Carbene-catalyzed atroposelective synthesis of axially chiral styrenes

Jia-Lei Yan,Weiyi Tian,Zhichao Jin,Tingting Li,Rakesh Maiti,Bivas Mondal,Shi-Chao Ren,Jun Xu,Yonggui Robin Chi

doi:10.1038/s41467-021-27771-x

Abstract

Axially chiral styrenes bearing a chiral axis between a sterically non-congested acyclic alkene and an aryl ring are difficult to prepare due to low rotational barrier of the axis. Disclosed here is an N-heterocyclic carbene (NHC) catalytic asymmetric solution to this problem. Our reaction involves ynals, sulfinic acids, and phenols as the substrates with an NHC as the catalyst. Key steps involve selective 1,4-addition of sulfinic anion to acetylenic acylazolium intermediate and sequential E-selective protonation to set up the chiral axis. Our reaction affords axially chiral styrenes bearing a chiral axis as the product with up to > 99:1 e.r., > 20:1 E/Z selectivity, and excellent yields. The sulfone and carboxylic ester moieties in our styrene products are common moieties in bioactive molecules and asymmetric catalysis.

Highlights

Chiral styrenes bearing a chiral axis between a sterically non-congested acyclic alkene and an aryl ring are difficult to prepare due to low rotational barrier of the axis
Chiral molecules are widely used as catalysts and ligands in asymmetric catalysis[1,2,3]
Axially chiral styrenes, which bear a chiral axis between a simple alkene and an aryl ring, are much less developed this kind of chirality was realized and intensively studied by Adams and co-workers in the 1940s14,23,24

Summary

Introduction

Chiral styrenes bearing a chiral axis between a sterically non-congested acyclic alkene and an aryl ring are difficult to prepare due to low rotational barrier of the axis. It is only in recent years that several approaches emerged for asymmetric access to axially chiral aryl-acyclic alkene scaffolds These remarkable studies include chiral amines catalyzed addition of carbon anions to ynals[33], Brønsted acids catalyzed addition of nucleophiles (e.g., sulfinic anions, 5H-oxazol-4-ones, and electrorich aromatic units) to in situ generated allenes[34,35,36,37,38,39,40,41,42,43], transition metal-catalyzed cross coupling[44,45,46], and desymmetrization/kinetic resolution strategies (Fig. 1b)[47,48,49,50,51]. This methodology opened a new gate for accessing axially chiral styrenes bearing acyclic alkenes

Methods

Results

Conclusion