Regiochemistry in radical cyclisations (4-exo-trig versus 5-endo-trig) of 2-halo-N-(3,4-dihydro-2-naphthyl)acetamides

Abstract

The regioselectivity in Bu₃SnH-mediated radical cyclisations (4-exo-trig versus 5-endo-trig) of a range of 2-halo-N-(3,4-dihydro-2-naphthyl)acetamides has been examined from the standpoint of the effects of substituents on the radical centre and on the nitrogen atom as well as the reaction temperature. When the substituent on the radical centre is a hydrogen or chlorine atom, 4-exo-trig cyclisation (β-lactam formation) is favoured in boiling toluene, while radical stabilising substituents such as methyl, phenyl, phenylthio, dimethyl and dichloro groups bring about 5-endo-trig cyclisation (γ-lactam formation) predominantly or exclusively. In boiling benzene, however, the predominant formation of β-lactam is observed for the methyl-substituent. On the other hand, no remarkable difference in the product distributions between the methyl and benzyl substituents on the nitrogen atom is observed. These results are discussed in terms of kinetic or thermodynamic considerations.