Scandium Tri¯uoromethanesulfonate as Catalyst in the Hydrogen/Deuterium Exchange of 1,3,5-Trimethoxybenzene: Evidence for a Direct Interaction of Scandium with the Aromatic Ring Carla Bisi Castellani, a, * Angelo Perotti, a Marta Scrivanti a and Giovanni Vidari b a Dipartimento di Chimica Generale, Universita Á di Pavia, Via Taramelli 12, 27100 Pavia, Italy b Dipartimento di Chimica Organica, Universita Á di Pavia, Via Taramelli 10, 27100 Pavia, Italy Received 12 June 2000; revised 25 July 2000; accepted 10 August 2000 Abstract ÐScandium tri¯uoromethanesulfonate in CD 3 OD is a very active catalyst for hydrogen/deuterium exchange at the aromatic nucleus of 1,3,5-trimethoxybenzene. The very low proticity of the system, spectrophotometric evidence, and easy iodination of the substrate point to the formation of a transient unprecedented arylscandium species as a plausible intermediate of the reaction. q 2000 Elsevier Science Ltd. All rights reserved. Introduction The use of scandium tri¯uoromethanesulfonate (tri¯ate) in homogeneous organic catalysis has expanded in the last decade. 1,2 Although it is generally accepted that Sc 31 exerts catalytic activity thanks to the strong oxophilicity and Lewis acid character, most papers simply deal with the preparative aspects of the described reactions and rarely investigate the mechanism in detail. However, a better knowledge of the role exerted by scandium tri¯ate should be very helpful for extending the use of this active catalyst in organic synthesis. Among several electrophilic aromatic substitution rections, only Friedel±Crafts acylation and deformylation of aromatic aldehydes have been reported to be catalyzed by Sc(OTf) 3 so far. During our previous studies on the anhydrous Sc(OTf) 3 catalyzed protiodeformylation of aromatic aldehydes in MeOD, 3 we observed that the fast deformylation of 1,3,5-trimethoxybenzaldehyde under very mild conditions was accompanied by a rapid and complete hydrogen/deuterium exchange of both the substrate and the deformylation product, i.e. 1,3,5- trimethoxybenzene (1), at all the positions of the aromatic nucleus. By contrast, the exchange did not exceed 15% in the absence of the Lewis acid. Sc(OTf) 3 assisted deuteriation reactions have never been described before in the literature. Hydrogen exchange is one of the most useful reactions for the study of the mechanism of electrophilic aromatic substi- tutions; moreover, 1,3,5-trimethoxybenzene is a particularly suitable substrate due to the activating effect of the methoxy groups. Therefore, it seemed worthy to investigate this reac- tion in detail. Our results point out to the intermediate formation of an unprecedented arylscandium species which may be involved in a number of Sc III -catalyzed reactions of arenes. Results and Discussion 1 H NMR measurements indicated that the deuteriation of 1 in the presence of anhydrous Sc(OTf) 3 (substrate 1.3 M in CD 3 OD; molar ratio substrate±catalyst6:1; 208C) followed a pseudo ®rst-order path, with K Sc 1.5£10 23 s 21 . Under the same experimental condi- tions, anhydrous lanthanum and yttrium tri¯ates also promoted the proton±deuterium exchange, albeit much less ef®ciently, the rate constants being K La 9£10 27 s 21 , and K Y 3£10 25 s 21 , respectively. ² The catalytic properties of Sc(OTf) 3 were then extended to the deuteriation of other aromatic compounds such as 1,3- dimethoxybenzene and 1,3,5-trimethylbenzene under the reaction conditions indicated above. The former compound, which did not give rise to any H/D exchange in the absence Tetrahedron 56 (2000) 8161±8166 Pergamon TETRAHEDRON 0040±4020/00/$ - see front matter q 2000 Elsevier Science Ltd. All rights reserved. PII: S0040-4020(00)00723-7 Keywords: scandium and compounds; exchange reactions; substitution; metalation. * Corresponding author. Tel: 139-0382-507343; fax: 139-0382-528544; e-mail: bisichem@unipv.it ² Since unavoidable traces of water affected the measurements to some extent, the reported values are merely indicative of the relative catalytic effect.