An efficient chemoselective general procedure for the synthesis of γ-substituted β,γ-unsaturated α-ketomethylthioesters from α,β-unsaturated ketones has been achieved through an unprecedented PPh3 ⋅HBr-DMSO mediated oxidative bromination and Kornblum oxidation sequence. The newly developed reagent system serves admirably for the synthesis of α-bromoenals from enals. Furthermore, AuCl3 -catalyzed efficient access to 3(2H)-furanones from the above intermediates under extremely mild conditions are described.

We report herein an efficient and mechanistically unique tandem chemoselective 1,2-/1,4-migrationo ft he thio group in keto thioesters that provides substituted butenolides in moderate to excellent yields.T hus, a-keto thioesters in the presence of stabilized phosphonate carbanions undergo tandem 1,2-sulfur migration;w hereas1 ,4-migration of the thio group has been achieved with the same thioest-ers after the treatment with Wittig reagents followed by BF 3 ·OEt 2 -catalyzed tandem reaction. Thec rossover experiments and the isolation of intermediates reveal as tepwise mechanism for botho ft hese transformations.Scheme 1. Commonstrategies for the 1,2-/1,4-migration of the thio group.

The potential of β,γ-unsaturated α-ketothioesters participating in hetero-Diels-Alder reaction has remained unexplored. We report herein the first study of a ZnI2-catalyzed highly diastereoselective inverse electron demand hetero-Diels-Alder reaction of β,γ-unsaturated α-ketothioesters with olefins to access highly substituted 3,4-dihydro-2H-pyrans. All the reactions proceed with cis-selectivity in moderate to excellent yields. Under similar reaction conditions, terminal alkynes undergo direct conjugate 1,4-addition to yield δ,ε-acetylenic α-ketothioesters. Furthermore, the utility of these cycloadducts has been demonstrated by an NBS-MeOH mediated stereospecific efficient access to fully substituted pyran rings. The product bromoethers undergo E2 elimination with DBU, resulting in substituted 3,6-dihydro-2H-pyrans. In addition, the thioester moiety of the products has been used for further transformations, such as amidations and Fukuyama coupling reactions.

Abstractα‐Keto thioesters, with two electrophilic carbon centres, have been found to react differently with β‐keto esters and isocyanoacetates. They undergo base induced Knoevenagel‐type condensation on the keto carbonyl group with β‐keto esters, followed by intramolecular cyclization and water addition leads to highly substituted γ‐hydroxybutenolides. On the other hand, substituted oxazole derivatives have been obtained using isocyanoacetates via nucleophilic displacement on the thioester carbonyl followed by intramolecular cyclization. Further functionalization of the γ‐hydroxybutenolides is also demonstrated via a BF3.OEt2‐mediated cation‐driven nucleophilic addition of terminal alkynes to access multiply substituted butenolides.magnified image

This report describes a gold(III)-catalyzed efficient general route to densely substituted chiral 3-formyl furans under extremely mild conditions from suitably protected 5-(1-alkynyl)-2,3-dihydropyran-4-one using H2 O as a nucleophile. The reaction proceeds through the initial formation of an activated alkyne-gold(III) complex intermediate, followed by either a domino nucleophilic attack/anti-endo-dig cyclization, or the formation of a cyclic oxonium ion with subsequent attack by H2 O. To confirm the proposed mechanistic pathway, we employed MeOH as a nucleophile instead of H2 O to result in a substituted furo[3,2-c]pyran derivative, as anticipated. The similar furo[3,2-c]pyran skeleton with a hybrid carbohydrate-furan derivative has also been achieved through pyridinium dichromate (PDC) oxidation of a substituted chiral 3-formyl furan. The corresponding protected 5-(1-alkynyl)-2,3-dihydropyran-4-one can be synthesized from the monosaccharides (both hexoses and pentose) following oxidation, iodination, and Sonogashira coupling sequences. Furthermore, to demonstrate the potentiality of chiral 3-formyl furan derivatives, a TiBr4 -catalyzed reaction of these derivatives has been shown to offer efficient access to 1,5-dicarbonyl compounds, which on treatment with NH4 OAc in slightly acidic conditions afforded substituted furo[3,2-c]pyridine.