Research On Radical-Mediated Reactions For The Synthesis Of Thiosulfonates And 3-Hydroxylisoquinolin-1,4-Diones

Thiosulfonates are widely used in the synthesis of pharmaceuticals,agrochemicals,and polymers because of their excellent biological activities and high reactivity.Moreover,thiosulfonates have been increasingly used as synthetic intermediates in organic synthesis due to their good reactivity and stability.Nitrogen-containing heterocyclic compounds with isoquinolinones scaffolds are the basic skeleton of many drug molecules and natural products,which have shown broad biological properties.Therefore,the synthesis of these compounds has become one of the research hotspots of organic synthesis.Radical reactions were applied in a range of organic transformations due to their unique advantages such as excellent reactivity,mild conditions,good selectivity,and functional group tolerance.Traditionally,the synthesis of thiosulfonates required the use of precious transition-metal catalysts,toxic reagents,and/or harsh reaction conditions.3?Hydroxylisoquinolin-1,4-diones can be prepared by the cyclization reaction of2?alkynylbenzamides,but it is difficult to efficiently control the reaction regioselectivity.Therefore,it is of great significance to develop simple and efficient procedures to synthesize thiosulfonates and 3?hydroxylisoquinolin-1,4-diones.This thesis mainly studies the efficient and green synthesis of thiosulfonates and 3?hydroxylisoquinolin-1,4-diones from inexpensive and readily available starting substrates under mild reaction conditions.This dissertation is divided into two parts:（1）reductive coupling of sodium sulfinates for the synthesis of thiosulfonates;（2）manganese-catalyzed radical 6-endo azacyclization of 2?alkynylbenzamides for the synthesis of 3?hydroxylisoquinolin-1,4-diones.The research contents include:1.A disproportionate coupling reaction of sodium sulfinates in the presence of acetyl chloride and Hantzsch ester is developed.This reaction provides an efficient approach to the synthesis of symmetrical/unsymmetrical thiosulfonates.The reaction takes place under very mild conditions with good functional group tolerance,leading to a range of thiosulfonates in moderate to excellent yields.2.A manganese-catalyzed cyclization of 2-alkynlbenzamide under O₂ balloon is developed for the synthesis of 3-hydroxylisoquinolin-1,4-diones.It is believed that the N-center radical-based 6-endo dig aza-cyclization proceeded in a regioselective manner.The isolated yields of products are 40-68%.