiation and first examples of group (V) metal complexes. Dalton Transactions 2009, 4987–5000.

64. Ortholithiation of phenyl imines has been observed for a limited number of other substrates. See: L. A. Flippin, J. M. Muchowski, and D. S. Carter, J. Org. Chem., 1993, 58, 2463-2467.

65. Baiz, T. I.; Schmidt, J. A. R., A discrete ortho-lithiated acetophenone imine derivative: Isolation, characterization, and synthesis of group IV metal complexes. Organometallics 2007, 26 (17), 4094-4097.

66. Martin, N. H.; Floyd, R. M.; Woodcock, H. L.; Huffman, S.; Lee, C. K., Computation of through-space NMR shielding effects in aromatic ring pi-stacked

complexes. Journal of Molecular Graphics and Modelling 2008, 26 (7), 1125- 1130.

67. Lambert, J. B.; Mazzola, E. P., Nuclear Magnetic Resonance Spectroscopy. Pearson Education Inc.: Upper Saddle River, NJ, 2004.

68. Pavia, D. L.; Lampman, G. M.; Kriz, G. S., Introduction to Spectroscopy. 3rd ed.; Thomson Learning, Inc.: Belmont, CA, 2001.

69. Selby, J. D.; Manley, C. D.; Feliz, M.; Schwarz, A. D.; Clot, E.; Mountford, P., New ligand platforms for developing the chemistry of the Ti=N-NR2 functional group and the insertion of alkynes into the N-N bond of a Ti=N-NPh2 ligand. Chemical Communications 2007, (46), 4937-4939.

70. Bailey, B. C.; Fout, A. R.; Fan, H. J.; Tomaszewski, J.; Huffman, J. C.; Gary, J. B.; Johnson, M. J. A.; Mindiola, D. J., Snapshots of an alkylidyne for nitride triple-bond metathesis. Journal of the American Chemical Society 2007, 129 (8), 2234-2235.

71. Bailey, B. C.; Basuli, F.; Huffman, J. C.; Mindiola, D. J., Terminal titanium(IV) (trimethylsilyl)imides prepared by oxidatively induced trimethylsilyl abstraction. Organometallics 2006, 25 (11), 2725-2728.

72. Bailey, B. C.; Huffman, J. C.; Mindiola, D. J.; Weng, W.; Ozerov, O. V., Remarkably stable titanium complexes containing terminal alkylidene, phosphinidene, and imide functionalities. Organometallics 2005, 24 (7), 1390- 1393.

73. Adams, N.; Bigmore, H. R.; Blundell, T. L.; Boyd, C. L.; Dubberley, S. R.; Sealey, A. J.; Cowley, A. R.; Skinner, M. E. G.; Mountford, P., New titanium imido synthons: Syntheses and supramolecular structures. Inorganic Chemistry 2005, 44 (8), 2882-2894.

74. Boyd, C. L.; Toupance, T.; Tyrrell, B. R.; Ward, B. D.; Wilson, C. R.; Cowley, A. R.; Mountford, P., Synthesis, structures, and reactions of titanium, scandium, and yttrium complexes of diamino-bis(phenolate) ligands: Monomeric, dimeric, neutral, cationic, and multiply bonded derivatives. Organometallics 2005, 24 (2), 309-330.

75. Hamaki, H.; Takeda, N.; Tokitoh, N., Nucleophilic attack toward group 4 metal complexes bearing reactive 1-aza-1,3-butadienyl and imido moieties. Inorganic Chemistry 2007, 46 (5), 1795-1802.

76. Basuli, F.; Huffman, J. C.; Mindiola, D. J., Reductive C-N bond cleavage of the NCCCN beta-diketiminate backbone: A direct approach to azabutadienyl and alkylidene-anilide scaffolds. Inorganica Chimica Acta 2007, 360 (1), 246-254.

77. Banerjee, S.; Odom, A. L., Synthesis and structure of a titanium hydrazido(2-) complex. Organometallics 2006, 25 (13), 3099-3101.

78. Aneetha, H.; Basuli, F.; Bollinger, J.; Huffman, J. C.; Mindiola, D. J., Ti(NMe2)4 and HNMe2Ph B(C6F5)4 : A convenient blend for effective catalytic carboamination of alkynes. Organometallics 2006, 25 (10), 2402-2404.

79. Hamaki, H.; Takeda, N.; Tokitoh, N., Reduction of tetravalent group 4 metal complexes supported by an extremely bulky, unsymmetrically substituted beta- diketiminato ligand leading to the regioselective C=N bond cleavage giving ring- contracted metal-imido complexes. Organometallics 2006, 25 (10), 2457-2464.

80. Kilgore, U. J.; Basuli, F.; Huffman, J. C.; Mindiola, D. J., Aryl isocyanate, carbodiimide, and isocyanide prepared from carbon dioxide. A metathetical group-transfer tale involving a titanium-imide zwitterion. Inorganic Chemistry 2006, 45 (2), 487-489.

81. Basuli, F.; Bailey, B. C.; Watson, L. A.; Tomaszewski, J.; Huffman, J. C.; Mindiola, D. J., Four-coordinate titanium alkylidene complexes: Synthesis, reactivity, and kinetic studies involving the terminal neopentylidene functionality. Organometallics 2005, 24 (8), 1886-1906.

82. McInnes, J. M.; Blake, A. J.; Mountford, P., Reactions of titanium imido complexes with alpha-diimines: Complexation versus Ti=N/C=N bond metathesis. Dalton Transactions 1998, (21), 3623-3628.

83. Dunn, S. C.; Mountford, P.; Robson, D. A., Cyclopentadienyl, indenyl and bis(cyclopentadienyl) titanium imido compounds. Dalton Transactions 1997, (3), 293-304.

84. Baiz, T. I. M.S. Thesis, Synthesis of group IV metal complexes employing a newly developed orthometallated imine ligand system. University of Toledo, Toledo, OH, 2007.

85. Farrugia, L. J., ORTEP-3 for windows - a version of ORTEP-III with a graphical user interface. Journal of Applied Crystallography 1997, 30, 565.

86. SMART, SMART: Area-Detector Software Package, v5.625; Bruker AXS, Inc.: Madison, WI, 1997-2001.

87. SAINT, SAINT: SAX Area-Detector Integration Program, V6.22; Bruker AXS, Inc.: Madison, WI, 1997-2001.

88. XPREP, XPREP: Reciprocal Space Exploration Program, V6.12; Bruker AXS, Inc.: Madison, WI, 2001.

89. SADABS, SADABS: Bruker/Siemens Area Detector Absorption Program, V2.03; Bruker AXS, Inc.: Madison, WI, 2001.

90. SHELXL-97, SHELXL-97: Structure Solution Program, V6.10; Bruker AXS, Inc.: Madison, WI, 2000.

Chapter 4

Isolation and Characterization of Main Group and Late Transition Metal Complexes using orthoMetallated Imine Ligands

4.1 Introduction

In Chapter two, we presented a detailed structural study of a series of ortholithiated imines.1-3 The coordination chemistry of these ortholithiated imines was also investigated with a number of early transition metals including titanium, zirconium, tantalum, and niobium.4-6 With the exception of compounds incorporating imido ligands, most of the metal complexes studied exhibited very low solubility in ethereal, aromatic or hydrocarbon solvents. Furthermore, in the course of our studies, it has become apparent that lithium reagents may not be the best way to access the chemistry supported by orthometallated imines. Lithium reagents commonly undergo undesirable side reactions reducing product yields when used in salt metathesis reactions with transition, main group, and lanthanide metal halides. One of the most common problems involves the formation of lithium halide adducts or “ate” salts, which have been observed in many cases when lithium reagents are reacted with metal chlorides.7-16 The formation of “ate”

97 salts may be responsible for the poor solubility observed for the group (IV) orthometallated imine complexes that we previously reported.6 In fact, we were recently able to isolate a hafnium “ate” salt incorporating an orthometallated imine ligand

(Chapter 3, compound 3-9). To help circumvent this difficulty, we decided to pursue alternative orthometallated imine complexes that could be used as transfer reagents in place of the lithiated species. In addition, the recent renaissance of main group organometallics in catalysis17-24 implies that these main group metal complexes may have applicability in catalytic transformations in their own right.

In some cases, “ate” salts have been found to be very useful reagents. For example, the most productive “ate” salts are the lithium cuprates, which have found broad utility in organic synthesis.25, 26 There are numerous examples of their use as coupling reagents, dating back to the early work of Henry Gilman.27 Efforts to avoid the limitations of “ate” salts have led to the investigation of zinc,28 magnesium,29-32 and tin32,

33 compounds, which have proven to be effective transfer reagents in coupling chemistry.

For example, it has been reported that the yields of niobium and tantalum alkyls are higher when alkyl zinc species are used instead of lithium reagents.34 Thus, zinc complexes have found extensive use as salt metathesis reagents for group (V) metals.

Magnesium species, in the form of bis-alkyls and Grignard reagents, have also been widely used as alkylating agents in organometallic synthesis, as well as organic synthesis.

n 32 Despite their toxic nature and unpleasant odor, tin reagents such as Bu3SnCp and

35 SnMe4 are often utilized in the alkylation of early transition metals. Thus, the lithium- free orthometallated imine starting materials based on zinc, magnesium and tin should

98 provide an advantageous alternative route to organometallic products utilizing these chelating ligands.

Recent investigations into main group organometallics have led to a range of interesting chemistry, while reaffirming that common and inexpensive metals such as magnesium and aluminum show great promise in catalysis. Hill and coworkers at the

University of Bath have performed truly pioneering work on group (II) catalysis, developing calcium-mediated intramolecular hydroamination,36 C-F bond activation,37 and intermolecular hydrophosphination.38, 39 There has also been a great deal of interest in calcium catalyzed polymerization.20 Other recent reports detail several examples of magnesium catalyzed hydroamination40-42 and the polymerization of lactide.43-46

Additionally, several research groups have recently investigated the polymerization of lactide using aluminum complexes.47-51 Bergman has demonstrated the aluminum catalyzed hydroamination of aminoalkenes using a phenylene-diamine supporting ligand.52 Herein, we detail the synthesis of several new late transition and main group orthometallated imines and their subsequent reactions with various electrophiles. These new metal complexes are expected to show utility as ligand transfer reagents and as precatalysts for organometallic transformations.

4.2 Results and Discussion

In order to study the reactivity of ortholithiated imines with main group and late transition metals, four of our previously reported ortholithiated imines were employed:

Li-L1, Li-L6, Li-L7 and Li-L8 (Scheme 4.1).4 In our previous work, it was noted that ortholithiated imines with bulky substituents at the 2- and 6-positions of the N-aryl group

99 significantly increased the stability of the resulting lithium salts,1 as well as their early transition metal complexes.4, 5 For this reason, ligands L7 and L8 were used primarily, while L1, the most stable N-alkyl ligand isolated to date, was used in some cases to ascertain any electronic or steric differences resulting from the presence of an alkyl group at this position. Initially our investigation focused on complexes containing magnesium, zinc, and tin because of their utility in coupling reactions.

R' R' O N Li N O H N R' iii R + 2 O R O R O O O

Scheme 4.1. The synthesis of ortholithiated imines via Schiff base condensation and

1 6 7 regiospecific lithiation (L : R = H, R’ = Cy; L : R = Me, R’ = 2,6-Et2C6H3; L : R = H,

i 8 i R’ = 2,6- Pr2C6H3; L : R = Me, R’ = 2,6- Pr2C6H3). Legend: (i) PTSA cat., toluene

reflux, 2-4 days; (ii) 0.99 eq. nBuLi, pentane, -78 °C.

The reaction of Li-L7 with ethyl magnesium bromide (EtMgBr) proceeded readily in a mixture of diethyl ether and toluene. The presumed product (L7)MgEt then

7 underwent a pseudo-Schlenk equilibrium resulting in a 1:1 mixture of (L )2Mg and

7 MgEt2. Recrystallization from diethyl ether yielded (L )2Mg(OEt2) (4-1) as a yellow solid in good yield (Scheme 4.2). Irreversible redistribution of ligands around group (II) metal centers has been previously noted.53 The 1H NMR spectrum of 4-1 was extremely broad at room temperature, indicating a great deal of fluxionality in solution. Low temperature 1H and 13C{1H} NMR spectroscopy at -48 °C eliminated most of the

100 broadness attributed to this fluxional behavior; lower temperature studies were not possible due to the poor solubility of the metal complex at these temperatures. The 1H

13 1 and C{ H} NMR spectra at -48 °C were typical for a C2 symmetric metal complex and resembled previously reported titanium imido complexes.4 Two proton resonances at 5.38 and 4.57 ppm, corresponding to the two chemically inequivalent protons of the methylene dioxy moiety, were observed, as well as a broad set of resonances at 3.21 and 0.73 ppm, which corresponded to a diethyl ether ligand. These observations imply a square pyramidal geometry about the magnesium center; two orthometallated imine ligands bind to the metal center forming the base of a square pyramid and a diethyl ether ligand is positioned axially. Other possible isomers of 4-1 would not correspond to the observed spectra. A trans arrangement of the anionic carbon donors of the ligands places the

O O O R' 2 O Li + 2 EtMgBr Mg N N - Et2Mg O - 2 LiBr N R' O O (4-1)

Scheme 4.2. The reaction of EtMgBr with Li-L7 yielded the bis-ligated magnesium

i complex 4-1 and an equivalent of Et2Mg (R’ = 2,6- Pr2C6H3). methylene dioxy protons of one ligand in proximity to the pi system of the N-aryl group of the adjacent ligand. This pi interaction causes a downfield chemical shift of the two methylene protons. This geometry also minimizes steric interactions between the bulky isopropyl groups of the N-aryl substituents.

101

The reactions of Li-L7 with aluminum precursors yielded two metal complexes

7 (Scheme 4.3). In the first case, treatment of AlCl3 with Li-L resulted in the formation of

7 a bis-ligated aluminum complex Al(L )2Cl (4-2a). Regardless of the relative ratio of Li-

7 L to AlCl3 used, 4-2 was the only product observed by NMR spectroscopy.

Crystallization from toluene at -25 °C yielded crystals suitable for X-ray crystallography.

One crystal that was subjected to data collection was found to be a mono-ligated

7 aluminum complex L AlCl2 (4-2b), which we believe is produced as a minor reaction product in very low yield. All attempts to synthesize 4-2b as a major reaction product

7 failed. Changing the solvent used and the ratio of Li-L to AlCl3 had no effect. The bulk of the crystals were found to be the bis-ligated complex, as expected based on 1H and

13C{1H} NMR spectra, as well as the elemental analysis results. The crystal structure

(Figure 4-1) showed a square pyramidal aluminum coordination sphere, in which the anionic carbons of the two orthometallated imines are trans (C1-Al1-C21 = 166.55(9)°)

1 with a C2 axis of symmetry colinear with the aluminum chloride bond. The H NMR spectrum of 4-2a showed two resonances for the methylene dioxy protons of the methylene dioxy ring at 5.13 and 4.52 ppm, which can again be attributed to an interaction between these protons and the pi system of the neighboring ligand, as can be

7 readily noted in the crystal structure. The reaction of Et2AlCl with Li-L yielded

7 1 Et2Al(L ) (4-3) in good yield. A single H NMR resonance for the methylene dioxy protons was observed at 5.31 ppm, due to a mirror plane of symmetry though the ligand backbone. Complex 4-3 may prove to be quite interesting in future reactivity studies since aluminum alkyls are often good precursors for the exploration of aluminum organometallic reactivity. For example, recent reports note that metal complexes

102 containing aluminum, a non-toxic and inexpensive metal, can be used for catalytic polymerization of lactide50, 51 as well as hydroamination.52

O O Cl R' N Al N R' O O Et Et 2 Et AlCl AlCl3 (4-2a) 2 O Al 2 2 O Li N - 2 LiCl N - 2 LiCl Major Product O O

Cl Cl (4-3) O Al N O

(4-2b) Minor Product

Scheme 4.3. Aluminum complexes incorporating one and two orthometallated imine

ligands were synthesized. The use of Et2AlCl allowed for the isolation of a mono-

i ligated aluminum complex (R’ = 2,6- Pr2C6H3).

103

7 Figure 4-1. ORTEP diagram (50% thermal ellipsoids) of Al(L )2Cl (4-2a). Hydrogen atoms and 3 toluene solvent molecules removed for clarity. Bond lengths (in Å): Al1-

C1 = 2.027(2), Al1-N1 = 2.104(2), Al1-Cl1 = 2.2050(9), C1-C2 = 1.368(3), C1-C6 =

1.421(3); angles (in °): C1-Al1-N1 = 80.17(9), C1-Al1-C21 = 166.55(9), N1-Al1-N2 =

123.43(8), C2-C1-C6 = 112.4(2).

104

7 Figure 4-2. ORTEP diagram (50% thermal ellipsoids) of Al(L )Cl2 (4-2b). Hydrogen atoms removed for clarity.

105

7 1 The reactions of Li-L and Li-L with ZnCl2 resulted in good yields of the

7 1 corresponding zinc complexes: Zn(L )2 (4-4) and Zn(L )2 (4-5) (Scheme 4.4). Crystals suitable for X-ray crystallography were grown from concentrated solutions of pentane (4-

4) and diethyl ether (4-5). Both complexes exhibited a distorted tetrahedral arrangement of the ligands around the zinc centers (Figures 4-3 and 4-4). Although the zinc-carbon and zinc-nitrogen bond lengths are very similar for the two complexes, there is a significant difference in the relative positions of the ligands around the two metal centers.

