Cobalt-Catalyzed Thioamide Directed C(arene)-H Annulation with Ynamide: Regioselective Access to 2-Amidoindenones.

Demonstrated herein is an unprecedented thioamide-directed cobalt (Co)-catalyzed umpolung annulation of sulfoximines enabled aryl thioamide with ynamide for the synthesis of highly substituted 2-amidoindenones. The cyclization is regioselective, making ß-C-C and α-C-CO bonds. The transformation is even successful on a gram scale, exhibiting broad scope with labile functional group tolerance and constructing 43 unusual 2-amidoindenones of structural diversity. Control experiments and mechanistic investigation validate the regioselectivity outcome in this transformation.

A 6-endo-dig Thiolative Cyclization of Yne-Ynamides: Access to Thiodihydropyridin-2-ones.

A straightforward regioselective intramolecular 6-endo-dig cyclization of yne-tethered ynamide is herein developed. The reaction involves an intramolecular enolate attack of ketene-N,O-acetals, generated in situ from yne-ynamide and methanesulfonic acid, to the alkyne moiety activated by a sulfonium cation. The transformation enables access to structurally diverse 5-(arylthio)-3,6-dihydropyridin-2(3H)-ones with broad functional group compatibility. The recovery of S-protecting groups and synthetic applications of the products make the transformation useful.

Cationic-palladium catalyzed regio- and stereoselective syn-1,2-dicarbofunctionalization of unsymmetrical internal alkynes.

π-Extended tetrasubstituted olefins are widely found motifs in natural products, leading drugs, and agrochemicals. Thus, development of modular strategies for the synthesis of complex all-carbon-substituted olefins always draws attention. The difunctionalization of unsymmetrical alkynes is an attractive approach but it has remained faced with regioselectivity issues. Here we report the discovery of a regio- and stereoselective syn-1,2-dicarbofunctionalization of unsymmetrical internal alkynes. A cationic Pd-catalyzed three-component coupling of aryl diazonium salts, aryl boronic acids (or olefins) and yne-acetates enables access to all-carbon substituted unsymmetrical olefins. The transformation features broad scope with labile functional group tolerance, building broad chemical space of structural diversity (94 molecules). The value of this synthetic method is demonstrated by the direct transformation of natural products and drug candidates containing yne-acetates, to enable highly substituted structurally complex allyl acetate analogues of biologically important compounds. Synthetic versatility of the carboxylate bearing highly substituted olefins is also presented. The reaction outcome is attributed to the in situ formation of stabilized cationic aryl-Pd species, which regulates regioselective aryl-palladation of unsymmetrical yne-acetates. Control experiments reveal the synergy between the carboxylate protecting group and the cationic Pd-intermediate in the regioselectivity and reaction productivity; density functional theory (DFT) studies rationalize the selectivity of the reaction.

Yb(iii)-catalysed syn-thioallylation of ynamides.

Reported herein is a syn-thioallylation of ynamides incorporating a sulfide moiety at the α-position and an allyl group at the ß-position of the ynamide. The transformation is successful under ytterbium(iii)-catalysis, providing access to highly substituted thioamino-skipped-dienes with broad substrate scope. Thus, tetrasubstituted olefins (with four different functional groups: amide, phenyl, thioaryl/alkyl, and allyl on the carbon centers) are made in a single step from readily accessible ynamides, preserving complete atom economy. The reaction can be extended to the synthesis of selenoamino dienes by ynamide syn-selenoallylation. DFT studies and control experiments provide insight into the reaction mechanism.

Enantioselective Gold(I)-Catalyzed Hydrative Cyclizations of N-Propargyl-ynamides into 3,6-Dihydropyridinones.

This study discloses the first enantioselective variant of the gold(I)-catalyzed hydrative cyclizations of ynamides, which have been implemented by using bis-gold(I) complexes of chiral diphosphines. Starting from N-propargyl-ynamides and water in the presence of p-toluenesulfonic acid, the cyclization reactions afford N-tosyl-3,6-dihydropyridin-2(1H)-ones in good isolated yields and with high levels of stereocontrol (20 examples, enantiomeric ratios up to 94:6).