3 - Intramolecular Radical Cyclizations

Abstract

Alkynyl radicals (sp carbon-centered radicals) are a highly energetic and highly reactive species. Therefore, the generation of an sp carbon-centered radical is rather difficult. The instability of the alkynyl radical is reflective of the strong bond dissociation energy of the C(sp)–H bond, which is estimated to be approximately 130 kcal/mol, nearly 20 kcal/mol higher than that of alkene, C(sp2)–H. The study on alkynyl radicals is, therefore, extremely limited, and only one method for the generation of phenylethynyl radical from phenyliodoacetylene has been reported. sp2 carbon-centered radicals formed by the treatment of aryl halides or vinyl halides with Bu3SnH/AIBN are σ radicals and much more reactive than sp3 carbon-centered radicals, which are π radicals. The high reactivity of sp2 carbon-centered radical reflects the stronger bond dissociation energies of sp2(C)–H and sp2(C)–sp3(C) bonds than those of sp3(C)–H and sp3(C)–sp3(C) bonds. Preparation of medium- and large-sized rings such as 12 ∼ 20-membered rings can be constructed by radical cyclization with highly diluted Bu3SnH using a syringe-pump, with endocyclization. The reason for this can be explained as follows: there is not much energy difference between the transition state of exocyclization and that of endocyclization, because the ring strain in the formation of these transition states is somewhat reduced due to their large ring-sized transition states. Consequently, tertiary or secondary carbon-centered radicals are predominantly formed via endocyclization.