Rhodium(Ⅰ)carbene Mediatedasymmetric O–H Insertion And Cyclopropanation Reactions

Carbene chemistry based on diazo decomposition has witnessed rapid development in the past two decades.Many highly efficient and selective catalytic systems have emerged for the asymmetric carbene transfer reactions,including X–H（X=C,O,N,S,Si,B,etc）bond insertion,cyclopropanation,and reactions involving ylide intermediates.Despite significant progress,challenges remain in achieving substrate compatibility and enantioselectivity control for challenging substrates,such as aliphatic amines,mercaptans,carboxylic acids,phosphoric acids,nitrogen-containing olefins,and multi-substituted alkenes.This dissertation addresses these challenges by focusing on two key reactions:the asymmetric O–H insertion of Rh（I）-carbene with phosphinic or phosphoric acids and the asymmetric cyclopropanation of Rh（I）-carbene with nitrogenous alkenes or polysubstituted alkenes.The main contents are as follows:In the study of asymmetric O–H insertion,a Rh（I）/diene-catalyzed asymmetricα-vinyldiazoacetates insertion into O–H bonds of phosphinic or phosphoric acids is developed using triethylamine trihydrofluoride（Et₃N-3HF）as an additive.This methodology enables the synthesis of a variety of chiral allylic phosphinates or phosphates with high enantioselectivities（56-98%）and yields（29-97%）.The catalytic system exhibits excellent functional group compatibility,accommodating electron-withdrawing or electron-donating groups on vinyldiazoacetates,as well as symmetric or unsymmetric substituents on phosphinic or phosphoric acids.Besides,by simple transformation of the products,derivatives such as chiral allylamine were obtained.In addition,NMR experiments indicate that the Et₃N-3HF additive acts as a hydrogen bond acceptor,passivating the acidity of the acids and enhancing the stability of chiral metal complexes.Furthermore,the observed kinetic isotope effect（k _H/k _D=4.6:1）suggests that the rate-determining step is likely the proton shift process in this reaction.For the asymmetric cyclopropanation of nitrogen-containing olefins,a highly enantioselective intermolecular reaction is achieved using a cationic Rh（I）/diene complex catalyst.This methodology allows the synthesis of chiral cyclopropylamides in good yields（29-93%）with high enantioselectivities（65-99%）and diastereoselectivities（>20:1dr）.The catalytic system exhibits remarkable tolerance towards various functional groups,such as aryl-,methyl-and propenyl-substitutedα-diazoesters and aryl-and alkyl-substituted vinylamides.Besides,NMR and kinetic experiments show that a resting-state of coordination between vinylamide and metal cente is formed in the first stage,supporting that the formation of Rh（I）-carbene is likely the rate-determining step of this reaction.Moreover,density functional theory（DFT）calculation reveals the reaction mechanism in accordance with the outer-sphere mechanism,in which the vinylamide substrate is located outside the coordination sphere of the metal.Meanwhile,the observed diastereoselectivity in this reaction also conform to the mechanism for the formation of trans-configuration products.For the asymmetric cyclopropanation of polysubstituted alkenes,a simple,broad-scope Rh（I）/chiral diene catalytic system has been developed that allows otherwise difficult-to-access bicyclic/penta-substituted cyclopropanes with simultaneous control of three vicinal carbon stereocenters in 49-99%yields with>20:1 dr,79-99%enantioselectivities through asymmetric intramolecular cyclopropanation of rather challenging tri-substituted allylic diazoacetates.The reaction exhibits good functional group compatibility,regio-and enantioselectivity for substrates such as aryl,heteroaryl-,alkenyl-substitutedα-diazoesters of different electrical properties,as well as a series of alkyl,alkenyl and aryl substituted alkenes,generating mainly cis-products.By manipulating the stereochemistry of alkenes,a pair of diastereomers of high optical purity,featured with three consecutive chiral centers were successfully attained.It is noteworthy that efficient conversion of the substrates can be achieved by using as low as 0.1 mol%（1/1000）load of catalyst.Meanwhile,transformation such as ring opening or partial reduction that retain the stereochemistry of the starting bicyclic/penta-substituted cyclopropane,enables simple access to a wide variety of chiral functionalized cyclopropane.Finally,a DFT calculation revealed theπ-πstacking interaction between the aromatic ring on diazoester and the phenyl ring on diene ligand which could play a key role of stereoselective control in the reaction.