Catalytic asymmetric transfer hydrogenation

The mechanism of the Meerwein-Pondorf-Verley reaction is by coordination of a Lewis acid to isopropanol and the substrate ketone, followed by intermolecular hydride transfer, by beta elimination [41]. Initially, the mechanism of catalytic asymmetric transfer hydrogenation was thought to follow a similar course. Indeed, Backvall et al. have proposed this with the Shvo catalyst [42], though Casey et al. found evidence for a non-metal-activation of the carbonyl (i.e., concerted proton and hydride transfer [43]). This follows a similar mechanism to that proposed by Noyori [44] and Andersson [45], for the ruthenium arene-based catalysts. By the use of deuterium-labeling studies, Backvall has shown that different catalysts seem to be involved in different reaction mechanisms [46]. 

These can be prepared by a) asymmetric dihydroxylation of allylic chlorides followed by acetonide formation and elimination with BuLi b) catalytic asymmetric transfer hydrogenation and c) reduction of alkynones with chiral metal hydrides, (a) Marshall, J. A. Jiang, H. Tetrahedron Lett. 1998, 39, 1493 Yadav, J. S. Chander, M. C. Rao, C. S. Tetrahedron Lett. 1989, 30, 5455 (b) Matsumura, K. Hashiguchi,... 

A method for the monoarylation of (15,25)-l,2-diaminocyclo-hexane by means of palladium-catalyzed aromatic amination has been recently described (eq 13). The resulting new ligands were tested in the catalytic asymmetric transfer hydrogenation of acetophenone. 

Catalytic asymmetric transfer hydrogenation is an efficient method for producing optically active alcohols and amines. Analysis of launched and development pharmaceuticals show that these types of chiral centers occur most frequently, so this technology is proving particularly valuable. The chapter will describe the background, development, and application of asymmetric transfer hydrogenation, with particular emphasis on Avecia s proprietary CATHy catalysts. 

The authors would like to thank the many Avecia employees that have been involved with development of the catalytic asymmetric transfer hydrogenation and especially Dr. Lynne Campbell, Dr. Ian Houson, Dr. David Moody. Professor Jonathan Williams of Bath University and Prof. Martin Wills of Warwick University. 

The reduction of the carbonyl group (and related functionalities) by catalytic methods has been successfully achieved by a number of methods. Rhodium and ruthenium complexes are the most popular catalysts used in the hydrogenation of ketones. While most catalyst systems of this type require the presence of additional chelating functionality on the substrate the recent development of highly active ruthenium(diamine) complexes allows the reduction of simple unfunctionalised ketones. Ruthenium catalysts have also been applied, with much success, to the catalytic asymmetric transfer hydrogenation of ketones in the presence of alcohols or formate. 

Kumaraswamy G, Padmaja M (2008) Enantioselective Total Synthesis of Eicosanoid and its Congener, Using Organocatalytic Cyclopropanation, and Catalytic Asymmetric Transfer Hydrogenation Reactions as Key Steps. J Org Chem 73 5198... 

Scheme 24 Catalytic asymmetric transfer hydrogenation of citral 61 and famesal 63...

Cotarca, L. Verzini, M. Volpicelli, R. Catalytic asymmetric transfer hydrogenation An industrial perspective. Chim. Oggi. 2014,32,36-41. 

Sun, X. Gavriilidis, A. Scalable reactor design for pharmaceuticals and fine chemicals production. 3. A novel gas-liquid reactor for catalytic asymmetric transfer hydrogenation with simultaneous acetone strip>ping. Org. Process Res. Dev. 2008,12,1218-1222. 

Hansen, K. B. Chilenski, J. R. Desmond, R. Devine, P. N. Grabowski, E. J. J. Heid, R. Kubryk, M. Mathre, D. J. Varsolona, R. Scalable, efficient process for the synthesis of (R)-3,5-bistrifluoromethylphenyl ethanol via catalytic asymmetric transfer hydrogenation and isolation as a DABCO inclusion complex. Tetrahedron Asymmetry 2003,14,3581-3587. 

Application of ATH in Stereoselective Synthesis Murlcatacln can be isolated as a scalemic mixture from the seeds of Annona muricata Muricatacin and epi-muricata-cin showed anti-proliferative activity against certain cell Unes. The enantioselective total synthesis of a potent cytotoxic agent (- -)- p/-muricatacin was reported by Kumarasw-amy et employing Noyori catalytic asymmetric transfer hydrogenation of benzyl 128 to (15,25)-1,2-diphenylethane-1,2-diol, which subsequently reacted with 129 to produce a key chiral intermediate 130 (Scheme 30.26). 

SCHEME 30.26. Noyori s catalytic asymmetric transfer hydrogenation in the synthesis of +)-epi-muricatacin. 

SCHEME 30.27. Catalytic asymmetric transfer hydrogenation with Noyori s catalyst as a key step in the total syntheses of diospongins A and B, eicosanoids, and synparvolides. 

Baratta W, Chelucci G, Herdtweck E, Magnolia S, Siega K, Rigo P. Highly diastereoselective formation of ruthenium complexes for efficient catalytic asymmetric transfer hydrogenation. Angew. Chem. Int. Ed. 2007 46(40) 7651-7654. 

Meyer N, Lough AJ, Morris RH. Iron(II) complexes for the efficient catalytic asymmetric transfer hydrogenation of ketones. Chemistry 2009 15(22) 5605-5610. 

Kumaraswamy G, Padmaja M. Enantioselective total synthesis of eicosanoid and its congener, using organocatalytic cyclopropanation, and catalytic asymmetric transfer hydrogenation reactions as key steps. J. Org. Chem. 2008 73 (13) 5198-5201. 

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