Direct Organocatalytic Chemoselective Synthesis of Pharmaceutically Active 1,2,3-Triazoles and 4,5'-Bitriazoles.

Carbonyl-containing 1,4,5-trisubstituted- and 1,4-disubstituted-1,2,3-triazoles are well-known for their wide range of applications in pharmaceutical and medicinal chemistry, but their high-yielding metal-free synthesis has always remained challenging, as no comprehensive protocol has been outlined to date. Owing to their structural and medicinal importance, herein, we synthesized various carbonyl-containing 1,4,5-trisubstituted- and 1,4-disubstituted-1,2,3-triazoles and unsymmetrical 4,5'-bitriazoles with high yields and chemo-/regioselectivity from the library of 2,4-diketoesters and azides in a sequential one-pot manner through the combination of organocatalytic enolization, in situ [3 + 2]-cycloaddition, and hydrolysis reactions. The commercial availability of the starting materials/catalysts, diverse substrate scope, performance in a one-pot manner, chemo-/regioselectivity of organo-click reaction, quick synthesis of unsymmetrical 4,5'-bitriazoles, a large number of synthetic applications, and numerous medicinal applications of carbonyl-containing 1,2,3-triazoles are the key attractions of this metal-free organo-click work.

Two-step, high-yielding total synthesis of antibiotic pyrones.

A simple two-step dialkylation protocol was developed to synthesize biologically active antibiotics photopyrones, pseudopyronines, and violapyrones from bio-renewable triacetate lactone in excellent yields. These pyrones are functionally modified into another set of pyrone natural products by a single -methylation reaction. The high-yielding gram scale synthesis of four natural products [pseudopyronine A, photopyrone A, pseudopyronine B and photopyrone C] demonstrated the viability for industrial applications.

Organocatalytic Reductive Amination of the Chiral Formylcyclopropanes: Scope and Applications.

We developed a sustainable three-component reductive amination protocol for the chemoselective coupling of optically active functionally rich donor-acceptor carbonyl-cyclopropanes with various amines under 10 mol % of diphenyl phosphate in the presence of Hantzsch ester as a hydride source. The catalytic selective reductive C-N coupling has wide advantages like no epimerization, no ring opening, large substrate scope, generating only mono -alkylation products and simultaneously resulting in chiral cyclopropane-containing amines possessing many applications in the medicinal chemistry. In this article, we have shown the synthetic applications of reductive C-N coupling reaction to make chiral α-carbonyl-cyclopropane containing amines , double C-N coupled cyclopropane-amines , unusual C-N/C-C coupled cyclopropane-amines , chiral -butylsulfinamide containing cyclopropanes , and functionally rich chiral cyclopropane-fused -heterocycles .

Direct organocatalytic transfer hydrogenation and C-H oxidation: high-yielding synthesis of 3-hydroxy-3-alkyloxindoles.

Readily available 3-alkylideneoxindoles were effectively reduced to 3-alkyloxindoles through transfer hydrogenation using Hantzsch ester as a reducing agent at ambient temperature and the greenness/sustainability of this protocol was assessed by correlation with Pd/C-mediated hydrogenation with hydrogen gas. Furthermore, an organocatalytic method was developed to access drug-like 3-alkyl-3-hydroxyoxindoles by C-H oxidation of 3-alkyl-indolin-2-one, using a catalytic amount of 1,1,3,3-tetramethylguanidine (TMG) as an organic base and dissolved oxygen in THF as an oxidant at room temperature. Key reaction intermediates were observed by controlled on-line ESI-HRMS experiments and identified by their corresponding mass (/) analysis.

Direct Organocatalytic Chemoselective Reductive Alkylation of Chiral 2-Aroylcyclopropanecarbaldehydes: Scope and Applications.

We developed a simple and practically feasible protocol for the chemoselective coupling of optically active functionally rich 2-aroylcyclopropanecarbaldehydes with various CH acids or active methylene compounds under 10 mol % of ()-proline in the presence of Hantzsch ester as a hydrogen source through a three-component reductive alkylation reaction. The metal-free, organocatalytic selective reductive C-C coupling method has wide advantages/applications like no epimerization, no ring opening, high carbonyl control, and large substrate scope, generating only monoalkylated 2-aroylcyclopropanes, and the resulting chiral products can be synthons in medicinal to material chemistry. We have also shown the synthetic applications of chiral CH-acid-containing 2-aroylcyclopropanes by transforming them into the interesting molecules of pyrimidine analogues , dimethyl cyclopropane-malonates , functionally rich dihydropyran , cyclopropane-alcohols , and cyclopropane-olefins .