Pyrrolidine, possible conformations

The opportunity for chelation in the various enolate intermediates offers a possible explanation for the observed diastereoselectivities. In the dianions derived from l-acyl-2-pyrrolidinemethanols strong chelation of both of the lithium cations should lead to a rigid enolate structure 9. It is reasonable to assume that the pyrrolidine ring is locked in one conformation. Since, according to models, it is difficult to attribute the observed high diastereoselectivity to steric hindrance, it is probable that the lone pair on the nitrogen directs the facial selectivity of electrophilic attack (see Section 1.1.1.3.3.1.) to one side of the enolate a-carbon. 

The four possible stereoisomers of the diastereomeric mixture of ( )-2-(lH-imidazol-4-yl)-cyclopropylamine (17) have not been separated yet (except very recently both tram isomers (Table 4) [25]), but as a result of this molecular modelling study it was observed that a congruent pharmacophoric conformation can only be adopted by the two tram configured isomers [24]. The conformationally restricted pyrrolidine derivatives immepyr (21) and SCH 50971 (22) support this pharmacophore... 

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