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Catalytic enantioselective synthesis of carbocyclic and heterocyclic spiranes via a decarboxylative aldol cyclization.

ABSTRACT: The synthesis of a variety of enantioenriched 1,3-diketospiranes from the corresponding racemic allyl ?-ketoesters via an interrupted asymmetric allylic alkylation is disclosed. Substrates possessing pendant aldehydes undergo decarboxylative enolate formation in the presence of a chiral Pd catalyst and subsequently participate in an enantio- and diastereoselective, intramolecular aldol reaction to furnish spirocyclic ?-hydroxy ketones which may be oxidized to the corresponding enantioenriched diketospiranes. Additionally, this chemistry has been extended to ?-allylcarboxy lactam substrates leading to a formal synthesis of the natural product (-)-isonitramine.

SUBMITTER: Inanaga K

PROVIDER: S-EPMC7574022 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Catalytic enantioselective synthesis of carbocyclic and heterocyclic spiranes <i>via</i> a decarboxylative aldol cyclization.

Inanaga Kazato K Wollenburg Marco M Bachman Shoshana S Hafeman Nicholas J NJ Stoltz Brian M BM

Chemical science 20200623 28

The synthesis of a variety of enantioenriched 1,3-diketospiranes from the corresponding racemic allyl β-ketoesters <i>via</i> an interrupted asymmetric allylic alkylation is disclosed. Substrates possessing pendant aldehydes undergo decarboxylative enolate formation in the presence of a chiral Pd catalyst and subsequently participate in an enantio- and diastereoselective, intramolecular aldol reaction to furnish spirocyclic β-hydroxy ketones which may be oxidized to the corresponding enantioenri ...[more]

PMID: 33133488

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