The importance of alkali cations in the [{RuCl2(p-cymene)}2]-pseudo-dipeptide-catalyzed enantioselective transfer hydrogenation of ketones.
We studied the role of alkali cations in the [{RuCl2(p-cymene)}2]-pseudo-dipeptide-catalyzed enantioselective transfer hydrogenation of ketones with isopropanol. Lithium salts were shown to increase the enantioselectivity of the reaction when iPrONa or iPrOK was used as the base. Similar transfer-hydrogenation systems that employ chiral amino alcohol or monotosylated diamine ligands are not affected by the addition of lithium salts. These observations have led us to propose that an alternative reaction mechanism operates in pseudo-dipeptide-based systems, in which the alkali cation is an important player in the ligand-assisted hydrogen-transfer step. DFT calculations of the proposed transition-state (TS) models involving different cations (Li+, Na+, and K+) confirm a considerable loosening of the TS with larger cations. This loosening may be responsible for the fewer interactions between the substrate and the catalytic complex, leading to lower enantiodifferentiation. This mechanistic hypothesis has found additional experimental support; the low ee obtained with [BnNMe3]OH (a large cation) as base can be dramatically improved by introducing lithium cations into the system. Also, the complexation of Na+, K+, and Li+ cations by the addition of [15]crown-5 and [18]crown-6 ethers and cryptand 2.1.1 (which selectively bind to these cations and, thus, increase their bulkiness), respectively, to the reaction mixture led to a significant drop in the enantioselectivity of the reaction. The lithium effect has proved useful for enhancing the reduction of different aromatic and heteroaromatic ketones.
Västilä
Patrik
P
Department of Organic Chemistry, The Arrhenius Laboratory, Stockholm University, 10691 Stockholm, Sweden.
Zaitsev
Alexey B
AB
Wettergren
Jenny
J
Privalov
Timofei
T
Adolfsson
Hans
H
D000468:Alkalies / Q000737:chemistry*; D002384:Catalysis; D002412:Cations / Q000737:chemistry; D000081007:Cymenes; D004151:Dipeptides / Q000737:chemistry*; D006865:Hydrogenation; D007659:Ketones / Q000737:chemistry*; D039821:Monoterpenes / Q000737:chemistry*; D017975:Ruthenium Compounds / Q000737:chemistry*; D013237:Stereoisomerism
D000468:Alkalies; D002412:Cations; D000081007:Cymenes; D004151:Dipeptides; D007659:Ketones; D039821:Monoterpenes; D017975:Ruthenium Compounds; C007210:4-cymene; C038365:ruthenium chloride