C O M M U N I C A T I O N S
potential for future methodology development. We selected the
dimerization of enals via NHC-catalyzed homoenolates as a model
reaction to probe the feasibility of this new strategy. While the
NHC-catalyzed synthesis of γ-butyrolactones has been the object
of many publications,14 a general enantioselective version of this
reaction has not yet emerged.15
AstraZeneca, and GlaxoSmithKline. We thank Wacker Chemical
and FMCLithium for reagent support and John M. Roberts (NU)
for assistance with X-ray crystallography. FQRNT (Fonds Que´be´-
cois de la Recherche sur la Nature et les Technologies) is also
gratefully acknowledged for a postdoctoral fellowship (B.C.-D).
Supporting Information Available: Experimental procedures and
spectral data for new compounds. This material is available free of
With the successful integration of Ti(IV) and NHC catalysis in
the synthesis of cyclopentenes, we commenced the investigation
of chiral titanium alkoxides as Lewis acids with NHC catalysis as
a way to access optically active γ-butyrolactones. Starting with 20
mol % (S)-Ti-BINOL and 15 mol % Imes-derived carbene led to
a low conversion of the starting material (Table 3, entry 1).
However, with (R,R)-Ti-TADDOL16 as the Lewis acid and 15 mol
% Imes, only the cis diastereoisomer was detected with 75% yield
and 38% ee (entry 2). Importantly, the observed enantiomeric excess
originates from the influence of the chiral Lewis acid and implicates
Ti(IV) catalysis is involved in the key bond forming event. By
reducing the temperature, the cis γ-butyrolactone could be obtained
in 60% yield and 60% ee, one of the highest levels of diastereo-
and enantioselectivity achieved to date for this transformation
(entry 3).
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In summary, a highly enantioselective and diastereoselective
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cooperative catalysis process integrating titanium(IV) and triazo-
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a broader substrate scope and higher stereoselectivity than previ-
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Acknowledgment. Financial support for this work has been
provided by the NIGMS (GM73072), the Sloan Foundation, Amgen,
JA910666N
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