ORGANIC
LETTERS
2001
Vol. 3, No. 3
457-459
Enantioselective Rhodium(I)-Catalyzed
Hydrogenation of Trifluoromethyl
Ketones
Yoshichika Kuroki,* Yuko Sakamaki, and Katsuhiko Iseki
Chemical DiVision, Daikin Industries, Ltd., Miyukigaoka, Tsukuba,
Ibaraki 305-0841, Japan
Received December 5, 2000
ABSTRACT
The asymmetric hydrogenation of trifluoromethyl ketones to yield chiral r-trifluoromethyl alcohols with enantiomeric excesses up to 98% was
achieved in the presence of chiral rhodium-(amidephosphine-phosphinite) complexes.
The catalytic asymmetric synthesis of chiral organofluorine
compounds has played an important role in the development
of medicines and materials based on the influence of
fluorine’s unique properties.1 Homochiral R-trifluoromethyl
alcohols are versatile intermediates for the synthesis of
antiferroelectric liquid crystalline molecules.2 Although a few
asymmetric catalyses for preparing the alcohols have been
reported,3 their synthesis has drawbacks such as insufficient
levels of enantioselectivity, low catalytic efficiencies, and
limited scope of the substrates. Recently, we reported that
the highly enantioselective synthesis of 1,1,1-trifluoroalkan-
2-ols can be successfully achieved by hydrogenating 1,1,1-
trifluoroalkan-2-one enol acetates in the presence of chiral
ruthenium catalysts.4 This paper discloses the asymmetric
hydrogenation of trifluoromethyl ketones catalyzed by chiral
rhodium-(amidephosphine-phosphinite) complexes to provide
chiral R-trifluoromethyl alcohols with up to 98% ee.
Recently, we found that chiral rhodium-(amidephosphine-
phosphinite) complexes, prepared from [Rh(COD)OCOCF3]2
and oxoProNOP ligands,5 catalyze the hydrogenation of 2,2-
difluoro-3-oxocarboxylates and 4,4,4-trifluoroacetoacetate to
give the corresponding â-hydroxy esters with good-to-
excellent enantioselectivity.6 The stereochemical outcome
from the latter â-keto ester indicated that the trifluoromethyl
group has a significant influence on the enantiotopic face
selection, prompting us to examine the hydrogenation of the
trifluoromethyl ketones using the chiral rhodium-(amide-
phosphine-phosphinite) complexes.
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(5) (a) Roucoux, A.; Agbossou, F.; Mortreux, A.; Petit, F. Tetrahedron:
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10.1021/ol006962s CCC: $20.00 © 2001 American Chemical Society
Published on Web 01/17/2001