Of nitrogen radicals and their cyclizations

The Generation of Nitrogen Radicals and Their Cyclizations for the Construction of the Pyrrolidine Nucleus... 

This chapter has attempted to present a thorough overview of alkaloid syntheses in which free-radical cyclizations have played a pivotal role. It is not meant to be a comprehensive review, but focusses on syntheses in which nitrogen plays a clear role in the cyclization process, either as an attenuator of radical reactivity (Sections 4,1.2 and 4.1.3), a tether (Section 4.1.4), or a radical acceptor (Section 4.1.5). Several other notable alkaloids syntheses have been reported in which carbocyclizations play the pivotal role and introduction of nitrogen is secondary, for example Sha s syntheses of (-)-dendrobine [76] and (-t-)-paniculatine [77], and Clive s synthesis of (+)-fredericamycin [78]. Syntheses in which nitrogen-centered radicals play a critical role are also known, such as the Zard synthesis of (—)-dendrobine [79]. My apologies to these authors for not elaborating on their fine contributions, to authors who have nicely used intermolecular radical addition reactions in alkaloid synthesis, and to others whose contributions may have escaped my attention. 

In stark contrast to azoalkanes, azoxy compounds rarely form radicals on heating or irradiation. Furthermore, they are unreactive to alkyl radical attack unless the reaction is intramolecular. For example, P-carbon centered radicals cyclize to azoxy nitrogen or oxygen and produce short-lived aminyl nitroxides that reopen or hydrazyl radicals that undergo fragmentation. The azoxy group is a powerful stabilizer of an adjacent radical center but the chemistry of a-azoxy radicals (hydrazonyloxides) and their dimers is not fully understood. 

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