Access to P-chiral phosphine oxides by enantioselective allylic alkylation of bisphenols.

Guo-Hui Yang,Jin-Pei Cheng,Xin Li,Yao Li

doi:10.1039/c8sc05439h

Abstract

A novel biscinchona alkaloid-catalyzed highly enantioselective desymmetrization reaction of bisphenol compounds with achiral Morita-Baylis-Hillman carbonate agents was developed. Through the asymmetric allylic alkylation strategy, a broad range of optically active P-stereogenic phosphine oxides were generated with excellent to good yields (up to 99%) and high enantioselectivities (up to 98.5 : 1.5 e.r.). The reaction was further investigated by the linear free energy relationship (LFER) analysis. A possible transition state was proposed and furthered verified by theoretical calculations.

Highlights

P-stereogenic compounds, in which the chirality is on the phosphorus atom, have been widely used as biologically active compounds,[1] chiral ligands[2] and useful building blocks.[3]
A novel biscinchona alkaloid-catalyzed highly enantioselective desymmetrization reaction of bisphenol compounds with achiral Morita–Baylis–Hillman carbonate agents was developed
Through the asymmetric allylic alkylation strategy, a broad range of optically active P-stereogenic phosphine oxides were generated with excellent to good yields and high enantioselectivities

Summary

Introduction

P-stereogenic compounds, in which the chirality is on the phosphorus atom, have been widely used as biologically active compounds,[1] chiral ligands[2] and useful building blocks.[3]. In continuation of our ongoing interest in the AAA strategy, we speculated that the privileged phosphorus compounds with P-stereogenic centers could be generated via the AAA reaction between bis(2-hydroxyphenyl)phosphinates and achiral MBH carbonates (Scheme 1b). This result indicated that the enantioselectivity of the studied desymmetrization reaction may be closely related to the steric hindrance of the substituent linked to the pre-stereogenic Pcenter.

Results

Conclusion