Journal of the American Chemical Society
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Corresponding Author
*reisman@caltech.edu
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D. J. J. Org. Chem. 2012, 77, 9989. (g) Shrestha, R.; Dorn, S. C. M.;
Weix, D. J. J. Am. Chem. Soc. 2013, 135, 751. (h) León, T.; Correa,
A.; Martin, R. J. Am. Chem. Soc. 2013, 2, 16.
ACKNOWLEDGMENT
We thank Prof. Brian Stoltz, Dr. Scott Virgil, and the Caltech Center for
Catalysis and Chemical Synthesis for access to analytical equipment, and
Sigma-Aldrich for a kind donation of chemicals. Fellowship support was
provided by the National Science Foundation (Graduate Research Fellow-
ship, A.H.C., Grant No. DGE‐1144469). S.E.R. is a fellow of the Alfred
P. Sloan Foundation and a Camille Dreyfus Teacher-Scholar. Financial
support from the California Institute of Technology, Amgen and Novartis
is gratefully acknowledged.
(9) Co-catalyzed reductive coupling reactions have also been re-
ported: (a) Amatore, M.; Gosmini, C. Angew. Chem., Int. Ed. 2008,
47, 2089. (b) Amatore, M.; Gosmini, C. Chem. Eur. J. 2010, 16,
5848. For a related Co-catalyzed reaction proposed to proceed by in
situ formation of a Grignard reagent, see: (c) Czaplik, W.; Mayer, M.;
Jacobi von Wangelin, A. Synlett 2009, 20, 2931.
(10) Reviews on alkyl halides in cross-couplings: (a) Netherton, M.
R.; Fu, G. C. Adv. Synth. & Catal. 2004, 346, 1525. (b) Frisch, A. C.;
Beller, M. Angew. Chem., Int. Ed. 2005, 44, 674. (c) Rudolph, A.;
Lautens, M. Angew. Chem., Int. Ed. 2009, 48, 2656.
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of 1a and DMBA in 30% v/v DMA/THF with 3 Å MS does not result
in formation of 1b. Due to challenges associated with in situ monitor-
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whether 1b is formed in situ and is the reactive substrate, or whether
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O
O
Me
O
(6) The catalytic asymmetric synthesis of α-quaternary ketones has
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1b
MeO
Me
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(17) The ee of ketone 3a is constant over the course of reaction,
whereas the ee of recovered 2a gradually increases to 17% at 94%
conversion. These results suggest that the two enantiomers of 2a react
at comparable rates, as only a very modest kinetic resolution occurs.
When enantioenriched 2a is employed, ketone 3a is obtained in 92%
ee and 2a is recovered without erosion of ee.
(18) The absolute stereochemistry of ketone 7a was assigned by
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(22) For contrasting mechanistic proposals, see refs 11c, 11d, and
12e.
(23) When the reaction between 1a and 2a is conducted in the
presence of 0.5 equiv of the radical inhibitor 2,6-bis(1,1-
dimethylethyl)-4-methylphenol (BHT), ketone 3a is isolated in 80%
yield and 92% ee. Alternatively, use of the electron transfer inhibitor
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