Synthesis and utilization of guanidine catalysts for applications directed towards the preparation of butenolide and modified amino acid derivatives

摘要

Development of guanidine catalysts is explored through direct iminium chloride andamine coupling, alongside a 2-chloro-l,3-dimethyl-IH-imidazol-:-3-ium chloride (DMC)induced thiourea cyclization. Synthesized achiral catalyst N-(5Hdibenzo[d,t][1,3]diazepin-6(7H)-ylidene)-3,5-bis(trifluoromethyl) aniline provedunsuccessful towards O-acyl migrations, however successfully catalyzed the vinylogousaldol reaction between dicbloro furanone and benzaldehyde. Incorporating chirality intothe guanidine catalyst utilizing a (R)-phenylalaninol auxiliary, generating (R)-2-((5Hdibenzo[d,t] [1,3 ]diazepin-6(7H)-ylidene ) amino )-3 -phenylpropan-l-ol, demonstratedenantioselectivity for a variety of adducts. Highest enantiomeric excess (ee) was affordedbetween dibromofuranone and p-chlorobenzaldehyde, affording the syn conformation in96% ee and the anti in 54% ee, with an overall yield of30%. Attempts to increaseasymmetric induction were focused on incorporation of axial chirality to the (R)phenylalaninolcatalyst using binaphthyl diamine. Incorporation of (S)-binaphthylexhibited destructive selectivity, whereas incorporation of (R)-binaphthyl demonstratedno effects on enantioselectivity. Current studies are being directed towards identifying thecatalytic properties of asymmetric induction with further studies are being aimed towardsincreasing enantioselectivity by increasing backbone steric bulk.