Asymmetric Synthesis Of Chiral Propargylamines And Chiral β-alkvnvl-β-aminos Acids Under Br(?)nsted Base Catalysis

Propargylamines are important intermediates for the synthesis of polyfunctional amino derivatives as well as natural products and pharmaceutical molecules and pesticide molecules(such as herbicide and fungicide), and that many propargylamines were found to have pharmacological function. β-Amino acids are key structural elements of peptides, peptidomimetics, pharmaceuticals and natural products. Among the various β-Amino acids, P-alkynyl-β-Amino acids represent a particularly intriguing subclass of compounds. So there are great significances to synthesis it. Chiral thiourea catalyst is an important component of the organic small molecular catalysts, which are easy prepared, mild service conditions and widely used.In this paper, we expound that chiral bifunctionnal tertiary amine thiourea catalyst catalyze asymmetric mannich reaction between C-alkynyl N,O-acetal and monothiomalonate, and we get the propargylamine and turn it intoβ-alkynyl-β-Amino acids in the end.The first part of this article expounds the history of chiral compounds as well as the progress of chiral thiourea catalyst to catalyse asymmetric mannich reaction and two traditional methods to synthesis propargylamines:a) the alkynylation of imines; b) the addition of carbon nucleophiles to C-alkynyl imines.The second part introducing the chiral bifunctionnal tertiary amine thiourea catalyst catalyze asymmetric mannich reaction between C-alkynyl N,O-acetal and monothiomalonate. We achieve excellent yield(85%), high enantioselectivity (up to 96% e.e.), when the reaction proceeded in toluene with 10 mol%catalyst F and reaction of three days at the designation (50℃) temperature. In addition, the substrates are extensive for heterocyclic and aliphatic C-alkynyl N,O-acetal. In a word, this a chiral bifunctionnal tertiary amine thiourea catalyst catalyze asymmetric mannich reaction between C-alkynyl N,O-acetal and monothiomalonate to synthesis propargylamines, and in the process of the reaction, there is a intermediate named C-alkynyl imine. It’s not only the first report of tertiary amine-thiourea catalyst catalyzed asymmetric mannich reaction involving C-alkynyl imines, but also the first report of tertiary amine-thiourea catalyst to in situ generating imines.In conclusion, chiral bifunctionnal thiourea catalyst has excellent performance, and it also can synthesis some more valuable compounds, and it must be much accounted that in situ generating imines. This is a very useful method to in situ generating imine and directly for the use of next reaction.