Synthesis of chiral catalyst modifiers by hydrosilylation of cinchonidine and their application in the hydrogenation of 1-phenylpropane-1,2-dione and ethyl pyruvate on a supported Pt/Al2O3 catalyst

Four new chiral modifiers were synthesized in order to investigate the effect of distal modifier substitution in the hydrogenation of ethyl pyruvate and 1-phenylpropane-1,2-dione on a supported Pt/Al2O3 catalyst. The chiral modifiers were prepared in good to moderate overall yields by Pt-catalyzed hydrosilylation of 9-O-TMS-protected cinchonidine with triethylsilane, triphenylsilane, his (dimethylsilyl) ethane and (+)(R)-methyl(1-ndphthyl)phenylsilane followed by cleavage of the silyl ether protective group. Comparison of the synthesized modifiers in enantioselective hydrogenation using cinchonidine as reference modifier is reported, as well as details on their synthesis and characterization. The X-ray crystal structure of the 11-(triphenylsilyl)-substituted cinchorridine analogue has been determined showing that this compound crystallizes in the open(3)-like conformation observed earlier for (-)-cinchonidine. In the hydrogenation of ethyl pyruvate, the new modifiers induced notable enantiomeric excesses (ee = 62-73 %), which, however, were slightly lower than the ee obtained with cinchonidine as the chiral catalyst modifier (ee = 84 %). The rate for the racemic reaction in the absence of a chiral modifier was up to threefold higher than the reaction rate with the distally substituted modifiers whereas with cinchonidine the reaction rate was close to that of the racemic hydrogenation. In the hydrogenation of 1-phenylpropane-1,2-dione, 11-(triethylsilyl)-10,11-dihydrocinchonidine induced an ee of 70 % at 50 % reactant conversion which was notably higher than the ee obtained with cinchonidine (55 %). The dependence of enantiomeric excess on the modifier structure is clearly different in the two cases (ethyl pyruvate vs. 1-phenylpropane-1,2-dione) indicating notable differences in the enantiodifferentiating mechanisms in these two model reactions. ((c) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005).