Asymmetric hydrogenations one by one: Differentiation of up to three β-ketocarboxylic acid derivatives based on ruthenium(II)-binap catalysis

Abstract

Noyori-type reductions of pairs of β-ketoamides and β-ketoesters with elemental hydrogen (4 bar) proceeded substrate by substrate. When Et 2NH2+[{RuCl(5)-binap}2](μ-Cl) 3- was employed as a catalyst in a methanol or ethanol solution, the substrates were reduced at room temperature in the order β-ketopyrrolidide ≥ β-ketopiperidide ≥ β-keto(N,N- diethylamide) > β-keto(alkyl esters) > β-keto(oligofluoroalkyl esters). This is the first time that β-ketoamides have been reduced asymmetrically (91 to >98% ee) under such mild conditions. Monitoring the concentrations of these β-ketocarboxyl acid derivatives and their respective hydrogenation products over the course of time showed that the most electron-rich substrate is captured by the catalyst preferentially and exothermically; whether this occurs reversibly or irreversibly remains to be determined. The hydrogenation product is subsequently formed. The last transformation includes the rate-determining step. The combination of these events explains why starting from appropriate mixtures of substrates a "first-choice substrate" reacted from early on while the "second-choice substrate" stayed virtually untouched over an extended period of time and reacted no earlier than after the "first-choice substrate" had disappeared. From then onward, however, the "second-choice substrate" also reacted relatively rapid-iy. © 2007 Wiley-VCH Verlag GmbH & Co. KGaA.