A novel family of (1-aminoalkyl)(trifluoromethyl)- and -(difluoromethyl)phosphinic acids - analogues of α-amino acids.

Natalia V Pavlenko,Igor I Gerus,Uwe Doeller,Yurii L Yagupolskii,Lothar Willms,Tatiana I Oos

doi:10.3762/bjoc.10.66

Abstract

A series of novel (1-aminoalkyl)(trifluoromethyl)- and -(difluoromethyl)phosphinic acids – analogues of proteinogenic and nonproteinogenic α-amino acids were prepared. The synthetic methodology was based on nucleophilic addition of (trifluoromethyl)phosphinic acid or (difluoromethyl)phosphinic acid or its ethyl ester to substrates with C=N or activated C=C double bonds. Analogues of glycine, phenylglycine, alanine, valine, proline, aminomalonic and aspartic acids were thus prepared. Three-component one-pot reactions of (trifluoromethyl)phosphinic acid and dibenzylamine with aldehydes were also tested to prepare the title compounds.

Highlights

For a long time aminophosphonic and aminophosphinic acids as isosters of aminocarboxylic acids have attracted a particular interest for the preparation of analogues of numerous natural products
The synthetic methodology was based on nucleophilic addition ofphosphinic acid orphosphinic acid or its ethyl ester to substrates with C=N or activated C=C double bonds
In this paper we exploit both routes to prepare (1-aminoalkyl)(trifluoromethyl)and -(difluoromethyl)phosphinic acids using P–H compounds bearing CF3 and CHF2 groups attached to phosphorus

Summary

Introduction

For a long time aminophosphonic and aminophosphinic acids as isosters of aminocarboxylic acids have attracted a particular interest for the preparation of analogues of numerous natural products. In this paper we exploit both routes to prepare (1-aminoalkyl)(trifluoromethyl)and -(difluoromethyl)phosphinic acids using P–H compounds bearing CF3 and CHF2 groups attached to phosphorus.

Results

Conclusion