The question of exo vs endo cyclisation. A joint experimental and ab initio study on the stereoselective synthesis of tetrahydrofurans and tetrahydropyrans via seleniranium ions

The reactivity of hydroxy selenides with catalytic amounts of perchloric acid in dichloromethane was investigated. Four different cyclisation modes (4-exo, 5-endo, 5-exo and 6-endo) of the intermediate seleniranium ion could occur. The reaction of the hydroxy selenides with primary and secondary hydroxyl groups in the same side chain led first to a mixture of tetrahydrofurans from the 5-exo cyclisation (kinetic products), then to a 68/32 mixture of tetrahydropyrans from the 6-endo cyclisation (thermodynamic products) probably via two diasteromeric seleniranium ions. Both experimental and ab initio (HF/3-21G∗) studies showed that the order of cyclisation of the intermediate seleniranium ion was 5-exo-tet<6-endo-tet<5-endo-tet<4-exo-tet. The factors on which regiochemistry of the 4-exo vs the 5-endo cyclisation and the 5-exo vs the 6-endo cyclisation of the seleniranium ions depend were analysed.