Internationale Ausgabe: DOI: 10.1002/anie.201502579 Synthetic Methods Deutsche Ausgabe: DOI: 10.1002/ange.201502579 Catalytic Ketone Hydrodeoxygenation Mediated by Highly Electrophilic Phosphonium Cations** Meera Mehta, Michael H. Holthausen, Ian Mallov, Manuel PØrez, Zheng-Wang Qu, Stefan Grimme,* and Douglas W. Stephan* Abstract: Ketones are efficiently deoxygenated in the presence of silane using highly electrophilic phosphonium cation (EPC) salts as catalysts, thus affording the corresponding alkane and siloxane. The influence of distinct substitution patterns on the catalytic effectiveness of several EPCs was evaluated. The deoxygenation mechanism was probed by DFT methods. Lewis acids are an important class of reagents in synthetic chemistry and mediate a wide variety of stoichiometric and catalytic transformations. [1] Indeed, such compounds find applications across a broad cross-section of the chemical community. Quintessential examples of Lewis acids, such as the classically simple group XIII compounds BH 3 , BF 3 , and AlMe 3 , possess a vacant acceptor p orbital. More recently, electron-withdrawing groups, such as perfluorinated arenes in boranes, have been installed to increase Lewis acidity, thus facilitating Lewis acid catalysis and frustrated Lewis pair (FLP) reactivity. [2] Strong Lewis acids based on group XIV cations, such as [Ph 3 C] + or [R 3 Si] + , [3] were mainly used stoichiometrically, as their high reactivity often hampers application in catalysis. In contrast, group XV cations are generally more chemically robust and the tendency of, for example, P V phosphonium cations [R 4 P] + to form neutral phosphoranes R 4 PX, is evidence for certain Lewis acidity. This property has been exploited in the development of fluoride ion sensors [4] as well as catalysts for (cyclo)addition reactions to polar or activated unsaturated substrates. [5] More recently, we have focused on enhancing this Lewis acidity by preparing more electrophilic phosphonium cations (EPCs) such as [(C 6 F 5 ) 3 PF] + (1), [(C 6 F 5 ) 2 PhPF] + (2), and [(C 6 F 5 )Ph 2 PF] + (3). We have demonstrated that the low- lying antibonding orbital [6] permits these species to act as highly effective catalysts for the hydrodefluorination of fluoroalkanes, [6] hydrosilylation of olefins, ketones, and alkynes, [7] and the dehydrocoupling of amines, acids, and thiols with silanes. [8] In the latter case, tandem transfer hydrogenation can also be effective with concurrent dehy- drocoupling reactions. [8] The scope of these EPCs has been broadened to include dicationic phosphonium species [(SIMes)PPh 2 F] 2+ (5) [9] and bifunctional bis(phosphonium) compounds. [10] The additional charge is manifested in even greater Lewis acidity. Hydrodeoxygenation of ketones has garnered increasing attention given its many applications in biofuels and fine- chemical syntheses. [11] Classic protocols for deoxygenation include the Barton–McCombie (R 3 SnH), [12] Clemmensen (Zn/Hg, HCl), [13] or Wolff–Kishner reductions (H 4 N 2 , KOH), [14] and these methods generally require harsh reaction conditions, use stoichiometric amounts of toxic reagents, and show poor functional-group tolerance. Heterogeneous catal- ysis employing, for example, PtO 2 [15] and Ni/Al 2 O 3 [16] and H 2 as the reducing agent is known, while a recent report has described the use of Pd/C [17] with polymethylhydrosiloxane (PMHS) for the reduction of aromatic ketones. Herein, we probe the ability of a range of EPCs (1–9 ; Figure 1) to effect ketone reduction. In the presence of silane, the P V Lewis acids 1–3 and 5–8 are shown to be effective catalysts for the deoxygenation of ketones under mild reaction conditions, thus affording the corresponding alkane and siloxane. In our initial efforts, reactions of dialkyl- and diaryl- ketones, 2-methylpentanone (10a) and benzophenone (11 a), respectively, and Et 3 SiH were performed in the presence of a catalytic amount of one of the Lewis acidic EPCs (1–9 ; Figure 1). By using 1.0 mol % of 1 [6] and 2.1 equivalents of Et 3 SiH in CD 2 Cl 2 , quantitative deoxygenation of both sub- Figure 1. The electrophilic phosphonium cations 1–9. [*] M. Mehta, Dr. M.H. Holthausen, I. Mallov, Dr. M. PØrez, Prof. Dr. D. W. Stephan Department of Chemistry, University of Toronto 80 St. George St, Toronto Ontario M5S 3H6 (Canada) E-mail: dstephan@chem.utoronto.ca Dr. Z.-W. Qu, Prof.Dr. S. Grimme Mulliken Center for Theoretical Chemistry Institut für Physikalische und Theoretische Chemie Universität Bonn, Beringstrasse 4, 53115 Bonn (Germany) [**] D.W.S. gratefully acknowledges the financial support of the NSERC of Canada and the award of a Canada Research Chair. M.H.H. thanks the Alexander von Humboldt Foundation for a Feodor Lynen Research Fellowship. Z.-W.Q. and S.G. are grateful for the financial support of the Deutsche Forschungsgemeinschaft (SFB 813). Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/anie.201502579. . Angewandte Zuschriften 8368 # 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim Angew. Chem. 2015, 127, 8368 –8372