The C1-Zn-C21 bond angle for 4-4 is 135.84(7)° while

O O R' N O Li R' 2 N Zn + ZnCl2 O - 2 LiCl N R' O O (4-4,4-5)

7 i 1 Scheme 4.4. The reactions of Li-L (R’ = 2,6- Pr2C6H3) and Li-L (R’ = Cy) yielded

the corresponding zinc complexes 4-4 and 4-5, where the ligands adopt a pseudo

tetrahedral geometry around the central zinc atom in each case. the C1-Zn1-C15 bond angle for 4-5 is 142.80(6)°. A similar increase in the bond angle of

N1-Zn-N2 is observed from 108.46(5)° for 4-4 to 112.08(5)° in 4-5. At the same time, there is a decrease in the bond angle of C1-Zn1-N2 from 125.29(6)° to 119.54(6)° for 4-4 and 4-5, respectively. The bite angles are almost identical for 4-4 (82.79(6)°) and 5

(83.69(6)°). The observed differences in bond angles are attributable to the bulky isopropyl groups of 4-4, as the slight changes in the relative orientation of the ligands help to decrease the steric interactions of the isopropyl groups in 4-4. In solution, 4-4 and

106

4-5 exhibit exceptionally different 1H NMR spectra. A single resonance at 5.33 ppm, corresponding to all four methylene dioxy protons, was observed in 4-4 whereas 4-5 has two resonances at 5.53 and 5.33 ppm, which is more typical of what one would expect for a tetrahedral complex incorporating this ligand system. The single resonance for the methylenedioxy protons of 4-4 could be due to coincidental overlap of the two signals, but is more likely due to some dynamic behavior of the methylenedioxy ring or complete ligand in solution. A C2 rotational axis of symmetry relates the two ligands, making them equivalent, but no symmetry operation exists to make the two methylenedioxy protons within a given ligand equivalent. Thus, coordination to the metal center in a tetrahedral geometry should yield diasterotopic methylenedioxy protons and lead to a 1H NMR spectrum like that observed for 4-5.

107

7 Figure 4-3. ORTEP diagram (50% thermal ellipsoids) of Zn(L )2 (4-4). Hydrogen atoms have been removed for clarity. Bond lengths (in Å): Zn1-C1 = 1.988(2), Zn1-N1

= 2.196(1), C1-C2 = 1.363(2), C1-C6 = 1.418(2); angles (in °): C1-Zn1-N1 = 82.79(6),

C1-Zn1-C21 = 135.84(7), N1-Zn1-N2 = 108.46(5), C1-Zn1-N2 = 125.29(6), C2-C1-C6

= 112.8(2).

108

1 Figure 4-4. ORTEP diagram (50% thermal ellipsoids) of Zn(L )2 (4-5). Hydrogen atoms have been removed for clarity. Bond lengths (in Å): Zn1-C1 = 1.991(2), Zn1-N1

= 2.147(1), C1-C2 = 1.368(2), C1-C6 = 1.422(2); angles (in °): C1-Zn1-N1 = 83.69(6),

C1-Zn1-C15 = 142.80(6), N1-Zn1-N2 = 112.08(5), C1-Zn1-N2 = 119.54(6), C2-C1-C6

= 112.5(1).

109

The reaction of Li-L7 with CuI yielded the copper complex CuL7 (4-6) in moderate yield (Scheme 4.5). Its NMR spectra were very similar to that of the starting material, Li-L7. Crystals suitable for X-ray diffraction were grown from a saturated diethyl ether solution, and compound 4-6 was found to be a dimer in the solid state, in which each copper center is bound to the anionic carbon donor of one ligand and the neutral nitrogen of a second ligand (Figure 4-5). The angle between the anionic carbon donor atom, copper center and the neutral nitrogen atom (C1-Cu1-N2) is 168.9(2)°.

Unlike the structure of Li-L7, the two ligands in 4-6 are no longer coplanar and it appears that the ligands have rotated away from each other in order to minimize the steric interactions of the bulky N-aryl groups. This rotation is somewhat limited due to the presence of a copper-copper bond, with a length of 2.472(1) Å. The C1-Cu1-Cu2 angle is

91.6(2)°, with each copper having a T-shaped coordination. The observed Cu-Cu bond distance is similar to other species previously reported. For example, White and coworkers published the structure of a dimeric complex supported by a bulky pyridine- based chelating C~N ligand with a Cu-Cu bond of 2.412(1) Å.54 In contrast, longer Cu-

Cu bond distances have been observed in other copper complexes utilizing ligands with less similarity to L7. Guastini and coworkers observed a bond distance of 2.750(2) Å for a dinuclear copper(I) benzoate species,55 while Lai and coworkers reported a bond distance of 2.940(1) Å for a copper(I) complex utilizing chelating phosphine ligands.56

The widely varying bond lengths observed are likely due to the nature of the ligands used. It seems that bulky chelating C~N ligands facilitate the formation of dinuclear copper complexes with relatively short Cu-Cu bonds. Copper complexes supported by orthometallated N,N-dimethylbenzylamines have been isolated and structurally

110 characterized by van Koten and Noltes. The lack of steric bulk found in this ligand set allowed for higher order clustering, and the tetranuclear copper complex that was isolated exhibited a very short Cu-Cu distance of 2.38 Å.57 Increasing the ratio of Li-L7 to CuI

7 1 yielded the lithium cuprate Cu(L )2Li (4-7) (Scheme 4.5). The H NMR spectrum of 4-7 clearly showed two inequivalent ligands that exhibit a limited degree of fluxional behavior. Low temperature NMR spectroscopy at temperatures down to -60 °C did not resolve this fluxionality. Peak broadening was most pronounced for the isopropyl moieties of a single N-aryl group, possibly indicating that one ligand in 4-7 is hemilabile.

Crystals suitable for single crystal X-ray diffraction were grown from an evaporated solution of toluene and diethyl ether. The crystal structure revealed a dimeric metal complex in which the central copper atom is coordinated by the anionic carbon donor atoms of two ligands and the nitrogen atom of one of those ligands (Figure 4-6). The lithium atom is bound to the other imine nitrogen, as well as the oxygen atom of the methylene dioxy ring on the adjacent ligand. The oxygen atom of a diethyl ether ligand and a lithium-copper bond complete the lithium center’s distorted tetrahedral geometry.

The distance between the lithium atom and the copper center is 2.46(1) Å, which is shorter than that reported by Power and coworkers for [Li2Cu3Ph6]2[Li4Cl2(Et2O)10] with a Li-Cu bond of 2.62(1) Å.57 Bau and coworkers have also isolated a lithium copper

58 cluster, [Cu4LiPh6][Li(Et2O)4], with a Li-Cu bond length of 2.52(3) Å. The very close contact in 4-7 seems to indicate the presence of a true Li-Cu bond. To the best of our knowledge, there have been no reports of other dinuclear copper-lithium complexes analogous to 4-7.

111

7 Figure 4-5. ORTEP diagram (50% thermal ellipsoids) of (CuL )2 (4-6). Hydrogen atoms have been removed for clarity. Bond lengths (in Å): Cu1-C1 = 1.908(5), Cu1-

N2 = 1.914(4), Cu1-Cu2 = 2.472(1), C1-C2 = 1.390(7), C1-C6 = 1.417(7); angles (in

°): C1-Cu1-N2 168.9(2), C1-Cu1-Cu2 = 91.6(2), C2-C1-C6 = 111.3(4), N1-Cu2-Cu1

= 98.9(1).

112

7 Figure 4-6. ORTEP diagram (50% thermal ellipsoids) of [Cu(L )2][Li(OEt2)] (4-7).

Hydrogen atoms have been removed for clarity. Bond lengths (in Å): Cu1-C1 =

1.940(6), Cu1-N1 = 2.310(5), C1-C2 = 1.381(8), C1-C6 = 1.437(9), Cu1-Li1 = 2.46(1),

Li1-O2 = 2.08(1), Li1-O5 = 1.94(1), Li1-N2 = 2.05(1); angles (in °): C1-Cu1-N1 =

80.6(2), C1-Cu1-C21 = 163.8(2), C1-Cu1-Li1 = 78.0(3), O5-Li1-Cu1 = 117.4(5), O2-

Li1-O5 = 120.3(6), N2-Li1-O2 = 108.5(5), C2-C1-C6 = 111.1(5).

113

O R' O O N O R' Cu Cu N 2 CuI CuI 2 O Li Li N Cu - 2 LiI N - LiI N O O O R' R' O O O (4-6) (4-7)

Scheme 4.5. The reaction of Li-L7 with differing amounts of CuI led to the

formation of two different products: a dimeric copper complex and a lithium cuprate

i (R’ = 2,6- Pr2C6H3).

The reactivity of ortholithiated imines with various electrophiles was also investigated.

7 n Li-L reacted with Bu3SnCl to yield 4-8, an air and moisture stable tin complex (Scheme

4.6). Tin reagents have shown broad utility as alkyl transfer reagents for both early35 and late transition metals.59 orthoMetallated tin complexes can also act as air and moisture stable alternatives to ortholithiated imines in some cases. Treatment of Li-L3 with MeI yielded the orthomethylated imine (4-9) (Scheme 4.6), while the reaction of Li-L1 with

Ph2PCl proved to be more difficult; no product was detected under a variety of attempted conditions. As the use of copper reagents to generate phosphines has been previously

60 7 reported, the reaction of Ph2PCl with Cu(L ) (4-6), generated in situ, was attempted and yielded the iminophosphine copper complex (4-10) (Scheme 4.7), although all attempts to isolate the copper-free iminophosphine from this reaction were unsuccessful. Crystals suitable for crystallographic analysis were grown from a saturated acetonitrile solution, and complex 4-10 was found to be a dimer in the solid state with bridging iodide ligands spanning two copper centers, which are both also chelated by iminophosphine ligands

(Figure 4-7). In order to produce the free iminophosphine, it was necessary to treat

114

Ph2PCl with the magnesium complex 4-1, yielding the iminophosphine 4-11 in moderate yield. The 31P NMR spectrum of 4-11 shows a single resonance at -23.8 ppm, consistent with a free aromatic iminophosphine,61 and the elemental analysis of 4-11 confirmed that it was free of magnesium.

R' R' nBu Sn N Li R' Me 3 n O N N Bu3SnCl CH3I O O R - LiCl O - LiI R R O O (4-8) (4-9)

7 i 6 Scheme 4.6. The reaction of Li-L (R = H, R’ = 2,6- Pr2C6H3) or Li-L (R = Me, R’ =

2,6-Et2C6H3) yielded the corresponding tin complex (4-8) and ortho-methylated

compound (4-9).

115

NPPh2 2 CuI R' Cu 2 Ph PCl 2 O Li 2 II N - 2 LiCl Cu O R' Ph2P N O

O (4-10)

Scheme 4.7. The investigation of copper reagents in place of lithium reagents led to the

i isolation of 4-10, an iminophosphine copper complex (R’ = 2,6- Pr2C6H3).

116

7 Figure 4-7. ORTEP diagram (50% thermal ellipsoids) of CuI(Ph2P-L ) (4-10).

Hydrogen atoms have been removed for clarity. Bond lengths (in Å): Cu1-I1 =

2.6412(9), Cu1-N1 = 2.100(6), Cu1-P1 = 2.220(2); angles (in °): N1-Cu1-P1 = 92.9(2),

I1-Cu1-N1 = 106.4(2), I1-Cu1-P1 = 111.85(6). Atoms labeled with “i” are generated by the following symmetry operator: -x+2/3, -y+1/3, -z+4/3.

117

8 The reaction of Li-L with I2 yielded an iodinated species 4-13, and its subsequent

Ullmann homocoupling resulted in an excellent yield of compound 4-14 (Scheme 4.8).

1 2 The H NMR spectrum of 4-14 has two doublets ( JHH = 0.6 Hz) at 6.01 and 5.94 ppm, consistent with a C2 symmetric molecule. There are numerous reports of C2 symmetric diamine62 and diimine ligands63 utilized for many processes, making 4-14 a useful new chiral diimine. It is easy to envision the production of 4-14 by reductive elimination of two ligands from a high oxidation state metal. Although we have previously observed this reaction on occasion in our group (IV) and (V) metal chemistry, it has been rare and generally not a problem with this ligand set. In contrast, oxidative coupling of a clearly related (though much less sterically bulky) orthometallated imine ligand in bis-ligated titanium complexes was found to be quite common by Mu and coworkers.64 Our attempts to produce copper(II) reagents as part of this investigation have always been thwarted by reductive elimination of 4-14 from transient copper(II) complexes that were produced, preventing the successful isolation of any related copper(II) complexes.

xs CuI O I 2 I N xs K R' N 2 O Li 2 N N - 2 LiI - CuI2 R' O O -KI O O O (4-13) (4-14)

8 Scheme 4.8. The reaction of Li-L with I2 yielded 4-13, which was subsequently

reacted with activated copper to give 4-14, the Ullmann-coupled product (R’ = 2,6-

i Pr2C6H3).

118

4.3 Conclusion

Various magnesium, zinc, and tin complexes with potential uses as transfer reagents in salt metathesis chemistry for the generation of new metal complexes were synthesized.

Of particular interest are the zinc and tin complexes. Zinc complexes have been noted to be superior to lithium reagents when used with group (V) metals giving higher yields of group (V) alkyls than lithium or magnesium reagents.34 Tin reagents can be used in some circumstances as air and moisture stable alternatives to lithium reagents.32 Several copper complexes were synthesized, including a lithium cuprate that shows evidence of a copper-lithium bond. One copper complex (4-6) was used in the synthesis of a piperonal imine based iminophosphine copper(I) complex, while the related magnesium complex

(4-1) allowed the successful synthesis of the metal free iminophosphine ligand (4-11).

Additionally, the reactivity of the ortholithiated imines was investigated with electrophiles such as I2 and iodomethane. Overall, orthometallated imines based on a piperonal scaffold have been shown to be excellent ligands for late transition and main group metals, as well as useful building blocks for more complex ligands, such as iminophosphines.

4.4 Experimental

4.4.1 General Methods and Instrumentation

General methods and instrumentation: All manipulations involving lithium reagents were performed under an inert N2 atmosphere using standard glove box and Schlenk techniques. Solvents were predried before use; methylene chloride was passed through

119 two columns of 4 Å molecular sieves and sparged with nitrogen. Pentane, diethyl ether, and toluene were passed through columns of activated alumina and 4 Å molecular sieves and sparged with nitrogen. Dimethoxyethane (DME) was dried over sodium metal, freeze-pump-thawed three times, and vacuum distilled. n-Butyl lithium (1.6 M in hexanes), ethylmagnesium bromide (3 M in diethyl ether), potassium and diphenylchlorophosphine were purchased from Strem Chemicals, Inc., and used as received. Copper(I) iodide was purchased from Acros and dried via heating at 100 °C for

12 hours under vacuum. Zinc chloride (anhydrous), aluminum chloride (anhydrous), diethylaluminum chloride (1.0 M in hexanes), tri-n-butyltin chloride, methyl iodide, iodine, methanol, ethyl acetate, magnesium sulfate and sodium sulfite were purchased from various commercial sources. Benzene-d6 was dried over sodium metal, freeze- pump-thawed three times, vacuum distilled and stored over 4 Å molecular sieves.

Toluene-d8 was dried over sodium metal, freeze-pump-thawed three times, and vacuum distilled. Chloroform-d1 was dried over calcium hydride, freeze-pump-thawed three times, vacuum distilled and stored over 4 Å molecular sieves. Silica gel (Porosity: 60 Å,

Particle size: 40-63 μm) was purchased from Sorbent Technologies and used as received.

1H and 13C NMR data were obtained on a 600 MHz Inova NMR or a 400 MHz VXRS

NMR spectrometer at ambient temperature at 599.9 MHz for 1H NMR and 150.8 MHz for 13C NMR and 399.95 MHz for 1H NMR and 100.56 MHz for 13C NMR, respectively.

1 All spectra were taken using C6D6, CDCl3, C7D8, or CD3CN as the NMR solvent. H

NMR shifts are given relative to the residual solvent resonances at 7.16, 7.26, 2.08, and

13 1.94 ppm, respectively, and C NMR shifts are given relative to C6D6 (128.1 ppm),

31 CDCl3 (77.2 ppm), C7D8 (20.4 ppm) and CD3CN (118.3 ppm). P NMR spectra were

120 externally referenced to 0.00 ppm with 5% H3PO4 in D2O. Unless otherwise noted, all

3 coupling constants are JHH. IR samples were prepared as Nujol mulls and taken between

KBr plates on a Perkin-Elmer XTL FTIR spectrophotometer. Melting points were observed on a capillary melting point (Uni-Melt) apparatus in sealed capillary tubes and are uncorrected. X-ray structure determinations were performed at the Ohio

Crystallographic Consortium, housed at The University of Toledo. Elemental analyses were determined by Atlantic Microlab, Inc., Norcross, GA or Galbraith Laboratories,

Inc., Knoxville, TN. High resolution mass spectrometry, using electrospray ionization, was performed at the University of Illinois Mass Spectrometry Laboratory, Urbana, IL.

4.4.2 Synthesis and Characterization of Reaction Products

Compounds H-L1,6,7,8 and Li-L1,6,7,8 were prepared in accordance with previously published literature methods.4, 6

7 (L )2Mg(OEt2) (4-1)

Method one: A Schlenk flask was charged with H-L7 (1.00 g, 3.23 mmol) and toluene

(20 ml) was added via cannula. Then, n-butyl lithium (2.02 ml, 3.23 mmol) was added dropwise via syringe and allowed to stir for 20 minutes. The reaction was cooled to 0 °C and EtMgBr (1.08 ml, 3.23 mmol) was added via syringe. The reaction was allowed to stir for 12 hours. The reaction was filtered to remove lithium salts, and the solvent was then removed via reduced pressure. The crude material was then crystallized from diethyl ether yielding 4-1 as a yellow solid (0.69 g, 60%). Method two: A Schlenk flask was charged with Li-L7 (0.70 g, 2.2 mmol) and diethyl ether (20 ml) was added via cannula.

121

The reaction was cooled to 0 °C and EtMgBr (0.71 ml, 2.1 mmol) was added via syringe.

