Asymmetric hydrogenations one by one: differentiation of up to three beta-ketocarboxylic acid derivatives based on Ruthenium(II)-binap catalysis.
Noyori-type reductions of pairs of beta-ketoamides and beta-ketoesters with elemental hydrogen (4 bar) proceeded substrate by substrate. When Et(2)NH(2) (+)[{RuCl(S)-binap}(2)](mu-Cl)(3)(-) was employed as a catalyst in a methanol or ethanol solution, the substrates were reduced at room temperature in the order beta-ketopyrrolidide > or = beta-ketopiperidide > or = beta-keto(N,N-diethylamide) > beta-keto(alkyl esters) > beta-keto(oligofluoroalkyl esters). This is the first time that beta-ketoamides have been reduced asymmetrically (91 to >98 % ee) under such mild conditions. Monitoring the concentrations of these beta-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 rapidly.
Kramer
Rainer
R
Institut für Organische Chemie und Biochemie, Universität Freiburg, Albertstrasse 21, 79104 Freiburg, Germany.
Brückner
Reinhard
R
D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry; D002264:Carboxylic Acids / Q000737:chemistry*; D002384:Catalysis; D004952:Esters / Q000138:chemical synthesis* / Q000737:chemistry; D006859:Hydrogen / Q000737:chemistry*; D006865:Hydrogenation; D015394:Molecular Structure; D017975:Ruthenium Compounds / Q000737:chemistry*; D013237:Stereoisomerism; D013816:Thermodynamics
D000577:Amides; D002264:Carboxylic Acids; D004952:Esters; D017975:Ruthenium Compounds; D006859:Hydrogen