DOI: 10.1002/chem.201100800 Zinc-Catalyzed Chemoselective Reduction of Esters to Alcohols Shoubhik Das, Konstanze Mçller, Kathrin Junge, and Matthias Beller* [a] Functionalized alcohols are of importance for the manu- facture of pharmaceuticals, agrochemicals, dyes, and numer- ous bioactive compounds (see below for selected examples of bioactive alcohols). Regarding their synthesis, the reduc- tion of esters to the corresponding alcohols provides a straightforward access. [1] Notably, for special products and on a laboratory scale, traditional boron and aluminium hy- dride-mediated reductions still prevail. [2] Compared to these stoichiometric reactions, catalytic methods offer more versa- tile strategies and might allow for improved selectivity. [3] Evidently, catalytic hydrogenation represents an ideal method for the reduction of esters, but sometimes low func- tional group tolerance and the necessity to use high pressure autoclaves impair its general use. [4] Although heterogeneous hydrogenation of fatty esters is performed in industry on bulk scale, [5] it needs high temperatures (200–300 8C) along with high hydrogen pressures (200–300 atm). On the other hand, homogeneously catalyzed hydrogenations have been only scarcely investigated until recently. [6] Relative to hydrogenations, catalytic hydrosilylations are a well-accepted tool, which are operationally simple to per- form and often allow for improved chemoselectivity and re- gioselectivity under mild conditions. [7] Hence, during the last decade metal-catalyzed hydrosilylations of esters have re- ceived considerable interest. To date, various catalyst sys- tems including Rh, [8] Ru, [9] Mo, [10] Ti, [11] In, [12] Mn, [13] Pd, [14] organo zinc, [15] and boron compounds [16] have proven to be effective for this reduction. Nevertheless, the development of a cost-effective, efficient, and highly selective catalyst for this transformation is still desirable because most of the known protocols either require expensive silanes or have limited functional group tolerance. The abundant availability, low toxicity and biomimetic nature [17] of zinc makes it a highly attractive candidate for catalysis. Based on our recent study on the zinc-catalyzed re- duction of amides, [18] herein we report a general and im- proved catalytic hydrosilylation of esters to generate alco- hols. Notably, excellent chemoselectivity is achieved in the presence of other reducible functional groups. Initially, the reaction of methyl phenylacetate 1a with (EtO) 2 MeSiH in THF was investigated as a model system to identify and optimize the critical reaction parameters (Table 1). As expected, no reaction occurred in the absence of any catalyst (Table 1, entry 1). In contrast, 10 mol% of in- expensive ZnACHTUNGTRENNUNG(OAc) 2 was an excellent catalyst and gave 2- phenylethanol 1b in 90 % yield, after hydrolysis with 25 % KOH in methanol (Table 1, entry 2). However, after apply- ing lower catalyst loadings of 7.5 and 5 mol % the yield de- creased to 70 and 45%, respectively (Table 1, entries 3 and 4). Surprisingly, other zinc sources such as ZnF 2 , ZnBr 2 , ZnI 2 , ZnACHTUNGTRENNUNG(ClO 4 ) 2 ·6H 2 O, and ZnACHTUNGTRENNUNG(NO 3 ) 2 ·6H 2 O were inactive and only Zn(2-ethyl hexanoate) 2 and ZnCl 2 showed a little activity (Table 1, entries 13–19). Other metal acetates (such as Cu and Fe) were also inactive (Table 1, entries 11–12). To exclude the influence of potential precious metal contami- nants in the catalyst precursor we also used zinc acetate from different suppliers (ABCR, Sigma Aldrich, and Acros). In all cases similar yields of the product were ob- tained in the model reaction. Next, we started to investigate the influence of different silanes on the reaction. In addition to (EtO) 2 MeSiH, several silanes such as PhSiH 3 , PhSiH 2 , and (EtO) 3 SiH were also active (Table 1, entries 5–7). However, disilanes like tetra- methyldisiloxane (TMDS) or polysilanes like polymethylhy- drosiloxane (PMHS) were completely inactive under our re- action conditions and only the starting ester was recovered after the reaction. It should be noted that the observed dif- ferences in reactivity of silanes combined with the possibility to use different catalysts allows for a tuning of chemoselec- tivity of multiple substituted substrates. This is not possible with classic organometallic hydrides or in reactions with hy- drogen. Scale up of the model reaction to 20 mmol resulted in no problems and produced phenylethanol (1b) in 90% yield after concomitant hydrolysis. [a] S. Das, K. Mçller, Dr. K. Junge, Prof. Dr. M. Beller Leibniz-Institut für Katalyse e.V. an der Universität Rostock Albert-Einstein-Str. 29a 18059 Rostock (Germany) Fax: (+ 49) 381-1281-51113 E-mail: matthias.beller@catalysis.de  2011 Wiley-VCH Verlag GmbH&Co. KGaA, Weinheim Chem. Eur. J. 2011, 17, 7414 – 7417 7414