Aminyl Radical Hofmann-Loffler-Freytag Reaction

Aminyl Radical Hofmann-Loffler-Freytag Reaction... 

In conclusion, the Hofmann-Loffler-Freytag reaction tends to give moderate and sometimes poor yields for the preparation pyrrolidines under the classic conditions. Nonetheless, the utility of this reaction to functionalize molecules via the aminyl radical mechanism plays an unique role in the tool box for the organic chemist, enabling transformations not easily achievable using other means. Furthermore, milder conditions and better yields can be achieved by taking advantages of the newer developments such as the Suarez modification. 

Electrophilic radical cyclizations of alkenyl aminium cation radicals have shown synthetic utility. Hofmann-Loffler-Freytag reactions do not compete with 5-exo cyclizations (75BSF1429). The homolytic cyclization of Af-chloroalkenylamines under acidic or Lewis acidic conditions has been studied primarily by Surzur and Stella, and the chemistry of these precursors for electrophilic aminyl radical generation has been reviewed [83AG(E)337]. Radical chain reactions can be initiated by heat, UV photol-... 

Recently, Kim has reported a modified Hofmann-Loffler-Freytag reaction under reducing conditions [70], Treatment of alkyl azides with Bu3SnH afforded N-tributylstannyl radicals. These radicals proved to be more reactive than ordinary aminyl radicals towards hydrogen atom abstraction presumably because of their higher nucleophilicity. Two examples are shown in Scheme 14. In the first one (Eq. 

The history of C-H amination can be traced to the earliest work of Hofmann involving the reactivity of /V-bi omoamines. chemistry later recognized by Loffler and Freytag for its potential to facilitate pyrrolidine synthesis from simple acyclic precursors [11]. The intermediacy of both haloamine and aminyl radical in this stepwise oxidation reaction is now generally accepted, as is the hyper-reactivity of... 

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