8-endo versus 7-exo cyclization of alpha-carbamoyl radicals. A combination of experimental and theoretical studies.
Atom transfer radical cyclization reactions of N-(4-pentenyl)iodoacetamides were investigated. The reactions were efficiently promoted by BF3.OEt2. For N-alkenyl-substituted iodoamides, excellent regioselectivity in favor of 8-endo cyclization was observed, while both 7-exo and 8-endo cyclization products were formed with the 8-endo cyclization preferred in the cases of N-(2-allylphenyl)-substituted iodoamides. Density functional theory calculations at the B3LYP/6-31G level revealed that both the s-trans and the s-cis conformational transition structures were feasible for the 8-endo cyclization of N-alkenyl-substituted alpha-carbamoyl radicals while 7-exo transition structures were much less stable. For the cyclization of N-(2-allylphenyl)-substituted alpha-carbamoyl radicals, the transition structures for 8-endo and 7-exo cyclizations were of comparable energy. These results were in excellent agreement with the experimental observations.
Liu
Li
L
Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Road, Shanghai 200032, China.
Chen
Qian
Q
Wu
Yun-Dong
YD
Li
Chaozhong
C
D003500:Cyclization; D005609:Free Radicals / Q000737:chemistry; D007460:Iodoacetamide / Q000138:chemical synthesis* / Q000737:chemistry; D008958:Models, Molecular; D008962:Models, Theoretical; D015394:Molecular Structure; D013237:Stereoisomerism
D005609:Free Radicals; D007460:Iodoacetamide