Pyrrolidines, generation by radical cyclizations

New cyclizations via photochemically generated aminyl radicals have been reported, including further examples of the Hofmann-Loeffler-Freytag reaction.313 Intramolecular addition of an aminyl radical, generated by photochemically induced nitrogen chlorine bond homoysis, is also accompanied by cyclization as illustrated by the conversion of the unsaturated N-chloroamide 378 to the pyrrolidine 379.314 Piperidine formation can also... 

Neutral aminyl radicals generated by anodic oxidation of lithium alkenyl amides undergo a stereoselective cyclization to cis-l-methyl-2,5-disubstituted pyrrolidines [249]. 

Neutral aminyl radicals were generated by the anodic oxidation of lithium 4-pentenylamides and underwent regioselective and stereoselective cyclization to 1 -methyl-2,5-c/. -disubstituted pyrrolidines 123 25. 

In this protocol the pyridine- and the pyrrolidine-ring of 1 are built up in a one-pot radical domino reaction." Photolysis of iodopyridone 11 in the presence of hexamethylditin provides radical 56, which attacks the reactive isonitrile 15. The resulting radical 57 reacts with the alkyne group in a 5-exo-dig cyclization (see Chapter 11). Next, the newly formed vinyl radical 58 cyclizes onto the aryl ring generating speeies 59. Final oxidation via a so far unknown mechanism yields 1 with 31 % yield. For the generation of radical 56 by photolysis two ways (A and B) are possible. 

Heating or photolytic treatment of A,A-dialkyl-A-haloamine in sulfuric acid or trifluoroacetic acid, followed by neutralization with a base, generates a pyrrolidine or piperidine skeleton. This is the Hofmann-Loffler-Frey tag reaction, and the reaction comprises of the formation of an electrophilic aminium radical, 1,5-H shift (6-membered transition state) or 1,6-H shift (7-membered transition state), formation of 4-haloalkyl ammonium or 5-haloalkyl ammonium, and its polar cyclization by neutralization with a base. Eq. 6.16 shows the formation of A-alkyl pyrrolidine (31) from A-chloro-A-alkyl-A-butylamine (30) in sulfuric acid [46, 47]. 

The photooxidation of m-unsaturated a-alkylsilylamines by the singlet excited state of DCN proceeds with selective desilylation to generate a-amino radicals from a-alkylsilylamine radical-cation. Cyclization of the a-amino radicals leads to substituted pyrrolidines and piperidines [42] (Scheme 20). 

Much work has been devoted to the synthesis of the pyrrolidine and pyrrolidone systems by free radical methods. For pyrrolidine derivatives it is preferable to initiate the cyclization from an aminyl radical generated from Af-chloro- or N-sulfeny-lamine. - ... 

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