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

Anna E Hurtley; Elizabeth A Stone; Anthony J Metrano; Scott J Miller

doi:10.1021/acs.joc.7b02339

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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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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

Anna E Hurtley, Elizabeth A Stone, Anthony J Metrano and Scott J Miller

Journal of organic chemistry, Vol.82(21), pp.11326-11336

11/03/2017

DOI: 10.1021/acs.joc.7b02339

PMCID: PMC5738245

PMID: 29020446

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https://www.ncbi.nlm.nih.gov/pmc/articles/5738245View

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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.

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Title: Subtitle: 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
Creators: Anna E Hurtley - Department of Chemistry, Yale University , P.O. Box 208107, New Haven, Connecticut 06520-8107, United States
Elizabeth A Stone - Department of Chemistry, Yale University , P.O. Box 208107, New Haven, Connecticut 06520-8107, United States
Anthony J Metrano - Department of Chemistry, Yale University , P.O. Box 208107, New Haven, Connecticut 06520-8107, United States
Scott J Miller - Department of Chemistry, Yale University , P.O. Box 208107, New Haven, Connecticut 06520-8107, United States
Resource Type: Journal article
Publication Details: Journal of organic chemistry, Vol.82(21), pp.11326-11336
DOI: 10.1021/acs.joc.7b02339
PMID: 29020446
PMCID: PMC5738245
NLM abbreviation: J Org Chem
ISSN: 0022-3263
eISSN: 1520-6904
Grant note: R01 GM068649 / NIGMS NIH HHS
Language: English
Date published: 11/03/2017
Academic Unit: Chemistry; Chemical and Biochemical Engineering
Record Identifier: 9984217436102771

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