Umpolung reactivity of difluoroenol silyl ethers with amines and amino alcohols. application to the synthesis of enantiopure alpha-difluoromethyl amines and amino acids.
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.
Huguenot
Florent
F
Institut de Chimie Moléculaire de Reims, CNRS - Université de Reims Champagne-Ardenne (UMR 6229), Faculté des Sciences, BP 1039, 51687 Reims Cedex 2, France.
Billac
Anne
A
Brigaud
Thierry
T
Portella
Charles
C
D000588:Amines / Q000138:chemical synthesis* / Q000737:chemistry*; D000596:Amino Acids / Q000138:chemical synthesis* / Q000737:chemistry; D000605:Amino Alcohols / Q000737:chemistry*; D004987:Ethers / Q000737:chemistry*; D015394:Molecular Structure; D012821:Silanes / Q000737:chemistry*; D013237:Stereoisomerism
D000588:Amines; D000596:Amino Acids; D000605:Amino Alcohols; D004987:Ethers; D012821:Silanes