Catalytic Asymmetric Hydrofunctionalization Of Enamides

Olefins are important industrial feedstocks.Efficient asymmetric synthetic methods based on olefins functionalization will greatly improve the value of these industrial chemicals.Among the methods for the synthesis of chiral molecules,enantioselective hydrofunctionalization of alkenes is both atom-and step-economic.However,the asymmetric hydrofunctionalization of multiple substituted alkenes represents a significant challenge because of the potential side reactions,low reactivity and difficulty associated with control of regio-and stereo-selectivity.To meet these challenges,we focus on catalytic regioselective and enantioselective hydrofunctionalization of internal alkenes.Using a directing group on the alkene substrate as a coordinating group,a twopoint binding mode of the substrate to the metal center enables effective catalytic activity.By taking advantage of substrate-directed strategy,we have developed the processes of the asymmetric carbon-carbon bonds and carbon-heteroatom bonds formation to construct single stereocenter,adjacent stereocenters and quaternary stereocenter.The mechanism studies indicated that the substrate-directed strategy plays an important role in the controlling of the regio-and stereoselectivities.My Ph D thesis focuses on the study of asymmetric hydroalkynylation and hydroboration of enamides.(1)In the asymmetric hydroalkynylation of enamides(Chapter 2),we have developed a rhodium-catalyzed enantioselective hydroalkynylation of enamides with terminal alkynes.The reaction occurs with complete ?-selectivity and high enantioselectivity.This novel strategy provides an efficient method to access chiral propargyl amides.The investigation of stereochemistry experiment revealed that the alkynylation occurs exclusively through a syn-addition process.Kinetic studies indicated that migratory insertion of the alkene to the rhodium hydride is turnover limiting.Computational studies revealed the origin of regio-and enantioselectivities.(2)In the asymmetric hydroboration of enamides(Chapter 3),the pinacolborane was used as both hydrogen and boron source.Firstly,we have developed a rhodiumcatalyzed regiodivergent hydroboration of enamides,which provided access to both ?-and ?-hydroboration products respectively.Computational studies revealed that the origin of regioselectivity was derived from the repulsive interaction between enamide and ligand.Based on the results,we have developed a rhodium-catalyzed regiodivergent and stereoselective hydroboration of enamides,which achieved both chiral ?-and ?-aminoboronic esters.Particularly,chiral ?-amino tertiary boronic esters and ?-aminoboronic esters containing two adjacent stereocenters have been synthesized with high regio-and enantioselectivities.In brief,we have developed a general method for the preparation of chiral ?-and ?-aminoboronic esters from the same substrate through the regio-divergent pathway.This method provided a new synthetic strategy for the preparation of related chiral compounds.In summary,we have achieved the catalytic asymmetric hydroalkynylation and hydroboration of enamides,which produced chiral propargyl amides and aminoboronic esters with a novel,concise and efficient synthetic strategy.The detailed mechanistic studies provided basis for the design of new hydrofunctionalization reactions of multisubstituted alkens.