Final Report Summary - SULFONAMIDES (The Catalytic Synthesis of Sulfonamides)
We have been working on the application of transition-metal catalysts for the synthesis of sulfonamides via carbon-hydrogen activation and carbon-sulfur bond formation, by using DABSO, an air-stable, easy-handled solid SO2 surrogate. We started by evaluating reaction system according to the analogy of carbonylative carbon-hydrogen bond activation reaction through all the reaction parameters, such as “SO2” source, palladium source, ligand, base, solvent, additive and temperature. Unfortunately, under a wide variety of different conditions no desired product was observed, and the majority of reactions returned only starting material (1-methylindole) and decomposed hydrazine (in case of N,N-dialkylhydrazine) or homocoupling product (in case of aryl boronic acid). This is presumably due to a problem of coexistence of oxidant and reductant in the reaction system.
We have also investigated the application of DABSO and ortho-iodo benzyl amines for the preparation of sulfonamides via intramolecular reactions using palladium catalysis. Due to the ortho-positioning causing steric hindrance, poor nuclephilic properties of secondary amine, and the excess of DABCO in the reaction, no desired transformation was observed under various conditions, but starting material was recovered unchanged, or the iodo-substituent was reduced in reaction system at high temperature.
Morever, we have explored a two-pot, three-step simple, potentially green synthetic methodology for the conversion of readily accessible N-aminosulfonamides to the corresponding sulfonamides without transition metal catalysis under mild reaction conditions in aqueous media, with good functional group tolerance.
We have also exmamined the use of DABSO for the hydrosulfination of functionalized alkenes under palladium catalysis to generate sulfonic acids or sulfonate esters via one-step synthetic methodology without employing toxic, gaseous SO2. Due to the instability and dissociation of formed sulfonic acid, and harsh reaction condition, this procedure is quite limited for further transformation.
However, we did developed another interesting reactions occured between alcohol and sulfur dioxide under basic condition. It could be performed at room temperature and have good functional group tolerance. In addition, we have inverstigated the methodology for the synthesis of useful heterocyclic sulfones by using DABSO, and we have currently got some important results. Further completion work is undergoing.
We have also investigated the application of DABSO and ortho-iodo benzyl amines for the preparation of sulfonamides via intramolecular reactions using palladium catalysis. Due to the ortho-positioning causing steric hindrance, poor nuclephilic properties of secondary amine, and the excess of DABCO in the reaction, no desired transformation was observed under various conditions, but starting material was recovered unchanged, or the iodo-substituent was reduced in reaction system at high temperature.
Morever, we have explored a two-pot, three-step simple, potentially green synthetic methodology for the conversion of readily accessible N-aminosulfonamides to the corresponding sulfonamides without transition metal catalysis under mild reaction conditions in aqueous media, with good functional group tolerance.
We have also exmamined the use of DABSO for the hydrosulfination of functionalized alkenes under palladium catalysis to generate sulfonic acids or sulfonate esters via one-step synthetic methodology without employing toxic, gaseous SO2. Due to the instability and dissociation of formed sulfonic acid, and harsh reaction condition, this procedure is quite limited for further transformation.
However, we did developed another interesting reactions occured between alcohol and sulfur dioxide under basic condition. It could be performed at room temperature and have good functional group tolerance. In addition, we have inverstigated the methodology for the synthesis of useful heterocyclic sulfones by using DABSO, and we have currently got some important results. Further completion work is undergoing.