Dynamic Kinetic Resolution of Secondary Alcohols

DKR of 1-phenylethanol by the combination of a Pseudomonas fluorescens lipase and a Rh complex. 

For fhe DKR of hydroxy esters [13] and p-haloalcohols [14], the Backvall group used Pseudomonas cepacia lipase (PCL) immobilized on ceramic (Lipase PS-C) instead 

5 DYNAMIC KINETIC RESOLUTION OF ALCOHOLS, AMINES, AND AMINO ACIDS 

We applied the DKR procedme to the asymmetric reductive acylation of ketones and the asymmetric hydrogenation of enol acetates [16]. In the asymmetric reductive 

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Zhu, Y-.Z., Fow, K.L., Chuah, G.K. and Jaenicke, S., Dynamic kinetic resolution of secondary alcohols combining enzyme-catalyzed transesterification and zeolite-catalyzed racemisation. Chem. Eur. J. 2007, 13, 541. 

Van Nispen, S.E.G.M., van Buijtenen, J., Vekemans, J.A.J.M., Meuldijk, J. and Hulshof, L.A., Efficient dynamic kinetic resolution of secondary alcohols with a novel tetrafluorosuccinato ruthenium complex. Tetrahedron Asymm., 2006, 17, 2299. 

Verzijl, G.K.M., de Vries, J.G. and Broxterman, Q.B., Removal of the acyl donor residue allows the use of simple alkyl esters as acyl donors for the dynamic kinetic resolution of secondary alcohols. Tetrahedron Asymm., 2005, 16, 1603. 

Figure 5 Dynamic kinetic resolution of secondary alcohols...

Dynamic kinetic resolutions of secondary alcohols and amines have been achieved by the combination of biocatalysts with metal catalysts.12 For example, a metal catalyst was used to racemize the substrate, phenylethanol, and a lipase was used for the enantioselective esterification as shown in Figure 12. The yield was improved from 50% in kinetic resolution without racemization of the substrate to 100% with metal catalyzed racemization. 

Kim M-J, Kim HM, Kim D et al (2004) Dynamic kinetic resolution of secondary alcohols by enzyme-metal combinations in ionic liquid. Green Chem 6 471-474... 

K., Kaynak, E.B., and Baeckvall, ).-E. (2005) Combined mthenium(II) and lipase catalysis for efhcient dynamic kinetic resolution of secondary alcohols. Insight into the racemization mechanism. J. Am. Chem. Soc., 127 (24), 8817-8825. 

M.L, and Mueller, T.N. (2006) Lipase/aluminum-catalyzed dynamic kinetic resolution of secondary alcohols. Angew. Chem. Int. Ed., 45 (39), 6567-6570. 

Today, dynamic kinetic resolution of secondary alcohols by combination of enzymes with transition metal catalysts, originally developed by Williams and Backvall, are perhaps the best developed methods (33-36). Hitherto the most successful catalyst designs have been based on half-sandwich ruthenium complexes, of which the pentaphenylcyclopentadienyl ruthenium complex has been claimed as the currently best racemization catalyst. Racemization is then based on reversible conversion of the alcohol into the corresponding ketone (Fig. 21, A). The dynamic kinetic resolution of 1-phenylethanol with isopropenyl acetate in toluene in the presence of Novozym 435, performed in preparative scale, is a good example of the use of ruthenium complexes (35). Another thoroughly studied racemization method (Fig. 21, B) is based on the use of acidic resins or zeolites. Here the racemization takes place through prochiral sp car-benium ion by simultaneous elimination and addition of water (37). The use of... 

Alternatively, they were also found to be good racemization catalysts. Iridium complexes, but also rhodium compounds, catalyzed the racemization step in the enzymatic dynamic kinetic resolution of secondary alcohols, and excellent results were reported for alkyl-aryl as well as dialkyl secondary alcohols. Finally, picolyl and pyridine functionalized N-heterocyclic carbene iridium complexes [(C N)Ir(Cp )Cl]Cl were moderately active catalysts for the polymerization of norbomene in the presence of methylaluminoxane as cocatalyst. ... 

Maviynsky D, Paivio M, LundeU K, Sillanpaa R, Kanerva LT, Leino R. Dicarbonylchloro(pentabenzylcyclopentadienyl) ruthenium as racemization catalyst in the dynamic kinetic resolution of secondary alcohols. Eur. J. Org. Chem. 2009 1317-1320. 

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