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 Michelangelo Gruttadauria, p Paolo Lo Meo and Renato Noto Dipartimento di Chimica Organica `E. Paterno Á', Viale delle Scienze, Parco d'Orleans II, 90128 Palermo, Italy Received 19 October 2000; revised 20 November 2000; accepted 7 December 2000 Abstract ÐThe 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 ®rst 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 p ) 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 cycli- sation and the 5-exo vs the 6-endo cyclisation of the seleniranium ions depend were analysed. q 2001 Elsevier Science Ltd. All rights reserved. 1. Introduction One of the most successful routes for the stereoselective synthesis of oxygenated heterocyclic rings is the reaction between a homoallylic or bishomoallylic alcohol and an electrophilic species. 1 Common electrophiles that induce such cyclisations through formation of a three membered ring intermediate are: Br 1 or I 1 , Hg(II), PhS 1 and PhSe 1 . The above reactions involve two possible cyclisation modes, exo and endo. Moreover, these cyclisations result in the formation of two new stereogenic centres. The stereo- chemical factor of major interest is the relationship that the new stereogenic centres bear to that already present in the substrate. Cyclisations by nucleophilic attack onto a three-membered ring intermediates 1 (Ehalogen 1 , PhSe 1 or PhS 1 ) can give a smaller ring 2 by a pure exo-tet transition state or a larger ring 3 by an endo cyclisation or, following Warren's nomen- clature, 2 by a hybrid endo/exo-tet cyclisation (Fig. 1). The regiochemistry of a 4-exo vs a 5-endo cyclisation n  1 or a 5-exo vs a 6-endo cyclisation n  2 will depend on a number of factors such as reorganisation in terms of bond angles and distances, stabilisation of an incipient positive charge on the carbon that undergoes the attack, stability of the ®nal ring. Probably, the 4-exo and the 5-endo cyclisation experience stabilising effects more than the 5-exo and the 6-endo cyclisation, whichever is the origin of these effects. 3 Previously 4 we have investigated the behaviour of mixtures of hydroxy selenides and hydroxy sul®des. The treatment of hydroxy selenides with a catalytic amount of perchloric acid causes a stereoconvergent elimination of water to give an intermediate seleniranium ion. The seleniranium ion can be considered as following from the corresponding alkene by treatment with the electrophilic phenylseleno species PhSe 1 . Recently 4e we have discussed the kinetic and thermo- dynamic control of the cyclisation of the hydroxy selenides 4. Now we would like to gain a deeper insight on the reac- tivity and regiochemical outcome of these cyclisations, and also performing a computational study of these reactions. We focussed our attention on a substrate that could, in prin- ciple, undergo the former four modes of cyclisation in order to investigate which cyclisation takes place faster and which is the thermodynamically favoured. As a matter of fact, four modes of cyclisation of the seleniranium ion 5 are possible: (i) cyclisation in the 5-endo mode to give 6; (ii) cyclisation Tetrahedron 57 (2001) 1819±1826 Pergamon TETRAHEDRON 0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved. PII: S0040-4020(00)01154-6 Figure 1. exo versus endo cyclisation. Keywords: cyclisation; selenium and compounds; theoretical studies. p Corresponding author. Tel.: 139-91-596919; fax: 139-91-596825; e-mail: organica@unipa.it