& Synthetic Methods A Well-Defined Monomeric Aluminum Complex as an Efficient and General Catalyst in the Meerwein–Ponndorf–Verley Reduction Brian McNerney, [a] Bruce Whittlesey, [a] David B. Cordes, [b] and Clemens Krempner* [a] Dedicated to Prof. Gerhard Roewer on the occasion of his 75 th birthday Abstract: The metal-catalyzed Meerwein–Ponndorf–Verley (MPV) reduction allows for the mild and sustainable reduc- tion of aldehydes and ketones but has not found wide- spread application in organic synthesis due to the high catalyst loading often required to obtain satisfactory yields of the reduced product. We report here on the syn- thesis and structure of a sterically extremely overloaded siloxide-supported aluminum isopropoxide capable of cat- alytically reducing a wide range of aldehydes and ketones (52 examples) in excellent yields under mild conditions and with low catalyst loadings. The unseen activity of the developed catalyst system in MPV reductions is due to its unique monomeric nature and the neutral donor isopro- panol weakly coordinating to the aluminum center. The present work implies that monomeric aluminum alkoxide catalysts may be attractive alternatives to transition-metal- based systems for the selective reduction of aldehydes and ketones to primary and secondary alcohols. The recent years have witnessed tremendous research efforts in sustainable catalysis primarily aimed at the use of readily available feedstocks, the development of metal-catalyzed atom-economic reactions, the reduction of chemical waste and most importantly the replacement of precious metals with more abundant and less toxic main group or first-row transi- tion metals. Classic examples of this development are iron-cat- alyzed hydrogenations, [1] transfer hydrogenations [2] and hydro- silylations [3] of aldehydes and ketones to primary and second- ary alcohols, respectively, which are important synthetic inter- mediates in the pharmaceutical and fine chemical industry. [4] Less explored in this regard is the classical and highly sus- tainable metal-catalyzed Meerwein–Ponndorf–Verley (MPV) re- duction of ketones and aldehydes, which exhibits exceptional chemoselectivity, is operationally simple and uses isopropanol as an inexpensive, safe and nontoxic reducing agent. [5] The MPV reduction proceeds via hydride transfer from a secondary alcohol to a carbonyl compound mediated by coordination to a Lewis acidic metal center, [6] most often aluminum [7] but also other metals have been employed [8] (Scheme 1). From the prospective of sustainability aluminum is an attrac- tive catalyst component as it is the most abundant metal on earth (only challenged by iron), environmentally benign and of relatively low toxicity. Many of its inorganic and organometallic compounds are commercially available at low cost. Despite these advantages, the homogeneous aluminum alkoxide medi- ated MPV reduction has not found widespread utility in syn- thetic organic chemistry and natural product synthesis, [9] pri- marily due to the high catalyst loadings required to obtain sat- isfactory yields of the reduction product and the rather narrow substrate scope. [7, 8, 10] The low activity of simple aluminum alk- oxides and aryloxides can largely be attributed to the forma- tion of Al ÀO bridged aggregated structures. These very stable aggregates seem to persist even in solution resulting in coordi- natively saturated aluminum centers of reduced Lewis acidity. We envisioned that a sterically encumbered bidentate disil- oxide ligand, which we developed recently, [11] would prevent the resulting cyclic aluminum complex from being aggregated and further enhance the electrophilicity of aluminum center owing to the electron-withdrawing properties of the siloxide groups. [12] Herein, we will demonstrate for the first time that this conceptually new approach, leads to a well-defined and thermally robust aluminum isopropoxide that is monomeric and thereby an exceptionally active catalyst in the MPV reduc- tion of ketones and aldehydes. The straightforward synthesis of the aluminum methyl com- plex 2 and the aluminum isopropoxide 3, is illustrated in Scheme 2. Compound 3 can conveniently be prepared in a one-pot procedure starting from the sterically encumbered 1,4-disilane-diol 1 [11] in yields of 70–80 %. Isopropoxide 3 is Scheme 1. Commonly accepted mechanism of the MPV reaction. [a] Dr. B. McNerney, Prof. Dr. B. Whittlesey, Prof. Dr. C. Krempner Department of Chemistry and Biochemistry, Texas Tech University Box 1061, Lubbock, Texas, 79409-1061 (USA) E-mail : clemens.krempner@ttu.edu [b] Dr. D. B. Cordes School of Chemistry, St. Andrew University Purdie Building Fife KY16 9ST, St. Andrews (UK) Supporting information for this article is available on the WWW under http ://dx.doi.org/10.1002/chem.201404994. Chem. Eur. J. 2014, 20, 14959 – 14964  2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim 14959 Communication DOI: 10.1002/chem.201404994