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. 2016 Feb 4;11(3):395-400.
doi: 10.1002/asia.201500907. Epub 2015 Nov 12.

Enantioselective Synthesis of 3,5,6-Substituted Dihydropyranones and Dihydropyridinones using Isothiourea-Mediated Catalysis

Daniel G Stark  1 , Louis C Morrill  1 , David B Cordes  1 , Alexandra M Z Slawin  1 , Timothy J C O'Riordan  2 , Andrew D Smith  3
Affiliations

Enantioselective Synthesis of 3,5,6-Substituted Dihydropyranones and Dihydropyridinones using Isothiourea-Mediated Catalysis

Daniel G Stark et al. Chem Asian J. .

Abstract

The scope of dihydropyranone and dihydropyridinone products accessible by isothiourea-catalyzed processes has been expanded and explored through the use of 2-N-tosyliminoacrylates and 2-aroylacrylates in a Michael addition-lactonization/lactamization cascade reaction. Notably, to ensure reproducibility it is essential to use homoanhydrides as ammonium enolate precursors with 2-aroyl acrylates, while carboxylic acids can be used with 2-N-tosyliminoacrylates, delivering a range of 3,5,6-substituted dihydropyranones and dihydropyridinones with high enantioselectivity (typically >90 % ee). The derivatization of the heterocyclic core of a 3,5,6-substituted dihydropyranone through hydrogenation is also reported.

Keywords: Michael addition; dihydropyranones; dihydropyridinones; enantioselective catalysis; isothioureas.

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Figures

Figure 1
Figure 1
Enantioselective synthesis of dihydropyranones and dihydropyridinones – overview of the field.
Figure 2
Figure 2
Enantioselective synthesis of dihydropyranones and dihydropyridinones – this work.
Scheme 1
Scheme 1
Initial results of the Michael addition‐lactonization. [a] Syringe pump addition of 1 (0.25 m in CH2Cl2) over 2 h.
Scheme 2
Scheme 2
Control experiment.
Figure 3
Figure 3
Molecular representation of X‐ray structure 12.
Scheme 3
Scheme 3
Derivatization of dihydropyranone 10.
Figure 4
Figure 4
Molecular representation of X‐ray structure 25.
Figure 5
Figure 5
Proposed catalytic cycle.
See this image and copyright information in PMC

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