A New Strategy for the Synthesis of alpha-Difluoromethyl-Substituted alpha-Hydroxy and alpha-Amino Acids.
A new method for the preparation of alpha-chlorodifluoromethyl-, alpha-bromodifluoromethyl-, and alpha-difluoromethyl-substituted alpha-hydroxy and alpha-amino acid esters 11, 19-21 is described. The key step of the synthesis is the regioselective alkylation of ketones 5, 7-9 and imines 16-18 with C-nucleophiles. The ketones 7-9 are readily available from 3,3,3-trifluorolactate 1 by a five-step procedure. Subsequent removal of the protecting groups from 19-21 provides the corresponding free amino acids 25, 26, 28.
Osipov
Sergey N.
SN
A. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, Vavilov str. 28, GSP-1, V-334, RUS-117813 Moscow, Russia, and Institute of Organic Chemistry, University of Leipzig, Talstrasse 35, D-04103 Leipzig, Germany.
Golubev
Alexander S.
AS
Sewald
Norbert
N
Michel
Thomas
T
Kolomiets
Alexey F.
AF
Fokin
Alexander V.
AV
Burger
Klaus
K