The reaction was allowed to stir for 12 hours. The solvent was removed via reduced pressure. The residue was taken up in toluene and filtered to remove lithium chloride, and the solvent was removed via reduced pressure. The crude material was crystallized from diethyl ether yielding 4-1 as a yellow solid (0.55 g, 73%). 1H NMR (ambient temperature, toluene-d8): δ 7.90 (s, 2H), 6.99 (s, 6H), 6.72 (d, 2H, 7.6 Hz), 6.51 (d, 2H,

7.6 Hz), 5.06 (br. s, 4H), 3.63 (br. s, 4H), 2.95 (br. s, 4H), 1.10 (d, 12H, 6 Hz), 1.09 (m,

1 18H); H NMR (-48 °C, toluene-d8): δ 7.92 (s, 2H), 7.13 (m, 2H), 7.06 (d, 2H, 7.2 Hz),

6.89 (d, 2H, 7.2 Hz), 6.67 (d, 2H, 7.6 Hz), 6.56 (d, 2H, 7.6 Hz), 5.38 (s, 2H), 4.57 (s, 2H),

4.24 (br. s, 2H), 3.21 (m, 4H), 2.62 (m, 2H), 1.43 (d, 6H, 6.4 Hz), 1.24 (d, 6H, 6.4 Hz),

1.03 (d, 6H, 6.4 Hz), 0.73 (br. s, 6H), 0.55 (d, 6H, 6.4 Hz); 13C{1H} NMR (-48 °C, toluene-d8): δ 174.5, 155.9, 149.8, 148.0, 147.4, 140.6, 140.3, 139.4, 124.7, 122.3, 122.2,

105.1, 98.5, 64.3, 29.5, 28.3, 25.7, 24.8, 22.8, 21.1, 13.9 (one aromatic carbon resonance not observed); IR: 1611 (s), 1555 (s), 1461 (s), 1400 (s), 1333 (m), 1242 (s), 1175 (s),

1096 (s), 1046 (s), 978 (m), 933 (s), 891 (w), 860 (w), 788 (s), 757 (s); Melting point:

151 °C dec.

7 Al(L )2Cl (4-2)

A Schlenk flask was charged with Li-L7 (0.50 g, 1.6 mmol) and toluene (40 ml) was added via cannula. A second Schlenk flask was charged with AlCl3 (0.10 g, 0.75 mmol) and toluene (5 ml) was added via cannula. The solution of Li-L7 was added via cannula to the stirring slurry of AlCl3. The reaction was allowed to stir for 12 hours. The crude reaction mixture was filtered through celite and the solvent removed via reduced pressure. The residue was dissolved in a minimal amount of toluene (5 ml), layered with

122 pentane and cooled to -25 °C. 4-2 was isolated as a yellow crystalline solid (0.32 g,

1 62%). H NMR (benzene-d6): δ 7.91 (s, 2H), 7.06 (d, 2H, 7.8 Hz), 6.96 (t, 2H, 7.8 Hz),

2 6.77 (d, 2H, 7.8 Hz), 6.55 (d, 2H, 7.8 Hz), 6.41 (d, 2H, 7.8 Hz), 5.13 (d, 2H, JHH = 1.2

2 Hz), 4.52 (d, 2H, JHH = 1.2 Hz), 3.52 (sept, 2H, 6.8 Hz), 2.59 (sept, 2H, 6.8 Hz), 1.40 (d,

6H, 6.8 Hz), 0.97 (d, 6H, 6.8 Hz), 0.92 (d, 6H, 6.8 Hz), 0.52 (d, 6H, 6.8 Hz); 13C{1H}

NMR (benzene-d6): δ 175.3, 153.9, 152.5, 144.7, 144.4, 141.3, 133.8, 128.6, 126.7,

125.7, 123.5, 121.9, 106.7, 100.5, 30.2, 28.7, 25.7, 25.6, 23.0, 21.1; IR: 1600 (s), 1548

(s), 1421 (s), 1379 (m), 1250 (s), 1174 (w), 1118 (s), 1056 (m), 987 (w), 929 (w), 798

(m), 727 (w), 695 (w); Anal. calcd. for C40H44AlClN2O4: C, 70.73; H, 6.53; N, 4.12.

Found: C, 70.37; H, 6.50; N, 3.99. Melting point: 182 °C dec.

7 Et2Al(L ) (4-3)

A Schlenk flask was charged with H-L7 (1.00 g, 3.23 mmol) and pentane (30 ml) was added via cannula. n-Butyl lithium (2.02 ml, 3.23 mmol) was added dropwise via syringe at room temperature. The slurry of Li-L7 was allowed to stir for 30 minutes, following which Et2AlCl (3.23 ml, 3.23 mmol) was added via syringe. The reaction was allowed to stir for 12 hours. The solvent was then removed via reduced pressure. The residue was dissolved in toluene and filtered, and the solvent was again removed via reduced pressure. The crude product was dissolved in pentane and cooled to -25 °C. 4-3 was

1 isolated as a yellow solid (0.92 g, 72%). H NMR (benzene-d6): δ 7.79 (s, 1H), 7.11-7.03

(m, 3H), 6.72 (d, 1H, 7.6 Hz), 6.55 (d, 1H, 7.6 Hz), 5.31 (s, 2H), 3.09 (sept, 2H, 6.8 Hz),

1.53 (t, 6H, 7.9 Hz), 1.22 (d, 6H, 6.8 Hz), 0.92 (d, 6H, 6.8 Hz), 0.54-0.41 (m, 4H);

13 1 C{ H} NMR (benzene-d6): δ 175.3, 155.0, 151.4, 142.4, 142.3, 136.1, 128.7, 127.9,

123

124.3, 107.8, 100.7, 28.3, 25.8, 22.9, 10.1, -0.20 (one aromatic carbon resonance is unobserved).

7 Zn(L )2 (4-4)

A Schlenk flask was charged with Li-L7 (0.50 g, 1.6 mmol) and toluene (30 ml) was added via cannula. A second Schlenk flask was charged with ZnCl2 (0.10 g, 0.73 mmol) and diethyl ether (15 ml) was added via cannula and cooled to 0 °C. The solution of Li-

7 L was added via cannula to the stirring slurry of ZnCl2 and the reaction was allowed to stir for 12 hours. The reaction was filtered and the solvent removed via reduced pressure.

The residue was dissolved in diethyl ether and cooled to -25 °C. 4-4 was isolated as a

1 white crystalline solid (240 mg, 47%). H NMR (benzene-d6): δ 7.90 (s, 2H), 7.03-6.97

(m, 6H), 6.75 (d, 2H, 7.8 Hz), 6.63 (d, 2H, 7.8 Hz), 5.33 (s, 4H), 3.26 (sept, 4H, 6.6 Hz),

13 1 1.09 (br. s, 12H), 0.72 (br. s, 12H); C{ H} NMR (benzene-d6): δ 172.7, 154.9, 150.1,

146.8, 140.7, 137.9, 135.5, 127.6, 125.7, 123.7, 106.4, 99.8, 28.2, 25.0 (br), 22.7 (br); IR:

1617 (s), 1569 (m), 1457 (m), 1416 (s), 1377 (m), 1358 (m), 1237 (s), 1107 (m), 1055 (s),

979 (w), 941 (w), 889 (w), 813 (w), 720 (w); Anal. calcd. for C40H44N2O4Zn: C, 70.43;

H, 6.50; N, 4.11. Found: C, 69.20; H, 6.32; N, 4.11. Melting point: 159 °C dec.

1 Zn(L )2 (4-5)

A Schlenk flask was charged with Li-L1 (0.25 g, 1.1 mmol) and toluene (25 ml) was added via cannula. A second Schlenk flask was charged with ZnCl2 (68 mg, 0.49 mmol) and diethyl ether (15 ml) was added via cannula and cooled to 0 °C. The solution of Li-

1 L was added via cannula to the stirring slurry of ZnCl2 and the reaction was allowed to stir for 12 hours, during which time it turned a light blue and then a pale yellow color.

124

The reaction was filtered and the solvent removed via reduced pressure. The residue was dissolved in diethyl ether and cooled to -25 °C. 4-5 was isolated as a white crystalline

1 solid (0.25 g, 97%). H NMR (benzene-d6): δ 7.77 (s, 2H), 6.85 (d, 2H, 7.8 Hz), 6.76 (d,

2 2 2H, 7.8 Hz), 5.53 (d, 2H, JHH = 1.8 Hz), 5.33 (d, 2H, JHH = 1.8 Hz), 2.98 (tt, 2H, 10.7

Hz, 4.2 Hz), 1.68-1.49 (m, 10H), 1.35-1.26 (m, 4H), 1.11-0.99 (m, 4H), 0.79-0.73 (m,

13 1 2H); C{ H} NMR (benzene-d6): δ 167.6, 155.1, 149.2, 139.6, 137.0, 125.8, 106.1, 99.6,

67.2, 34.8, 34.2, 25.5, 25.3, 25.2; IR: 1631 (s), 1609 (s), 1558 (s), 1504 (m), 1416 (s),

1376 (s), 1336 (m), 1323 (m), 1242 (s), 1207 (m), 1176 (s), 1109 (s), 1052 (s), 994 (w),

972 (m), 939 (s), 886 (w), 863 (s), 819 (s), 791 (s), 756 (s), 729 (w), 691 (w), 622 (m);

Melting point: 115 °C dec.

Cu(L7) (4-6)

A Schlenk flask was charged with Li-L7 (4.00 g, 12.7 mmol) and toluene (40 ml) was added via cannula. A second Schlenk flask was charged with CuI (3.65 g, 19.2 mmol) and diethyl ether (20 ml) was added via cannula. The solution of Li-L7 was added via cannula to the stirring slurry of CuI. The reaction was allowed to stir for 12 hours. The crude reaction mixture was filtered through celite twice and the solvent removed via reduced pressure. The residue was washed with pentane (2 x 30 ml) and dissolved in diethyl ether and cooled to -25 °C. 4-6 was isolated as a red micro-crystalline solid (2.47

1 g, 52%). H NMR (benzene-d6): δ 8.03 (s, 1H), 7.17 (m, 3H, overlapping with C6D5H),

6.75 (d, 1H, 7.8 Hz), 6.58 (d, 1H, 7.8 Hz), 5.21 (s, 2H), 3.57 (sept, 2H, 6.6 Hz), 1.27 (d,

13 1 6H, 6.6 Hz), 1.12 (d, 6H, 6.6 Hz); C{ H} NMR (benzene-d6): δ 177.3, 156.7, 148.5,

146.8, 141.4, 136.6 (br), 133.2 (br), 126.5, 123.9, 105.6, 99.1, 28.6, 14.7, 13.4 (one aromatic carbon resonance not observed); IR: 1594 (s), 1585 (s), 1543 (s), 1488 (w),

125

1465 (s), 1406 (s), 1342 (m), 1322 (m), 1264 (s), 1213 (w), 1172 (s), 1124 (m), 1118 (m),

1061 (m), 1043 (w), 980 (m), 945 (m), 889 (w), 853 (w), 794 (s), 755 (m); Melting point:

125 °C dec.

7 Cu(L )2Li (4-7)

A Schlenk flask was charged with Li-L7 (1.00 g, 3.17 mmol) and toluene (25 ml) was added via cannula. A second Schlenk flask was charged with CuI (0.28 g, 1.5 mmol) and diethyl ether (10 ml) was added via cannula. The solution of Li-L7 was added via cannula to the stirring slurry of CuI. The reaction was allowed to stir for 12 hours. The crude reaction mixture was filtered through celite and the solvent removed via reduced pressure. The residue was washed with pentane (2 x 25 ml) and 4-7 was isolated as an

1 orange-red powder (0.91 g, 90%). H NMR (benzene-d6): 8.19 (s, 1H), 8.05 (d, 1H, 8.4

Hz), 7.84 (s, 1H), 7.69 (br. s, 1H), 7.13-7.03 (m, 4H), 6.95 (d, 1H, 7.8 Hz), 6.87 (d, 1H,

7.2 Hz), 6.55 (d, 1H, 8.4 Hz), 6.51 (d, 1H, 7.8 Hz), 5.17 (s, 1H), 5.15 (s, 2H), 5.05 (s,

1H), 3.51 (v. br. s, 1H), 3.22 (v. br. s, 1H), 3.12-3.09 (m, 2H), 1.12 (d, 6H, 7.2 Hz), 1.07

13 1 (d, 6H, 7.2 Hz), 1.04 (d, 6H, 7.2 Hz), 0.94 (v. br. s, 6H); C{ H} NMR (benzene-d6):

161.1, 159.2, 150.9, 150.1, 149.9, 149.8, 148.9, 148.6, 146.7, 138.0, 131.6, 129.3, 125.7,

124.7, 124.5, 123.5, 123.4, 122.9, 116.2, 109.4, 108.4, 106.9, 101.6, 101.5, 28.7, 28.5,

28.3, 23.9, 23.7, 23.6; IR: 1634 (m), 1609 (s), 1576 (m), 1553 (m), 1460 (s), 1380 (s),

1259 (s), 1176 (m), 1096 (s), 1041 (s), 934 (m), 861 (w), 800 (s), 754 (m), 728 (w);

Melting point: 84 °C dec. n 7 Bu3Sn(L ) (4-8)

126

A Schlenk flask was charged with Li-L7 (1.00 g, 3.17 mmol) and toluene (30 ml) was

n added via cannula. The reaction was cooled to 0 °C and Bu3SnCl (0.78 ml, 0.93 g, 2.9 mmol) was added via syringe. The reaction was allowed to stir for 12 hours. The crude reaction mixture was filtered and the solvent removed via reduced pressure. The residue was purified via column chromatography (silica gel; 9:1 pentane/ethyl acetate) and 4-8

1 was isolated as a yellow oil (1.15 g, 68%). H NMR (benzene-d6): δ 8.19 (s, 1H), 7.33 (d,

1H, 7.2 Hz), 7.19 (d, 2H, 7.8 Hz), 7.14-7.12 (m, 1H), 6.64 (d, 1H, 7.2 Hz), 5.27 (s, 2H),

3.25 (sept, 2H, 7.2 Hz), 1.68-1.63 (m, 6H), 1.41-1.36 (m, 8H), 1.33-1.30 (m, 4H), 1.25 (d,

13 1 12H, 7.2 Hz), 0.83 (t, 9H, 8.4 Hz); C{ H} NMR (benzene-d6): δ 164.5, 155.4, 149.9,

148.6, 138.6, 136.4, 136.3, 124.8, 123.7, 120.2, 108.8, 100.1, 29.7, 28.2, 27.9, 24.3, 14.0,

12.9; IR: 1623 (s), 1564 (m), 1446 (s), 1329 (m), 1245 (s), 1178 (m), 1124 (m), 1053 (s),

945 (m), 846 (w), 807 (m), 737 (w), 653 (w); HRMScalc: 600.2864 for C32H50NO2Sn [M

+ + H] ; HRMSmeas: 600.2868.

Me-L6 (4-9)

A Schlenk flask was charged with H-L6 (5.00 g, 16.9 mmol) and toluene (100 ml) was added via cannula. The reaction was cooled to 0 °C and nBuLi (10.6 ml, 16.9 mmol) was added via syringe. The reaction was allowed to stir for 30 minutes, after which time methyl iodide (1.16 ml, 2.64 g, 18.6 mmol) was added via syringe and the reaction was allowed to stir for 30 minutes. The crude reaction mixture was filtered through celite and the solvent removed via reduced pressure. Crystallization from diethyl ether yielded 4-9

1 as a yellow crystalline solid (3.3 g, 63%). H NMR (benzene-d6): δ 7.12 (d, 2H, 7.2 Hz),

7.06-7.04 (m, 1H), 6.89 (d, 1H, 8.4 Hz), 6.57 (d, 1H, 8.4 Hz), 5.32 (s, 2H), 2.56 (s, 3H),

2.54-2.47 (m, 2H), 2.43-2.38 (m, 2H), 1.74 (s, 3H), 1.36 (t, 6H, 7.2 Hz); 1H NMR

127

(CDCl3): δ 7.18 (d, 2H, 7.2 Hz), 7.12-7.07 (m, 2H), 6.80 (d, 1H, 7.8 Hz), 6.03 (s, 2H),

13 1 2.61-2.45 (m, 7H), 2.06 (s, 3H), 1.28 (t, 6H, 7.6 Hz); C{ H} NMR (CDCl3): δ 168.7,

147.9, 147.3, 146.9, 135.9, 131.3, 126.1, 123.2, 121.7, 117.6, 105.8, 101.1, 24.7, 21.7,

14.1, 13.3; IR: 1856 (m), 1580 (s), 1468 (s), 1386 (s), 1271 (s), 1201 (m), 1117 (m), 1061

(s), 949 (m), 864 (m), 815 (s), 780 (s), 633 (s); HRMScalc: 310.1807 for C20H24NO2 for

+ [M + H] ; HRMSmeas: 310.1808. Melting point: 65-66 °C.

7 CuI(Ph2P-L ) (4-10)

A Schlenk flask was charged with H-L7 (1.13 g, 3.65 mmol) and toluene (25 ml) was added via cannula. nBuLi (2.3 ml, 3.7 mmol) was added via syringe. The reaction was allowed to stir for 30 minutes. A Schlenk flask was charged with CuI (0.71 g, 3.7 mmol) and diethyl ether (20 ml) was added via cannula. The toluene solution was then added to the slurry of CuI in diethyl ether; upon addition, a red color developed indicating formation of a copper complex. The reaction was allowed to stir for 30 minutes. Ph2PCl

(0.66 ml, 0.81 g, 3.7 mmol) was added via syringe; upon addition, a precipitate formed and the flask became slightly warm. The reaction was allowed to stir for 20 minutes. The solvent was removed via reduced pressure. The residue was taken up in warm dichloromethane (200 ml) and filtered through celite. The celite was rinsed with an additional portion of dichloromethane (100 ml). The dichloromethane was then removed from the combined solutions via reduced pressure. The crude material was washed with pentane (200 ml) and dried under vacuum, yielding 4-10 as an orange solid (2.06 g,

1 4 83%). H NMR (acetonitrile-d3): δ 8.13 (d, 1H, JPH = 1.2 Hz), 7.59-7.56 (m, 4H), 7.48-

4 7.41 (m, 6H), 7.32 (dd, 1H, 8.4 Hz, JPH = 1.8 Hz), 7.17-7.16 (m, 3H), 7.09 (d, 1H, 8.4

Hz), 5.72 (s, 2H), 2.99 (sept, 2H, 8.4 Hz), 0.99 (d, 12H, 8.4 Hz); IR: 1620 (s), 1575 (s),

128

1460 (s), 1420 (s), 1379 (s), 1339 (m), 1255 (s), 1175 (s), 1143 (m), 1099 (m), 1050 (s),

983 (w), 947 (m), 854 (w), 823 (m), 788 (m), 738 (s), 689 (s); HRMScalc: 556.1467 for

+ C32H32CuNO2P for [M - I] ; HRMSmeas: 556.1470. Melting point: 188 °C dec.

7 Ph2P-L (4-11)

A Schlenk flask was charged with 4-1 (0.28 g, 0.39 mmol) and diethyl ether (20 ml) was added via cannula. Then, Ph2PCl (0.15 ml, 0.18 g, 0.86 mmol) was added dropwise via syringe to the stirring solution of 4-1. The reaction was allowed to stir for 14 hours, after which time silica gel was added and the volatiles were removed via reduced pressure.

