Synthesis of Heterocyclic Compounds Containing a Carbonyl Moiety by Radical Carbonylations

5 Synthesis of Heterocyclic Compounds Containing a Carbonyl Moiety by Radical Carbonylations 

A variety of methods are available for the synthesis of heterocyclic carbonyl compounds by radical cyclization. For example, the cyclization of alkoxycarbonyl radicals is particularly useful for the synthesis of five- and six-membered ring lactones [80]. Recent applications of this cyclization method include Zard s photoly-tical transformation of an alkoxycarbonyl dithiocarbonate having a double bond which can serve as a key step in the synthesis of ( )-cinnamolide and RA. Evans s enantioselective synthesis of 4-hydroxy butenolide terminus, which is applicable to the synthesis of mucocin [81J. Amidyl radical cyclizations are frequently utilized for the synthesis of five- and six-membered ring lactams [82]. However, this section only focuses on recent methods for heterocyclic carbonyl compounds by an n-i-1 type strategy based on radical carbonylations. 

4-1-1 and 5-1-1 annulation protocols may be induced from alkyl bromides or sele-nides and tolerate the use of both aldimines and ketimines [88]. 

In view of the nucleophilic character usually exhibited by acyl radicals in their additions to C-C multiple bonds, these cyclizations are unusual, since the addition takes place at the more electron-rich nitrogen atom. However, reactions at higher concentrations of tin hydride clearly show that the 5-exo mode of cycliza-tion is kinetically as well as thermodynamically favored. A further mechanistic possibility involves nucleophilic attack by the lone pair of the imine nitrogen electrons on the acyl radical, a process which is not a radical cyclization, but rather an ionic cyclization onto the carbonyl of an acyl radical. 

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