OXIDATIVE CARBONYLATION OF PHENYLACETYLENE CATALYZED BY PD(II) AND CU(I) - EXPERIMENTAL TESTS OF 41 COMPUTER-GENERATED MECHANISTIC HYPOTHESES

We describe an experimental study of the reaction mechanism of phenyla cetylene oxidative carbonylation to methyl ester of phenylpropiolic ac id catalyzed by Pd(II) and Cu(I), PhC=CH + CO + MeOH + 2NaOAc + 2CuCl( s) --> PhC=CCOOMe + 2AcOH + 2NaCl + 2CuCl, which was closely guided by recent computational research on the generation of reaction mechanism s. Our initial mechanistic studies of this reaction were based on info rmal (non-computer-generated) mechanistic hypotheses. When experiments at 20 degrees C and 1 atm led us to reject four of five mechanistic p ossibilities for the reaction, we turned to formulating new hypotheses with the aid of the computer programs ChemNet, which generated a reac tion network consisting of 233 elementary steps, and MECHEM, which unc overed 41 simplest hypothetical pathways from within the reaction netw ork. Our subsequent analysis of these 41 hypothetical mechanisms sugge sted a highly informative experiment based on the CH3OH/CH3OD kinetic isotope effect. The ratio between the rates of ester formation in nond euterated and deuterated methanol was close to unity, suggesting that O-H bond scission occurs after the rate-limiting transmetalation step CuC=CPh + PdCl2 --> ClPdC=CPh + CuCl. This experiment led to rejecting 32 out of the ill hypotheses. Four more mechanisms were rejected base d on the results of preliminary experimental studies. Further work is needed to discriminate among the five remaining mechanisms. (C) 1998 E lsevier Science B.V.