All-carbon [3 + 2] cycloaddition in natural product synthesis.

Zhuo Wang,Junyang Liu

doi:10.3762/bjoc.16.251

Abstract

Many natural products possess interesting medicinal properties that arise from their intriguing chemical structures. The highly-substituted carbocycle is one of the most common structural features in many structurally complicated natural products. However, the construction of highly-substituted, stereo-congested, five-membered carbocycles containing all-carbon quaternary center(s) is, at present, a distinct challenge in modern synthetic chemistry, which can be accessed through the all-carbon [3 + 2] cycloaddition. More importantly, the all-carbon [3 + 2] cycloaddition can forge vicinal all-carbon quaternary centers in a single step and has been demonstrated in the synthesis of complex natural products. In this review, we present the development of all-carbon [3 + 2] cycloadditions and illustrate their application in natural product synthesis reported in the last decade covering 2011–2020 (inclusive).

Highlights

The highly-substituted, stereo-congested, five-membered carbocycle containing contiguous stereocenters is one of the most common structural features in many structurally complicated, biologically important natural products [1,2,3,4,5,6,7] (Figure 1)
We present the development of the all-carbon [3 + 2] cycloaddition and discuss its application in natural product synthesis reported from 2011–2020
Enyne 118, which was prepared in two steps from 117, was subjected to rhodium-catalyzed intramolecular [3 + 2] cycloaddition in the presence of carbon monoxide to give tricycle 119 bearing the desired vicinal quaternary carbon stereocenters in 86% yield

Summary

Introduction

The highly-substituted, stereo-congested, five-membered carbocycle containing contiguous stereocenters is one of the most common structural features in many structurally complicated, biologically important natural products [1,2,3,4,5,6,7] (Figure 1). Scheme 4: Natural product syntheses that make use of palladium-catalyzed intermolecular [3 + 2] cycloadditions of TMM. The proposed catalytic cycle of this elegant rhodium-catalyzed intramolecular [3 + 2] cycloaddition begins with the reaction between the rhodium catalyst Rh(I)LCl and alcohol 110 to give complex A through alcoholysis [50,51] (Scheme 8B).

Results

Conclusion