Asymmetric synthesis: XII:Stereocontrolled electrophilic-nucleophilic α,α'-substitution of the pyrrolidine ring

The synthesis of 2-cyano-5-oxazolopyrrolidine 3 , a chiral pyrrolidine synthon, is described. Conditions were established that permitted sequential chemoselective reactions at the C-2 aminonitrile (electrophilic substitution) and at the C-5 aminoether (nucleophilic substitution) centres of 3 . A stereospecific decyanation of the alkylated aminonitrile allowed the formation of the first asymmetric centre at C-2 of the pyrrolidine ring. The first enantioselective synthesis of (+)-(S)-trans-2-heptyl-5-ethyl-pyrrolidine 9 , a component of the venom of the ant Solenopsis punctaticeps served as an example of the method. Both enantiomers of cis-2-heptyl-5-ethyl pyrrolidine 13 were obtained from the minor diastereomers 7 and 8 which were formed on reaction of oxazolidines 5a and 5b with Grignard reagents. The stereochemical outcome of the substitution reactions is discussed. In addition, full data on the synthesis of ant venon alkaloid (+)- (S)-trans-2-heptyl-5-butyl-pyrrolidine and its cis stereomer are given.