Rhodium Alkenylcarbenes: Novel Reactivity and Precursors Open Access

Parr, Brendan Thomas (2013)

Permanent URL: https://etd.library.emory.edu/concern/etds/dj52w5170?locale=en


The stability imparted to a rhodium-bound carbene intermediate by an electron donating substituent is obviated by the broad range of efficient and enantioselective transformations these intermediates undergo. Introduction of an olefinic p-donor group has enabled the development of new reactions in which this non-innocent moiety participates directly in the rhodium-catalyzed reaction.

Alkenyl substituted diazoacetates are particularly efficient substrates for tandem ylide formation/[2,3]-sigmatropic rearrangement between allyl alcohols and rhodium carbenes. The reaction has been studied with appropriately functionalized secondary alcohols for the synthesis of products containing vicinal stereogenic centers in exceptional stereoselectivity. In addition, modification of reaction conditions has enabled the implementation of primary alcohols, previously deemed incompatible, as competent partners.

The tandem ylide formation/[2,3]-sigmatropic rearrangement of allyl alcohols and alkenyldiazoacetates generates functionalized products capable of participating in a cascade of reactions. Due to the efficiency and limited byproducts associated with the rhodium carbene transformation, the domino sequence can be conducted as a one-pot process for the direct synthesis of cyclopentanes or cyclohexanes, depending upon the substitution of the starting alcohol. The individual reactions and intermediates have been studied in detail to understand various chirality transfer processes involved, in an effort to diagnose the limitations.

The 4-substituted-1,2,3-triazole nucleus has been identified as a viable precursor for a range of classical and novel carbene transformations. A unified strategy for the synthesis of triazole-based alkenylcarbene precursors for rhodium-catalyzed transformation has been developed. These substrates have been applied to classical, enantioselective transformations of alkenyldiazoacetates, including a detailed study of the tandem cyclopropanation/Cope rearrangement. These rhodium carbene precursors exhibit improved stability and ease of handling compared with their alkenyldiazoacetate counterparts.

Triazole-based carbene precursors have been found to exhibit an array of orthogonal reactivity compared with their diazo equivalents, due to an apparent propensity for the formation of zwitterionic intermediates upon addition of electron rich p-nucleophiles. Many of these reactions involve cyclization of the zwitterion through the imine moiety, resulting in the synthesis of nitrogenous heterocycles. In addition, formal C-H functionalization of aromatic heterocycles and arenes via electrophilic aromatic substitution reactions to generate diaryl enamines has been developed.

Table of Contents

Table of Contents

List of Abbreviations i

List of Schemes ix

List of Tables xiv

List of Figures xvii

Chapter 1 Overview of Donor/Acceptor Rhodium(II) Carbene Intermediates 1

1.1 Introduction 1

1.2 References 9

Chapter 2 Tandem Ylide Formation/[2,3]-Sigmatropic Rearrangement of Rhodium(II) Carbenes and Allyl Alcohols 15

2.1 Introduction 15

2.2 Results & Discussion 28

2.2.1 Tandem Ylide Formation/[2,3]-Sigmatropic Rearrangement of Chiral Secondary Allyl Alcohols 28

2.2.2 Tandem Ylide Formation/[2,3]-Sigmatropic Rearrangement of Primary Allyl Alcohols 42

2.3 Conclusions 56

2.4 Experimental Section 58

2.4.1 General Considerations 58

2.4.2 General Procedures 60

2.4.3 Procedures and Characterization Data 63

2.5 References 102

Chapter 3 Asymmetric Cyclopentane/Cyclohexane Synthesis by a Rhodium(II) Carbene-Initiated Cascade 111

3.1 Introduction 111

3.2 Results & Discussion 123

3.2.1 Cyclopentane Synthesis 123

3.2.2 2nd Generation Cyclopentane Synthesis 140

3.2.3 Cyclohexane Synthesis 158

3.3 Conclusions 169

3.4 Experimental Section 170

3.4.1 General Considerations 170

3.4.2 General Procedures 172

3.4.3 Procedures and Characterization Data 174

3.5 References 223

Chapter 4 Triazoles as Alkenyl-Substituted Rhodium(II) Carbene Precursors: Synthesis and Application 237

4.1 Introduction 237

4.2 Results & Discussion 255

4.3 Conclusions 274

4.4 Experimental Section 275

4.4.1 General Considerations 275

4.4.2 General Procedures 277

4.4.3 Procedures and Characterization Data 279

4.5 References 311

Chapter 5 Heterocycle Synthesis from Reaction of Triazole Rhodium(II) Carbene Precursors and Electron-Rich p-Bonds 317

5.1 Introduction 317

5.2 Results & Discussion 331

5.2.1 Pyrrole Synthesis 331

5.2.2 Formal [3 + 2]- versus [4 + 3]-Cycloadditions 342

5.2.3 Enamine Synthesis 353

5.3 Conclusions 359

5.4 Experimental Section 360

5.4.1 General Considerations 360

5.4.2 General Procedures 362

5.4.3 Procedures and Characterization Data 363

5.5 References 376

Appendix 402

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