Of nitrogen radicals in pyrrolidine

Bowman and coworkers described another nice approach in this field combining one anionic and two radical cyclization steps (Scheme 2.160) [368], Thus, they were able to construct differenttypes of nitrogen-containing heterocycles such as annulated pyrrolidines 2-724 and spiropyrrolidines 2-726 as well as indolizidines as 2-729. 

Secondary alicyclic amines, such as pyrrolidine and piperidine, have many properties typical of the corresponding aliphatic amines. Metabolic oxidation at secondary alicyclic nitrogens results in the formation of hydroxylamines, which may then undergo enzymic or non-enzymic conversion to nitrones, and in some cases to nitroxide radicals. For example, the 2-substituted piperidino derivative (- )-anabasine (1), a tobacco alkaloid, is metabolized initially to a hydroxylamine (2) and then to the nitrone (3), when incubated with liver and... 

A few reactions of nitrogen compounds interesting from a stereochemical aspect have been reported. Tokuda and coworkers [372] reported the stereochemically clear result that lithium alkeynylamides undergo a highly stereoselective cyclization by anodic oxidation to give C75-1-methyl-2,5-disubstituted pyrrolidines in reasonable yields, as in Eq. (59). The cyclization seems to proceed via neutral amino radicals. 

In common with the general increasing interest in synthetic applications of free-radical cyclizations, this year has seen a high level of interest in the synthesis of nitrogen heterocycles by such processes. Padwa et al. have reported the synthesis of a range of N-benzenesulphonyl-pyrrolidines (220) and -piperidines... 

Two routes to the pyrrolidine system involving the generation of nitrogen-centred radicals have appeared. N-Methyl-cis-2,5-disubstituted pyrrolidines (232) may be obtained in moderate yields... 

Although 2,5-dimethyl-1-hydroxypyrrole was synthesized in 1886 by Knorr, the parent 1-hydroxypyrrole was obtained only 90 years later. These compounds have not been widely investigated. The corresponding radicals, the pyrrole 1-oxyls, their 2,5-dihydro derivatives, and particularly the pyrrolidine 1-oxyls, if the adjacent positions to the nitrogen atom are substituted, can be stable. Many of these pyrrolidines have been prepared and used as spin labels. Only one 1-hydroxypyrrole, an antitumor antibiotic, has so far been isolated from living systems. 

Hydrogen abstraction under conditions similar to those in Section 3.8.1 may occur also from nitrogen compounds, with formation of amidyl free radicals. The results vary, depending on the substrate for example, 6-amino derivatives of steroids were converted into TV-substituted pyrrolidines [127], Medium-sized lactams underwent transannular cyclization to bicyclic lactams [128], and bicyclic carbinolamides afforded mainly -fragmentation products (Table 3.7). 

Azides are highly valuable radical acceptors that form nitrogen-centered radicals after addition onto them, as in the case of the transformation of 31 into 32. This reaction opens new possibilities for making pyrrolidines. Murphy, for instance, disclosed the synthesis of ( )-horsfihne and ( )-coerulescine by tandem cyclization of iodoaryl alkenyl azides such as 29 [42]. By the same strategy and using precursor 33, formal syntheses of ( )-vindohne [43] and ( )-aspidospermidine [44] have been rendered possible (Scheme 10). 

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