Reactions Of Diazo Compounds In Chemical Catalysis

My research contains two parts:1)the first part focused on discovering new multicomponent reactions involving the trapping of zwitterionic intermediates and developing asymmetric reactions;2)the second part focused on developing transition metal-catalyzed reactions of propargylic diazoesters.Multicomponent reaction has attracted considerable attention owning to its high efficiency for constructing multiple bonds in single step.Thus,discovering new multicomponent reactions is in high demand in modern organic chemistry.Moreover,developing asymmetric multicomponent reactions is a much more challenging goal in organic synthesis as well as provides an opportunity to further understand existed chemical reactions.As part of our ongoing interest in discovering novel multicomponent reactions via trapping active intermediates,we envision that zwitterionic intermediates generated by reactions of indoles and rhodium-stabilized carbenes can be trapped by a third component instead of collapse of zwitterionic intermediates furnishing C-H insertion products.Our group has developed dirhodium(?)acetate and chiral phosphoric acid co-catalyzed asymmetric multicomponent reactions.This strategy is successfully employed in our multicomponent reaction of indoles,diazocompounds and imines.Applying this method,we are able to construct a variety of chiral indole derivatives using different combinations of easily obtained starting materials.To further understand the proton transfer pathway of the zwitterionic intermediate,we carried out a deuterium isotope labeling experiment,which indicates an "indirect proton transfer" in the reaction.The observation provides us an opportunity to design a chiral proton-transfer shuttle to achieve the asymmetric C-H functionalization.Divergent-oriented synthesis(DOS)is a strategy that emphasizes efficiency of chemical library synthesis of small molecular with complexity as well as skeletal diversity.In 2003,Stuart L.Schreiber and co-workers have proposed there are two general approaches for planning synthesis pathways that generate skeletal diversity:reagent-based approach and substrate-based approach.Both of the approaches have achieved great success on building molecular complexity,and numerous examples have illustrated the utilities of these approaches.Even with higher efficiency of constructing molecular complex and structural diversity,catalyst-based approach,which catalyst works as a function of diversity,has been neglected.As part of our ongoing interest in carbene chemistry,we asked the question "which one will occur first if both functional groups are present in the same molecule and what will happen to the other one?" To answer the question,we synthesized propargyl phenyldiazoacetate,which has a possibility to generate either metal carbene species,and then studied the reactivity under a variety of reaction conditions.We disclosed that 1)Rh,Pd,Hg,Ru,Ag and Cu catalysts work well in carbene/alkyne cascade reactions;2)Gold catalyst exhibits a unique catalytic reactivity,which not only selectively activates alkyne group but also remains the dinitrogen in the final product.In the process of studying propargyl phenyldiazoacetate with a broad selection of gold catalysts under various conditions of temperatures,solvents and additives,we found reactions using a 4-chloropyridine-N-oxide in stoichiometric amounts resulted in the formation of(Z)-diene and a product anticipated from diene-diazo[4+2]-cycloaddition.This leads to the discovery of the first intramolecular.[4+2]-cycloaddition between a 1,3-diene and a diazo ester.Then I successfully isolated the(E)-diene and studied the kinetic version of this reaction.Also,thermal reactions with the E-isomers form the products from[4+2]-cycloaddition with AH(?)298 = 15.6 kcal/mol and ?S(?)298 =-27.3 cal/(mol·deg).The Z-isomer is inert to[4+2]-cycloaddition under these conditions.Furthermore,Hammett plot of this unique reaction was also studied.Cascade reaction,a consecutive series of transformations occurred in one step,is noted for efficient construction of molecular complex,high atom economy and economies of time,labor,resource management.Due to these benefits,discovery of novel cascade reactions has been keeping in high demand as well as a challenging task of modern organic synthesis.Substrates with multiple functional groups are considered crucial and fundamental to the discovering cascade reactions.Inspired by gold-catalyzed[4+3]-cycloaddition of propargyl esters and unsaturated imines,we decided to use a modified propargyl system in which benzoate is replaced by phenyldiazoacetate that was expected to produce the azepine product that retained the phenyldiazoacetate functionality.Instead,a new and unexpected transformation occurred that reorganized the reactant atoms to convert the reactant ester to a diketone and rearrange the reactant atoms.To further understand this extensive process,we used the NMR spectroscopy to monitor the process.An intermediate was observed within 5 min that rapidly rearranged to diketone.Then the intermediate was isolated by quenching the reaction after 5 min.Purified by silica gel chromatography,the isolated was converted to diketone at 80? in 90%yield without added catalyst.