Nitrosoalkenes: Underappreciated Reactive Intermediates for Formation of Carbon–Carbon Bonds

This paper is dedicated to my longtime friend and colleague, Professor Philip DeShong, on the occasion of his 70^th birthday.

Abstract

This Account describes studies carried out by my group during the past decade on both intra- and intermolecular conjugate additions of carbon nucleophiles to nitrosoalkenes. Using the Denmark protocol for the generation of nitrosoalkenes from α-chloro-O-silyloximes, a number of bridged and fused bicyclic ring systems can be prepared via the intramolecular version of this process. Intermolecular conjugate addition reactions of nitrosoalkenes with a wide variety of ester enolates as coupling partners can also be achieved efficiently using a similar procedure. Some stereochemical aspects of these nucleophilic additions have been studied with both acyclic and cyclic nitrosoalkenes. This methodology has been applied as key steps in synthetic approaches to some complex indole and Myrioneuron alkaloids.

1 Introduction

2 Conjugate Additions of Nitrosoalkenes

2.1 Background

2.2 Intramolecular Reactions

2.3 Intermolecular Reactions

2.4 Stereochemical Aspects

3 Applications to Natural Product Synthesis

3.1 Angustilodine and Related Alkaloids

3.2 Approach to Apparicine-Type Alkaloids

3.3 Myrioneurinol

4 Summary and Outlook

Key words

conjugate additions - alkaloid synthesis - total synthesis - enolonium ion equivalent - umpolung - indole alkaloids - Myrioneuron alkaloids

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