Ruthenium-Catalyzed Hydrogen Transfer Reactions : Mechanistic Studies and Chemoenzymatic Dynamic Kinetic Resolutions

Abstract: The main focus of this thesis lies on transition metal-catalyzed hydrogen transfer reactions. In the first part of the thesis, mechanistic investigations on a ruthenium complex, Ru(CO)2Cl(η5-C5Ph5) utilized for the catalytic racemization of sec-alcohols were conducted.The reaction between 5-hexen-2-ol and Ru(CO)2(Ot-Bu)(η5-C5Ph5) was studied with the aim to elucidate the origin of the slow racemization rate observed for this sec-alcohol. Two diastereomers of an alkoxycarbonyl complex, which had the double bond coordinated to ruthenium, were characterized by NMR and in situ FT-IR spectroscopy. The observed inhibition on the rate of racemization for substrates with double bonds provided further confirmation of the importance of a free coordination site on ruthenium for β-hydride elimination. Furthermore, we observed that CO exchange, monitored by 13C NMR using 13CO, occurs with both the precatalyst, Ru(CO)2Cl(η5-C5Ph5), and the active catalytic intermediate, Ru(CO)2(Ot-Bu)(η5-C5Ph5). It was also found that added CO has an inhibitory effect on the rate of racemization of (S)-1-phenylethanol. Both these observations provided strong support for reversible CO dissociation as a key step in the racemization mechanism.In the second part of this thesis, Ru(CO)2Cl(η5-C5Ph5) was combined with an enzymatic resolution catalyzed by a lipase, leading to several efficient dynamic kinetic resolutions (DKR). DKR of exocyclic allylic alcohols afforded the corresponding acetates in high yields and with excellent ee. The products were utilized as synthetic precursors for α-substituted ketones and lactones. DKR of a wide range of homoallylic alcohols afforded the products in good to high yields and with high ee. The homoallylic acetates were transformed into 5,6-dihydropyran-2-ones in a short reaction sequence. Furthermore, DKR of a wide range of aromatic β-chloroalcohols afforded the products in high yields and with excellent ee. The β-chloro acetates were further transformed into chiral epoxides.