Solvent-Promoted Regio- and Stereoselectivity in Ru-Catalyzed Hydrocarboxylation of Terminal Alkynes: A DFT Study

Abstract

DFT calculations at the M06L-D3(SMD)/LANL2TZ(f)/6-311+G(d,p)//M06L/LANL2DZ/6-31G(d)* level were performed to explore the mechanism, solvent effect, and origin of selectivity in the hydrocarboxylation of terminal alkynes catalyzed by (PCy3)2(CO)RuHCl. This catalytic system offers a unique example in which selectivity in enol-ester synthesis is controlled in presence of different solvent media under mild reaction conditions. In CH2Cl2 solvent the regioselective gem-enol-ester (Pg) was preferred, whereas stereoselective Z-enol-ester (PZ) was observed exclusively in THF medium. We have unraveled the complete catalytic mechanism involving the following steps: a) alkyne coordination with subsequent nucleophilic attack and, finally, b) product elimination leading to the Markovnikov product Pg in both solvent media. Herein, the rate-limiting nucleophilic attack step requires an activation barrier of 20.5 (21.0) kcal mol−1, which is 5.7 (5.6) kcal mol−1 lower than the crucial vinylidene formation step encountered for anti-Markovnikov addition. Interestingly, a new reaction avenue unfolds under explicit THF medium, in which the inherent coordinating nature of the solvent becomes effective in altering the product regioselectivity. Under such an event, a highly facile ligandassisted proton shuttle (LAPS) mechanism is propagated, leading to vinylidene complex 11A. This intriguing mechanistic scenario facilitates favorably furnishing the PZ product rather than the Pg isomer by 4.3 kcal mol−1.