Asymmetric cyanation of imines via dipeptide-derived organophosphine dual-reagent catalysis.

Hong-Yu Wang,Chang-Wu Zheng,Zhuo Chai,Gang Zhao,Jia-Xing Zhang

doi:10.1038/ncomms12720

Hong-Yu Wang, Chang-Wu Zheng + Show 3 more

Open Access

https://doi.org/10.1038/ncomms12720

Copy DOI

Abstract

Over the past few decades, enantioselective phosphine organocatalysis has evolved rapidly into a highly efficient catalytic strategy for a range of useful reactions. However, as restricted by the traditional catalytic modes, some important reactions, such as asymmetric Strecker-type reactions, have thus far been out of reach of this strategy. Reported herein is an application of enantioselective phosphine organocatalysis for asymmetric Strecker-type reactions, enabled by a dual-reagent catalyst system in which the key organophosphorus zwitterion intermediate, generated in situ by mixing a chiral dipeptide-derived multifunctional organophosphine with methyl acrylate, is used as a highly efficient chiral Lewis base catalyst. The high efficiency of this catalytic system is demonstrated in the asymmetric cyanation of isatin-derived ketimines and azomethine aldimines as well as in the kinetic resolution of racemic 3-substituted azomethines. Mechanistic studies provide experimental evidence for the intermediacy of the putative zwitterion and its role as a catalytically active Lewis base.

Highlights

Over the past few decades, enantioselective phosphine organocatalysis has evolved rapidly into a highly efficient catalytic strategy for a range of useful reactions
A general catalytic mode for organophosphine catalysis involves the nucleophilic addition of a chiral organophosphine to an electrophilic reactant to form a zwitterion intermediate, which subsequently reacts with an appropriate partner to deliver the desired product and regenerate the phosphine catalyst (Fig. 1a)
We report a dual-reagent catalytic system consisting of a chiral dipeptide-derived multifunctional organophosphine and methyl acrylate, which serves as a highly efficient Lewis base catalyst for the asymmetric cyanation of isatin-derived ketimines a From general activation mode to dual-reagent catalysis

Summary

Introduction

Over the past few decades, enantioselective phosphine organocatalysis has evolved rapidly into a highly efficient catalytic strategy for a range of useful reactions. Reported is an application of enantioselective phosphine organocatalysis for asymmetric Strecker-type reactions, enabled by a dual-reagent catalyst system in which the key organophosphorus zwitterion intermediate, generated in situ by mixing a chiral dipeptide-derived multifunctional organophosphine with methyl acrylate, is used as a highly efficient chiral Lewis base catalyst. A general catalytic mode for organophosphine catalysis involves the nucleophilic addition of a chiral organophosphine to an electrophilic reactant (usually an electron-deficient alkene) to form a zwitterion intermediate, which subsequently reacts with an appropriate partner to deliver the desired product and regenerate the phosphine catalyst (Fig. 1a) This traditional catalytic route nicely facilitates control of the stereoselectivity via the formation of a covalent C–P bond between the organophosphine catalyst and the electrophilic reactant. Excellent yields and ees c Dual-reagent catalysis as a Lewis base in the cyanation of imines with Me3SiCN

Methods

Results

Conclusion