Multicomponent Reactions Via Trapping Of Active Sulfur Ylide Intermediates With Electrophilic Reagents

Multicomponent reactions(MCRs)involving metal carbenes have unique advantages in the construction of compounds with diverse structures and functions,which has attracted more and more attention from chemical researchers.Our group have committed to developing a multi-component reaction based on metal carbene involved electrophilic trapping of active ylide intermediates,which include ammonium-based ylide intermediates that formed by amines nucleophilic attack on metal carbene,and hydroxyl ylide intermediates that formed by alcohols attack on metal carbene.As a continuation of our group’s electrophilic trapping strategy in the developement of multicomponent reaction,we realized the MCRs based on electrophilic trapping of active sulfur ylide intermediates which formed by nucleophilic attacking of metal carbene with thiophenols in this thesis.Sulfur-containing compounds exist widely in nature or in drug active molecules,and are widely used in organic synthesis as important synthetic intermediates.Carbenemediated sulfur-hydrogen insertion reaction is an effective way to construct carbonsulfur bonds.This S-H insertion reaction is generally considered to proceed through the formation of sulfur ylide intermediates,followed by 1,2-hydrogen migration.The MCRs based on electrophilic trapping active intermediates have been developed by our research group,and we successfully extended this multi-component reaction through the trapping of active sulfur ylide intermediates in this thesis.With the strategy of synergistic catalysis,we first realized the three-component reaction based on electrophilic trap of active sulfur ylide intermediates.The electrophilic reagents have been extensively explored and the reactions have provided a novel method for the construction of sulfur compounds with structural diversity.In chapter 2,we have developed a mild and efficient method for the construction of a series of ?-sulfur-substituted ketones.The three-component trapping reaction of diazo compounds,thiophenols and α,β-unsaturated ketones was achieved in high yields and moderate diastereoselectivities in the presence of rhodium acetate and scandium trifluoromethanesulfonate cocatalytic system.Controlled experiments excluded the step-by-step reaction process,and suggested the possibility of an intermolecular process of scandium trifluoromethanesulfonate activated α,β-unsaturated ketones electrophilic trapping of in situ generated active sulfur ylide intermediates.The Michael type electrophilic trap of active sulfur ylide intermediates was successfully achieved by this method.This method also provides experimental evidence to support the existence of active sulfur ylide intermediates in traditional metal carbene-catalyzed sulfurhydrogen insertion reactions.In chapter 3,we have achieved the first asymmetric three-component reaction of diazo compounds,thiophenols and imines co-catalyzed by rhodium acetate and chiral binaphthol phosphoric acid.This is the first enantioselective trapping of active sulfur ylide intermediates.This transformation is proposed to proceed via the generation of active sulfur ylide intermediates by the reaction of metal carbene with thiophenols,and subsequently electrophilic trapped by the phosphoric acid-activated imines.With this method,a series of α-mercapto-β-amino esters were obtained in good yields with moderate to good stereoselectivities.In chapter 4,we have developed an efficient method for asymmetric synthesis of a series of sulfur-containing spirooxindole-fused heterocycles.Through the synergistic catalytic strategy of rhodium acetate and chiral phosphoric acid,we achieved the reaction between 2-mercaptophenyl ketones and 3-diazooxindoles.With this method,a series of spirooxindole-thiaindan derivatives bearing two contiguous quaternary carbon stereogenic centers were obtained in high yields with high stereoselectivities.We believe that the high stereoselectivity of the reaction is due to the activation of the double hydrogen bond of phosphoric acid,and propose the possible transition state of the reaction.