The Stereochemical Effect of HFIP on Asymmetric Rhodium(II)-Catalyzed Cyclopropanation Open Access

Abstract

Cyclopropane rings are featured in a wide range of pharmaceutically relevant molecules. Accordingly, asymmetric rhodium(II)-catalyzed cyclopropanation between alkenes and diazo compounds has tremendous synthetic utility for being highly diastereoselective and highly enantioselective. In these reactions, the presence of 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) can preserve catalytic activity by deactivating poisonous nucleophiles; however, it was recently discovered that HFIP also has a unique influence on the stereoselective profiles of chiral dirhodium catalysts. Using representative alkene carbene traps and aryldiazoacetates, this study quantifies how HFIP can offer either enantioenrichment or enantioinversion depending on the ligand architecture of the chiral dirhodium catalyst used for cyclopropanation. 

Table of Contents

1. Introduction to Rhodium(II) Catalysis

1.1. Rhodium(II) Carbene Chemistry

1.2. Asymmetric Rhodium(II)-Catalyzed Cyclopropanation

2. Introduction to HFIP in Rhodium(II) Catalysis

2.1. Unique Properties of HFIP

2.2. HFIP as a Tool for Deactivating Poisonous Nucleophiles

2.3. HFIP as a Tool for Modulating Stereoselectivity

3. Investigation of HFIP’s Stereochemical Effect on Asymmetric Rhodium(II)-Catalyzed Cyclopropanation

3.1. Enantioenrichment with Rh2(NTTL)4 and Derivatives

3.2. Enantioinversion with Rh2(TCPTAD)4

3.3. Conclusions and Future Directions

4. Supporting Information

4.1. General Procedure for Cyclopropanation Reactions

4.2. Procedures for Novel Ligand Synthesis

4.3. Characterization of Products

4.4. Chromatograms: Chiral HPLC and Chiral SFC

5. References

About this Honors Thesis

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School	Emory College
Department	Chemistry
Degree	B.S.
Submission	Honors Thesis
Language	English
Research Field	Chemistry, Organic
Keyword	Cyclopropanation Rhodium Carbene Chemistry Stereoselectivity Catalysis HFIP
Committee Chair / Thesis Advisor	Huw Davies, Emory University
Committee Members	Matthew Weinschenk, Emory University Richard Himes, Emory University

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