Enantioselective [3+3] atroposelective annulation catalyzed by N-heterocyclic carbenes

Changgui Zhao,Kristin Munkerup,Jian Wang,Fangyi Li,Donghui Guo,Kuo-Wei Huang

doi:10.1038/s41467-018-02952-3

Abstract

Axially chiral molecules are among the most valuable substrates in organic synthesis. They are typically used as chiral ligands or catalysts in asymmetric reactions. Recent progress for the construction of these chiral molecules is mainly focused on the transition-metal-catalyzed transformations. Here, we report the enantioselective NHC-catalyzed (NHC: N-heterocyclic carbenes) atroposelective annulation of cyclic 1,3-diones with ynals. In the presence of NHC precatalyst, base, Lewis acid and oxidant, a catalytic C–C bond formation occurs, providing axially chiral α-pyrone−aryls in moderate to good yields and with high enantioselectivities. Control experiments indicated that alkynyl acyl azoliums, acting as active intermediates, are employed to atroposelectively assemble chiral biaryls and such a methodology may be creatively applied to other useful NHC-catalyzed asymmetric transformations.

Highlights

Chiral molecules are among the most valuable substrates in organic synthesis
An elegant route to synthesize axially chiral biaryls was demonstrated via an aromatic ring
3gt 61%, 92:8 er Chiral N-heterocyclic carbenes (NHCs) as versatile catalysts have been well studied in last few decades[36,37,38,39,40,41,42,43], but most of the reports are only focused on the assembly of central chirality

Summary

Introduction

Chiral molecules are among the most valuable substrates in organic synthesis They are typically used as chiral ligands or catalysts in asymmetric reactions. Recent progress for the construction of these chiral molecules is mainly focused on the transition-metal-catalyzed transformations. Control experiments indicated that alkynyl acyl azoliums, acting as active intermediates, are employed to atroposelectively assemble chiral biaryls and such a methodology may be creatively applied to other useful NHC-catalyzed asymmetric transformations. Chiral N-heterocyclic carbenes (NHCs) as versatile catalysts have been well studied in last few decades[36,37,38,39,40,41,42,43], but most of the reports are only focused on the assembly of central chirality

Methods

Results

Conclusion