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Catalytic Enantioselective Synthesis of 3-Piperidines from Arylboronic Acids and Pyridine.

ABSTRACT: Piperidines are frequently found in natural products and are of importance to the pharmaceutical industry. A generally useful asymmetric route to enantiomerically enriched 3-substituted piperidines remains elusive. Here we report a cross-coupling approach to enantioenriched 3-piperidines from pyridine- and sp²-hybridized boronic acids. The key step involves a Rh-catalyzed asymmetric reductive Heck reaction of aryl, heteroaryl, or vinyl boronic acids and phenyl pyridine-1(2H)-carboxylate to provide 3-substituted tetrahydropyridines in high yield and excellent enantioselectivity with a wide functional group tolerance. A three-step process involving i) partial reduction of pyridine, ii) Rh-catalyzed asymmetric carbometalation, and then iii) another reduction provides access to a wide variety of enantioenriched 3-piperidines, including clinically used materials such as Preclamol and Niraparib.

SUBMITTER: Mishra S

PROVIDER: S-EPMC10326878 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

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Catalytic Enantioselective Synthesis of 3-Piperidines from Arylboronic Acids and Pyridine.

Mishra Sourabh S Karabiyikoglu Sedef S Fletcher Stephen P SP

Journal of the American Chemical Society 20230622 26

Piperidines are frequently found in natural products and are of importance to the pharmaceutical industry. A generally useful asymmetric route to enantiomerically enriched 3-substituted piperidines remains elusive. Here we report a cross-coupling approach to enantioenriched 3-piperidines from pyridine- and sp2-hybridized boronic acids. The key step involves a Rh-catalyzed asymmetric reductive Heck reaction of aryl, heteroaryl, or vinyl boronic acids and phenyl pyridine-1(2H)-ca ...[more]

PMID: 37345648

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