Topics in Catalysis 13 (2000) 195–199 195 Bifunctional copper catalysts. Part II. * Stereoselective synthesis of (-)-menthol starting from (+)-citronellal N. Ravasio, N. Poli, R. Psaro, M. Saba and F. Zaccheria Centro C.N.R. CSSCMTBSO, Via Venezian 21, 20133 Milano, Italy E-mail: nravasio@csmtbo.mi.cnr.it The one-step transformation of (+)-citronellal into (-)-menthol has been realised with yield ∼90% and stereoselectivity up to 80% under mild conditions in the presence of Cu/SiO 2 by exploiting the presence of acidic and hydrogenation sites on the catalyst surface, the unusual reducibility of an olefinic bond under these conditions and the chemoselectivity of the process. Keywords: copper catalysts, bifunctional catalysis, stereoselectivity, (-)-menthol 1. Introduction During our continuous studies on the selectivity prop- erties exhibited by non-conventional copper catalysts, we often identified acid-catalysed reactions taking place under hydrogenation conditions [2]. We therefore focussed our attention on separating the role played by the supports, on the one hand, from that played by the metal or, if any, by molecular hydrogen, on the other hand. Moreover, we began to look for the set up of processes where our catalysts can promote both an hydrogenation and an acid-catalysed step at the same time. It is well known that in a typical synthetic pathway for the production of a fine chemical, a very large portion of all reaction steps, up to 50%, are catalysed by homogeneous or heterogeneous acids and bases, and another 10–20% are catalytic hydrogenations [3]. Therefore, to reduce the num- ber of steps by carrying out two of them in one pot and in the presence of the same catalyst, appeared to us as a good point to look at. Finally, as we are always interested in tuning the prod- ucts stereochemistry by modifying the hydrogenation reac- tion conditions, we tried to exploit the bifunctional features of copper catalysts to modify the stereochemical pathway of the process. A very interesting case was represented by the synthesis of bicyclic ethers and in particular by the synthesis of cis- dihydropinol 1 [1a]. When the hydrogenation of carvone 2 was carried out in the presence of Cu/SiO 2 –TiO 2 or Cu/SiO 2 –ZrO 2 this ether was formed through reduction to the saturated alcohol 3 and nucleophilic attack of the hydroxy group to the C=C double bond activated as carbocation. Formation of 1 is highly stereoselective, the cis iso- mer being formed with more than 95% stereoselectivity (scheme 1). ∗ See: part I [1a], part III [1b]. We could show that an equilibrium exists on the cat- alyst surface among the four isomers of 3 and that the acid-catalysed cyclization reaction is much faster than the hydrogenation one, thus abstracting from the mixture the isomer that gives the cis ether, namely the equatorial, axial which is the main one produced in the presence of copper catalysts, as soon as it forms. This shifts the hydrogena- tion step towards formation of this isomer and we observe a very high stereoselectivity. In a program aimed at the substitution of homogeneous Lewis acids with heterogeneous ones in organic synthesis, we recently reported that citronellal 4 can be easily cyclized to isopulegol 5 in the presence of acidic mixed oxides but also of some silica, giving the product with very high yield and fairly good stereoselectivity towards the valuable (-)- isopulegol isomer [4]. This reaction represents an interme- diate step in the Takasago process for (-)-menthol, where it is carried out in the presence of ZnBr 2 , with excellent stereoselectivity, but only 70% chemical yield [5]. When we tried to use supported copper catalysts, we found that the presence of the metal reduces very much the reaction rate for cyclization 4 → 5 and produces a small but definite increase in selectivity. If 5 could be hydro- genated in the presence of these catalysts the one-pot–two- steps transformation of 4 into menthol 6 could be realised by introducing H 2 once isopulegol 5 is formed. This paper presents these results in the stereoselective transformation of (+)-citronellal (scheme 2). Scheme 1.  J.C. Baltzer AG, Science Publishers