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. 2017 May 15;56(21):5821-5824.
doi: 10.1002/anie.201702402. Epub 2017 Apr 19.

Control of Vicinal Stereocenters through Nickel-Catalyzed Alkyl-Alkyl Cross-Coupling

Xin Mu  1 , Yu Shibata  1 , Yusuke Makida  1 , Gregory C Fu  1
Affiliations

Control of Vicinal Stereocenters through Nickel-Catalyzed Alkyl-Alkyl Cross-Coupling

Xin Mu et al. Angew Chem Int Ed Engl. .

Abstract

Vicinal stereocenters are found in many natural and unnatural compounds. Although metal-catalyzed cross-coupling reactions of unactivated alkyl electrophiles are emerging as a powerful tool in organic synthesis, there have been virtually no reports of processes that generate, much less control, vicinal stereocenters. In this investigation, we establish that a chiral nickel catalyst can mediate doubly stereoconvergent alkyl-alkyl cross-coupling, specifically, reactions of a racemic pyrrolidine-derived nucleophile with cyclic alkyl halides (as mixtures of stereoisomers) to produce vicinal stereocenters with very good stereoselectivity.

Keywords: alkylation; asymmetric synthesis; cross-coupling; nickel; zinc.

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Figures

Figure 1
Figure 1
Stereoconvergent metal-catalyzed alkyl–alkyl cross-couplings.
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References

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    1. For use of a racemic nucleophile, see: Cordier CJ, Lundgren RJ, Fu GC. J. Am. Chem. Soc. 2013;135:10946–10949.We speculate that enantioconvergence is achieved through reversible homolysis of the nickel–pyrrolidinyl bond.

    1. For use of a racemic electrophile, see: Saito B, Fu GC. J. Am. Chem. Soc. 2008;130:6694–6695.Schmidt J, Choi J, Liu AT, Slusarczyk M, Fu GC. Science. 2016;354:1265–1269.

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