Synthesis of chiral N-phosphinyl α-imino esters and their application in asymmetric synthesis of α-amino esters by reduction.

Yiwen Xiong,Guigen Li,Lingmin Wu,Yi Pan,Jianlin Han,Haibo Mei

doi:10.3762/bjoc.10.57

Abstract

A variety of chiral N-phosphinyl α-imino esters have been synthesized for the first time from ketoesters and phosphinylamide, which were then reduced by L-selectride to give the corresponding N-phosphinyl-protected α-amino esters. The reduction proceeded very well with excellent chemical yields (88–98%) as well as high diastereoselectivities (96:4 to 99:1). Some of these products could be obtained without column chromatography and recrystallization. The chiral phosphinyl auxiliary could be easily cleaved under acidic conditions.

Highlights

Introduction αImino esters play a very important role in the field of imine chemistry [1,2,3], because the ester group can serve as an activator to enhance the reactivity of the C=N double bond, making the following nucleophilic addition easier [4,5]
We have developed a method for the synthesis of chiral N-phophinyl α-imino esters for the first time, which have been used as precursors for asymmetric reductions with L-Selectride as reductant
Varieties of α-amino esters were obtained in excellent chemical yields and almost completely controlled diastereoselectivities

Summary

Introduction

Introduction αImino esters play a very important role in the field of imine chemistry [1,2,3], because the ester group can serve as an activator to enhance the reactivity of the C=N double bond, making the following nucleophilic addition easier [4,5]. The isolation of the N-phosphinyl α-imino esters was very difficult and only 26% isolated yield of this product was obtained. In our continuous efforts on the chiral N-phosphonyl imine chemistry, we tried to develop novel N-phosphinyl protected α-imino esters and to use them for the asymmetric synthesis of α-amino esters.

Results

Conclusion