Hofmann-Loffler-Freytag reaction Mechanism

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. 

The Hofmann-Loffler-Freytag reaction involves a 1,5-hydrogen transfer to a nitrogen atom. This reaction has been reviewed [61-63], and a recent update is available [35] (see also Chapter 5.1, Volume 2). Its mechanism has been investigated [64], and the formation of an aminium radical has been postulated (Scheme 12). The strong... 

Proposed here is a tentative mechanism for the Hofmann-Loffler-Freytag reaction. 

The combination of an aryl- or alkylsulfonamide, 3 equiv. PhI(OAc)2 and substoichiometric I2 is able to promote C-H animation of simple hydrocarbons in the absence of any metal catalyst [120]. These reactions are best performed neat (10-fold excess of substrate relative to RS02NH2) at 50°C and appear to operate with reasonable selectivity to give benzylic sulfonamide products. Over-oxidation to the sulfonylimine is noted in some cases. A proposed reaction mechanism posits the intermediacy of a sulfonamidyl radical, formed from the AModosulfonamide. This pathway parallels in many ways the mechanism invoked for the Hofmann-Loffler-Freytag process. 

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