Hydrosilylation of cinchonidine and 9-O-TMS-cinchonidine with triethoxysilane: application of 11-(triethoxysilyl)-10,11-dihydrocinchonidine as a chiral modifier in the enantioselective hydrogenation of 1-phenylpropane-1,2-dione

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

“…Based on the previous ab initio calculations with cinchonidine and 11-(triethoxysilyl)-10,11-dihydrocinchonidine, [17] the most stable conformations for both of these compounds were very similar open(3) forms. Thus, even relatively large substituents in the distal C-3 position would not appear to result in dramatic changes in the conformational equilibrium.…”

“…(-)-Cinchonidine (Aldrich, 96 %), triethylsilane (Gelest, 99+ %), triphenylsilane (Fluka, Ն99 %) and platinum-divinyltetramethyldisiloxane complex (Karstedt's catalyst, 2.1-2.4 % Pt concentration in xylene, Gelest) were used as received. Synthesis of 9-O-(trimethylsilyl)cinchonidine was carried out as described previously, [17] 1,2-bis(dimethylsilyl)ethane was prepared by reduction of 1,2-bis(chlorodimethylsilyl)ethane (Gelest, 97 %) with LiAlH 4 and vacuum-distilled prior to use. [27] The chiral silane (+)-(R)-methyl(1-naphthyl)phenylsilane, was prepared according to a literature procedure.…”

“…Catalyst modification by the 11-triethylsilyl-substituted cinchonidine derivative 4a in toluene provided a similar ee enhancement compared to cinchonidine (ee = 70 % vs. 55 %) as observed earlier with the 11-triethoxysilyl analogue in ethyl acetate (Table 4). [17] Also the regioselectivity (B+C vs. D+E) was slightly enhanced. The 11-triphenylsilyl analogue 4b gave a similar ee than obtained with 1 (ee = 53 % and 55 %, respectively).…”

“…As described previously, [17] in the first step, cinchonidine (1) is treated with chlorotrimethylsilane/TEA in THF to provide 9-O-(trimethylsilyl)cinchonidine (2) as a fairly pure solid in admixture with approximately 10 % 9-O-(trimethylsilyl)-10,11-dihydrocinchonidine in 96 % yield. The concomitant formation of the dihydrocinchonidine analogue of 2 results from the 10,11-dihydrocinchonidine impurity in commercial cinchonidine.…”

“…[17] In the prior investigation, the role of the bulky silyl substituent attached to the distal part of the quinuclidine moiety of cinchonidine remained ambigious, although it was shown by HartreeFock calculations that its influence on the conformational energetics are likely to be minor. The previous investigation raised the following questions: 1) What is the effect of varying the distal moiety of the cinchona alkaloid modifier on enantioselectivity of the hydrogenation reaction?…”