Green and Facile Synthesis of Spirocyclopentanes Through NaOH-Promoted Chemo- and Diastereo-Selective (3 + 2) Cycloaddition Reactions of Activated Cyclopropanes and Enamides.

Xun Zhu,Lutai Pan,Chengli Mou,Bo Zhou,Zhichao Jin,Dingwu Pan

doi:10.3389/fchem.2020.00542

Abstract

A chemo- and diastereo-selective (3 + 2) cycloaddition reacition between Donor-Acceptor (D-A) cyclopropanes and α,β-unsaturated enamides is developed for efficient access to spiro(cyclopentane-1,3'-indoline) derivatives. Simple, inexpensive and readily available NaOH is used as the sole catalyst for this process. A broad range of D-A cyclopropanes could be used as the C-3 synthons to react with oxindole-derived α,β-unsaturated enamides. The structurally sophisticated spiro(cyclopentane-1,3'-indoline) derivatives bearing up to 3 adjacent chiral centers are afforded in excellent yields as single diastereomers.

Highlights

Spirocyclopentanes are interesting structural units with broad applications in organic synthesis and medicinal chemistry
We have disclosed that the D-A cyclopropanes could be activated by simple NaOH and reacted with α,β-unsaturated imines to give a variety of bioactive cyclopenta(c)pyridine derivatives in generally excellent yields and moderate diastereoselectivities (Pan et al, 2019) (Figure 2b)
The R substituent on the phenyl group of the indoline motif of the α,β-unsaturated enamides 2 could be either electrondonating groups (Table 2, 3b and 3c) or electron-withdrawing groups (3d to 3n), with most of the spirocyclic products being afforded in good to excellent yields and diastereo-selectivities

Summary

INTRODUCTION

Spirocyclopentanes are interesting structural units with broad applications in organic synthesis and medicinal chemistry. We have disclosed that the D-A cyclopropanes could be activated by simple NaOH and reacted with α,β-unsaturated imines to give a variety of bioactive cyclopenta(c)pyridine derivatives in generally excellent yields and moderate diastereoselectivities (Pan et al, 2019) (Figure 2b). This approach has provided us with a green and facile method for the construction of structurally complex molecules from D-A cyclopropanes with simple and inexpensive reaction catalysts. The less nucleophilicity of the enol moiety of the intermediate III might be another reason for the difficult formation of the enone 1,4addition products

RESULTS AND DISCUSSION

CONCLUSION

DATA AVAILABILITY STATEMENT