Access to Endo-Azabicyclo[3.1.0]hexane-6-carboxamides via Rhodium Catalyzed Cyclopropanations of Secondary Diazoacetamides Open Access

Abstract

Synthetic organic chemistry has been crucial towards the development of new drug candidates. However, as biological targets become more complex, the ability to access various elaborate scaffolds has become increasingly valuable. The pharmaceutical industry’s dependence on chemical reactions involving sp²-rich scaffolds, coupled with the higher success rates of sp³-rich candidates, highlights a significant gap in synthetic methodologies to access more potent scaffolds for drug discovery. Recently, endo-azabicyclo[3.1.0]hexanes-6-carboxamides have become a popular structural motif, however reliable and efficient methodologies to access this scaffold has been underdeveloped. The [2+1] cycloaddition of five-membered cyclic alkenes with carbenes is an attractive method for constructing the bicyclo[3.1.0] scaffold, and a vast library of chiral dirhodium catalysts available for this transformation could allow for further control of reaction selectivity. Herein, we report a rhodium-catalyzed [2+1] cycloaddition of secondary diazoacetamides to access endo-azabicyclo[3.1.0]hexane-6-carboxamides, from which the corresponding exo scaffold can be rapidly accessed through a base-mediated epimerization. The reaction proceeds well with a wide range of secondary diazoacetamides and highlights the shortcomings of tertiary diazoacetamides as effective carbene precursors in reactions with electron-deficient alkene systems.

Table of Contents

1.    Introduction                                                                                                                    1-6

2.    Results/Discussion                                                                                                        7-11

3.    Conclusion                                                                                                                  12-13

4.    References                                                                                                                   14-19

5.    Supplementary Information                                                                                     S1-S100

a.    References – Supplementary Information.                                                 S10-S11

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
Committee Chair / Thesis Advisor	Davies, Huw, Emory University
Committee Members	Dai, Mingji, Emory University Himes, Richard, Emory University

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