DOI: 10.1002/asia.201000317 Facile and Efficient Reduction of Ketones in the Presence of Zinc Catalysts Modified by Phenol Ligands Stephan Enthaler,* Bjçrn Eckhardt, Shigeyoshi Inoue, Elisabeth Irran, and Matthias Driess [a] Introduction Alcohols have an extensive range of applications including, for example, as building blocks and synthons for pharma- ceuticals, agrochemicals, polymers, in the syntheses of natu- ral compounds, auxiliaries, ligands and as key intermediates in organic syntheses. [1] One key approach to their synthesis is the reduction of ketones or aldehydes. Besides the reduc- tion with metal hydrides (e.g., NaBH 4, LiAlH 4 ), the applica- tion of transition metal catalysts offers efficient and versatile strategies, such as the addition of organometallic compounds to aldehydes, hydrosilylation, and hydrogenation of carbonyl functionalities. [2] Catalytic hydrogenation or transfer hydro- genation of C =O bonds are the most direct routes to alco- hols. Nonetheless, catalytic hydrosilylation is an alternative to (transfer) hydrogenation, because of mild reaction condi- tions and simplicity. [3] Furthermore, the C =O bond is first re- duced to a silyl ether (CH-OSiR 3 ), which functions as a pro- tecting group of the alcohol and allows sensitive additional transformations. Up to now, manifold catalysts for the hy- drosilylation of carbonyl compounds rely on precious metals, such as rhodium, ruthenium, and iridium. [4] Less-ex- pensive metals, such as titanium, zinc, tin, copper, and iron have also been investigated. [5] In the case of zinc catalysts, only a few reports are available. Pioneering work in the field was reported by Mimoun and co-workers. [6] Later on, several research groups enhanced this method for increased group tolerance, in situ deprotection of the silyl ether, the application of PMHS (polymethylhydrosiloxane) as inexpen- sive hydride source or incorporation of chirality. [7] However, some catalyst systems display some drawbacks: the use of catalyst loadings above 1.0 mol % and long reaction times. Hence, the development of better methods is desired. Herein, we report the successful application of a homogene- ous hydrosilylation catalyst based on diethyl zinc modified by phenol ligands; this catalyst has excellent performance and is capable of reducing a variety of aromatic and aliphat- ic ketones. Results and Discussion It was shown by Mimoun and co-workers that unmodified ZnEt 2 was not able to catalyze the hydrosilylation of car- bonyl compounds. The addition of ligands to ZnEt 2 was found to significantly improve the outcome of the reaction. Most ligands that have been used were based on diamine li- gands. In addition, some groups demonstrated the usefulness of zinc diamine catalysts in combination with alcohols. [7a,e,f] We wanted to investigate whether one could apply catalysts containing Zn ÀO bonds in the absence of nitrogen-contain- ing ligands, because the highly oxophilic character of the zinc should improve the stability of the catalyst. Indeed, DFT calculations showed a higher bond energy for the Zn À O bond in [MeOZnMe] (73.9 kcal mol À1 ) compared with the N À Zn bond in the analogous [Me 2 NZnMe] (53.5 kcal Keywords: catalysis · hydrosilyla- tion · ketones · phenol ligands · zinc Abstract: In the present study, the zinc-catalyzed hydrosilylation of various ke- tones to give their corresponding alcohols has been examined in detail. Diethyl zinc that can be modified by easily accessible phenol ligands allows the efficient reduction of various aryl and alkyl ketones. By using a practical in situ catalyst, ex- cellent turnover frequencies up to 1000 h À1 and a broad functional group tolerance were achieved. [a] Dr. S. Enthaler, B. Eckhardt, Dr. S. Inoue, Dr. E. Irran, Prof. Dr. M. Driess Technische Universität Berlin Department of Chemistry Cluster of Excellence “Unifying Concepts in Catalysis” Straße des 17. Juni 135, 10623 Berlin (Germany) Fax: (+ 49) 3031429732 E-mail : stephan.enthaler@tu-berlin.de Chem. Asian J. 2010, 5, 2027 – 2035  2010 Wiley-VCH Verlag GmbH&Co. KGaA, Weinheim 2027