Expanding the scope of asymmetric electrophilic atom-transfer reactions: titanium- and ruthenium-catalyzed hydroxylation of beta-ketoesters.

Patrick Y Toullec, Cristina Bonaccorsi, Antonio Mezzetti, Antonio Togni

Index: Proc. Natl. Acad. Sci. U. S. A. 101(16) , 5810-4, (2004)

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Abstract

The enantioselective formation of a quaternary stereogenic center coinciding with a hydroxylation process is a very rare reaction from a homogeneous catalysis point of view. Indeed, to our knowledge, no asymmetric transition-metal-catalyzed direct hydroxylation has been reported before. We describe here our initial study concerning the enantioselective alpha-hydroxylation of various beta-ketoesters catalyzed by Lewis-acidic complexes. Specifically, it was found that the Ti complex [TiCl(2)((R,R)-1-Np-TADDOLato)(MeCN)(2)] affords the hydroxylated products in high yield and enantioselectivities up to 94% enantiomeric excess when using 2-(phenylsulphonyl)-3-(4-nitrophenyl)oxaziridine as the oxidizing agent. Chiral enantiopure compounds of the latter type have been used previously in stoichiometric asymmetric hydroxylation reactions. We also show that, in a complementary approach with H(2)O(2) as the oxidant, the Ru(II) complex [RuCl(OE(2))((S,S)-PNNP)]PF(6) catalyzes the same type of transformation in a case of substrates showing a very substantial extent of enolization under reaction conditions; being, however, unreactive toward only weakly enolized beta-ketoesters.