Regioselective transformation of alkynes into cyclic acetals and thioacetals with a gold(I) catalyst: comparison with Brønsted acid catalysts Laura L. Santos, Violeta R. Ruiz, Maria J. Sabater, Avelino Corma * Instituto de Tecnologı ´a Quı ´mica, UPV-CSIC, Avenida de Los Naranjos s/n, 46022 Valencia, Spain article info Article history: Received 16 May 2008 Accepted 10 June 2008 Available online 13 June 2008 abstract Au(I) catalyzes the transformation of alkynes into cyclic acetals and thioacetals at much higher rate than Brønsted acids. The reaction appears to be general for a range of alkynes and diols or dithiols, which are efficiently transformed with high selectivities. One of the salient features of this reaction process is the high reactivity of the enol ether or enol thioether intermediates, which undergo a rapid isomerization reaction to afford the cyclic acetals or thioacetals, so that isolation or subsequent activation processes are not required. This type of reactions allows us to synthesize a series of fragrances. Ó 2008 Elsevier Ltd. All rights reserved. 1. Introduction Cyclic acetals and thioacetals are important molecules for pro- tecting carbonyl groups in organic synthesis 1 and for the genera- tion of chiral auxiliaries for asymmetric induction. 2 They also have interest for the production of polymers, pharmaceuticals and fra- grances. 3–5 Classical methods to obtain cyclic acetals involve the reaction of an aldehyde or ketone with an alcohol with azeotropic removal of water or transacetalization reactions. When the ketone is not stable, this procedure involves large excess of reactant and tedious work-up procedures. 1,6 Recently, the direct transformation of unactivated alkynes into ketones or acetals upon water or alcohol addition, respectively, has become one of the most useful func- tionalizations of simple alkynes, and a variety of catalysts have been extensively studied. 7–9 For instance, transition metals salts in- cluding mercury(II), 7 palladium(II) 8 as well as a Zeise-type plati- num compound 9 catalyze the hydration of many alkynes to afford ketones; whereas formation of cyclic acetals has been described to occur with the assistance of a cationic iridium complex. 10 In the case of gold, it has been recently reported that this metal working either in homogeneous or heterogeneous phase can efficiently catalyze reactions involving alkynes. 11 Indeed, it has been described that the use of cationic gold(I) complexes for the direct formation of dimethyl acetals from alkynes by addition of methanol, and protons as cocatalyst, 12 whereas gold(III) efficiently catalyzes the addition of water and methanol to nonactivated alkynes forming ketones and acetals. 13 It should be remarked that despite the fact that di- methyl acetals were successfully obtained with this Au(III) catalyst, direct conversion of alkynes into cyclic acetals was not possible. AuCl or AuCl 3 can also be used as catalysts in the formation of in- teresting bicyclic ketals by using two intramolecular hydroxyl groups as nucleophiles. 14 Similarly, a combination of intra- molecular and intermolecular additions in the case of a homo- propargylic alcohol can be catalyzed by AuPPh 3 Cl/AgBF 4 , in the presence of 10% acid. 15 In this work we present that gold(I)/AgBF 4 can catalyze very efficiently the formation of cyclic acetals and thioacetals with five to eight membered ring from alkynes and diols and thiols, without adding acid. To the best of our knowledge there is no precedent for forming this last type of compounds from alkynes using gold cat- alysts. We can oversee interesting applications of this reaction and, as one example, the synthesis of a molecule with blossom orange scent is presented. We will show that with this catalyst the for- mation of cyclic acetals and thioacetals takes place in a direct way through a two step transformation starting from alkynes and diols or thiols to afford enol ethers(thioethers) intermediates. In our reaction system, the intermediate reaction product undergoes a rapid isomerization to the corresponding cyclic acetal and thio- acetal so that isolation of the enol ether/thioether is not required. One of the main advantages of this experimental procedure is that most of the inconveniences associated with classical acetalization reactions, such as the use of an excess of reagent or tedious work-up procedures can be overcome. 2. Results and discussion 2.1. Synthesis of acetals and thioacetals with Au(I)/Ag(I) system The reaction of 1,2-ethanediol with a series of alkynes such as phenylacetylene, benzylacetylene and 1-hexyne was carried out at * Corresponding author. Tel.: þ34 96 3877800; fax: þ34 96 3877809. E-mail address: acorma@itq.upv.es (A. Corma). Contents lists available at ScienceDirect Tetrahedron journal homepage: www.elsevier.com/locate/tet 0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved. doi:10.1016/j.tet.2008.06.032 Tetrahedron 64 (2008) 7902–7909