DOI: 10.1002/cctc.201300952 On the Catalysis of the Cycloisomerization of 1,6-Dienes with Tin(IV) Salts: The Important Role of a Water Molecule Paola Nava, [a] Yannick Carissan, [a] Jean Drujon, [a] Fanny Grau, [b] Julien Godeau, [b] Sylvain Antoniotti, [b] Elisabet DuÇach,* [b] and StØphane Humbel* [a] Introduction The cycloisomerisation of unsaturated substrates is one of the most straightforward and atom-economical ways to obtain car- bocycles and heterocycles with high degrees of diversity and complexity. [1–6] A dichotomy has been observed for 1,6-diene derivatives, transition-metal-catalysed cycloisomerisation mainly leads to unsaturated five-membered-ring carbocycles, [2] whereas cycloisomerisations catalysed by Lewis and Brønsted acids undergo carbocationic cyclisations through p–cation in- termediates or carbocations to afford six-membered-ring car- bocycles (Scheme 1). In the latter case, the size of the ring formed is driven by the substitution of the double bonds in- volved in the process and the subsequent stability of the inter- mediate carbocations. We have described a cycloisomerisation reaction of non-acti- vated 1,6-dienes catalysed by Lewis superacids such as tin tri- flate, Sn(OTf) 4 , and tin triflimidate, Sn(NTf 2 ) 4 , which lead effi- ciently and selectively to six-membered-ring carbocycles. [7] In this reaction, tin(IV) was used for the first time as the catalyst for the cyclisation of non-activated olefins. The unusual reactivity observed with tin(IV) salts was a source of questions on the nature of the intermediates in- volved, on the nature of the active catalyst and on the precise role of protons in the process. On the latter aspect, in many re- actions that involve metal catalysts, and particularly metallic triflates and triflimidates, the question of whether or not a su- peracidic proton could be the true catalyst is of concern. [8–12] Furthermore, the salt could be simply a provider of triflic or tri- flimidic acid, which leads to protic-superacid-catalysed processes. [8–11] An experiment frequently performed to prove the protic nature of the active species is the addition of 2,6-di-tert-butyl- pyridine (2,6-DTBP) to the catalytic reaction medium. If the process becomes inhibited by the presence of the hindered base, it is generally concluded that it is catalysed by a protic acid. However, some mechanisms that involve metal catalysis might, for instance, include a protolysis step at the end of the catalytic cycle. The presence of the hindered base in the medium would inhibit such a step that is essential to recover the catalyst. Such inhibition would result in the apparent inhib- A diene cycloisomerisation reaction catalysed by tin(IV) triflimi- date is studied by using DFT computations. It is proposed that the mechanism does not involve the direct addition of the tin(IV) cation to a double bond because the catalyst regenera- tion step would be energetically unfeasible. We show that a water molecule may play a decisive role to enable the smooth completion of the catalytic cycle. The proposed active catalyst is thus a hydrated triflimidate salt. The hydrolysis and hydration energies are computed for three ligands of SnL 4 ,L = triflate (OTf), triflimidate (NTf 2 ) and a chlorosulfonate model (OSO 2 Cl). The diastereoselectivity observed in the cycloisomeri- sation is discussed in light of the transition-state geometries. The hypothesis of hidden Brønsted acid catalysis is discussed and ruled out on the basis of new experimental results. Scheme 1. Methyl-substituted 1,6-diene cycloisomerisations (E, E’ = MeO 2 C, EtO 2 C, NC, etc.) for transition metal and Brønsted or Lewis superacid catalysis. [a] Dr. P.Nava, Dr. Y. Carissan, J. Drujon, Prof. S. Humbel Aix Marseille UniversitØ, Centrale Marseille CNRS, iSm2 UMR 7313 13397, Marseille (France) Fax: (+ 33) 4-91-28-82-34 E-mail : stephane.humbel@univ-amu.fr [b] Dr. F. Grau, Dr. J. Godeau, Dr. S. Antoniotti, Dr. E. DuÇach UniversitØ de Nice Sophia Antipolis CNRS, Institut de Chimie de Nice, UMR 7272 Parc Valrose, 06108 Nice cedex 2 (France) Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/cctc.201300952.  2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim ChemCatChem 2014, 6, 500 – 507 500 CHEMCATCHEM FULL PAPERS