ORGANIC
LETTERS
2009
Vol. 11, No. 24
5578-5581
Highly Catalytic Asymmetric Addition of
Deactivated Alkyl Grignard Reagents to
Aldehydes
Chao-Shan Da,*,†,‡ Jun-Rui Wang,† Xiao-Gang Yin,† Xin-Yuan Fan,† Yi Liu,† and
Sheng-Li Yu†
Institute of Biochemistry & Molecular Biology, School of Life Sciences, State Key
Laboratory of Applied Organic Chemistry, Lanzhou UniVersity, Lanzhou 730000, China
Received September 9, 2009
ABSTRACT
Generally used and highly reactive RMgBr reagents were effectively deactivated by bis[2-(N,N-dimethylamino)ethyl] ether and then were employed
in the highly enantioselective addition of Grignard reagents to aldehydes. The reaction was catalyzed by the complex of commercially available
(S)-BINOL and Ti(Oi-Pr)4 under mild conditions. Compared with the other observed Grignard reagents, alkyl Grignard reagents showed higher
enantioselectivity and they achieved >99% ee.
Asymmetric addition of Grignard reagents to aldehydes is a
powerful C-C bond formation reaction to generate chiral
secondary alcohols with numerous biologic activities.1
Because of the high reactivity of Grignard reagents, however,
previous investigations were mainly focused on employing
more than stoichiometric chiral auxiliaries2 or chiral cosol-
vents3 with modest to high enantioselection at extremely low
temperatures. So currently two principal successful highly
catalytic enantioselective procedures are involved in achiev-
ing optically pure secondary alcohols. The procedures are
addition of organozinc to aldehydes4 and hydrogenation of
ketones.5
Only recently were two effective catalytic asymmetric
protocols disclosed with Grignard reagents. One is that
Grignard reagents were transferred into dialkyl or diaryl zinc6
in advance and then such diorgnozinc reagents were used to
add to aldehydes. This protocol essentially is the catalytic
† School of Life Sciences.
‡ State Key Laboratory of the Applied Organic Chemistry.
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10.1021/ol9020942 2009 American Chemical Society
Published on Web 11/12/2009