Indium-Catalyzed Cycloisomerization of 1,6-Cyclohexenylalkynes

Efficient four- and five-step routes to access functionalized bicyclo[3.2.1]oct-2-ene and bicyclo[3.3.1]nonadiene via indium-mediated cycloisomerization of 1,6-enynes has been developed. This atom-economical catalytic process was optimized and relied on the efficiency of InCl3 leading to the preparation of functionalized bicyclic adducts in up to 99% isolated yield. The cyclization occurred on two different processes (5-exo versus 6-endo pathway) and were influenced by the substitution of the alkynyl moiety. The exo process was favored for non-substituted alkynes whereas the endo pathway was generally observed for substituted alkynes. Then, the presence of electron-withdrawing groups on the aryl substituted alkyne increased the ratio of the exo isomer. DFT calculations were performed on stability of intermediates and corroborated the intervention of InCl3.