Umpolung reactivity of difluoroenol silyl ethers with amines and amino alcohols. application to the synthesis of enantiopure alpha-difluoromethyl amines and amino acids

Florent Huguenot; Anne Billac; Thierry Brigaud; Charles Portella

doi:10.1021/jo702328v

Umpolung reactivity of difluoroenol silyl ethers with amines and amino alcohols. application to the synthesis of enantiopure alpha-difluoromethyl amines and amino acids

J Org Chem. 2008 Apr 4;73(7):2564-9. doi: 10.1021/jo702328v. Epub 2008 Mar 11.

Authors

Florent Huguenot¹, Anne Billac, Thierry Brigaud, Charles Portella

Affiliation

¹ Institut de Chimie Moléculaire de Reims, CNRS - Université de Reims Champagne-Ardenne (UMR 6229), Faculté des Sciences, BP 1039, 51687 Reims Cedex 2, France.

PMID: 18331052
DOI: 10.1021/jo702328v

Abstract

Difluoroenol silyl ethers, produced in situ from acylsilanes and CF3TMS, react as electrophiles with amines to give difluoroimines, via the corresponding hemiaminal adduct, as evidenced by 19F NMR spectroscopy. Reaction with (R)-phenylglycinol led to 2-difluoromethyloxazolidines. After separation of the diastereomers, reduction with LAH and Strecker-type synthesis gave enantiopure alpha-difluoromethylamines and alpha-difluoromethyl-alpha-amino acids, respectively.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amines / chemical synthesis*
Amines / chemistry*
Amino Acids / chemical synthesis*
Amino Acids / chemistry
Amino Alcohols / chemistry*
Ethers / chemistry*
Molecular Structure
Silanes / chemistry*
Stereoisomerism

Substances

Amines
Amino Acids
Amino Alcohols
Ethers
Silanes