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Research On Asymmetric Reactions Of Imines Bearing A Heterocycle Catalyzed By Squaramides

Posted on:2016-06-24Degree:DoctorType:Dissertation
Country:ChinaCandidate:H X HeFull Text:PDF
GTID:1221330476950693Subject:Applied Chemistry
Abstract/Summary:PDF Full Text Request
Organocatalysts catalyzed asymmetric reaction is an important method for modern chiral synthesis. The development of excellent organocatalysts and highly efficient stereoselective reactions is currently an important topic in organic catalysis. In this thesis,based on the literature survey, we have designed and synthesized a series of chiral squaramides, and applied them in various asymmetric reactions. The main work is as following:Firstly, an efficient enantioselective aza-Henry reaction of nitroalkanes to imines bearing a benzothiazole moiety catalyzed by a cinchona-based squaramide has been developed. In the reaction of imines, the corresponding products were obtained in good to excellent yields(up to 99%) with excellent enantioselectivities(up to >99% ee) for most of the aromatic substituted imines. The imines with electron-withdrawing groups gave better yields than those bearing electron-donating groups in the aza-Henry reaction. Moreover, a one-pot three-component enantioselective aza-Henry reaction using 2-aminobenzothiazoles,aldehydes, and nitromethane was also developed. Moderate to good yields and high enantioselectivities were obtained in the one-pot cases(up to 98% ee). On the basis of the absolute configuration of the products determined by X-ray analysis, we propose a possible mechanism for this aza-Henry reaction. The novel derivatization compound was obtained in good yield with retained excellent enantioselectivity.Secondly, a series of chiral squaramides have been applied in enantioselective Mannich reaction of imines bearing a heterocycle with malonates, the ?-amino ester derivatives containing a heterocycle moiety in high yields(up to 99%) and excellent enantioselectivities(up to 98%) in most cases. The effect of solvent, temperature, and catalyst loading was investigated and a possible transition state model was proposed. This study has highlighted that a series of malonates were evaluated and the excellent yield and enantioselectivity obtained.Highly enantioselective Mannich reactions of imines bearing a benzothiazole moiety with tert-butyl acetoacetate, catalyzed by a cinchona-based squaramide organocatalyst havebeen developed. The corresponding benzothiazole β-keto ester derivatives were obtained in high yields(up to 99%) and with excellent enantioselectivities(up to 98% ee).Finally, an organocatalytic enantioselective Strecker reaction for the synthesis ofα-amino nitriles bearing a thiazole moiety catalyzed by a cinchona-based squaramide was developed. Under the optimal reaction conditions, the corresponding products were obtained in good to excellent yields(up to 99%) with excellent enantioselectivities(up to98% ee) for most of aromatic substituted imines. In addition, two trifunctional squaramides with amino acid residue were synthesized, and good enantioselectivities(up to 89% ee)were also achieved in the model reaction. The product could also be reduced with Li Al H4 to afford the corresponding amine, which reacted readily with triphosgene to afford the imidazolidinone without the loss of stereochemical purity. This work is the first highly enantioselective Strecker reaction catalyzed by squaramide organocatalysts...
Keywords/Search Tags:squaramide, imines, asymmetric catalysis, aza-Henry reaction, Mannich reaction, Strecker reaction
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