The crude reaction adsorbed on the silica gel was added to the top of a column of silica gel and eluted with 5:1 pentane/ethyl acetate. The iminophosphine 4-11 was crystallized

1 from pentane as a green-yellow crystalline solid (123 mg, 64%). H NMR (benzene-d6): δ

4 4 9.42 (d, 1H, JPH = 3.0 Hz), 8.14 (dd, 1H, 8.4 Hz, JPH = 3.0 Hz), 7.47-7.44 (m, 4H), 7.18

(d, 2H, 7.2 Hz), 7.13 (t, 1H, 7.2 Hz), 7.06-7.04 (m, 6H), 6.68 (d, 1H, 8.4 Hz), 4.89 (s,

13 1 2H), 3.23 (sept, 2H, 6.6 Hz), 1.18 (d, 12H, 6.6 Hz); C{ H} NMR (benzene-d6): δ 160.9

3 3 2 (d, JPC = 29.1 Hz), 151.3 (d, JPC = 2.2 Hz), 150.2 (d, JPC = 7.5 Hz), 150.1, 138.1, 136.3

2 1 2 (d, JPC = 9.3 Hz), 135.4 (d, JPC = 20.5 Hz), 133.5 (d, JPC = 19.5 Hz), 128.6, 128.5 (d,

3 4 1 JPC = 6.9 Hz), 124.6, 123.5, 123.4 (d, JPC = 5.3 Hz), 118.4 (d, JPC = 27.3 Hz), 110.6,

31 1 100.9, 28.5, 23.8; P{ H} NMR (benzene-d6): δ -23.8; IR: 1633 (s), 1603 (s), 1435 (s),

1381 (s), 1339 (s), 1259 (s), 1240 (s), 1226 (s), 1179 (s), 1135 (s), 1096 (s), 1052 (s),

1005 (w), 953 (s), 900 (w), 857 (m), 836 (m), 803 (m), 788 (w), 753 (s), 739 (s), 692 (s);

Anal. calcd. for C32H32NO2P: C, 77.87; H, 6.53; N, 2.84. Found: C, 77.00; H, 6.44; N,

2.82. Melting point = 111–113 °C.

129

I-L7 (4-12)

A Schlenk tube was charged with Li-L1 (0.39 g, 1.2 mmol) and toluene (20 ml) was added via cannula. Then, solid I2 (0.32 g, 1.2 mmol) was added. The reaction was allowed to stir for two hours at ambient temperature. The reaction was subsequently quenched with a saturated aqueous sodium sulfite solution (20 ml). The layers were then separated and the organic layer washed with deionized water (2 x 30 ml). The organic layer was dried over magnesium sulfate and the solvent removed via reduced pressure, yielding a dark brown solid following crystallization from methanol (0.29 g, 55%). 1H

NMR (benzene-d6): δ 8.50 (s, 1H), 7.96 (d, 1H, 8.4 Hz), 7.20 (d, 2H, 7.2 Hz), 7.16 (t, 1H, obscured by residual C6D5H), 6.43 (d, 1H, 8.4 Hz), 5.08 (s, 2H), 3.22 (sept, 2H, 7.2 Hz),

1 1.24 (d, 12H, 7.2 Hz); H NMR (chloroform-d1): δ 8.31 (s, 1H), 7.87 (d, 1H, 8.9 Hz),

7.22-7.13 (m, 3H), 6.91 (d, 1H, 8.9 Hz), 6.13 (s, 2H), 3.00 (sept, 2H, 6.5 Hz), 1.22 (d,

13 1 12H, 6.5 Hz); C{ H} NMR (chloroform-d1): δ 163.8, 149.9, 148.9, 148.7, 137.9, 130.4,

124.4, 123.7, 123.3, 108.8, 101.2, 77.5, 28.1, 23.8; IR: 1633 (s), 1591 (s), 1456 (s), 1327

(s), 1252 (s), 1182 (m), 1114 (m), 1041 (s), 930 (s), 856 (w), 829 (m), 804 (w), 747 (s);

+ HRMScalc: 436.0774 for C20H23INO2 [M + H] ; HRMSmeas: 436.0775. Melting point: 164-

165 °C.

I-L8 (4-13)

A Schlenk tube was charged with Li-L8 (0.51 g, 1.6 mmol) and toluene (30 ml) was added via cannula. Subsequently solid I2 (0.40 g, 1.6 mmol) was added. The reaction was allowed to stir for two hours at ambient temperature. The reaction was quenched with a saturated aqueous sodium sulfite solution (30 ml) and the organic fraction was washed

130 with deionized water (2 x 30 ml). The organic fraction was dried over magnesium sulfate and the solvent removed via reduced pressure, yielding 4-13 as a brown solid following

1 crystallization from methanol (0.51 g, 74%). H NMR (chloroform-d1): δ 7.21 (d, 2H, 7.8

Hz), 7.13 (t, 1H, 7.8 Hz), 6.98 (d, 1H, 7.8 Hz), 6.86 (d, 1H, 7.8 Hz), 6.08 (s, 2H), 3.09

(sept, 2H, 6.6 Hz), 2.10 (s, 3H), 1.27 (d, 6H, 6.6 Hz), 1.21 (d, 6H, 6.6 Hz); 13C{1H} NMR

(chloroform-d1): δ 170.1, 149.8, 146.1, 145.2, 140.6, 136.3, 123.9, 123.2, 122.5, 108.5,

100.8, 70.3, 27.9, 23.6, 23.3, 22.1; IR: 1647 (m), 1590 (m), 1453 (s), 1373 (m), 1242 (s),

1140 (w), 1098 (w), 1033 (s), 918 (m), 805 (m), 770 (w); HRMScalc: 450.0930 for

+ C21H25INO2 [M + H] ; HRMSmeas: 450.0934. Melting point: 138-139 °C.

8 (L )2 (4-14)

A Schlenk tube was charged with CuI (2.61 g, 13.7 mmol) and potassium metal (0.53 g,

14 mmol) in the glove box and dimethoxyethane (30 ml) was added via cannula. The reaction was allowed to stir for four hours at ambient temperature. Then 4-13 (0.50 g, 1.1 mmol) was added as a solid and the reaction was allowed to stir an additional 12 hours.

The reaction was quenched with water (20 ml) and filtered through a plug of celite, which was washed with diethyl ether (2 x 20 ml). The layers were then separated and the organic layer washed with deionized water (4 x 30 ml). The organic layer was dried over magnesium sulfate and the solvent removed via reduced pressure. Crystallization from

1 pentane yielded 4-14 as a dark brown solid (0.33 g, 92%). H NMR (chloroform-d1): δ

7.30 (d, 2H, 7.8 Hz), 7.08 (d, 4H, 7.2 Hz), 7.03 (t, 2H, 7.2 Hz), 6.93 (d, 2H, 7.8 Hz), 6.01

2 2 (d, 2H, JHH = 0.6 Hz), 5.94 (d, 2H, JHH = 0.6 Hz), 2.67 (sept, 2H, 7.2 Hz), 2.55 (sept,

2H, 7.2 Hz), 1.91 (s, 6H), 1.08 (d, 6H, 7.2 Hz), 1.07 (d, 6H, 7.2 Hz), 1.05 (d, 6H, 7.2 Hz),

13 1 1.03 (d, 6H, 7.2 Hz); C{ H} NMR (chloroform-d1): δ 168.2, 147.9, 146.4, 146.3, 136.4,

131

136.3, 136.0, 123.4, 123.1, 123.0, 122.5, 115.6, 108.2, 101.7, 27.9, 27.7, 24.1, 23.6, 23.5,

23.3, 21.2; IR: 1641 (m), 1458 (s), 1362 (w), 1334 (w), 1185 (w), 1099 (w), 1048 (s), 936

+ (w), 801 (m), 758 (m); HRMScalc: 645.3692 C42H49N2O4 for [M + H] ; HRMSmeas:

645.3685. Melting point: 186-188 °C.

4.5 Crystallography of 4-2a, 4-2b, 4-4, 4-5, 4-6, 4-7 and 4-10

A summary of crystal data and collection parameters for crystal structures of 4-2a, 4-2b,

4-4, 4-5, 4-6, 4-7 and 4-10 are provided in Table 4.1. Detailed descriptions of data collection, as well as data solution, are provided below. ORTEP diagrams were generated with the ORTEP-3 software package.65 For each sample, a suitable crystal was mounted on a glass fiber using Paratone-N hydrocarbon oil. The crystal was transferred to a Siemens SMART66 diffractometer with a CCD area detector, centered in the X-ray beam, and cooled to 140 K using a nitrogen-flow low-temperature apparatus that had been previously calibrated by a thermocouple placed at the same position as the crystal.

An arbitrary hemisphere of data was collected using 0.3° ω scans, and the data were integrated by the program SAINT.67 The final unit cell parameters were determined by a least-squares refinement of the reflections with I > 2σ(I). Data analysis using Siemens

XPREP68 and the successful solution and refinement of the structure determined the space group. Empirical absorption corrections were applied for 4-2a, 4-2b, 4-4, 4-5, 4-6,

4-7 and 4-10 using the program SADABS.69 Equivalent reflections were averaged, and the structures were solved by direct methods using the SHELXTL software package.70

Unless otherwise noted, all non-hydrogen atoms were refined anisotropically.

132

4-2a: X-ray quality crystals were grown from a toluene solution at -25 °C. Three toluene solvent molecules were present in the asymmetric unit. The carbon atoms of two solvent molecules were refined anisotropically. The third toluene molecule was disordered over two positions; its carbon and hydrogen atoms were both modeled isotropically. The final cycle of full-matrix least-squares refinement was based on 8984 observed reflections and 616 variable parameters and converged yielding final residuals:

R = 0.0679, Rall = 0.0801, and GOF = 1.082.

4-2b: X-ray quality crystals were grown from a saturated toluene solution at -

25°C. The final cycle of full-matrix least-squares refinement was based on 4580 observed reflections and 236 variable parameters and converged yielding final residuals:

R = 0.0352, Rall = 0.0387, and GOF = 1.047.

4-4: X-ray quality crystals were grown from a pentane solution at -25 °C. The final cycle of full-matrix least-squares refinement was based on 7032 observed reflections and 425 variable parameters and converged yielding final residuals: R =

0.0392, Rall = 0.0521, and GOF = 1.024.

4-5: X-ray quality crystals were grown from a diethyl ether solution at -25 °C.

The final cycle of full-matrix least-squares refinement was based on 5448 observed reflections and 316 variable parameters and converged yielding final residuals: R =

0.0331, Rall = 0.0372, and GOF = 1.052.

4-6: X-ray quality crystals were grown from a diethyl ether solution at -25 °C.

The final cycle of full-matrix least-squares refinement was based on 4650 observed

133 reflections and 433 variable parameters and converged yielding final residuals: R =

0.0823, Rall = 0.0896, and GOF = 1.011.

4-7: X-ray quality crystals were grown from an evaporating diethyl ether/toluene solution. The final cycle of full-matrix least-squares refinement was based on 5455 observed reflections and 478 variable parameters and converged yielding final residuals:

R = 0.0897, Rall = 0.1171, and GOF = 1.215.

4-10: X-ray quality crystals were grown from an acetonitrile solution at ambient temperature. Additional electron density corresponding to diffuse disordered solvent was observed, but not modeled, in the final crystallographic model. The final cycle of full- matrix least-squares refinement was based on 3977 observed reflections and 343 variable parameters and converged yielding final residuals: R = 0.0407, Rall = 0.0789, and GOF =

1.037.

134

Table 4.1. Crystallographic data for compounds 4-2a, 4-2b, 4-4, 4-5, 4-6, 4-7 and 4-10

Compound 4-2a 4-2b 4-4 4-5

Formula C40H44AlClN2O4•3(C7H C20H22AlCl2NO2 C40H44N2O4Zn C28H32N2O4Zn

8) Formula weight 955.60 406.27 682.14 525.93

Space group P-1 P21/n P21/n P21/n

Temperature (K) 140 140 140 140

a (Å) 13.732(3) 10.0807(8) 10.6393(4) 12.040(2)

b (Å) 14.066(3) 16.688(1) 18.9992(7) 17.360(4)

c (Å) 15.398(3) 12.164(1) 17.3022(7) 12.560(3)

α (°) 71.820(4) 90.00 90.00 90.00

β (°) 71.903(4) 98.214(2) 96.823(1) 111.76(3)

γ (°) 77.483(4) 90.00 90.00 90.00

V (Å3) 2662.4(9) 2025.3(3) 3472.7(2) 2438.2(8)

Z 2 4 4 4

3 Densitycalc (g/cm ) 1.192 1.332 1.305 1.433

Diffractometer Siemens SMART Siemens SMART Siemens SMART Siemens SMART

Radiation Mo-Kα (λ = 0.71073 Å) Mo-Kα (λ = 0.71073 Å) Mo-Kα (λ = 0.71073 Å) Mo-Kα (λ = 0.71073 Å)

Monochromator Graphite Graphite Graphite Graphite

Detector CCD detector CCD detector CCD detector CCD detector

Scan type, width ω, 0.3° ω, 0.3° ω, 0.3° ω, 0.3°

Scan speed (s) 20 25 30 25

Reflections measured Hemisphere Hemisphere Hemisphere Hemisphere

2θ range (°) 2.88-52.74 4.18-56.66 4.28-56.64 4.00-56.56

Crystal dimensions (mm) 0.25 x 0.20 x 0.10 0.10 x 0.08 x 0.06 0.10 x 0.10 x 0.05 0.20 x 0.10 x 0.05

Reflections measured 26328 29012 37110 27171

Unique reflections 10900 5049 8644 6048

Observations (I > 2σ(I)) 8984 4580 7032 5448

Rint 0.0426 0.0358 0.0492 0.0521

Parameters 616 236 425 316

R, Rw, Rall 0.0679, 0.1916, 0.0801 0.0352, 0.0969, 0.0387 0.0392, 0.1101, 0.0521 0.0331, 0.0887, 0.0372

GoF 1.082 1.047 1.024 1.052

135

Table 4.1. continued

Compound 4-6 4-7 4-10

Formula C40H44Cu2N2O4 C44H54CuLiN2O5 C64H64Cu2I2N2O4P2

Formula weight 743.85 761.37 1367.99

Space group P-1 P21/n R-3

Temperature (K) 140 140 140 a (Å) 8.495(2) 10.700(2) 26.4506(3) b (Å) 12.599(3) 30.090(6) 26.4506(3) c (Å) 17.341(4) 13.070(3) 24.4412(8)

α (°) 92.75(3) 90.00 90.00

β (°) 90.63(3) 97.30(3) 90.00

γ (°) 107.11(3) 90.00 120.00

V (Å3) 1771.3(6) 4174(1) 14808.9(5)

Z 2 4 9

3 Densitycalc (g/cm ) 1.395 1.212 1.381

Diffractometer Siemens SMART Siemens SMART Siemens SMART

Radiation Mo-Kα (λ = 0.71073 Å) Mo-Kα (λ = 0.71073 Å) Mo-Kα (λ = 0.71073 Å)

Monochromator Graphite Graphite Graphite

Detector CCD detector CCD detector CCD detector

Scan type, width ω, 0.3° ω, 0.3° ω, 0.3°

Scan speed (s) 20 25 25

Reflections measured Hemisphere Hemisphere Hemisphere

2θ range (°) 2.36-49.42 2.70-49.76 2.44-52.72

Crystal dimensions (mm) 0.08 x 0.08 x 0.05 0.20 x 0.10 x 0.10 0.10 x 0.05 x 0.05

Reflections measured 9385 28009 27977

Unique reflections 5742 7202 6459

Observations (I > 2σ(I)) 4650 5455 3977

Rint 0.0467 0.0632 0.0864

Parameters 433 478 343

R, Rw, Rall 0.0823, 0.2220, 0.0896 0.0897, 0.2176, 0.1171 0.0407, 0.1550, 0.0789

GoF 1.011 1.215 1.037

136

References 1. Beck, J. F.; Neshat, A.; Schmidt, J. A. R., Structural characterization of novel ortho-lithiated imines. European Journal of Inorganic Chemistry 2010, (32), 5146-5155.

2. Baiz, T. I. M.S. Thesis, Synthesis of group IV metal complexes employing a newly developed orthometallated imine ligand system. University of Toledo, Toledo, OH, 2007.

3. Neshat, A. Ph.D. Dissertation, Group V imido complexes bearing mono-anionic acetophenone imine ligands. University of Toledo, Toledo, OH, 2011.

4. Neshat, A.; Seambos, C. L.; Beck, J. F.; Schmidt, J. A. R., Mono-anionic acetophenone imine ligands: Synthesis, ortho-lithiation and first examples of group (V) metal complexes. Dalton Transactions 2009, (25), 4987-5000.

5. Beck, J. F.; Baiz, T. I.; Neshat, A.; Schmidt, J. A. R., Titanium imido complexes utilizing orthometallated derivatized acetophenone and piperonal imine ligands: Synthesis, isolation, and characterization. Dalton Transactions 2009, (25), 5001- 5008.

6. Baiz, T. I.; Schmidt, J. A. R., A discrete ortho-lithiated acetophenone imine derivative: Isolation, characterization, and synthesis of group IV metal complexes. Organometallics 2007, 26, 4094-4097.

7. Hitchcock, P. B.; Huang, Q. G.; Lappert, M. F.; Wei, X. H.; Zhou, M. S., Synthesis and structures of some heterometallic [(Li, Y)2, (M3, Ce) (M = Li or Na), (Li, Zr2) and (Li, Zr)4] oligomeric diamides derived from 1,2- bis(neopentylamino)benzene. Dalton Transactions 2006, (24), 2991-2997.

8. Wu, Z. Z.; Diminnie, J. B.; Xue, Z. L., Synthesis and characterization of unusual dichloro(amido)-bridged zirconium complexes. X-ray crystal structures of (Me2N)3Zr(μ-Cl)2(μ-NMe2)Zr(NMe2)2(THF) and Cl(Me2N)2Zr(μ-Cl)2(μ- NMe2)Zr(NMe2)2(THF). Inorganic Chemistry 1998, 37 (10), 2570-2574.

9. Witt, E.; Stephan, D. W., Synthesis and characterization of cyclopentadienyl titanium(aryloxide)sulfide complexes. Inorganic Chemistry 2001, 40 (15), 3824- 3826.

