Heterogeneous Catalysis DOI: 10.1002/anie.200805838 Selective Isomerization of Epoxides to Allylic Alcohols Catalyzed by TiO 2 -Supported Gold Nanoparticles Christos Raptis, Hermenegildo Garcia,* and Manolis Stratakis* Epoxides play a dominant role as valuable intermediates in organic processes. They provide an array of addition products through either nucleophilic opening or electrophilic activa- tion, or they isomerize to carbonyl compounds or allylic alcohols depending on the reaction conditions (acidic or basic). Regarding their isomerization to allylic alcohols under homogeneous reaction conditions, relatively few procedures are known. The reaction with alkylamide bases [1] or Schloss- ers Li/K mixed superbases [2] converts epoxides into allylic alcohols. Sharpless and Lauer [3] presented a method for the isomerization of epoxides to allylic alcohols by using organo- selenium chemistry. Under acidic reaction conditions, epox- ides primarily isomerize to carbonyl compounds [4] by the Meinwald rearrangement, and allylic alcohols are often formed as by-products. The isomerization of epoxides to allylic alcohols, through a radical pathway ([Cp 2 TiCl], Cp = C 5 H 5 ) and in moderate yields, is also known. [5] An alternative unprecedented catalytic mechanism to convert an epoxide into an allylic alcohol would require the development of a mild heterogeneous bifunctional acid/base catalyst. Upon activation of the epoxide moiety by the acidic sites, the basic sites would abstract, in a rather concerted way, a hydrogen atom from the a-carbon atom (with respect to the epoxide functionality) to produce an allylic alcohol (Scheme 1). Our concept is reminiscent of the use of amphoteric aluminum alkoxides or amides [6] under homoge- neous reaction conditions. Unfortunately, these reagents act either in stoichiometric or multimolar amounts relative to the epoxide. There a few examples in the literature concerning the isomerization of epoxides under heterogeneous catalysis. Amphoteric oxides such as Al 2 O 3 , ZrO 2 , TiO 2 , [7] or Li 3 PO 4 (the last for the industrial production of allyl alcohol from propylene oxide) [8] have been used as catalysts. However, the reactions generally proceed at elevated temperatures to form, apart from allylic alcohols, mixtures of products. Indeed, in tests of the isomerization of a model substrate (6,7-epoxyger- anyl acetate (1), Table 1) over TiO 2 or SnO 2 in refluxing 1,2- dichloroethane as the solvent (100 mg of TiO 2 or SnO 2 per 0.1 mmol of substrate), the allylic alcohol 1a was formed; however, several cyclization products, [9] which are typical for an acid-catalyzed pathway, also appear in comparable amounts relative to 1a. Moreover, the reaction is extremely slow as it proceeds to 15–20% conversion after 24 hours, and requires a week to reach completion. As a result, new by- products start to form and the reaction mass balance falls to less than 60 %. To improve the reactivity/selectivity of the isomerization process, we turned our attention to TiO 2 supported on gold nanoparticles, a material that has received tremendous attention in recent years as a catalyst for alcohol [10a–e] and aldehyde [10a–c,d] oxidation wherein O 2 is employed as the oxidant. It has been proposed that the TiO 2 surface stabilizes cationic gold species, [11] such as Au I , which are detectable by X-ray photoelectron spectroscopy (XPS). We envisioned such species acting as Lewis acid sites to activate the epoxide, whereas the surrounding oxygen atoms from the TiO 2 support could act as basic sites and catalyze the isomerization according to the concept presented in Scheme 1. Gold nanoparticles have demostrated unique activity for promot- ing chemical transformations of organic compounds which do not occur by using conventional catalysts. [12] We were pleased to find that Au/TiO 2 [13] was a perfect catalyst for our purposes. Upon treatment of 1 with Au/TiO 2 suspended in 1,2-dichloro- ethane the reaction proceeds smoothly and goes to comple- tion within two to three hours at 80 8C. Allylic alcohol 1a was the only product formed in a yield greater than 90 % after isolation. Prompted by this result, we examined a series of epoxides and found that the reaction is quite general; the yields are high, and in many cases the product selectivity is remarkable. The results are summarized in Table 1. Apart from 1, terpenoid epoxides 2–4, which are prone to undergo acid- catalyzed cyclization, [9] exclusively provide their isomeric allylic alcohols 2a–4a in high yields. a-Pinene oxide (7), a highly sensitive substrate towards acids, [14] reacts to primarily give trans-pinocarveol (7a) and a mixture of campholenic Scheme 1. Schematic representation of the isomerization of an epoxide into an allylic alcohol using a bifunctional acid/base catalyst. LA = Lewis acid, B = Lewis base. [*] C. Raptis, Prof. Dr. M. Stratakis Department of Chemistry, University of Crete Voutes 71003, Iraklion (Greece) E-mail: stratakis@chemistry.uoc.gr Prof. Dr. H. Garcia Instituto de Tecnologia Quimica CSIC-UPV Universidad Politecnica de Valencia 46022 Valencia (Spain) E-mail: hgarcia@qim.upv.es Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/anie.200805838. Angewandte Chemie 3133 Angew. Chem. Int. Ed. 2009, 48, 3133 –3136  2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim