Advances in the stereoselective synthesis of antifungal agents and ...

Chapter 2 45PhaxeqP 1MP 2axeqPhP 2MP 1PhPhTOP VIEWSIDE VIEWFigure 2.5: Orientation of posphophenyl groups in BINAPThus, spatial characteristics exert a significant influence on thesubstrate coordination sites allowing for exceptional efficiency in BINAPcatalysis.A wide variety of functionalized ketones can be converted into theirrespective optically pure alcohols via homogeneous hydrogenation in thepresence of halogen-containing Ru-BINAP catalysts in alcoholic media.The reaction proceeds in a higly enantioselective and predictable fashion. Ageneral mechanism which describes this selective process involves initialcoordination of the carbonyl oxygen and the α or β adjacent heteroatom(such as nitrogen, oxygen or halogen) to create a five to seven memberedmetal chelated ring complex prior to hydrogen transfer.In the BINAP-Ru catalyzed reaction, diverse polar functionalitiesfacilitate the hydrogenation of the neighboring carbonyl group and allow theefficient enantioface differentation. The halogen containing complexes oftype RuX 2 -BINAP, the dimeric triethylamine complex or dicarboxylatecomplex, Ru(OCOR)2-Binap, may be used as catalyst, depending on theketonic substrates. Methanol or ethanol are the solvents of choice.The reaction with a substrate:catalyst molar ratio of 2200:230 proceedswith a reasonable rate at room temperature using an initial hydrogenpressure of 40-100 atm.Noyori, in 1979, reported also the use of optically pure 2,2' dihydroxy-1,1'- binaphthyl as LiAlH 4 chelating agent. The 1,1' Binaphthol itself has anaxial asymmetry and possesses an extremely high ability of chiralrecognition 15 .BINAL-H 21e is prepared by modification of LiAlH 4 with (R)- or (S)-binaphthol and one equivalent of ethanol (Scheme 2.8).