Palladium-Catalyzed Synthesis Of Unsymmetrical Disulfides

Disulfides are prevalent in different fields such as life science,natural products,food chemistry,pharmaceuticals and materials due to their unique pharmacological and physiochemical properties.Although various synthetic strategies have been developed,the synthesis of unsymmetrical disulfides is still challenging in terms of synthetic efficiency and selectivity.In this thesis,various unsymmetrical disulfides have been effectively prepared via thiols exchange with readily accessible symmetrical disulfides under PdCl2/DMSO catalysis.The newly developed method features operational simplicity,excellent functional group tolerance,broad substrate scope,and mild conditions.This reaction is especially useful for late-stage functionalization of bioactive scaffolds and organic functional materials.This transformation could be further extended to thiol/diselenide and thiol/ditelluride exchange for the synthesis of RS-SeR’ and RS-TeR’.The dissertation includes the following three parts:Part Ⅰ:In this chapter,we firstly have a review on the importance of disulfide compounds and their preparation.Then,we propose a research plan of this thesis.Part Ⅱ:In this chapter,we optimized the reaction conditions for the synthesis of unsymmetrical disulfides from commercial or readily prepared mercaptans and disulfides.Experiments revealed that PdCl2/DMSO catalytic system can give the desired unsymmetrical disulfides in good to excellent yields.This synthetic method has the following advantages:(1)Simple and mild reaction conditions;(2)excellent substrate scope;(3)gram-scale reaction with comparable yield;(4)excellent functional group compatibility with no need to protect the free amino,hydroxyl and carboxylic acid groups in the substrates.Subsequently,we performed several control reactions to investigate the reaction mechanism,and finally we proposed a possible reaction mechanism for this transformation.Part Ⅲ:In this chapter,the synthetic application of this catalytic reaction has been further investigated.It is found that this reaction is particularly suitable for the post-functionalization of bioactive molecules such as amino acids,peptides and drugs,as well as the preparation of disulfidecontaining organic dyes represented by pyrene and BODIPY.Meanwhile,we have successfully extended the transformation to the construction of compounds containing S-Se and S-Te bonds.