10. Firth, A. V.; Witt, E.; Stephan, D. W., Thermal reactions of titanium thiolates: Terminal titanium sulfides in C-S bond cleavage reactions. Organometallics 1998, 17 (17), 3716-3722.

137

11. Lubben, T. V.; Wolczanski, P. T.; Vanduyne, G. D., Preparation of group-4A complexes containing tri-tert-butylmethoxide (tritox), a steric cyclopentadienyl equivalent. Organometallics 1984, 3 (7), 977-983.

12. Nelsen, M. J.; Girolami, G. S., Synthesis and characterization of zirconium 2- pentafluorophenyl complexes: X-ray crystal structures of [ZrCl2(C6F5)4 ] and 3- [ZrF2(C6F5)5) ]. Journal of Organometallic Chemistry 1999, 585 (2), 275-284.

13. Polamo, M.; Leskela, M., Formation of tetrahydrofuran adducts of LiZrCl5 in the reaction of Li(NPh2) and ZrCl4: Crystal structures of [Li(THF)4][ZrCl5(THF)] and Li(THF)3-μ-Cl-ZrCl4(THF). Acta Chemica Scandinavica 1997, 51 (1), 44-48.

14. Schadle, C.; Meermann, C.; Tornroos, K. W.; Anwander, R., Rare earth metal phenyl(trimethylsilyl)amide complexes. European Journal of Inorganic Chemistry 2010, (18), 2841-2852.

15. Hannedouche, J.; Collin, J.; Trifonov, A.; Schulz, E., Intramolecular enantioselective hydroamination catalyzed by rare earth binaphthylamides. Journal of Organometallic Chemistry 2011, 696 (1), 255-262.

16. Guino-o, M. A.; Campana, C. F.; Ruhlandt-Senge, K., A unique heterobimetallic benzyl calciate - an organometallic mixed-metal species involving a heavy alkaline-earth metal. Chemical Communications 2008, (14), 1692-1694.

17. Roesky, H. W., The renaissance of aluminum chemistry. Inorganic Chemistry 2004, 43 (23), 7284-7293.

18. Power, P. P., Main-group elements as transition metals. Nature 2010, 463 (7278), 171-177.

19. Lei, H.; Fettinger, J. C.; Power, P. P., Synthesis and structures of low-valent alkynyl tin and germanium complexes supported by terphenyl ligands: Heavier group 14 element enediyne analogues. Organometallics 2010, 29 (21), 5585- 5590.

20. Harder, S., From limestone to catalysis: Application of calcium compounds as homogeneous catalysts. Chemical Reviews 2010, 110 (7), 3852-3876.

21. Arrowsmith, M.; Hill, M. S.; Kociok-Kohn, G., Suppression of schlenk equilibration and heavier alkaline earth alkyl catalysis: A dearomatization strategy. Organometallics 2011, 30 (6), 1291-1294.

22. Krieck, S.; Gorls, H.; Westerhausen, M., Synthesis and characterization of rare examples of stable potassium and arylcalcium triethylboranate complexes. Inorganic Chemistry Communications 2010, 13 (12), 1466-1469.

138

23. Sarish, S. P.; Nembenna, S.; Nagendran, S.; Roesky, H. W., Chemistry of soluble beta-diketiminatoalkaline earth metal complexes with M-X bonds (M = Mg, Ca, Sr; X = OH, Halides, H). Accounts of Chemical Research 2011, 44 (3), 157-170.

24. Lichtenberg, C.; Jochmann, P.; Spaniol, T. P.; Okuda, J., The allylcalcium monocation: A bridging allyl ligand with a non-bent coordination geometry. Angewandte Chemie International Edition 2011, 50 (25), 5753–5756.

25. Eaborn, C.; Hitchcock, P. B.; Smith, J. D.; Sullivan, A. C., Preparation and crystal-structure of the tetrahydrofuran adduct of lithium bis[tris(trimethylsilyl)methyl]cuprate, [Li(THF)4][Cu[C(SIMe3)3]2] - the 1st structural characterization of a Gilman reagent. Journal of Organometallic Chemistry 1984, 263 (2), C23-C25.

26. Breit, B.; Schmidt, Y., Directed reactions of organocopper reagents. Chemical Reviews 2008, 108 (8), 2928-2951.

27. Eisch, J. J., Henry Gilman: American pioneer in the rise of organometallic chemistry in modern science and technology. Organometallics 2002, 21 (25), 5439-5463.

28. Schormann, M.; Varkey, S. P.; Roesky, H. W.; Noltemeyer, M., Preparation of bistrimethylsilylmethylniobiumtetrafluoride and the application of KHF2 and n Bu4NHF2 as fluorinating reagents. Journal of Organometallic Chemistry 2001, 621 (1-2), 310-316.

29. Sinnema, P.-J.; van der Veen, L.; Spek, A. L.; Veldman, N.; Teuben, J. H., Titanium dichloro, bis(carbyl), aryne, and alkylidene complexes stabilized by linked cyclopentadienyl amido auxiliary ligands. Organometallics 1997, 16 (20), 4245-4247.

30. Hagadorn, J. R.; Arnold, J., Titanium(II), -(III), and -(IV) complexes supported by benzamidinate ligands. Organometallics 1998, 17 (7), 1355-1368.

31. Buijink, J. K. F.; Meetsma, A.; Teuben, J. H.; Kooijman, H.; Spek, A. L., Alkylation and reductive dimerization of half-sandwich imido vanadium dichlorides. Journal of Organometallic Chemistry 1995, 497 (1-2), 161-170.

32. Ishiyama, T.; Mizuta, T.; Miyoshi, K.; Nakazawa, H., synthesis and characterization of some zirconium and hafnium complexes with a phosphide- pendant cyclopentadienyl ligand. Organometallics 2003, 22 (5), 1096-1105.

33. Shaw, S. L.; Morris, R. J.; Huffman, J. C., Monoindenyl halides of zirconium and 5 5 hafnium - the preparation of [h -(C9H7)ZrCl3]n and [(h -C9H7)HfCl2(m-C)]2 and 5 the crystal-structure of [(h -C9H7)HfCl2(m-Cl)]2. Journal of Organometallic Chemistry 1995, 489 (1-2), C4-C6.

139

34. Moorhouse, S.; Wilkinson, G., Bis[(trimethylsilyl)methyl]- and bis(neopentyl)- zinc, and tris[(trimethylsilyl)methyl]aluminium-diethyl ether (1/1); Their use as alkylating agents in forming niobium and tantalum alkyls. Journal of the Chemical Society, Dalton Transactions 1974, (20), 2187-2190.

35. Santinis, C.; Riess, J. G., Preparation of monomethyl-niobium(V) and monomethyl-tantalum(v) halides and of some of their complexes. Dalton Transactions 1973, (22), 2436-2440.

36. Crimmin, M. R.; Casely, I. J.; Hill, M. S., Calcium-mediated intramolecular hydroamination catalysis. Journal of the American Chemical Society 2005, 127 (7), 2042-2043.

37. Barrett, A. G. M.; Crimmin, M. R.; Hill, M. S.; Hitchcock, P. B.; Procopiou, P. A., Trifluoromethyl coordination and C-F bond activation at calcium. Angewandte Chemie-International Edition 2007, 46 (33), 6339-6342.

38. Crimmin, M. R.; Barrett, A. G. M.; Hill, M. S.; Hitchcock, P. B.; Procopiou, P. A., Heavier group 2 element catalyzed hydrophosphination of carbodiimides. Organometallics 2008, 27 (4), 497-499.

39. Crimmin, M. R.; Barrett, A. G. M.; Hill, M. S.; Hitchcock, P. B.; Procopiou, P. A., Calcium-catalyzed intermolecular hydrophosphination. Organometallics 2007, 26 (12), 2953-2956.

40. Zhang, X.; Emge, T. J.; Hultzsch, K. C., Intramolecular aminoalkene hydroamination catalyzed by magnesium complexes containing multidentate phenoxyamine ligands. Organometallics 2010, 29 (22), 5871-5877.

41. Dunne, J. F.; Fulton, D. B.; Ellern, A.; Sadow, A. D., Concerted C-N and C-H bond formation in a magnesium catalyzed hydroamination. Journal of the American Chemical Society 2010, 132 (50), 17680-17683.

42. Crimmin, M. R.; Arrowsmith, M.; Barrett, A. G. M.; Casely, I. J.; Hill, M. S.; Procopiou, P. A., Intramolecular hydroamination of aminoalkenes by calcium and magnesium complexes: A synthetic and mechanistic study. Journal of the American Chemical Society 2009, 131 (28), 9670-9685.

43. Ejfler, J.; Krauzy-Dziedzic, K.; Szafert, S.; Jerzykiewicz, L. B.; Sobota, P., Synthesis, characterization, and catalytic studies of (aryloxido)magnesium complexes. European Journal of Inorganic Chemistry 2010, (23), 3602-3609.

44. Liu, Y. C.; Lin, C. H.; Ko, B. T.; Ho, R. M., Ring-opening polymerization of beta-butyrolactone catalyzed by efficient magnesium and zinc complexes derived from tridentate anilido-aldimine ligand. Journal of Polymer Science Part A- Polymer Chemistry 2010, 48 (23), 5339-5347.

140

45. Wang, L. Y.; Ma, H. Y., Highly active magnesium initiators for ring-opening polymerization of rac-lactide. Macromolecules 2010, 43 (16), 6535-6537.

46. Xu, X.; Chen, Y. F.; Zou, G.; Ma, Z.; Li, G. Y., Magnesium, zinc, and calcium complexes based on tridentate nitrogen ligands: Syntheses, structures, and catalytic activities to the ring opening polymerization of rac-lactide. Journal of Organometallic Chemistry 2010, 695 (8), 1155-1162.

47. Thibault, M. H.; Fontaine, F. G., Aluminium complexes bearing functionalized trisamido ligands and their reactivity in the polymerization of epsilon- caprolactone and rac-lactide. Dalton Transactions 2010, 39 (24), 5688-5697.

48. Gong, S. G.; Ma, H. Y., beta-Diketiminate aluminium complexes: Synthesis, characterization and ring-opening polymerization of cyclic esters. Dalton Transactions 2008, (25), 3345-3357.

49. Munoz-Hernandez, M. A.; McKee, M. L.; Keizer, T. S.; Yearwood, B. C.; Atwood, D. A., Six-coordinate aluminium cations: Characterization, catalysis, and theory. Dalton Transactions 2002, (3), 410-414.

50. Chisholm, M. H.; Lin, C. C.; Gallucci, J. C.; Ko, B. T., Binolate complexes of lithium, zinc, aluminium, and titanium; Preparations, structures, and studies of lactide polymerization. Dalton Transactions 2003, (3), 406-412.

51. Chisholm, M. H.; Patmore, N. J.; Zhou, Z. P., Concerning the relative importance of enantiomorphic site vs. chain end control in the stereoselective polymerization of lactides: reactions of (R,R-salen)- and (S,S-salen)-aluminium alkoxides LAlOCH2R complexes (R = CH3 and S-CHMeCl). Chemical Communications 2005, (1), 127-129.

52. Koller, J.; Bergman, R. G., Aluminium-catalyzed intramolecular hydroamination of aminoalkenes. Chemical Communications 2010, 46 (25), 4577-4579.

53. Han, R.; Parkin, G., Ligand redistribution reactions of tris(3,5- dimethylpyrazolyl)hydroboratomagnesium alkyl derivatives, crystal structure of 3 (h -HB(3,5-Me2Pz)3)2Mg. Journal of Organometallic Chemistry 1990, 393 (3), C43-C46.

54. Papasergio, R. I.; Raston, C. L.; White, A. H., Syntheses and crystal-structures of complexes [M2R2] [M = Cu, Ag, or Au, R = 2-C(SiMe3)2C5H4N] and [Cu42- + CH(SiMe3)C5H4N] - electrochemical generation of [Cu2R2]2 . Journal of the Chemical Society-Dalton Transactions 1987, (12), 3085-3091.

55. Toth, A.; Floriani, C.; Chiesivilla, A.; Guastini, C., Dinuclear copper(I) benzoato complexes binding isocyanides and azo-compounds. Inorganic Chemistry 1987, 26 (2), 236-241.

141

56. Lin, Y. Y.; Lai, S. W.; Che, C. M.; Fu, W. F.; Zhou, Z. Y.; Zhu, N. Y., Structural variations and spectroscopic properties of luminescent mono- and multinuclear silver(I) and copper(I) complexes bearing phosphine and cyanide ligands. Inorganic Chemistry 2005, 44 (5), 1511-1524.

57. van Koten, G.; Noltes, J. G., Group IB organometallic chemistry structural characterization of some 2-(dimethylamino)-methyl-substituted phenylcopper compounds R4Cu4. Journal of Organometallic Chemistry 1975, 84 (1), 129-138.

58. Khan, S. I.; Edwards, P. G.; Yuan, H. S. H.; Bau, R., Structures of the Cu4MgPh6 and [Cu4LiPh6] clusters: 1st example of a magnesium-containing transition metal cluster compound. Journal of the American Chemical Society 1985, 107 (6), 1682-1684.

59. Salo, E. V.; Guan, Z. B., Late transition metal complexes with bisazaferrocene ligands for ethylene oligomerization. Organometallics 2003, 22 (24), 5033-5046.

60. Hicks, J. D.; Hyde, A. M.; Cuezva, A. M.; Buchwald, S. L., Pd catalyzed N- arylation of secondary acyclic amides: Catalyst development, scope, and computational study. Journal of the American Chemical Society 2009, 131 (46), 16720-16734.

61. Reddy, K. R.; Tsai, W. W.; Surekha, K.; Lee, G. H.; Peng, S. M.; Chen, J. T.; Liu, S. T., Ligand effects on palladium complex catalyzed copolymerization of ethylene/carbon monoxide. Journal of the Chemical Society-Dalton Transactions 2002, (8), 1776-1782.

62. Evano, G.; Blanchard, N.; Toumi, M., Copper mediated coupling reactions and their applications in natural products and designed biomolecules synthesis. Chemical Reviews 2008, 108 (8), 3054-3131.

63. Nakamura, A.; Ito, S.; Nozaki, K., Coordination insertion copolymerization of fundamental polar monomers. Chemical Reviews 2009, 109 (11), 5215-5244.

64. Zhao, D. P.; Gao, B.; Gao, W.; Luo, X. Y.; Tang, D. H.; Mu, Y.; Ye, L., New titanium complexes with symmetric or asymmetric cis-9,10- dihydrophenanthrenediamide ligands formed through sequential intramolecular C- C bond forming reactions. Inorganic Chemistry 2011, 50 (1), 30-36.

65. Barnes, C. L., ORTEP-3 for windows - a version of ORTEP-III with a graphical user interface. Journal of Applied Crystallography 1997, 30 (1), 568-568.

66. SMART: Area-Detector Software Package, 5.625; Bruker AXS, Inc.: Madison, WI, 1997-2001.

67. SAINT: SAX Area-Detector Integration Program, 6.22; Bruker AXS, Inc.: Madison, WI, 1997-2001.

142

68. XPREP: Reciprocal Space Exploration Program, 6.12; Bruker AXS, Inc.: Madison, WI, 2001.

69. SADABS: Bruker/Siemens Area Detector Absorption Program, 2.03; Bruker AXS, Inc.: Madison, WI, 2001.

70. SHELXTL-97, Structure Solution Program, 6.10; Bruker AXS, Inc.: Madison, WI, 2000.

143

Chapter 5

Hydroamination of 1,1-Dimethylallene with Primary Aryl Amines Under Mild Conditions: An Atom-Economical Route to N-(1,1-Dimethyl-2-Propenyl)-Anilines

5.1 Introduction

We have previously demonstrated that alicyclic 3-iminophosphines are effective ligands for use in palladium-catalyzed hydroamination of allenes,1 1,3-dienes1, 2 and alkynes.2 Our initial work detailed the hydroamination of 1,3-cyclohexadiene and phenyl acetylene in moderate yields using a diphenylphosphine-derived 3-iminophosphine precatalyst: [(3IP)Pd(allyl)]OTf.2 Recently, we reported the hydroamination of 3- methyl-1,2-butadiene (1,1-dimethylallene) and 2,3-dimethyl-1,3-butadiene with a wide variety of secondary amines using a related catalyst: [(3IPAr)Pd(allyl)]OTf.1 Inclusion of a six-membered alicyclic backbone and an aromatic imine substituent in this second- generation catalyst significantly improved catalysis. For example, the hydroamination of

3-methyl-1,2-butadiene with morpholine yielded the linear allylic amine in nearly quantitative yield at room temperature in only 4 hours using [(3IPAr)Pd(allyl)]OTf, while the original catalyst, [(3IP)Pd(allyl)]OTf, yielded a mixture of the linear and branched products in a combined yield of only 89% under the same conditions. 144

In general, the synthesis of allylic amines via transition metal catalysis has long been of interest, with many allylic amination catalysts developed utilizing various metals, including iridium,3 rhodium,4 palladium5 and iron.6 The iridium, rhodium and iron catalysts often display a high degree of selectivity for the branched (kinetic) product, whereas most palladium catalysts favor the linear (thermodynamic) product.6-10 Another method to generate allylic amines involves the hydroamination of allenes or 1,3-dienes, which has the advantage of a higher degree of atom economy compared to allylic amination.11 There are several examples of intermolecular hydroamination of allenes yielding allylic amines, including those of Bertrand,12-14 Widenhoefer15, 16 and

Yamamoto,17-19 although most of these systems lack selectivity for the more desirable branched product. However, Widenhoefer16 has observed the opposite regioselectivity to that reported by Yamamoto19 and Bertrand,14 providing for isolation of the highly desirable branched allylic amine. This is likely due to the room temperature conditions that Widenhoefer utilized, compared to the higher temperatures required for the Bertrand and Yamamoto catalysts. In general, allylic amines are desirable because they can be further functionalized using transformations such as asymmetric hydroboration,20 hydroformylation,21 amino Claisen rearrangement,22 and alkene metathesis23 as part of the synthesis of value added molecules, such as natural products or pharmaceuticals.24

Aryl amino Claisen rearrangement is a useful reaction for the synthesis of ortho- allylic anilines, which have further synthetic utility in the construction of heterocycles.25-

30 Despite the apparent utility of the aryl amino Claisen rearrangement, there are relatively few reports utilizing this reaction. This can be attributed to the slow reaction rates, low yields and high reaction temperatures generally required.31-33 Branched N-

145 allylic anilines have proven cumbersome to synthesize via standard organic techniques.

