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. 2020 Jun 23;11(28):7390-7395.
doi: 10.1039/d0sc02366c. eCollection 2020 Jul 28.

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

Kazato Inanaga  1 , Marco Wollenburg  1 , Shoshana Bachman  1 , Nicholas J Hafeman  1 , Brian M Stoltz  1
Affiliations

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

Kazato Inanaga et al. Chem Sci. .

Abstract

The synthesis of a variety of enantioenriched 1,3-diketospiranes from the corresponding racemic allyl β-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 β-hydroxy ketones which may be oxidized to the corresponding enantioenriched diketospiranes. Additionally, this chemistry has been extended to α-allylcarboxy lactam substrates leading to a formal synthesis of the natural product (-)-isonitramine.

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Figures

Fig. 1
Fig. 1. Examples of 1,3-diketospiranes and their stereochemical properties.
Fig. 2
Fig. 2. (A) Previously reported example of an interrupted allylic alkylation reaction. (B) Development of an enantioselective variant, and application to the synthesis of 1,3-diketospiranes.
Fig. 3
Fig. 3. Mechanistic proposal including Brønsted acid-mediated catalyst turnover (A– represents conjugate base of the Brønsted acid additive).
Scheme 1
Scheme 1. Formal synthesis of (–)-isonitramine.
See this image and copyright information in PMC

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