Asymmetric Mannich Reaction Of Cyclic ?-Imino Esters And Synthetic Studies Toward Cyano-pyrazoles And Cyano-alkenes

Chiral?-amino acids are the basic unit of proteins,and have been widely embed-ded in many biologically active molecules such as drugs.It is of great value to develop catalytic asymmetric synthetic strategies to access these compounds.Asymmetric addi-tion reaction of?-imino esters is one of the most effective methods.On the other hand,cyano moiety is an important nitrogen-containning function group,and versatile syn-thetic studies of nitriles are still of high interest.In this context,a total of 103 new compounds were synthesized.In the first part,we have developed Br(?)nsted acid-catalysed asymmetric Mannich reaction of six-membered cyclic?-imino esters with enamides.The optimal catalyst is the chiral BINOL-derived phosphoric acid with 2,4,6-trimethylphenyl substituted at the3,3'-position.The wide substrate scope,mild reaction conditions,and constantly excel-lent enantioselecticities(>95%ee in most cases)render this protocol highly practical for the rapid construction of valuable noncanonical?-amino ketone derivatives,and then can be converted into unnatural chiral?-amino acids with Pd(OH)₂/C under hy-drogen atmosphere.In the second part,we presented a facile approach to a diverse collection of 1,4-disubstituted-3-mono-or difluoromethylpyrazoles.By utilizing our previously devel-oped cyanopyrazoles as key building blocks followed by further oxidative acylation of C4-substited furanyl,a commercialized fungicide Fluxapyroxad and its 7 analogues were successfully obtained within 5-6 steps.The in vitro fungicidal activity against 14kinds of phytopathogens were assessed.Notably,the monofluoromethylated analogue exhibited remarkable in vitro fungicidal activity towards several phytopathogens.In the third part,we used 1,1-bis(benzenesulfonyl)alkenes as starting material and KCN as the cyanation reagent to produce a series of cis-1,2-dicyanoolefins in one pot manner.This reaction was conducted in the presence of tetrabutylammonium bromide and NH₄Cl/K₃PO₄ under phase-transfer conditions.Further transformation of the ob-tained product allows for access to imide and dicarboxylic acid compounds.