Steric and electronic effects in the enantioselective hydrogenation of activated ketones on platinum: Directing effect of ester group

Steric effects in the Pt-catalyzed asymmetric hydrogenation of nine different alpha-ketoesters were studied by variation of the bulkiness at the keto and ester side of the substrates. and by using cinchonidine (1213), its 6'-methoxy derivative quinine. and o-phenyl derivative PhOCD as chiral modifiers. In the presence of CD, the (R)-enantiomer always formed in good to high ee (up to 96%), independent of the steric bulkiness of the alpha-ketoester. None of the mechanistic models developed for ketone hydrogenation on P-1 are conform to the observations. Only additional steric effects in the modifiers and replacement Of toluene by acetic acid as a reaction medium enhanced the sensitivity of the catalyst system to steric effects in the substrates (ee = 0-94%). An important mechanistic consequence of the observations is that on CD-modified Pt preferred adsorption of the a-ketoester on the si-side is directed by the position of the ester group relative to the modifier, independent of the steric bulkiness on any side of the keto-carbonyl group. Ester, carboxyl, amido, carbonyl, acetal. and trifluoromethyl functions have similar directing effects. but when both trifluoromethyl and an ester or carbonyl groups are present in the Molecule, the latter function is dominant. The directing effect of the electron-withdrawing (-activating) function on adsorption of the ketone is obviously related to the electronic environment provided by the chiral modifier. The critical role of electronic interactions is supported by the remarkable influence of aryl substituents in the hydrogenation of ethyl benzoylformates. (c) 2006 Elsevier Inc. All rights reserved.