DOI: 10.1002/chem.200800920 Solvent-Dependent Changes in the Triazolinedione–Alkene Ene Reaction Mechanism Georgios C. Vougioukalakis, Manolis M. Roubelakis, Mariza N. Alberti, and Michael Orfanopoulos* [a] Introduction The ene reaction of triazolinedione [1] (RTAD, R = methyl or phenyl), one of the most reactive neutral enophiles, with al- kenes that bear allylic hydrogen atoms, to form N-allylura- zoles [Eq. (1)] apart from being synthetically useful, [2] has attracted considerable mechanistic [3–9] and theoretical atten- tion [10] for many years. A number of mechanisms and key intermediates (Figure 1) have been proposed for this reac- tion. Among these, the formation of a closed, three-mem- bered aziridinium imide (AI) intermediate (Figure 1) was the most popular, and initially found support in the results of trapping experiments. [11,12] Subsequently, isotope effect measurements on deuterium-labeled tetramethylethylenes (TMEs) [3,4] and 2-butenes [5,6] also suggested the formation of an AI intermediate in the rate-determining step of the reac- tion. Thus, large intramolecular kinetic isotope effects (KIEs) were found in the ene reactions of RTADs with the cis-related methyl and deuteriomethyl groups in substrates 1 and 2 (H/D isotopic competition; Scheme 1), whereas only a small isotope effect was observed with the trans-related groups in compound 3 (no isotopic competition). AI inter- mediates have also been observed spectroscopically in the reactions of biadamantylidene, [13] trans-cycloheptene, [14] and trans-cyclooctene [15] with RTADs. Furthermore, because all of the methyl groups of TME are symmetry equivalent, sim- ilar isotopic competition would have been expected for sub- strates 1, 2, and 3 in a concerted mechanism; however, this was found not to be the case. On this basis, a one-step mech- anism was excluded. Abstract: The influence of the solvent on the triazolinedione–alkene ene reac- tion mechanism has been investigated. Both inter- and intramolecular kinetic isotope effects with tetramethylethy- lenes and 2,2,2-(trideuterio)methyl-7- methyl-2,6-octadiene-[D 3 ]-1,1,1 pro- vide, for the first time, strong evidence for changes in the mechanism of the re- action on going from non-protic to polar protic solvents. In non-protic polar or apolar solvents, an aziridinium imide that equilibrates to an insignifi- cant extent with an open intermediate (a dipolar or a polarized biradical) is formed irreversibly in the first, rate-de- termining step of the reaction, which is followed by fast hydrogen abstraction. On the contrary, in polar protic sol- vents, hydrogen abstraction is rate lim- iting, allowing the main dipolar inter- mediate to equilibrate with its open in- termediate(s) as well as with the start- ing reagents. Keywords: ene reaction · kinetic isotope effects · reaction mechanism · solvent effects · triazolinediones [a] Dr. G. C. Vougioukalakis, Dr. M. M. Roubelakis, Dr. M. N. Alberti, Prof. Dr. M. Orfanopoulos Department of Chemistry, University of Crete Voutes 71003, Heraklion, Crete (Greece) Fax: (+ 30)281-054-5001 E-mail: orfanop@chemistry.uoc.gr Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.200800920. Figure 1. Proposed intermediates for the triazolinedione ene reaction. Chem. Eur. J. 2008, 00,0–0 # 2008 Wiley-VCH Verlag GmbH&Co. KGaA, Weinheim These are not the final page numbers! ÞÞ &1& FULL PAPER