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J Org Chem. 2017 Nov 3;82(21):11326-11336. doi: 10.1021/acs.joc.7b02339.

Desymmetrization of Diarylmethylamido Bis(phenols) through Peptide-Catalyzed Bromination: Enantiodivergence as a Consequence of a 2 amu Alteration at an Achiral Residue within the Catalyst.

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1
Department of Chemistry, Yale University , P.O. Box 208107, New Haven, Connecticut 06520-8107, United States.

Abstract

Diarylmethylamido bis(phenols) have been subjected to peptide-catalyzed, enantioselective bromination reactions. Desymmetrization of compounds in this class has been achieved such that enantioenriched products may be isolated with up to 97:3 er. Mechanistically, the observed enantioselectivity was shown to be primarily a function of differential functionalization of enantiotopic arenes, although additional studies unveiled a contribution from secondary kinetic resolution of the product (to afford the symmetrical dibromide) under the reaction conditions. Variants of the tetrapeptide catalyst were also evaluated and revealed a striking observation-enantiodivergent catalysis is observed upon changing the achiral amino acid residue in the catalyst (at the i+2 position) from an aminocyclopropane carboxamide residue (97:3 er) to an aminoisobutyramide residue (33:67 er) under a common set of conditions. An expanded set of catalysts was also evaluated, enabling structure/selectivity correlations to be considered in a mechanistic light.

PMID:
29020446
PMCID:
PMC5738245
DOI:
10.1021/acs.joc.7b02339
[Indexed for MEDLINE]
Free PMC Article

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