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Enantioselective Giese Additions of Prochiral α-Amino Radicals.

ABSTRACT: Amines featuring an adjacent stereocenter are important building blocks, and recent years have seen remarkable growth in methods forming these via prochiral α-amino radical intermediates. However, very few can exert control over the newly formed stereocenter. We disclose a strategy to overcome this in the context of one of the most widely used radical carbon-carbon bond forming reactions, the Giese reaction. Incorporation of a removable basic heteroarene into the substrate enables a network of attractive noncovalent interactions between a phosphoric acid catalyst, the subsequently formed α-amino radical, and the Giese acceptor, allowing the catalyst to exert control during the C-C bond forming step. Deprotection of the products leads to analogues of γ-aminobutyric acid. We anticipate that this strategy will be applicable to other asymmetric radical transformations in which catalyst control is presently challenging.

SUBMITTER: Lahdenpera ASK

PROVIDER: S-EPMC9756345 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Enantioselective Giese Additions of Prochiral α-Amino Radicals.

Lahdenperä Antti S K ASK Bacoş P David PD Phipps Robert J RJ

Journal of the American Chemical Society 20221201 49

Amines featuring an adjacent stereocenter are important building blocks, and recent years have seen remarkable growth in methods forming these via prochiral α-amino radical intermediates. However, very few can exert control over the newly formed stereocenter. We disclose a strategy to overcome this in the context of one of the most widely used radical carbon-carbon bond forming reactions, the Giese reaction. Incorporation of a removable basic heteroarene into the substrate enables a network of a ...[more]

PMID: 36454604

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