The Research Of Chiral Auxiliary Reagents In Asymmetric Alkylation Reaction

Oxazolidinone,2-phenenylimino-2-oxazolidine, camphorsultam, prolinol and so on, are the chiral auxiliary reagents used commonly. They are used widely in asymmetric reaction, such as alkylation, with high stereoselectivity and chemical yield. Thiazolidinethione are mainly used for asymmetric Aldol reaction with high stereoselectivity. But the reports that thiazolidinethione induces asymmetric alkylation reaction with halohydrocarbon have not been seen. This thesis investigates thiazolidinethione reacts with halohydrocarbon systematically and synthetizes (R)-and (S)-2-propyloctanoic acid which are the drugs treat Alzheimer disease with2-phenenylimino-2-oxazolidine as chiral auxiliary.1. Investigation of thiazolidinethione reacted with halohydrocarbon and acyl chloride:1) Preparation of chiral auxiliary reagent (S)-4-benzylthiazolidine-2-thione:L-phenylalaninol as raw material was reacted with KOH(aq) and CS2to get (S)-4-benzylthiazolidine-2-thione at110℃with yield81%.2) Thiazolidinethione reacted with halohydrocarbon and acyl chloride:Whether in existence of base (LDA, NaHMDS, n-BuLi) or Lewis acid-base (TiC14, DIPEA),(S)-1-(4-benzyl-2-thioxothiazolidin-3-yl)propan-1-one reacted with halohydrocarbon get S-alkylation products, instead of a-alkylation products which are expected. Change halohydrocarbon with acyl chloride which are more lively, we get O-acylation products instead of α-acylation products. And we speculate possible reaction mechanism.2.2-Phenenylimino-2-oxazolidine induces asymmetric alkylation to synthetize (R)-and (S)-2-propyloctanoic acid:1) Preparation of chiral auxiliary reagent (R)-and (S)-N-(4-benzyloxazolidin-2-ylidene)benzenamine:D-and L-phenylalaninol as raw materials, were reacted with phenyliso-thiocyanate firstly. Then in existence of NaOH(aq) and TsCl,(R)-and (S)-N- (4-benzyloxazolidin-2-ylidene)benzenamine were synthesized by cyclization reaction with yield73.3%and71.6%.2) Induced asymmetric alkylation to synthesize (R)-and (S)-2-propyloctanoic acid:(R)-and (S)-N-(4-benzyloxazolidin-2-ylidene)benzenamine were treated by acylation, alkylation and relief reaction. At last we get (R)-and (S)-2-propyloctanoic acid with total yield of20.7%,19.8%, and optical yield of98.7%,97.5%respectively.