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Catalytic Enantioselective Synthesis of Difluorinated Alkyl Bromides.

ABSTRACT: We report an iodoarene-catalyzed enantioselective synthesis of ?,?-difluoroalkyl bromide building blocks. The transformation involves an oxidative rearrangement of ?-bromostyrenes, utilizing HF-pyridine as the fluoride source and m-CPBA as the stoichiometric oxidant. A catalyst decomposition pathway was identified, which, in tandem with catalyst structure-activity relationship studies, facilitated the development of an improved catalyst providing higher enantioselectivity with lower catalyst loadings. The versatility of the difluoroalkyl bromide products was demonstrated via highly enantiospecific substitution reactions with suitably reactive nucleophiles. The origins of enantioselectivity were investigated using computed interaction energies of simplified catalyst and substrate structures, providing evidence for both CH-? and ?-? transition state interactions as critical features.

SUBMITTER: Levin MD

PROVIDER: S-EPMC7537710 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Catalytic Enantioselective Synthesis of Difluorinated Alkyl Bromides.

Levin Mark D MD Ovian John M JM Read Jacquelyne A JA Sigman Matthew S MS Jacobsen Eric N EN

Journal of the American Chemical Society 20200824 35

We report an iodoarene-catalyzed enantioselective synthesis of β,β-difluoroalkyl bromide building blocks. The transformation involves an oxidative rearrangement of α-bromostyrenes, utilizing HF-pyridine as the fluoride source and <i>m</i>-CPBA as the stoichiometric oxidant. A catalyst decomposition pathway was identified, which, in tandem with catalyst structure-activity relationship studies, facilitated the development of an improved catalyst providing higher enantioselectivity with lower catal ...[more]

PMID: 32799536

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