The Synthesis Of A Pharmaceutical Intemediate (Amino Acid Ester)-research On A Catalyst-free N-H Insertion Reaction Cascade Of α-nitrodiazoesters

Amino acid (ester) has played an important role in our daily life.Regardless of water, proteins synthesized by dehydrated amino acid(ester)s are the most commonly found substance in the cell, bone andmuscle of human body. Meanwhile, among all the500amino acid weknow in the nature, some of them could not be synthesized by our body.However, to prepare all the amino acid by chemistry methodology hasalways been the dream of chemists. As a result, chemists have keptsearching for an efficient, low cost and enantioselective way to prepareamino acid, since the first one was discovered200years ago.Being a comprehensive reaction type ulized in drug discovery, newmaterial exploring and new chemical entity synthesized, N-H insertionrection has improved a lot in the last50years. With more understanding ofit, we begin to realize that it will play a more important role in thesynthesizing of amino acid, which actually is the most direct and simpleway to do it.However, most known successful N-H insertions are contributingtheir success to the trasition metal catalysts. It was not until last year that aresearch group published their discovery of organo catalysis of N-Hinsertion by urea to afford the desired amino acid esters. After we dobioisosterism to urea to introduce our pyrimidinone into the same reaction system, we were afforded with a positive result. Surprisingly, when wetried to screen a better solvent for the reaction system, we were astonishedto find that system that undergo N-H insertion with methanol as solventand without any catalyst worked the same as one with catalyst.To investigate more comprehensively on the unpublished rectionsysterm, we have further optimized the temperature, time and molarity ofthe reaction mixture to afford the best one. Later, we tried lots of newnucleophile with different stereoelectronic effect and steric hindrance toobtain some new compound. When monitoring and purifying thementioned reactions, we were interested in every minor part of the reactionmixture to support our plausible reaction mechanism. Indeed, there is stillsome room to take in our future study in the N-H insertion.