Facile synthetic route to enantiopure unsymmetric cis‐2,5‐disubstituted pyrrolidines

Abstract

The (+/-)-cis-5-arylcarbamoyl-2-ethoxycarbonylpyrrolidines 6a-g were firstly synthesized in 53-64% yields by using meso-diethyl-2,5-dibromoadipate 3 and (S)-(-)-1-phenylethylamine in three steps. The diastereomeric mixture (S;2S,5R)-(-)-7 and (S;2R,5S)-(+)-8 were prepared by the Grignard reaction and separated by a flash column chromatography in 29 and 52% yields. The absolute configurations of (+)-8 was confirmed by X-ray crystallographic analysis and the enantiopure pyrrolidines (2S,5R)-(-)-9/(2R,5S)-(+)-9 and (2S,5R)-(-)-10/(2R,5S)-(+)-10 were obtained in good yields.

Efficient synthesis of unnatural dipeptides based on cis-2,5-disubstituted pyrrolidine

“…Previously, we have reported a facile access to enantiopure cis-2,5-disubstituted pyrrolidines (Fig. 1, compounds A and B) using meso-diethyl-2,5-dibromoadipate and (S)-(-)-1-phenylethylamine as starting materials (Wang et al 2007). With this background and in continuation of our previous work, we report in this paper an efficient construction of unnatural dipeptides from phenylalanine and cis-2,5-disubstituted pyrrolidines.…”

“…The monoacid cis-1 was obtained in 76% yield by previously reported protocol of selective monohydrolysis (Wang et al 2007) of diethyl cis-1-[(S)-1-phenylethyl]pyrrolidine-2,5-dicarboxylate (Yamamoto et al 1993). The coupling reactions of monoacid cis-1 with L-and D-phenylalanine ethyl ester hydrochloride were investigated, respectively.…”

One-pot tandem cyclization of enantiopure asymmetric cis-2,5-disubstituted pyrrolidines: Facile access to chiral 10-heteroazatriquinanes

“…2) [9]. The preparations of compounds 5a , 5b , 6a and 6b were also reported in [9], but our previously published structures for compounds 5a and 5b were not completely correct, because the B–N dative bonds were missing.…”

“…2) [9]. The preparations of compounds 5a , 5b , 6a and 6b were also reported in [9], but our previously published structures for compounds 5a and 5b were not completely correct, because the B–N dative bonds were missing. The aim of the following procedures was to obtain several novel bifunctional N -hetereocyclic carbenes (NHCs) [10–14] from compounds 4 through three steps, including reduction, debenzylation and cyclization (Scheme 1), but this failed.…”

Facile Access to Unnatural Dipeptide-Alcohols Based on cis-2,5-Disubstituted Pyrrolidines

“…In our previous work, we reported the efficient construction of enantiopure unsymmetric cis -2,5-disubstituted pyrrolidines ( Figure 1 , compounds A – D ) using meso -diethyl-2,5-dibromoadipate and ( S )-(−)-1-phenylethylamine as starting materials [ 17 , 18 , 19 ]. Herein, we describe a facile route to unnatural dipeptide-alcohols from phenylalaninol and cis -2,5-disubstituted pyrrolidines.…”