Organocatalytic Asymmetric Sp~3-sp~2 Oxidative Coupling

Recently,the oxidative coupling of two C-H bonds has emerged as a powerful transformation available for forging new C-C bonds.However,the development of this transformation into a general,catalytic and enantioselective process still remains a great challenge because it is difficult not only to couple the two unreactive C-H bonds into a new C-C bond but also to control the absolute configuration of the newly generated stereocenter.Meanwhile,the current oxidative coupling reactions are usually required the use of various transition metals.However,transition-metal-catalyzed transformations often suffer from some drawbacks in pharmaceutical industrial applications as it is high cost,air and moisture sensitivity,and may leave toxic trace metal contaminants.The tetrahydroisoquinoline derivatives are widely exists in many natural compounds,it is important organic synthesis skeleton for many drug molecules and natural products of tetrahydroisoquinolines with a stereocenter at the C1 position.So through cross oxidation dehydrogenation coupling of activated tetrahydroisoquinoline to develop new tetrahydroisoquinoline skeleton attracted much attention in recent years.Various nucleophiles have been employed to form Mannich addition products.However,Morita-Baylis-Hillman type products have rarely been synthesized.Intense efforts have been made for amplification the structurally diverse family of substituted butyrolactam derivatives for their synthetic significance in recent years.Among them,most of the reactions occurred in the y-position of a,?-unsaturated y-butyrolactam,but using the a-position of a,?-unsaturated y-butyrolactam to form the adducts with electrophiles is rare,so the study for the a-position of a,?-unsaturated y-butyrolactam is very urgent.We have disclosed the first example on asymmetric oxidative coupling reaction of tertiary amines with a,P-unsaturated y-butyrolactam to construct the MBH-typed products with the help of a bifunctional thiourea catalysis under mild conditions,pro,viding a feasible synthesis strategy strategy for many compounds that have important chemical characteristics and pharmaceutical properties.