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Synthesis of enantioenriched 2,2-disubstituted pyrrolidines via sequential asymmetric allylic alkylation and ring contraction.

ABSTRACT: The synthesis of a variety of enantioenriched 2,2-disubstituted pyrrolidines is described. A stereogenic quaternary center is first formed utilizing an asymmetric allylic alkylation reaction of a benzyloxy imide, which can then be reduced to a chiral hydroxamic acid. This compound can then undergo a thermal "Spino" ring contraction to afford a carbamate protected 2,2-disubstituted pyrrolidine stereospecifically. These pyrrolidines can be further advanced to enantioenriched indolizidine compounds. This reaction sequence allows access to new molecules that could be useful in the development of pharmaceutical agents.

SUBMITTER: Goldstein EL

PROVIDER: S-EPMC10038171 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Synthesis of enantioenriched 2,2-disubstituted pyrrolidines via sequential asymmetric allylic alkylation and ring contraction.

Goldstein Elizabeth L EL Takada Hirokazu H Sumii Yuji Y Baba Katsuaki K Stoltz Brian M BM

Tetrahedron 20220806

The synthesis of a variety of enantioenriched 2,2-disubstituted pyrrolidines is described. A stereogenic quaternary center is first formed utilizing an asymmetric allylic alkylation reaction of a benzyloxy imide, which can then be reduced to a chiral hydroxamic acid. This compound can then undergo a thermal "Spino" ring contraction to afford a carbamate protected 2,2-disubstituted pyrrolidine stereospecifically. These pyrrolidines can be further advanced to enantioenriched indolizidine compounds ...[more]

PMID: 36968983

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