In 2001, Ward and coworkers outlined a 4-step synthesis,22 analogous to that of Jolidon and Hansen from several decades before,34 to generate branched allylic amines. Modern advances in catalysis now allow easier access to these compounds via allylic amination5 or the hydroamination of dienes16, 35, 36 in one step. To our knowledge, there has been no methodological report of the coupling of allylic amination or hydroamination of allenes with aryl amino Claisen rearrangement in one pot to generate ortho-allylic anilines.

Kheinman and coworkers do postulate an aryl amino Claisen rearrangement as part of a thermal synthesis of 2-ethyl-2-methyl-2,3-dihydro-1H-indole, an insecticide, where their allylic amine starting material is synthesized via the hydroamination of isoprene with aniline.37

Herein, we report the use of a new 3-iminophosphine catalyst,

[(3IPtBu)Pd(allyl)]OTf, for the hydroamination of 3-methyl-1,2-butadiene at room temperature, generating the branched allylic amine product exclusively. Hydroamination of 3-methyl-1,2-butadiene was also coupled to an aryl amino Claisen rearrangement in a one-pot, two-step synthesis of 2-(3-methyl-2-butenyl)-anilines. Using this methodology, many new N-allylic and ortho-allylic anilines were produced and characterized for the first time, demonstrating the excellent utility of these new palladium catalysts.

5.2 Results and Discussion

The 3-iminophosphine (3IPtBu; 5-3) was synthesized in an analogous fashion to our previous ligands (Scheme 5.1)1, 2 and isolated in moderate yield as a dark red oil. Its

4 imine proton resonance appeared at 8.88 ppm, coupled to the phosphorus nucleus ( JPH =

146

6.0 Hz), and its 31P{1H} NMR spectrum showed a single resonance at 13.2 ppm.

tBu Reaction of 5-3 with [Pd(allyl)Cl]2 (0.5 equiv.) yielded (3IP )Pd(allyl)Cl (5-4) in moderate yield (62%; Scheme 5.2). A single resonance at 42.7 ppm was observed in the

t t t O Cl O Cl N Bu Bu2P N Bu i iii iv ii

5-1 5-2 5-3

tBu Scheme 5.1. Synthesis of alicyclic 3IP (5-3). Legend: (i) 2 eq. DMF, 1.6 eq. POCl3, 0

°C, 12 h; (ii) ice, NaHCO3; (iii) 1.5 eq. tert-butylamine, Et2O, molecular sieves, 0 °C, 12

t h; (iv) 1.0 eq. LiP Bu2, Et2O, 0 °C, 2 h.

31P NMR spectrum of 5-4, indicating coordination of phosphorus to the palladium center while only broad resonances corresponding to the allylic protons were noted in its 1H

NMR spectrum. Many of the resonances in the 1H, 13C{1H} and 31P{1H} NMR spectra of 5-4 were broad due to its fluxionality and cooling to -60 °C did not eliminate its fluxional behavior. Reaction of 5-4 with AgOTf afforded [(3IPtBu)Pd(allyl)]OTf (5-5) in

+ OTf - Pd Pd t NtBu tBu P Cl t t Bu2P 2 Bu2P N Bu i ii NtBu

5-3 5-4 5-5

Scheme 5.2. Metallation of 5-3 yielding the palladium complexes 5-4 and 5-5.

Legend: (i) 0.5 eq. [Pd(allyl)Cl]2, CH2Cl2, 25 °C, 1 h; (ii) 1.0 eq. AgOTf,

CH2Cl2/toluene (3:1), 25 °C, 4 h. good yield as a brown powder after recrystallization. A 31P resonance at 61.8 ppm and an

147 upfield shift of 1.3 ppm for the imine proton indicated chelation of the ligand to the metal center in 5-5.

X-ray quality crystals of 5-5 were successfully grown, and its crystal structure

(Figure 5-1) revealed a palladium center supported by a chelating neutral 3- iminophosphine ligand with a bite angle of 92.52(6) degrees, an η3-allyl ligand and an outer sphere triflate anion. The ligand is puckered, rising above the coordination plane of the pseudo-square planar palladium center, resulting in a boat like conformation of this six-membered ring.

Figure 5-1. ORTEP diagram (50% thermal ellipsoids) of 5-5. Hydrogen atoms and triflate anion removed for clarity. Bond lengths (in Å): Pd1-N1 = 2.134(2), N1-C1 =

1.273(3), C1-C2 = 1.467(4), C2-C3 = 1.345(4), P1-C3 = 1.842(3), Pd1-P1 = 2.3356(8); angles (in °): N1-Pd1-P1 92.52(6), C1-N1-Pd1 = 123.3(2), C3-P1-Pd1 = 101.23(9).

148

The hydroamination of 1,1-dimethylallene with anilines proceeded readily at room temperature using catalytic [(3IPtBu)Pd(allyl)]OTf (5-5). Production of greater than

98% yield of the branched allylic amine was achieved in as little as 12-20 hours for several substrates (A; Table 5.1). Mild heating of the reaction (70 °C) increased the rate of catalysis and was necessary for halogenated anilines, which were found to be unreactive at room temperature. Heating at 70 °C for long periods of time (several days) resulted in formation of a palladium mirror, while heating to 115 °C resulted in rapid conversion to the linear (thermodynamic) product (B; Table 5.1) as part of a complex reaction mixture with yields much lower than those observed via lower temperature methods. Moderate (alkyl) to strong (methoxy, dimethylamino) electron-donating groups enhanced catalysis significantly compared to unsubstituted aniline. In contrast, halogenated substrates (F, Cl, Br) showed lower conversion than aniline and required heating to 70 °C for productive catalysis to take place. Additionally, small amounts of the linear products were observed in the NMR spectra of the chlorinated anilines. 4-

(Trifluoromethoxy)aniline proved to be completely unreactive, while 3-nitroaniline and

4-aminopyridine were not screened due to a lack of amine solubility. Steric effects also played an important role in this catalysis. Specifically, substituents at the ortho positions were found to virtually halt catalysis, even when the reaction was heated. The only exception to this trend was 2-methoxyaniline, which was observed to undergo hydroamination by 1H NMR spectroscopy, although conversion to the allylic amine was extremely low (10%) even after heating for 20 hours at 70 °C.

Although the catalytic hydroamination of 1,1-dimethylallene at room temperature yielded excellent results, reaction at elevated temperatures caused an oligomerization of

149

1,1-dimethylallene that was clearly visible in the 1H and 13C{1H} NMR spectra. Control experiments showed that 5-5 effectively catalyzed this oligomerization in the absence of amine, indicating that this process is independent of the hydroamination reaction. In contrast, at room temperature no oligomerization was detectible on the normal catalytic timescale. To help circumvent this side reaction, 2 equiv. of allene were used during the catalytic studies. For each catalytic hydroamination (Table 5.1), reaction progress was readily monitored by 1H NMR spectroscopy. As the allene and aryl amine resonances disappeared, a distinct set of product allylic amine resonances developed. A representative example is that observed for the hydroamination of 1,1-dimethylallene with 4-tertbutylaniline (Table 1, entry 6). In its 1H NMR spectrum, the product allylic amine is readily distinguished by the appearance of coupled doublets at 7.12 and 6.61 ppm (3J = 8.8 Hz), corresponding to its ortho and meta protons. The product allylic group appears as three doublets of doublets at 5.87 (3J = 17.2 Hz, 10.4 Hz), 5.07 ppm (3J = 17.2

Hz, 2J = 1.6 Hz), and 4.94 (3J = 10.4 Hz, 2J = 1.6 Hz), as well as a singlet at 1.22 ppm

(6H). This general splitting pattern was observed for all of the N-(1,1-dimethyl-2- propenyl)-anilines produced and is consistent with known examples in literature.5, 16

It was found that the hydroamination of 1,1-dimethylallene could be coupled to an aryl amino Claisen rearrangement reaction to produce substituted 2-allyl-anilines in one- pot, starting from 1,1-dimethylallene and an aniline (Table 5.2). This two-step, one-pot reaction sequence worked very well for a wide variety of the substrates originally screened for catalytic hydroamination. One notable characteristic of this reaction is that

150

Table 5.1. Hydroamination of 1,1-dimethylallene with anilines yielding N-(1,1- dimethyl-2-propenyl)-anilines.

+ NH2 HN HN - OTf t Pd t Bu2P N Bu + CCH2 + 5 mol% R R R AB

Entry Amine Temp. Conversion (A:B)a

1 aniline 25 °C 60 (100:0)

2 3-methylaniline 25 °C >98 (100:0)

3 3-ethylaniline 25 °C 73 (100:0)

4 4-methylaniline 25 °C >98 (100:0)

5 3,4-dimethylaniline 25 °C >98 (100:0)

6 4-tertbutylaniline 25 °C 88 (100:0)

7 3-methoxyaniline 25 °C 62 (100:0)

8 4-methoxyaniline 25 °C >98b (100:0)

9 4-(methylthio)aniline 25 °C 56 (100:0)

10 4-dimethylaminoaniline 25 °C >98b (100:0)

11 3-chloroaniline 70 °C 36 (72:28)

12 4-chloroaniline 70 °C 57 (75:25)

13 3-fluoroaniline 70 °C 50 (100:0)

14 4-fluoroaniline 70 °C 65 (100:0)

15 4-bromo-3-methylaniline 70 °C 17 (100:0)

aCatalytic procedure: amine (0.5 mmol) was added to a mixture of tBu [(3IP )Pd(allyl)]OTf (5 mol%) and benzene-d6 (0.8 ml). Subsequently, allene (1.0 mmol) was added and the reaction was sealed. Conversion was determined via NMR spectroscopy after 20 hours. b Reaction conversion reported at 12 hours.

151

Table 5.2. Hydroamination of 1,1-dimethylallene coupled with aryl amino Claisen rearrangement.

NH2

+ CCH 1) 5 mol% 5-5 2 2) 10 mol% HOTf R' R

HN NH2 NH2 + +

R' R' R' R R R B C D

Entry Amine Time (h) Conversion (B:C) or (B:C:D)

1 (R, R’ = H) 72 51 (0:100)

2 (R = H; R’ = Me) 20 >98 (0:50:50)

3 (R = H, R’ = Et) 20 70 (0:50:50)

4 (R = Me, R’ = H) 72 >98 (12:88)

6 (R = tBu, R’ = H) 20 90 (0:100)

9 (R = SMe, R’ = H) 20 53 (0:100)

13 (R = H, R’ = F) 72 61(26:74:0)

Catalytic procedure: amine (0.5 mmol) was added to a mixture of tBu [(3IP )Pd(allyl)]OTf (5 mol%) and benzene-d6 (0.8 ml). Subsequently allene (1.0 mmol) was added and the reaction was sealed. After 20 hours, triflic acid (7.5 mg, 10 mol%) was added and the reaction was heated to 70 °C for the time indicated.

152 the amino Claisen rearrangement of N-allylic-3-fluoroaniline proceeded with regiospecificity to yield exclusively 2-allyl-3-fluoroaniline. When methyl or ethyl groups were located at the 3 position 1:1 mixtures of 2- and 6-allyl-anilines were observed

(Table 5.2, entries 2 and 3). In order to effect these transformations, after hydroamination for 20 hours with 5-5 (5 mol%), the reaction was uncapped and triflic acid (10 mol%) was added. The reaction was then heated to 70 °C and the conversion to the 2-(3-methyl-2-butenyl)-anilines was monitored via 1H NMR spectroscopy. Products were identified in the 1H NMR spectra by characteristic triplets of multiplets at approximately 5 ppm corresponding to the allylic proton and doublets around 3 ppm for the methylene protons of the 3-methyl-2-butenyl group, an evident change in the splitting pattern compared to the intermediate N-allylic species.

5.3 Conclusion

It was demonstrated that alicyclic 3-iminophosphines are superb ligands for the palladium catalyzed, room-temperature hydroamination of 3-methyl-1,2-butadiene with anilines. This catalytic process is an effective means for the synthesis of N-(1,1- dimethyl-2-propenyl)-anilines in good to near quantitative yield. These N-allylic anilines are the kinetic products of this hydroamination reaction and possess a terminal vinylic moiety, making them especially useful product amines. Although yields were lower and heating of the reaction was required for the halogenated substrates, the hydroamination of fluorinated anilines proceeded in moderate yield. To our knowledge, this is the first example of the hydroamination of 3-methyl-1,2-butadiene with fluorinated anilines. A subsequent acid-catalyzed aryl amino Claisen rearrangement of the product N-(1,1-

153 dimethyl-2-propenyl)-anilines allowed for a one-pot synthesis of 2-(3-methyl-2-butenyl)- anilines from 1,1-dimethylallene and substituted anilines. Both N-(1,1-dimethyl-2- propenyl)-anilines and 2-(3-methyl-2-butenyl)-anilines are desirable compounds because of their applicability in the synthesis of heterocycles that are common in many natural products and pharmaceuticals.25, 37, 38

5.4 Experimental

5.4.1 General Methods and Instrumentation

All manipulations involving lithium reagents were performed under an inert N2 atmosphere using standard glove box and Schlenk techniques. Solvents were predried before use; THF and methylene chloride were passed through columns of 4Å molecular sieves and sparged with nitrogen. Pentane, diethyl ether, and toluene was passed through columns of activated alumina and 4 Å molecular sieves and sparged with nitrogen.

Benzene-d6 was dried over sodium metal, freeze-pump-thawed three times, and vacuum distilled and stored over 4 Å molecular sieves. Chloroform-d1 was dried over calcium hydride, freeze-pump-thawed three times, and vacuum distilled and stored over 4 Å molecular sieves. Phosphorus oxychloride, tert-butylamine, cyclopentanone, dimethylformamide, and di-(tert-butyl)chlorophosphine were purchased commercially and used as received. Triflic acid was purchased from Acros Organics; silver triflate, n- butyl lithium and allylpalladium chloride dimer were purchased from Strem Chemicals,

Inc.; 3-methyl-1,2-butadiene (1,1-dimethylallene) was purchased from Sigma-Aldrich.

Each was used as received. Anilines were purchased from Sigma-Aldrich or another commercial source and dried over calcium hydride, either neat (liquid anilines) or as solutions in methylene chloride (solid anilines). Liquid anilines were freeze-pump-

154 thawed three times, and vacuum distilled. Solutions of solid anilines in methylene chloride were freeze-pump-thawed three times, filtered and the methylene chloride removed via reduced pressure. Silica gel (Porosity: 60 Å, Particle size 40-63 μm) was purchased from Sorbent Technologies and used as received. 1H and 13C NMR data were obtained on a 600 MHz Inova NMR or a 400 MHz VXRS NMR spectrometer at ambient temperature at 599.9 MHz for 1H NMR and 150.8 MHz for 13C NMR and 399.95 MHz for 1H NMR and 100.56 MHz for 13C NMR, respectively. All spectra were taken using

1 C6D6 or CDCl3 as the NMR solvent. H NMR shifts are given relative to the residual solvent resonances at 7.16 ppm and 7.26 ppm, respectively, and 13C NMR shifts are given

31 relative to C6D6 (128.1 ppm) and CDCl3 (77.16 ppm). P NMR spectra were externally referenced to 0.00 ppm with 5% H3PO4 in D2O. Unless otherwise noted, all coupling

3 constants are JHH. IR samples were prepared as Nujol mulls and taken between KBr plates on a Perkin-Elmer XTL FTIR spectrophotometer. Melting points were observed on a capillary melting point (Uni-Melt) apparatus in sealed capillary tubes and are uncorrected. X-ray structure determinations were performed at The University of Notre

Dame, Notre Dame, Indiana. Elemental analyses were determined by Atlantic Microlab,

Inc., Norcross, GA. High resolution mass spectrometry, using electrospray ionization, was performed at the University of Illinois Mass Spectrometry Laboratory, Urbana, IL.

5.4.2 Catalyst Synthesis

2 t Compounds 5-1 and 5-2 were synthesized using existing literature methods. LiP Bu2 was

39, 40 initially synthesized using a procedure analogous to that used for LiPPh2; however, the procedure of Schneider and coworkers was found to be superior.41

155

3IPtBu (5-3):

A Schlenk flask was charged with 5-2 (0.86 g, 4.6 mmol) and 40 ml of diethyl ether was added via cannula. The reaction was cooled to 0 °C. A second Schlenk flask was charged

t in a nitrogen filled glove box with LiP Bu2 (0.741 g, 4.87 mmol). Diethyl ether (30 ml)

t was added, causing the white solid to completely dissolve. The LiP Bu2 solution was then transferred via cannula to the rapidly stirring solution of 5-2. The reaction was allowed to stir for 2 hours at 0 °C, during which time a white precipitate appeared. The solvent was then removed via reduced pressure and 5-3 was extracted from the dark red semi-solid mass with pentane (2 x 25 ml). Removal of solvent under vacuum yielded 5-3 as a red

1 4 liquid (0.92 g, 68%). H NMR (CDCl3): δ 8.88 (d, JPH = 6.0 Hz, 1H), 2.87-2.84 (m, 2H),

3 3 2.68-2.66 (m, 2H), 1.85 (pseudo pent, JHH = 7.8 Hz, JHH = 7.2 Hz, 2H), 1.22 (s, 9H),

3 13 1 3 1.18 (d, JPH = 12.0 Hz, 18H); C{ H} NMR (CDCl3): δ 155.2 (d, JPC = 19.8 Hz), 155.0

2 1 2 3 (d, JPC = 28.4 Hz), 147.1 (d, JPC = 34.7 Hz), 57.4, 39.7 (d, JPC = 6.6 Hz), 33.0 (d, JPC =

1 2 31 1 5.8 Hz), 32.8 (d, JPC = 19.8 Hz), 30.8 (d, JPC = 14.0 Hz), 30.2, 23.7 (br); P{ H} NMR

(CDCl3): δ 13.2; IR: 2953 (s), 2900 (s), 2848 (w), 2712 (w), 1654 (m), 1618 (m), 1560

(w), 1467 (m), 1388 (w), 1361 (m), 1330 (w), 1298 (m), 1257 (m), 1215 (m), 1173 (m),

1094 (m), 1068 (m), 1016 (m), 963 (w), 927 (w), 895 (w), 854 (w), 802 (m), 655 (w), 608

(m); HRMScalc.: 295.2429 for C18H34NP; HRMSmeas.: 295.2416.

