Resolution of ketones

Scheme 9.11 Successful dynamic kinetic resolution of ketone rac-13.

K. Naemura, K. Kittaka, M. Murata, H. Ida, K. Hirose, Y. Tobe, Lipase-Catalyzed Enantioselective Alcoholysis of Enol Acetates Optical Resolution of Ketones and Aldehydes Using Lipases in Organic Solvents , Enantiomer 1996, 1, 219-222. 

Resolution, of ketones with a-phenyl-ethylamine bisulfite complex, 49, 97... 

The presence of the aldehyde as cyanide acceptor is essential to achieve the resolution of ketone cyanohydrins with good enantioselectivities. The unreacted (S)-ketone cyanohydrin and the (R)-co-bromoaldehyde cyanohydrin formed could be isolated in moderate to good enantiopurity (50 to 95% and 75 to 92% respectively) [53]. 

Figure 32. Kinetic resolutions of ketones through Baeyer-Villiger oxidation...

Fig. 4.116 Dynamic kinetic resolution of ketones using CHMO-containing recombinant E. coli.

Resolution of Ketones. Brucine has not been used very extensively for the resolution of neutral compounds. However, in some cases, ketones or ketone derivatives may form diastereomeric inclusion complexes with brucine, providing an opportunity for their resolution. For example, the cyanohydrin of a bicyclic ketone has been resolved by this procedure (eq 10). Following resolution of the cyanohydrin, the ketone was regenerated and determined to be of 94% ee. 

A new method for the resolution of ketones depends upon the formation of an iminium salt containing an optically active anion.2 A ketone of one type, exemplified by (1), is converted into the pyrrolidine enamine (2), which is then treated with d-10-camphorsulfonic acid (3) to give the salt (4), which was resolved by systematic crystallization. Each enantiomeric salt was then crystallized and hydrolyzed to a pure enantiomeric ketone (1). 

A mixture of 2,3-0-isopropylidene-L-butanediol and 0.5 N HCl stirred and refluxed with distillation of the resulting acetone from a glass helices-padced column until the temp, reaches 100° -> L(+)-2,3-butanediol. Y 91%. - The product is used for the resolution of ketones by gas-liq. chromatography after their conyer-sion into diastereomeric ketals. J. J. Plattner and H. Rapoport, Am. Soc. 93, 1758 (1971) methods of resolution, reyiew, s. P. H. Boyle, Quart. Rev. 25, 323 (1971). 

Scheme 2.24 Dynamic kinetic resolution of ketone IPS catalyzed by CHMO-containing...

The ability to catalyze the asymmetric hydrogenation of aliphatic ketones provides an opportunity to extend the scope of these reactions to the dynamic kinetic resolution of ketones that contain a stereocenter in the enolizable a-position. The catalysts containing bisphosphine and diamine ligands are activated by base, and the base used to activate the metal catalyst can also catalyze the racemization of the ketone. An example of such a process is shown in Equation 15.76. ... 

Other Methods.—The discovery that the addition of the lithio-derivative of the resolvable sulphoximine (9) to ketones is reversible has generated a method for the resolution of ketones (Scheme 13). The method is applicable to a range of ketones, working particularly well for envelope-shaped bicyclic ketones, where the diastereoface specificity of the addition is high. 

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