One-pot utilization of heterogeneous and enzymatic catalysis: Synthesis of R-1-phenylethyl acetate from acetophenone Pa ¨ivi Ma ¨ ki-Arvela, Serap Sahin, Narendra Kumar, Jyri-Pekka Mikkola, Kari Era ¨ nen, Tapio Salmi, Dmitry Yu. Murzin * A ˚ bo Akademi University, Process Chemistry Centre, FI-20500 Turku, Finland 1. Introduction Cascade catalysis, where several consecutive reaction steps are performed in one-pot without the separation of intermediate products, has recently attracted considerable attention. The potential benefits in cascade conversions are the decreased production of waste as well as lower equipment costs. The current processes including several separation and reaction steps are time consuming both from the point of development and scaling-up. There exist several examples of cascade catalysis [1], which apply different combinations of catalysts: bio-bio [2], bio-chemo [3] and chemo-chemo [4] cascades. Moreover different reaction steps, like reductions [2], oxidations [5], esterifications [6], decarboxylations [7], etc., have been investigated in cascade conversions. For bio- chemo transformations there are several examples of combining enzymatic and homogeneous catalysis. At the same time one-pot systems, when heterogeneous and enzymatic reactions are efficiently combined are very rare. The main challenge is in rather different experimental conditions required for them, thus the reports in the literature describe systems where heterogeneous and enzymatic catalysis are separated either in space [8] or time [9]. Optically active alcohols are conventionally prepared via kinetic resolution from racemates [10], which implies the intrinsic limitation of 50% yield of the desired enantiomer. In dynamic kinetic resolution (DKR) [11,12], studied especially by Ba ¨ckvall and co-workers [12], transition metal catalysts were used as additional catalysts for racemization of the undesired enantiomer resulting in molar fractions close to 100% of the desired enantiomer. Additionally zeolites have been reported to be active in the racemization of 1-phenylethanol [8] and Pd/C in the racemization of chiral amines [13]. One potential method to obtain a more environmentally viable process compared to the existing one is to use a cheap raw material, acetophenone, which is hydrogenated to R-1-phenylethanol and the formed inter- mediate is acylated in the same pot to R-1-phenylethyl acetate (Fig. 1). This reaction has been demonstrated over a chemo-biocata- lytic system containing both a homogeneous Ru catalyst and an enzyme [14]. Synthesis method could be more industrially attractive, if heterogeneous catalysts could be used instead of a homogeneous counterpart. A sequential method, in which acetophenone was hydrogenated over a heterogeneous Pd/ silica/alumina catalyst in the first step followed by the acylation with immobilized enzyme in the second step was recently demonstrated [9]. According to our knowledge, one-pot synthesis of R-1-phenylethyl acetate starting from acetophenone hydro- genation, has not been previously performed over a hetero- geneous metal-supported catalyst and an immobilized lipase. This approach is successfully demonstrated in the current work over a Pd/MgO catalyst and over an immobilized lipase. Besides the first demonstration of utilization both heterogeneous and enzymatic catalysts in one pot, the main focus of the present study was the effect of the catalyst support. Catalysis Today 140 (2009) 70–73 ARTICLE INFO Article history: Available online 19 September 2008 Keywords: One-pot synthesis Acylation Hydrogenation Heterogeneous catalyst ABSTRACT One-pot synthesis of R-1-phenylethyl acetate was investigated starting from hydrogenation of acetophenone over a metal-supported catalyst followed by acylation of the formed R-1-phenylethanol over an immobilized lipase. The most promising catalyst for the hydrogenation step was Pd/Al 2 O 3 , which in combination with an immobilized lipase yielded maximally 22% R-1-phenylethyl acetate. The support acidity had a crucial effect on the selectivity towards the desired product. ß 2008 Elsevier B.V. All rights reserved. * Corresponding author. Fax: +358 22154479. E-mail address: dmurzin@abo.fi (D.Yu. Murzin). Contents lists available at ScienceDirect Catalysis Today journal homepage: www.elsevier.com/locate/cattod 0920-5861/$ – see front matter ß 2008 Elsevier B.V. All rights reserved. doi:10.1016/j.cattod.2008.07.037