Enantiospecific synthesis of N-benzyl-2-alkyl pyrrolidines and piperidines mediated by chiral organoborane reagents

Asymmetric routes to substituted piperidines

“…Not only does this provide a simple route to diverse 2-substituted piperidines, but either enantiomeric series is accessible by use of appropriate chiral boranes (Scheme 11). 26 The use of chiral borane reagents as catalysts has been only moderately successful, but used in conjunction with a chiral auxiliary, the matched reagents can lead to very high asymmetric induction-see the section concerning Diels-Alder reactions of imines.…”

Efficient and Practical Synthesis of (R)-2-Methylpyrrolidine

“…However, this procedure required large reaction volumes and multiple recrystallizations (4×) to achieve >97% ee and only proceeded in 28% overall yield. Although there have been a number of methods reported for the synthesis of enantiomerically pure 1 , most suffer from inefficient enzymatic resolution protocols of synthetic intermediates or involve multiple steps employing toxic reagents or costly chiral auxiliaries. , While investigating an enantioselective synthesis of 1 , a report by Ku and co-workers at Abbott 6 appeared describing the synthesis and preparation of 1 which was closely related to our own route and that described by Kostyanovsky and co-workers (Scheme ) . The Abbott preparation involved a five-step synthesis beginning with expensive l -prolinol 2 , required the use of a large excess (10 equiv) of costly LiI, and resulted in the isolation of 1 as an extremely hygroscopic HCl salt in 63% overall yield from 2 .…”

Strategy for the Enantioselective Synthesis of trans-2,4-Disubstituted Piperidines: Application to the CCR3 Antagonist IS811

“…Formation of the piperidine ring was achieved by treating bismesylate 6b with solvent n -propylamine. This protocol is based on that used by Singaram for the synthesis of ( S )- N -benzylconiine . In the present case, the dialkylation afforded 7a in essentially quantitative yield.…”