NHC-Catalyzed Dual Stetter Reaction: A Mild Cascade Annulation for the Syntheses of Naphthoquinones, Isoflavanones, and Sugar-Based Chiral Analogues.

The N-heterocycle carbene (NHC)-catalyzed dual Stetter cascade reaction is discovered through coupling of ß-nitrostyrene with phthalaldehyde under mild conditions to furnish valuable aryl-naphthoquinones. The generality of the new reaction is validated through the development of a C-C and O-C bond forming Stetter cascade reaction using salicylaldehydes to obtain functionalized dihydroisoflavanones. The mild NHC organocatalysis is successfully employed for the construction of optically pure sugar-based naphthoquinones and dihydroisoflavanones. Herein, NHC is found as a unique and powerful organocatalyst to construct homoatomic C-C cross-coupling, heteroatomic O-C bond formation, and cascade cyclization utilizing NO2 as a leaving group at ambient temperature. A mechanistic pathway of the new metal-free catalysis is predicted on the basis of our ESI-MS study of the ongoing reaction and literature.

PdII-Catalyzed Oxidative Aldehyde-sp2C-H Functionalization and Cyclization Using NHC with Mild Oxidant DMSO for the Selective Synthesis of Esters, Sugar-Based Analogues, and ß-Hydroxy Chromanones: An 18O-Labeling Study.

We assume formation of acyl-PdII-N-heterocyclic-carbene (NHC) organometalics for diverse C-O/O-C and C-C/C-O coupling catalysis of direct functionalization and cyclization reactions. We report the first use of dimethyl sulfoxide (DMSO) as an oxidant under an inert atmosphere to O2-sensitive NHC for oxidative transformations. In situ generated imidazolium halides are utilized as a precursor of NHC and as a source of alkyl group for the sp2C-H functionalization of aldehydes to esters under mild conditions. In contrast to the reported NHC-catalyzed esterification strategies, the outstanding substrate scope of this mild catalysis approach is established through synthesis of thermally labile sugar-based chiral esters. Our competition experiments using various unsymmetrical imidazolium halides revealed an ascending rate of migratory aptitude among methyl ≪ allyl < crotyl < cinnamyl < benzyl moiety. DMSO is used as an oxidant for both esterification and cyclization reactions, and the transfer of the DMSO-oxygen to ester is confirmed using an 18O-labeling experiment. The diverse activity using DMSO-oxygen to acyl-PdII-NHC is verified by developing a unique C-C-coupled cyclization with side-chain hydroxylation of olefin to achieve valuable ß-hydroxy chromanones.

Synthesis of new N-acryl-1-amino-2-phenylethanol and N-acyl-1-amino-3-aryloxypropanols and evaluation of their antihyperlipidemic, LDL-oxidation and antioxidant activity.

As a part of our drug discovery program, we identified an alkaloidal amide i.e. Aegeline (V) isolated from the leaves of Aegle marmelos as a dual acting agent (antihyperlipidemic and antihyperglycemic). In continuation of this program, we synthesized new N-acyl-1-amino-2-alcohols (N-acrylated-1-amino-2-phenylethanol and N-acylated-1-amino-3-aryloxypropanols) via Ritter reaction and screened for their in-vivo antihyperlipdemic activity in Triton induced hyperlipidemia model, LDL-oxidation and antioxidant activity. Compounds 3, 11 and 13 showed good antihyperlipidemic activity, LDL-oxidation as well as antioxidant activity and comparable activity with marketed antidyslipidemic drug.

Synthesis of biaryls via AlCl3 catalyzed domino reaction involving cyclization, dehydration, and oxidation.

A new chemical access has been developed to synthesize biaryls from substituted acetophenones, phenylacetones, dihydrochalcone, and 2-acetylnaphthalene in reasonably good yields at room temperature via a domino reaction sequence of AlCl(3) catalyzed cyclization, dehydration, and then oxidation.