Abstract

We describe an experimental study of the reaction mechanism of phenylacetylene oxidative carbonyl ation to methyl ether of phenylpropiolic acid catalyzed by Pd(II) and Cu(I), which was closely guided by recent computational research on the generation of reaction mechanisms. Our initial mechanistic studies of this reaction were based on informal (non-computer-generated) mechanistic hypotheses. When experiments at 20 degrees C and 1 atm led us to reject four of five mechanistic possibilities for the reaction, we turned to formulating new hypotheses with the aid of the computer programs ChemNet, which generated a reaction network consisting of 233 elementary steps, and MECHEM, which uncovered 41 simplest hypothetical pathways from within the reaction network. Our subsequent analysis of these 41 hypothetical mechanisms suggested a highly informative experiment based on the CH3OH/CH3OD kinetic isotope effect. The ratio between the rates of ester formation in nondeuterated and deuterated methanol was close to unity, suggesting that O-H bond scission occurs after the rate-limiting transmetalation step CuCCPh + PdCl2 --> ClPdCCPh + CuCl. This experiment led to rejecting 32 out of the 41 hypotheses. Four more mechanisms were rejected based on the results of preliminary experimental studies. Further work is needed to discriminate among the five remaining mechanisms.

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