Pyrrolidine ring construction

Kim et al. used an enantioselective catalytic phase transfer alkylation, together with a ring-closing metathesis for pyrrolidine ring construction, to first synthesize the phenanthroindolizidine (-)-antofine [(-)-3] [63, 63]. Two similar approaches were developed, but only the later approach is illustrated in Scheme (8). As the key intermediate of this synthetic pathway, 77 is in enantiomerically pure form and was achieved by using a... 

The heteroatom version of the vinylcyclopropane rearrangement serves to facilitate alkaloid construction. Scheme 13 outlines a strategy for the pyrrolizidine alkaloid isoretronecanol 211 90). Use of a carboxaldehyde (i.e. 213) as a synthon for the primary alcohol provides an ability to adjust stereochemistry. It also sets up formation of the pyrrolidine ring bearing the aldehyde by an aldol-type condensation of an enol of the aldehyde onto an imine derived from 214. Because of the lability of such systems, introduction of X=PhS imparts stability. The resultant azacyclopentene translates to an imine 215 using the iminocyclopropane rearrangement methodology. Simple condensation of the primary amine 216 with aldehyde 37a then initiates this... 

The combination of the characteristics of the fullerene skeleton with the fused pyrrolidine ring is of great importance for the construction and synthesis of materials with novel properties. The most attractive feature of fulleropyrrolidines is... 

Pandey, G., Banerjee, P., and Gadre, S.R. (2006) Construction of enantiopure pyrrolidine ring system via asymmetric [3 + 2] cycloaddition of azomethineylides. Chemical Reviews, 106, 4484—4517. 

The stemona alkaloid stemonamide (49) was synthesized starting from a-stannyl acetate 47 and 2-stannyl pyrrolidine 48. The oxidative coupling of stannyl acetate 47 with acetylenic silyl enol ether affords the functionalized C-7 unit which corresponds to the side arm of the pyrrolidine ring. Then, introduction of the C-7 unit to the pyrrolidine ring is performed by the oxidative generation of acyliminium ion. The carbon skeleton of stemonamide was thus constructed efficiently as shown in Scheme 19 by employing organotin compounds. ... 

Intramolecular displacement of benzylic chlorides by nitrile anions was previously demonstrated as an efficient method making substituted pyrrolidines " however, the question of enanti-oselectivity was not addressed. Recent works on the synthesis of substituted cyclopentane showed that intramolecular enolate displacement of benzylic phosphate proceeded in clean inversion. Thus, it was envisioned that an appropriately substituted cyano phosphonate could be used to construct the pyrrolidine ring (Scheme 5.23). This intermediate could potentially be produced by the addition of a fert-butylamine to acrylonitrile. The desired amine could be produced via reaction... 

Construction of enantiopure pyrrolidine ring system via asymmetric [3 + 2] cycloaddition of azomethine ylides 06CRV4484. 

Lepadiformine is a not-too-complicated tricyclic alkaloid, which finds some attention in the synthetic community [31], The first synthesis hy Funk [32] constructs the rings sequentially (Scheme 11.24). The functionality initially needed to facilitate the Diels-Alder addition has been cleverly used to build the pyrrolidine ring. 

Chiou et (d. [81] investigated the hydroformylation-acetalization in the framework of the synthesis of pyrrolidinoindolines and tetrahydrofuranoin-dolines (Scheme 5.89). The hydroformylation occurred in the a-position of the aryl ring. Double cyclization constructed the fused pyrrolidine ring in a stereoselective maimer. Based on this protocol, a variety of pharmacologically important alkaloids were synthesized. By application of the corresponding allyl alcohol as starting material, the THF-based physovenine was prepared. 

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