Diastereoselective reversible C-C bond exchange of oxindole-thiazolidienediones for dynamic combinatorial chemistry.

We herein describe a diastereoselective aldol exchange involving isatins and thiazolidinediones, providing oxindolyl-thiazolidienediones in aqueous media at pH 6. This equilibrium can also be achieved with oxindole exchange as well as cross-exchange within reasonable timescales. These metal and organic catalyst free reversible reactions provide a unique opportunity for the evolution of dynamic combinatorial libraries (DCLs) for target directed dynamic combinatorial chemistry (DCC) and system chemistry.

Cycloaddition of N-sulfonyl and N-sulfamoyl azides with alkynes in aqueous media for the selective synthesis of 1,2,3-triazoles.

The cycloaddition of N-sulfonyl and N-sulfamoyl azides with terminal alkynes generally produces amide derivatives via ketenimine intermediates. We herein delineate a Cu(I) catalyzed method using a prolinamide ligand that selectively generate N-sulfonyl and sulfamoyltriazoles in aqueous media by inhibiting the cleavage of the N1-N2 bond of 5-cuprated triazole intermediates. The present method is mild and tolerant to air, moisture and a wide range of functional groups thereby providing an easy access to a variety of triazole products.

A [3+2] cycloaddition-1,2-acyl migration-hydrolysis cascade for regioselective synthesis of 1,2,3-triazoles in water.

A cascade sequence involving [3+2] cycloaddition, 1,2-acyl migration and hydrolysis produces 2H-1,2,3-triazoles via the regioselective formation of N2-carboxyalkylated triazoles. The reaction proceeds in aqueous media through intriguing reaction kinetics using a CuI-prolinamide catalyst system. Prolinamide promotes the novel organocatalytic 1,2-acyl migration as well as hydrolysis of the resulting N2-carboxyalkylated triazoles.

Domino Grignard Addition and Oxidation for the One-Pot Synthesis of C2-Quaternary 2-Hydroxyindoxyls.

We herein delineate an unexplored reactivity of 3-hydroxyoxindoles toward Grignard addition enabling a rapid access to a broad range of unnatural C2-quaternary 2-hydroxyindoxyls in high yields. The reaction proceeds via a mechanistically intriguing one-pot 1,2-hydride shift followed by autoxidation pathway. The utility of this method is demonstrated by the synthesis of a new class of bis-indoxyl spirofuran derivatives.

Divergent and Orthogonal Approach to Carbazoles and Pyridoindoles from Oxindoles via Indole Intermediates.

The previously unexplored Grignard addition to oxindoles provides a regiospecific approach to 2- and 2,3-disubstituted indole derivatives in high yields via a one-pot aromatization driven dehydration pathway. This method allows a convenient preparation of diallyl indoles that are used as ring-closing metathesis (RCM) precursors for the orthogonal synthesis of pyrido[1,2- a]indoles and carbazoles. The synthetic utility of this method is illustrated by the synthesis of a microtubulin inhibitor and naturally occurring carbazole alkaloids.

"On Water'' Promoted Ullmann-Type C-N Bond-Forming Reactions: Application to Carbazole Alkaloids by Selective N-Arylation of Aminophenols.

The Ullmann-type cross coupling of a variety of aromatic, aliphatic amines with aryl halides is reported using a CuI-based catalytic system in combination with an easily accessible prolinamide ligand in aqueous media. The method is mild and tolerant to air, moisture, and a wide range of functional groups, providing a novel way to access a variety of aminated products. Secondary amines like heteroaromatic amines and nucleobases have also been used, affording the corresponding coupling products in good to excellent yields. Moreover, this method has been employed for chemoselective C-N arylation of aminophenols and further utilized for the synthesis of carbazole natural products, avoiding the protection and deprotection steps.