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Synfacts 2014; 10(1): 0043
DOI: 10.1055/s-0033-1340452
Metal-Catalyzed Asymmetric Synthesis and Stereoselective Reactions
© Georg Thieme Verlag Stuttgart · New York

Arylation of Racemic Secondary Benzylic Electrophiles by Nickel Catalysis

Contributor(s):
Mark Lautens
,
Christine M. Le
Do H.-Q, Chandrashekar ER. R, Fu GC * California Institute of Technology, Pasadena and Massachusetts Institute of Technology, Cambridge, USA
Nickel/Bis(oxazoline)-Catalyzed Asymmetric Negishi Arylations of Racemic Secondary Benzylic Electrophiles to Generate Enantioenriched 1,1-Diarylalkanes.

J. Am. Chem. Soc. 2013;
135: 16288-16291
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Publication History

Publication Date:
13 December 2013 (online)

 
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Key words

nickel - Negishi cross-coupling - enantioconvergency - 1,1-diarylalkanes

Significance

The 1,1-diarylalkane motif is found in a number of the top-selling pharmaceuticals. Therefore, the development of stereoselective methods to access this motif is a worthwhile pursuit. The authors report a two-step stereoconvergent synthesis of 1,1-diarylalkanes starting from racemic benzylic alcohols, which proceeds in excellent yields and with excellent enantioselectivities.


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Comment

A previous report by the same group disclosed a nickel-catalyzed enantioconvergent Negishi arylation of propargylic carbonates that was not applicable to the use of racemic benzylic carbonates (J. Am. Chem. Soc. 2012, 134, 2966). The current method generates a benzylic mesylate in situ. The authors propose that the lithium iodide additive transforms the mesylate into an alkyl iodide, which can then participate in the Negishi cross-coupling.


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