Stereoselective benzylic α-acylamino radical cyclisation: a model study for the Tacaman indole alkaloid skeleton

Abstract

Radical cyclisation with tributyltin hydride of the α-phenylsulfanyl lactam 6, prepared in nine steps from D-ribose via the corresponding phthalimide, gives the all-cis tetrahydropyrido[2,1-a]isoindolone 7 stereoselectively as the major diastereomer. The structure of the product is established by ¹H NMR spectroscopy and corroborated by formation of the cis-lactone 8. The diastereoselectivity is shown to be controlled by the allylic/homoallylic cis-ketal group, and a transition state is proposed. The sequence constitutes the first simple model study for C/D ring fusion of the Tacaman indole alkaloid skeleton via the relatively unexplored C-3–C-14 bond disconnection.