Alkylidene Meldrum's Acids as Platforms for the Vinylogous Synthesis of Dihydropyranones.

Upon Brønsted base organocatalysis, ketone-derived alkylidene Meldrum's acids proved to be competent vinylogous platforms able to undergo a formal (4+2) cycloaddition reaction with dihydro-2,3-furandione, providing an unprecedented route to 3,6-dihydropyran-2-ones as spiro[4.5]decane derivatives with up to 98 % ee thanks to the commercially available Takemoto catalyst. Preliminary investigation showed that this reaction could be extended to other activated ketones, establishing these alkylidene Meldrum's acids as a novel C4-synthon in the vinylogous series.

Chiral Tertiary Amine Catalyzed Asymmetric [4 + 2] Cyclization of 3-Aroylcoumarines with 2,3-Butadienoate.

Coumarins and 2H-pyran derivatives are among the most commonly found structural units in natural products. Therefore, the introduction of 2H-pyran moiety into the coumarin structural unit, i.e., dihydrocoumarin-fused dihydropyranones, is a potentially successful route for the identification of novel bioactive structures, and the synthesis of these structures has attracted continuing research interest. Herein, a chiral tertiary amine catalyzed [4 + 2] cyclization of 3-aroylcoumarines with benzyl 2,3-butadienoate was reported. In the presence of Kumar's 6'-(4-biphenyl)-ß-iso-cinchonine, the desired dihydrocoumarin-fused dihydropyranone products could be obtained in up to 97% yield and 90% ee values.

An Enantioselective Assembly of Dihydropyranones through an NHC/LiCl-Mediated in situ Activation of α,ß-Unsaturated Carboxylic Acids.

A straightforward N-heterocyclic carbene (NHC)/LiCl-mediated synthesis of dihydropyranones from α,ß-unsaturated carboxylic acids and 1,3-dicarbonyl compounds was realized through the in situ activation strategy. The key advantages of this protocol include ready availability and high stability of starting materials, good yields, and excellent enantioselectivity.

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

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.