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Dynamic kinetic resolution of biaryl atropisomers via peptide-catalyzed asymmetric bromination.

ABSTRACT: Despite the widespread use of axially chiral, or atropisomeric, biaryl ligands in modern synthesis and the occurrence of numerous natural products exhibiting axial chirality, few catalytic methods have emerged for the direct asymmetric preparation of this compound class. Here, we present a tripeptide-derived small-molecule catalyst for the dynamic kinetic resolution of racemic biaryl substrates. The reaction proceeds via an atropisomer-selective electrophilic aromatic substitution reaction using simple bromination reagents. The result is an enantioselective synthesis that delivers chiral nonracemic biaryl compounds with excellent optical purity and good isolated chemical yields (in most cases a >95:5 enantiomer ratio and isolated yields of 65 to 87%). A mechanistic model is advanced that accounts for the basis of selectivity observed.

SUBMITTER: Gustafson JL

PROVIDER: S-EPMC3066098 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature

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Dynamic kinetic resolution of biaryl atropisomers via peptide-catalyzed asymmetric bromination.

Gustafson Jeffrey L JL Lim Daniel D Miller Scott J SJ

Science (New York, N.Y.) 20100601 5983

Despite the widespread use of axially chiral, or atropisomeric, biaryl ligands in modern synthesis and the occurrence of numerous natural products exhibiting axial chirality, few catalytic methods have emerged for the direct asymmetric preparation of this compound class. Here, we present a tripeptide-derived small-molecule catalyst for the dynamic kinetic resolution of racemic biaryl substrates. The reaction proceeds via an atropisomer-selective electrophilic aromatic substitution reaction using ...[more]

PMID: 20522769

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