Asymmetric Synthesis of 2-Azabicyclo[3.1.0]hexane-3-carboxylic Acid

作者：Fu Xinghua^*; Fan Jianjian; Zou Aizong; Yu Juan; He Guangke; Zhu Hongjun

来源：Chinese Journal of Organic Chemistry, 2014, 34(8): 1616-1622.

DOI：10.6023/cjoc201403004

• 2-azabicyclo[3.1.0]hexane-3-carboxylic acid
• glutamic acid
• DMAP catalytic cyclization
• hydrolysis reaction
• asymmetric synthesis

2-Azabicyclo[3.1.0]hexane-3-carboxylic acids were obtained via amino protection, 4-dimethylaminopyridine (DMAP) catalytic cyclization, reduction-dehydration into alkene, asymmetric Simmons-Smith reaction and hydrolysis reaction from glutamic acid. The intermediates and target products were characterized by H-1 NMR and C-13 NMR. (R-1,3 S,5R)-2-(tert-Butoxycarbony1)-2-azabicyclo[3.1.0]hexane-3 -carboxylic acid and (1S,35,58)-2-(tert-butoxycarbonyl )-2-azabicyclo[3.1.0]hexane-3-carboxylic acid were analyzed by X-ray diffraction as well. The process conditions about DMAP catalytic cyclization reaction, Simmons-Smith reaction and hydrolyzation were discussed. The results show that the yield of (R)-1,2-di-tert-butyl 5-oxopyrrolidine- 1,2-dicarboxyate was 82% at the ratio of n(DMAP) : n(di-tert-butyl dicarbonate) : n(pyridine)= 0.40 : 4.0 :1.0. The ratio of cis/trans-form varied with the reaction time in Simmons-Smith reaction, which gave a best ratio of 6 : 1 at 19.5 h. The total yield is 30%, and the de value is 72%.

• 出版日期2014-8