Mechanism of the Alkoxycarbonylation of Alkynes in the Presence of the Pd(OAc)₂/PPh₂Py/CH₃SO₃H Catalytic System

Abstract

The mechanism of the carbonylation of alkynes promoted by the Pd(OAc)2/2-pyridyldiphenylphosphine/methanesulfonic acid catalytic system has been studied. The carbonylation of 2-butyne in the presence of methanol affords stereospecifically the methyl ester of (E)-2-methyl-2-butenoic acid, indicating that the addition of H and COOCH3 moieties proceeds with cis stereochemistry. Experiments carried out using 1-alkynes and CH3OD reveal that the catalyst also promotes the exchange of the terminal hydrogen of the alkyne with the deuterium of the alcohol. 1H NMR experiments show that upon addition of phenylacetylene to a CD2Cl2 solution containing the catalyst and CH3OH a palladium complex having a 2-styryl group bound to the metal center, Pd−C(C6H5)CH2, is formed. This species can be invoked as an intermediate to account for both the H/D exchange and the carbonylation reaction. Carbonylation of 2-butyne in the presence of a 1/1 mixture of CH3OH and CH3OD indicates that a fairly large isotope effect (k H/k D = 6.4) is operative. All these results suggest that the carbonylation of alkynes proceeds via the protonation of a Pd(0)−alkyne species to give a Pd−vinyl complex, followed by CO insertion and alcoholysis.

Bifunctional Organometallic Catalysts Involving Proton Transfer or Hydrogen Bonding

“…The 2-pyridyl group on a phosphine moiety, as shown in 8, enables a highly selective alkoxycarbonylation of terminal alkynes, increasing reaction rates by factors of over 1000 times those obtained with only phenyl groups on the ligand. [54][55][56] Although several roles of the pyridine nitrogen atom and added acid have been discussed, the most recent evidence suggests [55] that a pyridinium moiety may help protonate a p-bound alkyne (in 8) to form a cationic vinyl complex (9).…”

Alkoxycarbonylation of 3,3,3-Trifluoropropyne: an Intriguing Reaction to Prepare Trifluoromethyl-Substituted Unsaturated Acid Derivatives

“…This finding contrasts with our previous observation that, in the presence of Drent×s catalytic system, the addition of the H and COOR moieties to the C-C triple bond of 2-butyne occurs in a stereospecific cis-fashion. [11] Although some peculiar features of Pd-hydride chemistry can rationalise this finding (see below), it further highlights the outstanding influence exerted by the trifluoromethyl moiety on the reaction.…”

“…[11] In fact, an increase of the P(CO) should mainly enhance the rate of the CO insertion which leads to the formation of the acyl intermediates. This would result in an enhanced formation of the kinetically controlled regioisomer.…”

Deuterium Naturally Present in Solvent and Site-Specific Isotope Population of Deuterium-Enriched Solute

“…13,15,16 Labeling the specific sites of molecules with isotopes has made it easier to examine chemical reaction mechanisms. [17][18][19] Proton-deuteron exchange has been used to distinguish the surface sites and inner sites of proteins 4,20 and inorganic materials. 21 Site-specific natural isotope fractionation has been measured to trace the geographical origin and production year of agricultural products, and to detect mixing and adulteration in food and beverages.…”