Chiral dirhodium catalysts design, synthesis and application in asymmetric carbenoid transformations and silver-catalysis of vinylogous fluorination Open Access

Qin, Changming (2014)

Permanent URL: https://etd.library.emory.edu/concern/etds/hx11xf726?locale=en
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Abstract

The first chapter gives an overview about carbene precursors, dirhodium catalysts and general metallocarbene transformations.

The second chapter is devoted to exploring the D4-symmetric dirhodium phosphonate catalysis of cyclopropanation and C-H functionalization via decomposition of donor/acceptor diazoacetates.

The third chapter describes the development of Rh2(R-BTPCP)4, which was found to be an effective chiral catalyst for enantioselective reactions of aryl- and styryldiazoacetates. The advantages of Rh2(R-BTPCP)4 include its ease of synthesis and its tolerance to the size of the ester group in the styryldiazoacetates and the use of dichloromethane as solvent. Computational studies suggest that the catalyst adopts a D2-symmetric arrangement, but when the carbene binds to the catalyst, two of the ligands rotate outwards to make room for the carbenoid and the approach of the substrate to the carbenoid.

The fourth chapter focuses on enantioselective synthesis of 2-arylbicyclo[1.1.0]butane-carboxylates. The dirhodium-catalyzed reaction of 2-diazo-5-arylpent-4-enoates can be controlled by appropriate choice of catalyst and catalyst loading to form either 2-arylbicyclo[1.1.0]butane carboxylates or cyclohexene derivatives.

The fifth chapter concentrates on vinylogous transformations of metallovinylcarbenes. An enantioselective formal [3+2]-cycloaddition between nitrones and vinyldiazoacetates was first described. Rhodium-catalyzed reaction of vinyldiazoacetates with nitrones results in a formal [3+2]-annulation to generate 2,5-dihydroisoxazoles with high levels of asymmetric induction. The cascade reaction begins with a vinylogous addition event, followed by ring-closure/hydride migration/alkene isomerization cascade. Dirhodium triarylcyclopropane carboxylates are the optimum catalysts.

The sixth chapter describes a silver-catalyzed vinylogous fluorination of vinyldiazoacetates in the presence of triethyl amine-hydrofluoride. Application of this method to the fluorination of farnesol and steroid derivatives was achieved.

The seventh chapter further emphasizes the importance of sterically demanding dirhodium catalyst in site selective C-H functionalization. The more sterically demanding dirhodium tetrakis(triarylcyclopropane-carboxylate) catalysts, (Rh2(R-BPCP)4), favor C-H functionalization of primary C-H bonds. Highly site selective and enantioselective C-H functionalization of a variety of simple substrates containing primary benzylic, allylic and methoxy C-H bonds was achieved with this catalyst. The utility of this approach has been demonstrated in the late-stage primary C-H functionalization of cedrene and steroid.

Table of Contents

Chapter I Introduction to Rhodium Carbenes....................................................................1

1.1 Rhodium Carbenes…………………………………………………...…………….1

1.2 Dirhodium Catalysts…………………………………………………………...…...3

1.3Metallocarbene Transformations…………………………………………...………8

Chapter II Exploration of D4-Symmetric Dirhodium Tetraphosphonates as Catalysts for Donor/Acceptor Carbenoid Reaction………………..…………………………………..15

2.1 Introduction………………………………………………………………………..15

2.2 Results and Discussion…………………………………………………………….18

2.2.1 Synthesis of Rh2(R-BNP)4…………………………………………………….18

2.2.2 Rh2(R-BNP)4-Catalyzed Cyclopropanation………………………..…………19

2.2.3 Rh2(R-BNP)4-Catalyzed C-H Functionalization…………………………...…23

2.2.4 Rh2(R-CBNP)4: Design, Synthesis and Evaluation…………………………......24

2.3 Conclusion…………………………………………………………………………26

Chapter III Development of Sterically Hindered D2-Symmetric Dirhodium Catalyst Derived from Cyclopropane Carboxylate Ligands: Design, Synthesis and Initial Evaluation………………………………...……………………………………………...28

3.1 Introduction………………………………………………………………………..28

3.2 Results and Discussion…………………………………………………………….31

3.2.1 Dirhodium Cyclopropane Carboxylate Catalysts: Synthesis and Evaluation...31

3.2.2 Scope of Rh2(R-BTPCP)4-Catalyzed Carbenoid Reaction...............................39

3.2.3 Computational Modeling and Stereoselectivity Rationale…………………...47

3.3 Conclusion………………………………………………………………………...53

Chapter IV Influence of Sterically Bulky Catalysts on Intramolecular Cyclopropanation: Enantioselective Synthesis of 2-Arylbicyclo[1.1.0]butane Carboxylates………………..55

4.1 Introduction………………………………………………………………………..55

4.2 Results and Discussion……………………………………………………………56

4.2.1 Discovery and Optimization………………………………………………….56

4.2.2 Scope of Bicyclo[1.1.0]butane and Cyclohexene…………………………….60

4.2.3 Mechanistic Insights of Cyclohexene Formation…………………………….62

4.3 Conclusion………………………………………………………………………...64

Chapter V Influence of Sterically Crowded Dirhodium Catalysts on the Vinylogous Transformations of Metallovinylcarbenes………………………...……………………..66

5.1 Introduction………………………………………………………………………..66

5.1.1 Seminal work on vinylogous reactivity………………………………………66

5.1.2 Recent results on vinylcabenoid reactions………………………………........71

5.2 Formal [3+2]-Annulation of Nitrones with Vinylcarbenes………….………….. 75

5.2.1 Discovery and Optimization……………………………………………...…..75

5.2.2 Substrate Scope in Formal [3+2]-Annulation………………………………...76

5.2.3 Proposed Mechanism of Formal [3+2]-Annulation………………………….79

5.2.4 Discovery of an Intriguing Cascade Sequence……………………….………79

5.3 Conclusion………………………………………………………………………..82

Chapter VI Vinylogous Fluorination of Vinyldiazoacetates……………….…………..83

6.1 Introduction……………………………….….…………………………………..83

6.2 Optimization Studies……………………………………………………………..84

6.3 Scope of Vinylogous Fluorination of Vinyldiazoacetates………………………..85

6.4 Conclusion………………………………………………………………………..88

Chapter VII Selective C-H Functionalization of Activated Primary C-H Bonds….......................................................................................................................…90

7.1 Introduction………………………………………………………………………90

7.2 Results and Discussion…………………………………………………………..94

7.2.1 Discovery and Optimization………………………………………………...94

7.2.2 Substrate Scope in Selective C-H bond functionalization…………...……...95

7.3 Conclusion……………………………………………………………………….103

References……………………………………………………………………………...105

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