(3IPtBu)Pd(allyl)Cl (5-4):

A Schlenk flask was charged in a nitrogen filled glove box with 5-3 (0.92 g, 3.1 mmol), and dichloromethane (30 ml) was added via cannula. A second Schlenk flask was

156 charged in a nitrogen filled glove box with [Pd(allyl)Cl]2 (0.57 g, 1.6 mmol), and dichloromethane (20 ml) was added via cannula, causing the yellow solid to dissolve completely. The [Pd(allyl)Cl]2 solution was then transferred via cannula to the stirring solution of 5-3. The reaction was allowed to stir for 1 hour. The solvent was then removed via reduced pressure, and the solid was extracted with pentane (2 x 35 ml) yielding 5-4 as a light brown solid after removal of pentane under vacuum (0.93 g, 62%).

1 H NMR (CDCl3): δ 9.36 (v. br. s., 1H), 5.38-5.31 (m, 1H), 4.60 (v. br. s., 2H), 3.60 (v.

3 br. s., 2H), 2.99-2.96 (m, 2H), 2.79-2.76 (m, 2H), 1.91-1.88 (m, 2H), 1.41 (d, JPH = 14.4

13 1 3 1 Hz, 18H), 1.18 (s, 9H); C{ H} NMR (CDCl3): δ 155.6 (d, JPC = 9.6 Hz), 153.7 (d, JPC

2 2 = 13.7 Hz), 139.7 (v. br.), 115.4 (d, JPC = 18.6 Hz), 80.4 (d, JPC = 27.7 Hz), 58.2, 57.9

3 2 (v. br.), 40.8 (d, JPC = 7.2 Hz), 33.4 (d, JPC = 37.2 Hz), 31.0 (v. br.), 30.5 (v. br.), 29.9,

3 31 1 23.3 (d, JPC = 16.8 Hz); P{ H} NMR (CDCl3): δ 42.7 (v. br.); IR: 1610 (m), 1557 (s),

1460 (s), 1366 (s), 1261 (w), 1208 (m), 1176 (m), 1062 (w), 1020 (w), 954 (w), 905 (w),

+ 807 (m), 723 (w); HRMScalc: 442.1855 for C21H39NPPd [M - Cl] ; HRMSmeas: 442.1859.

Melting point: 106 °C dec.

[(3IPtBu)Pd(allyl)]OTf (5-5):

Method one: A Schlenk flask was charged in a nitrogen filled glove box with both 5-4

(0.52 g, 1.1 mmol) and AgOTf (0.28 g, 1.1 mmol), and on a Schlenk line, dichloromethane (30 ml) was added via cannula, causing a gray precipitate to form immediately. The reaction mixture was filtered to remove AgCl, and the filtrate was pumped down to an oily solid. Then, the solution was washed with 30 ml of pentane.

Upon removal of residual pentane under vacuum a brown solid (5-5) was isolated (0.49 g,

157

77%). An analytically pure sample was recrystallized from a THF solution layered with pentane.

Method two: A Schlenk flask was charged in a nitrogen filled glove box with both 5-3

(0.40 g, 1.4 mmol) dissolved in 15 ml of dichloromethane and [Pd(allyl)Cl]2 (0.25 g, 0.68 mmol) dissolved in dichloromethane (20 ml). After swirling the Schlenk flask to ensure complete mixing, a solution of AgOTf (0.36 g, 1.4 mmol) in 20 ml of dichloromethane/toluene (3:1) was added causing a gray precipitate to form immediately.

The reaction was filtered and the solvent was removed under reduced pressure. The residue was dissolved in a minimal amount of THF and layered with pentane. After cooling to –30 °C, compound 5-5 was isolated as a brown crystalline solid (0.51 g, 64%).

1H NMR showed no difference in purity compared to that obtained after recrystallization utilizing method one.

1 4 H NMR (CDCl3): δ 8.06 (d, JPH = 2.4 Hz, 1H), 5.61-5.54 (m, 1H), 5.26-5.23 (m, 1H),

3.99-3.94 (m, 2H), 3.09-3.04 (m, 2H), 2.91-2.89 (m, 2H), 2.62 (d, 11.4 Hz, 1H), 2.03-

3 3 1.98 (m, 2H), 1.41 (d, JPH = 14.1 Hz, 9H), 1.40 (s, 9H), 1.24 (d, JPH = 14.1 Hz, 9H);

13 1 3 2 C{ H} NMR (CDCl3): δ 162.0 (d, JPC = 2.4 Hz), 156.2 (d, JPC = 13.6 Hz), 134.8 (d,

1 2 2 JPC = 15.3 Hz), 119.1 (d, JPC = 5.3 Hz), 87.6 (d, JPC = 25.8 Hz), 65.4, 50.3, 40.1, 39.3

1 2 1 2 (d, JPC = 13.4 Hz), 38.2 (d, JPC = 10.3 Hz), 37.8 (d, JPC = 16.2 Hz), 30.8 (d, JPC = 6.4

2 3 31 1 Hz), 30.7 (d, JPC = 5.8 Hz), 30.4, 23.8 (d, JPC = 3.4 Hz); P{ H} NMR (CDCl3): δ 61.8;

IR: 1614 (w), 1459 (s), 1372 (m), 1258 (s), 1150 (m), 1090 (m), 1025 (s), 800 (w). Anal. for C22H39F3NO3PPdS (592.01 g/mol): C 44.63, H 6.64, N 2.37; found C 44.46, H 6.61,

N 2.38. Melting point: 138-139 °C.

158

5.4.3 General Procedure for Catalytic Hydroamination of 1,1-Dimethylallene

All manipulations were performed in a nitrogen filled glove box. To a solution of

tBu [(3IP )Pd(allyl)]OTf (14.8 mg, 5 mol%) in 0.8 ml of benzene-d6, an aniline (0.5 mmol) was added, followed by 1,1-dimethylallene (68 mg, 1.0 mmol). The reaction was allowed to stand for 12 to 20 hours. The products were purified via column chromatography

(silica gel; 5:1 pentane/ethyl acetate) and solvent was removed via reduced pressure.

5.4.3.1 Characterization of Hydroamination Products

N-(1,1-Dimethyl-2-propenyl)-aniline (5-1a),42 N-(1,1-dimethyl-2-propenyl)-3-methylaniline (5-2a),6 N-(1,1-dimethyl-2-propenyl)-4-methyl-aniline (5-4a),6 N-(1,1-dimethyl-

2-propenyl)-3-methoxy-aniline (5-7a),6 N-(1,1-dimethyl-2-propenyl)-4-methoxy-aniline

(5-8a),6 N-(1,1-dimethyl-2-propenyl)-3-chloro-aniline (5-11a),6 N-(3-methyl-2-butenyl)-

3-chloro-aniline (5-11b),6 N-(1,1-dimethyl-2-propenyl)-4-chloro-aniline (5-12a),43 and N-

(3-methyl-2-butenyl)-4-chloro-aniline (5-12b)44 were identified by comparison to published NMR data.

N-(1,1-dimethyl-2-propenyl)-3-ethyl-aniline (5-3a)

1 H NMR (C6D6): δ 7.12 (t, 7.9 Hz, 1H), 6.63 (d, 7.9 Hz, 1H), 6.58 (d, 7.9 Hz, 1H), 6.50

2 (s, 1H), 5.92 (dd, 14.6 Hz, 10.4 Hz, 1H), 5.12 (dd, 14.6 Hz, JHH = 1.2 Hz, 1H), 4.98 (dd,

2 10.4 Hz, JHH = 1.2 Hz, 1H), 3.34 (s, 1H), 2.51 (q, 7.6 Hz, 2H), 1.18 (t, 7.6 Hz, 3H), 1.15

13 1 (s, 6H); C{ H} NMR (C6D6): δ 147.2, 146.8, 144.9, 129.1, 117.6, 115.9, 113.6, 112.5,

+ 54.5, 29.6, 28.3, 16.0; HRMScalc: 190.1596 for C13H20N [M + H] ; HRMSmeas: 190.1599.

159

N-(1,1-dimethyl-2-propenyl)-3,4-dimethyl-aniline (5-5a)

1 4 H NMR (C6D6): δ 6.91 (d, 10.5 Hz, 1H), 6.63 (dd, 10.5 Hz, JHH = 2.4 Hz, 1H), 6.56 (d,

4 2 JHH = 2.4 Hz, 1H), 5.98 (dd, 17.6 Hz, 13.5 Hz, 1H), 5.10 (dd, 17.6 Hz, JHH = 0.8 Hz,

2 1H), 4.98 (dd, 13.5 Hz, JHH = 0.8 Hz, 1H), 3.80 (s, 1H), 2.07 (s, 3H), 2.05 (s, 3H), 1.18

13 1 (s, 6H); C{ H} NMR (C6D6): δ 146.7, 144.4, 136.9, 130.4, 126.9, 119.6, 115.4, 113.0,

+ 55.7, 28.3, 20.4, 19.1; HRMScalc: 190.1596 for C13H20N [M + H] ; HRMSmeas: 190.1597.

N-(1,1-dimethyl-2-propenyl)-4-tert-butylaniline (5-6a)

1 H NMR (C6D6): δ 7.12 (d, 8.8 Hz, 2H), 6.61 (d, 8.8 Hz, 2H), 5.87 (dd, 17.2 Hz, 10.4 Hz,

2 2 1H), 5.07 (dd, 17.2 Hz, JHH = 1.6Hz, 1H), 4.94 (dd, 10.4 Hz, JHH = 1.6 Hz, 1H), 3.24 (br

13 1 s, 1H), 1.22 (s, 6H), 1.10 (s, 9H); C{ H} NMR (C6D6): δ 147.0, 144.7, 140.2, 125.8,

+ 116.2, 112.4, 54.6, 34.0, 31.9, 28.4; HRMScalc: 218.1909 for C15H24N [M + H] ;

HRMSmeas: 218.1907.

N-(1,1-dimethyl-2-propenyl)-4-methylthio-aniline (5-9a)

1 H NMR (C6D6): 7.20 (d, 8.7 Hz, 2H), 6.53 (d, 8.7 Hz, 2H), 5.82 (dd, 17.6 Hz, 10.8 Hz,

2 2 1H), 5.05 (dd, 17.6 Hz, JHH = 1.2 Hz, 1H), 4.95 (dd, 10.8 Hz, JHH = 1.2 Hz, 1H), 3.44 (s,

13 1 1H), 2.14 (s, 3H), 1.09 (s, 6H); C{ H} NMR (C6D6): δ 146.2, 131.2, 126.4, 125.3,

+ 116.7, 112.8, 54.5, 28.2, 18.9; HRMScalc: 208.1161 for C12H18NS [M + H] ; HRMSmeas:

208.1160.

160

N-(1,1-dimethyl-2-propenyl)-4-dimethylamino-aniline (5-10a)

1 H NMR (C6D6): δ 6.76 (d, 8.9 Hz, 2H), 6.63 (d, 8.9 Hz, 2H), 6.00 (dd, 17.9 Hz, 10.8 Hz,

2 2 1H), 5.11 (dd, 17.9 Hz, JHH = 1.2 Hz, 1H), 4.98 (dd, 10.8 Hz, JHH = 1.2 Hz, 1H), 2.99

13 1 (br s, 1H), 2.58 (s, 6H), 1.18 (s, 6H); C{ H} NMR (C6D6): δ 147.6, 145.5, 138.4, 120.5,

+ 114.9, 112.0, 55.3, 41.7, 28.3; HRMScalc: 205.1705 for C13H21N2 [M + H] ; HRMSmeas:

205.1703.

N-(1,1-dimethyl-2-propenyl)-3-fluoro-aniline (5-13a)

1 3 H NMR (C6D6): δ 6.87-6.84 (m, 1H), 6.40-6.38 (m, 1H), 5.95 (dd, 6.6 Hz, JHF = 2.4,

5 1H), 5.80 (dd, 6.6 Hz, JHF = 1.8 Hz, 1H), 5.42 (dd, 17.9 Hz, 10.8 Hz, 1H), 4.75 (dd, 17.9

2 2 Hz, JHH = 1.2 Hz, 1H), 4.65 (dd, 10.8 Hz, JHH = 1.2 Hz, 1H), 2.78 (s, 1H), 0.70 (s, 6H);

13 1 1 3 C{ H} NMR (C6D6): δ 148.3 (d, JCF = 271.4 Hz), 144.3, 129.1 (d, JCF = 10.2 Hz),

4 3 2 111.6, 110.0 (d, JCF = 2.1 Hz), 107.5 (d, JCF = 2.4 Hz), 102.5 (d, JCF = 21.6 Hz), 101.9

2 + (d, JCF = 25.8 Hz), 53.0, 26.5; HRMScalc: 180.1189 for C11H15FN [M + H] ; HRMSmeas:

180.1190.

N-(1,1-dimethyl-2-propenyl)-4-fluoro-aniline (5-14a)

1 3 4 H NMR (C6D6): δ 6.78 (t, 8.4 Hz, JHF = 8.4 Hz, 2H), 6.41 (dd, 8.4 Hz, JHF = 4.8 Hz,

2 2H), 5.80 (dd, 17.4 Hz, 10.2 Hz, 1H), 5.02 (dd, 17.4 Hz, JHH = 1.2 Hz, 1H), 4.93 (dd,

2 13 1 10.2 Hz, JHH = 1.2 Hz, 1H), 3.03 (s, 1H), 1.05 (s, 6H); C{ H} NMR (C6D6): δ 156.7 (d,

1 4 3 2 JCF = 235.7 Hz), 146.4, 143.2 (d, JCF = 2.1 Hz), 117.6 (d, JCF = 7.1 Hz), 115.4 (d, JCF =

+ 22.0 Hz), 112.7, 54.7, 28.1; HRMScalc: 180.1189 for C11H15FN [M + H] ; HRMSmeas:

180.1189.

161

N-(1,1-dimethyl-2-propenyl)-4-bromo-3-methylaniline (5-15a)

1 4 H NMR (C6D6): δ 7.22 (d, 8.9 Hz, 1H), 6.24 (d, JHH = 2.9 Hz, 1H), 6.17 (dd, 8.9 Hz,

4 2 JHH = 2.9 Hz, 1H), 5.72 (dd, 17.4 Hz, 10.2 Hz, 1H), 4.96 (dd, 17.4 Hz, JHH = 1.2 Hz,

2 1H), 4.87 (dd, 10.2 Hz, JHH = 1.2 Hz, 1H), 3.10 (br s, 1H), 2.18 (s, 3H), 1.00 (s, 6H);

13 1 C{ H} NMR (C6D6): δ 146.3, 145.9, 137.9, 132.6, 118.5, 115.1, 112.9, 112.3, 54.5,

+ 28.1, 23.2; HRMScalc: 254.0544 for C12H17BrN [M + H] ; HRMSmeas: 254.0542.

5.4.4 General Catalytic Procedure for Aryl Amino Claisen Rearrangement

After undergoing hydroamination for 20 hours (see above), the reaction was uncapped and triflic acid (7.5 mg, 10 mol%) was added. The reaction was then heated to 70 °C for

20 hours. The product was purified via column chromatography (silica gel; 5:1 pentane/ethyl acetate) and solvent was removed via reduced pressure.

5.4.4.1 Characterization of Aryl Amino Claisen Rearrangement Products

2-(3-methyl-2-butenyl)-aniline (5-1c)22 was identified by comparison to published NMR data. Compounds (5-2c/d) and (5-3c/d) were isolated as inseparable mixtures; the high resolution mass spectrometry data represent the mixtures of isomers.

2-(3-methyl-2-butenyl)-3-methyl-aniline (5-2c) and 2-(3-methyl-2-butenyl)-5-methylaniline (5-2d)

1 (5-2c) H NMR (C6D6): δ 6.96 (t, 7.2 Hz, 1H), 6.57 (d, 7.2 Hz, 1H), 6.31 (d, 7.2 Hz, 1H),

4.97 (tm, 6.6 Hz, 1H), 3.04 (d, 6.6 Hz, 2H), 2.13 (s, 3H), 1.55 (s, 3H), 1.54 (s, 3H);

162

13 1 C{ H} NMR (C6D6): δ 145.2, 136.6, 132.7, 129.7, 124.7, 122.7, 119.6, 114.2, 30.8,

1 25.7, 20.3, 17.8. (5-2d) H NMR (C6D6): δ 6.93 (d, 7.2 Hz, 1H), 6.63 (d, 7.2 Hz, 1H),

6.17 (s, 1H), 5.19 (tm, 6.6 Hz, 1H), 3.11 (d, 6.6 Hz, 2H), 2.13 (s, 3H), 1.51 (s, 3H), 1.50

13 1 (s, 3H); C{ H} NMR (C6D6): δ 145.5, 136.7, 132.3, 126.9, 123.1, 123.0, 121.1, 116.5,

+ 27.0, 25.7, 20.3, 17.7; HRMScalc: 176.1439 for C12H18N [M + H] ; HRMSmeas: 176.1439.

2-(3-methyl-2-butenyl)-3-ethyl-aniline (5-3c) and 2-(3-methyl-2-butenyl)-5-ethyl- aniline (5-3d)

1 (5-3c) H NMR (C6D6): δ 6.98 (t, 6.6 Hz, 1H), 6.64 (d, 6.6 Hz, 1H), 6.31 (d, 6.6 Hz, 1H),

5.00 (tm, 6.0 Hz, 1H), 3.16 (d, 6.0 Hz, 2H), 2.51 (q, 7.8 Hz, 2H), 1.55 (s, 3H), 1.51 (s,

13 1 3H), 1.08 (t, 7.8 Hz, 3H); C{ H} NMR (C6D6): δ 145.8, 143.2, 132.4, 127.1, 124.0,

1 123.4, 119.5, 114.1, 27.2, 26.5, 25.6, 17.8, 16.0. (5-3d) H NMR (C6D6): δ 6.98 (d, 6.6

Hz, 1H), 6.69 (d, 6.6 Hz, 1H), 6.22 (s, 1H), 5.19 (tm, 6.0 Hz, 1H), 3.05 (d, 6.0 Hz, 2H),

2.44 (q, 7.8 Hz, 2H), 1.55 (s, 3H), 1.50 (s, 3H), 1.12 (t, 7.8 Hz, 3H); 13C{1H} NMR

(C6D6): δ 145.2, 142.8, 132.6, 129.8, 123.2, 123.1, 118.3, 114.3, 30.8, 29.1, 25.7, 17.7,

+ 16.2; HRMScalc: 190.1596 for C13H20N [M + H] ; HRMSmeas: 190.1596

2-(3-methyl-2-butenyl)-4-methyl-aniline (5-4c)

1 H NMR (C6D6): δ 6.92 (s, 1H), 6.88 (d, 7.8 Hz, 1H), 6.40 (d, 7.8 Hz, 1H), 5.26 (tm, 6.6

Hz, 1H), 3.12 (d, 6.6 Hz, 2H), 3.00 (br s, 2H), 2.20 (s, 3H), 1.61 (s, 3H), 1.56 (s, 3H);

13 1 C{ H} NMR (C6D6): δ 142.9, 132.7, 130.5 (2C), 127.4, 126.0, 123.0, 115.9, 31.2, 25.7,

+ 20.8, 17.7; HRMScalc: 176.1439 for C12H18N [M + H] ; HRMSmeas: 176.1436.

