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. 2014 Mar 12;136(10):3788-91.
doi: 10.1021/ja500706v. Epub 2014 Feb 27.

Catalytic enantioselective cyclization/cross-coupling with alkyl electrophiles

Huan Cong  1 , Gregory C Fu
Affiliations

Catalytic enantioselective cyclization/cross-coupling with alkyl electrophiles

Huan Cong et al. J Am Chem Soc. .

Abstract

As part of our ongoing effort to expand the scope of cross-coupling reactions of alkyl electrophiles, we have pursued a strategy wherein the nucleophilic coupling partner includes a pendant olefin; after transmetalation by such a substrate, if β-migratory insertion proceeds faster than direct cross-coupling, an additional carbon-carbon bond and stereocenter can be formed. With the aid of a nickel/diamine catalyst (both components are commercially available), we have established the viability of this approach for the catalytic asymmetric synthesis of 2,3-dihydrobenzofurans and indanes. Furthermore, we have applied this new method to the construction of the dihydrobenzofuran core of fasiglifam, as well as to a cross-coupling with a racemic alkyl electrophile; in the latter process, the chiral catalyst controls two stereocenters, one that is newly generated in a β-migratory insertion and one that begins as a mixture of enantiomers.

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Figures

Figure 1
Figure 1
Asymmetric cross-couplings of alkyl electrophiles.
Figure 2
Figure 2
Complementary approaches to generating a precursor (A) for catalytic enantioselective cyclizations.
Scheme 1
Scheme 1. Catalytic Asymmetric Synthesis of the 2,3-Dihydrobenzofuran Core of Fasiglifam
See this image and copyright information in PMC

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