title: Controlling regioselectivity in cyclization of unsaturated amidyl radicals: 5-exo versus 6-endo.
abstract: Intramolecular cyclization of an amidyl radical onto an olefin provides an appealing method for the synthesis of lactams and other nitrogen-containing heterocycles. Here we conducted the first, systematic theoretical study on the regioselectivity in the cyclization of various types of pent-4-enamidyl radicals that carried synthetically relevant substituents. It was found that the cyclization of most of the substituted pent-4-enamidyl radicals produced the 5-exo products (gamma-lactams) almost exclusively. Marcus theory analysis showed the involvement of both the thermodynamic (stabilization of the starting double bond or the resulting radical center) and intrinsic (mainly steric effects) contributions in determining the 5-exo selectivity. Nonetheless, in two types of systems we found that the delta-lactams became the favored products through the 6-endo cyclization. In one of the systems an aromatic substituent was placed at the C4-position, whereas in the other system an electron-rich aromatic ring was incorporated into the pent-4-enamidyl radical backbone at the C2- and C3-positions. This unprecedented 6-endo mode of amidyl radical cyclization provided an interesting route for the preparation of mono- and bicyclic delta-lactams (pyridinones).
authors: Department of Chemistry, University of Science and Technology of China, Hefei 230026, China.
authors: Yi-Yun
authors: YY
authors: Yu
authors: Yao
authors: Y
authors: Fu
authors: Miao
authors: M
authors: Xie
authors: Lei
authors: L
authors: Liu
authors: Qing-Xiang
authors: QX
authors: Guo
mesh_terms: D000577:Amides / Q000737:chemistry; D003500:Cyclization; D005609:Free Radicals / Q000737:chemistry*; D007769:Lactams / Q000138:chemical synthesis* / Q000737:chemistry; D008958:Models, Molecular; D015394:Molecular Structure; D011728:Pyridones / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D000577:Amides; D005609:Free Radicals; D007769:Lactams; D011728:Pyridones