163

2-(3-methyl-2-butenyl)-4-tert-butylaniline (5-6c)

1 4 4 H NMR (C6D6): δ 7.19 (d, JHH = 2.0 Hz, 1H), 7.12 (dd, 8.0 Hz, JHH = 2.0 Hz, 1H), 6.44

(d, 8.0 Hz, 1H), 5.26-5.23 (m, 1H), 3.16 (d, 6.0 Hz, 2H), 3.04 (s, 2H), 1.59 (s, 3H), 1.57

13 1 (s, 3H), 1.32 (s, 9H); C{ H} NMR (C6D6): δ 143.0, 141.2, 132.7, 126.8, 125.6, 124.2,

+ 123.3, 115.7, 34.1, 31.9, 31.8, 25.7, 17.8; HRMScalc: 218.1909 for C15H24N [M + H] ;

HRMSmeas: 218.1902.

2-(3-methyl-2-butenyl)-4-(methylthio)aniline (5-9c)

1 4 4 H NMR (C6D6): 7.26 (d, JHH = 2.5 Hz, 1H), 7.17 (dd, 7.9 Hz, JHH = 2.5 Hz, 1H), 6.28

(d, 7.9 Hz, 1H), 5.15 (tm, 7.2 Hz, 1H), 3.03 (s, 2H), 2.99 (d, 7.2 Hz, 2H), 2.17 (s, 3H),

13 1 1.57 (s, 3H), 1.49 (s, 3H); C{ H} NMR (C6D6): δ 144.2, 133.4, 132.2, 131.9, 129.5,

+ 122.2, 116.3, 113.7, 30.9, 25.7, 18.9, 17.6; HRMScalc: 208.1160 for C12H18NS [M + H] ;

HRMSmeas: 208.1157.

2-(3-methyl-2-butenyl)-3-fluoroaniline (5-13c)

1 5 4 H NMR (C6D6): δ 6.85 (dd, 8.3 Hz, JFH = 2.3 Hz, 1H), 6.73 (td, 8.3 Hz, JFH = 3.0 Hz,

3 1H), 6.13 (dd, 8.3 Hz, JFH = 4.8 Hz, 1H), 5.09 (tm, 7.2 Hz, 1H), 2.90 (d, 7.2 Hz, 2H),

13 1 1 2.83 (br s, 2H), 1.56 (s, 3H), 1.45 (s, 3H); C{ H} NMR (C6D6): δ 157.0 (d, JFC = 234.9

3 4 3 Hz), 141.2 (d, JFC = 2.0 Hz), 133.9, 126.6 (d, JFC = 6.6 Hz), 121.6, 116.2 (d, JFC = 7.4

2 2 Hz), 116.0 (d, JFC = 22.4 Hz), 113.4 (d, JFC = 32.0 Hz), 30.7, 25.6, 17.2; HRMScalc:

+ 180.1189 for C11H15FN [M + H] ; HRMSmeas: 180.1188.

164

5.5 Crystallography of [(3IPtBu)Pd(allyl)]OTf (5-5)

A summary of crystal data and collection parameters for the crystal structure of

[(3IPtBu)Pd(allyl)]OTf (5-5) is provided in Table 5.3. A detailed description of data collection, as well as data solution, is provided below. The ORTEP diagram was generated with the ORTEP-3 software package.45 A suitable crystal was mounted on a glass fiber using Paratone-N hydrocarbon oil. The crystal was transferred to a Bruker

APEX-II diffractometer with a CCD detector,46 centered in the X-ray beam, and cooled to 153 K using a nitrogen-flow low-temperature apparatus that had been previously calibrated by a thermocouple placed at the same position as the crystal. An arbitrary hemisphere of data was collected using 0.3° ω scans, and the data were integrated by the program SAINT.47 The final unit cell parameters were determined by a least-squares refinement of the reflections with I > 2σ(I). Data analysis using Siemens XPREP48 and the successful solution and refinement of the structure determined the space group.

Empirical absorption corrections were applied using the program SADABS.49

5-5: X-ray quality crystals were grown from a THF solution layered with pentane.

The final cycle of full-matrix least-squares refinement was based on 4490 observed reflections and 289 variable parameters and converged yielding final residuals: R =

0.0328, Rall = 0.0421, and GOF = 1.069.

165

Table 5.3. Crystallographic data for 5-5

tBu Compound [(3IP )Pd(allyl)]OTf (5-5)

Formula C22H39F3NO3PPdS Formula weight 591.97

Space group P21/c Temperature (K) 153 a (Å) 11.227(2) b (Å) 8.450(2) c (Å) 27.587(6) α (°) 90.00 β (°) 91.82(3) γ (°) 90.00 V (Å3) 2615.9(9) Z 4 3 Densitycalc (g/cm ) 1.503 Diffractometer Bruker APEX-II

Radiation Mo-Kα (λ = 0.71073 Å) Monochromator Graphite Detector CCD detector Scan type, width ω, 0.3° Scan speed (s) 10 Reflections measured Hemisphere 2θ range (°) 3.62 - 52.74 Crystal dimensions (mm) 0.120 x 0.134 x 0.206 Reflections measured 30828 Unique reflections 5334 Observations (I > 2σ(I)) 4490

Rint 0.0430 Parameters 289

R, Rw, Rall 0.0328,0.0817, 0.0421 GoF 1.069

166

References

1. Kuchenbeiser, G.; Shaffer, A. R.; Zingales, N. C.; Beck, J. F.; Schmidt, J. A. R., Palladium(II) 3-iminophosphine (3IP) complexes: Active precatalysts for the intermolecular hydroamination of 1,2-dienes (allenes) and 1,3-dienes with aliphatic amines under mild conditions. Journal of Organometallic Chemistry 2011, 696, 179-187.

2. Shaffer, A. R.; Schmidt, J. A. R., Palladium(II) 3-iminophosphine complexes as intermolecular hydroamination catalysts for the formation of imines and enamines. Organometallics 2008, 27 (6), 1259-1266.

3. Yamashita, Y.; Gopalarathnam, A.; Hartwig, J. F., Iridium-catalyzed, asymmetric amination of allylic alcohols activated by Lewis acids. Journal of the American Chemical Society 2007, 129 (24), 7508–7509.

4. Padwa, A.; Flick, A. C.; Leverett, C. A.; Stengel, T., Rhodium(II)-catalyzed aziridination of allyl-substituted sulfonamides and carbamates. Journal of Organic Chemistry 2004, 69 (19), 6377-6386.

5. Dubovyk, I.; Watson, I. D. G.; Yudin, A. K., Chasing the proton culprit from palladium-catalyzed allylic amination. Journal of the American Chemical Society 2007, 129 (46), 14172–14173.

6. Plietker, B., Regioselective iron-catalyzed allylic amination. Angewandte Chemie- International Edition 2006, 45 (36), 6053-6056.

7. Johns, A. M.; Liu, Z. J.; Hartwig, J. F., Primary tert- and sec-allylamines via palladium-catalyzed hydroamination and allylic substitution with hydrazine and hydroxylamine derivatives. Angewandte Chemie-International Edition 2007, 46 (38), 7259-7261.

8. You, S. L.; Zhu, X. Z.; Luo, Y. M.; Hou, X. L.; Dai, L. X., Highly regio- and enantioselective Pd-catalyzed allylic alkylation and amination of monosubstituted allylic acetates with novel ferrocene P,N-ligands. Journal of the American Chemical Society 2001, 123 (30), 7471-7472.

9. Faller, J. W.; Wilt, J. C., Palladium/BINAP(S)-catalyzed asymmetric allylic amination. Organic Letters 2005, 7 (4), 633-636.

10. Faller, J. W.; Wilt, J. C., Regioselectivity in the palladium/(S)-BINAP(S)- catalyzed asymmetric allylic amination: Reaction scope, kinetics, and stereodynamics. Organometallics 2005, 24 (21), 5076-5083.

11. Trost, B. M., Atom economy-a challenge for organic synthesis: Homogeneous catalysis leads the way. Angewandte Chemie-International Edition 1995, 34 (3), 259-281.

167

12. Lavallo, V.; Frey, G. D.; Donnadieu, B.; Soleilhavoup, M.; Bertrand, G., Homogeneous catalytic hydroamination of alkynes and allenes with ammonia. Angewandte Chemie-International Edition 2008, 47 (28), 5224-5228.

13. Zeng, X. M.; Frey, G. D.; Kinjo, R.; Donnadieu, B.; Bertrand, G., Synthesis of a simplified version of stable bulky and rigid cyclic (Alkyl)(amino)carbenes, and catalytic activity of the ensuing gold(I) complex in the three-component preparation of 1,2-dihydroquinoline derivatives. Journal of the American Chemical Society 2009, 131 (24), 8690-8696.

14. Zeng, X. M.; Soleilhavoup, M.; Bertrand, G., Gold-catalyzed intermolecular Markovnikov hydroamination of allenes with secondary amines. Organic Letters 2009, 11 (15), 3166-3169.

15. Widenhoefer, R. A., Recent developments in enantioselective gold(I) catalysis. Chemistry-a European Journal 2008, 14 (18), 5382-5391.

16. Duncan, A. N.; Widenhoefer, R. A., Gold(I)-catalyzed intermolecular hydroamination of allenes with arylamines. Synlett 2010, (3), 419-422.

17. Nishina, N.; Yamamoto, Y., Gold-catalyzed hydrofunctionalization of allenes with nitrogen and oxygen nucleophiles and its mechanistic insight. Tetrahedron 2009, 65 (9), 1799-1808.

18. Nishina, N.; Yamamoto, Y., Gold-catalyzed intermolecular hydroalkoxylation of allenes; Difference in mechanism between hydroalkoxylation and hydroamination. Tetrahedron Letters 2008, 49 (33), 4908-4911.

19. Nishina, N.; Yamamoto, Y., Gold-catalyzed intermolecular hydroamination of allenes: First example of the use of an aliphatic amine in hydroamination. Synlett 2007, (11), 1767-1770.

20. Lillo, V.; Fernandez, E.; Segarra, A. M., Catalytic asymmetric hydroboration of heterofunctional allylic substrates: An efficient heterogenized version. Tetrahedron-Asymmetry 2007, 18 (8), 911-914.

21. Zhou, J. Q.; Alper, H., Synthesis of pyrrolidines and pyrrolidinones by the rhodium complex catalyzed cyclization of unsaturated amines. Journal of Organic Chemistry 1992, 57 (12), 3328-3331.

22. Cooper, M. A.; Lucas, M. A.; Taylor, J. M.; Ward, A. D.; Williamson, N. M., A convenient method for the aromatic amino-Claisen rearrangement of N-(1,1- disubstituted-allyl)anilines. Synthesis-Stuttgart 2001, (4), 621-625.

23. Yang, Q.; Alper, H.; Xiao, W. J., Efficient method for the synthesis of chiral pyrrolidine derivatives via ring-closing enyne metathesis reaction. Organic Letters 2007, 9 (5), 769-771.

168

24. Johannsen, M.; Jorgensen, K. A., Allylic amination. Chemical Reviews 1998, 98 (4), 1689-1708.

25. Cooper, M. A.; Francis, C. L.; Holman, J. W.; Kasum, B.; Taverner, T.; Tiekink, E. R. T.; Ward, A. D., The reactions of N-substituted 2-(dimethylallyl)aniline compounds with phenylselanyl halides. Australian Journal of Chemistry 2000, 53 (2), 123-129.

26. Francis, C. L.; Ward, A. D., Attempted heterocyclic syntheses through electrophilic ring closure reactions of 2-allylaniline systems containing larger side chains. Australian Journal of Chemistry 1994, 47 (11), 2109-2117.

27. Raner, K. D.; Ward, A. D., Heterocyclic syntheses through electrophilic ring- closure reactions of ortho-allylaniline systems. Australian Journal of Chemistry 1991, 44 (12), 1749-1760.

28. Nicolaou, K. C.; Roecker, A. J.; Hughes, R.; van Summeren, R.; Pfefferkorn, J. A.; Winssinger, N., Novel strategies for the solid phase synthesis of substituted indolines and indoles. Bioorganic & Medicinal Chemistry 2003, 11 (3), 465-476.

29. Yepez, A. F.; Palma, A.; Stashenko, E.; Bahsas, A.; Amaro-Luis, J. M., 2-Allyl- N-benzyl substituted alpha-naphthylamines as building blocks in heterocyclic synthesis. New and efficient syntheses of benz[e]naphtho[1,2-b]azepine and naphtho[1,2-b]azepine derivatives. Tetrahedron Letters 2006, 47 (32), 5825-5828.

30. Ayala, S. L. G.; Stashenko, E.; Palma, A.; Bahsas, A.; Amaro-Luis, J. M., Sequential amino-Claisen rearrangement/intramolecular 1,3-dipolar cycloaddition/reductive cleavage approach to the stereoselective synthesis of cis- 4-hydroxy-2-aryl-2,3,4,5-tetrahydro-1(1H)-benzazepines. Synlett 2006, (14), 2275-2277.

31. Majumdar, K. C.; Bhattacharyya, T.; Chattopadhyay, B.; Sinha, B., Recent advances in the aza-Claisen rearrangement. Synthesis-Stuttgart 2009, (13), 2117- 2142.

32. Jain, S.; Pandey, N.; Kishore, D., Lewis acid catalyzed amino-Claisen rearrangement: A facile one pot synthesis of 2-allylarylamines from N- allylarylamines. Indian Journal of Chemistry Section B-Organic Chemistry Including Medicinal Chemistry 2007, 46 (3), 529-531.

33. Anderson, W. K.; Lai, G. F., Boron-trifluoride diethyl-ether complex-catalyzed aromatic amino-Claisen rearrangements. Synthesis-Stuttgart 1995, (10), 1287- 1290.

34. Jolidon, S.; Hansen, H. J., Investigations on aromatic amino-Claisen rearrangements. Helvetica Chimica Acta 1977, 60 (3), 978-1032.

169

35. Yi, C. S.; Yun, S. Y., Ruthenium-catalyzed intermolecular coupling reactions of arylamines with ethylene and 1,3-dienes: Mechanistic insight on hydroamination vs ortho-C-H bond activation. Organic Letters 2005, 7 (11), 2181-2183.

36. Petrushkina, E. A.; Mysova, N. E.; Orlinkov, A. V., Palladium(II)-catalyzed amination of isoprene with aniline. Russian Journal of General Chemistry 2005, 75 (6), 910-914.

37. Petrushkina, E. A.; Kalinin, V. N.; Ivanova, G. B.; Kheinman, V. A., Synthesis of 2-ethyl-2-methyl-2,3-dihydro-1H-indole, a new insecticide exhibiting juvenile hormone activity. Russian Journal of General Chemistry 2006, 76 (12), 1953- 1957.

38. Barluenga, J.; Rodriguez, F.; Fananas, F. J., Recent advances in the synthesis of indole and quinoline derivatives through cascade reactions. Chemistry-an Asian Journal 2009, 4 (7), 1036-1048.

39. Zhu, K. M.; Achord, P. D.; Zhang, X. W.; Krogh-Jespersen, K.; Goldman, A. S., Highly effective pincer-ligated iridium catalysts for alkane dehydrogenation. DFT calculations of relevant thermodynamic, kinetic, and spectroscopic properties. Journal of the American Chemical Society 2004, 126 (40), 13044-13053.

40. Shaffer, A. R. Ph.D. Thesis, Synthesis, Reactivity, and Catalysis of 3- Iminophosphine Palladium Complexes. University of Toledo, Toledo, OH, 2009.

41. Meiners, J.; Friedrich, A.; Herdtweck, E.; Schneider, S., Facile double C-H activation of tetrahydrofuran by an iridium PNP pincer complex. Organometallics 2009, 28 (21), 6331-6338.

42. Ohshima, T.; Miyamoto, Y.; Ipposhi, J.; Nakahara, Y.; Utsunomiya, M.; Mashima, K., Platinum-catalyzed direct amination of allylic alcohols under mild conditions: Ligand and microwave effects, substrate scope, and mechanistic study. Journal of the American Chemical Society 2009, 131 (40), 14317-14328.

43. Jolidon, S.; Hansen, H. J., Thermal and acid-catalyzed rearrangement of N-(α,α- dimethylallyl)-anilines. Helvetica Chimica Acta 1976, 30 (1), 21-23.

44. Xu, C. D.; Lu, S. M.; Huang, X., The reaction of allyldialkyltelluronium bromides with anilines. Heteroatom Chemistry 1994, 5 (1), 7-8.

45. Barnes, C. L., ORTEP-3 for windows - a version of ORTEP-III with a graphical user interface. Journal of Applied Crystallography 1997, 30 (1), 565-568.

46. APEX-II: Area-Detector Software Package, 2.1; Bruker Analytical X-ray Systems, Inc.: Madison, WI, 2006.

47. SAINT: SAX Area-Detector Integration Program, 6.22; Bruker AXS, Inc.: Madison, WI, 1997-2001.

170

48. XPREP: Reciprocal Space Exploration Program, 6.12; Bruker AXS, Inc.: Madison, WI, 2001.

49. SADABS: Bruker/Siemens Area Detector Absorption Program, 2.03; Bruker AXS, Inc.: Madison, WI, 2001.

171