Palladium-catalyzed carbonylation of alkynes.

Abstract

This thesis describes the palladium-catalyzed carbonylation of alkynes with formic acid. Terminal alkynes react with formic acid in the presence of catalytic amounts of Pd(OAc)$\sb2$ and suitable phosphine ligands (120 psi of CO gas pressure, 100-110$\sp\circ$C) to produce the unsaturated carboxylic acids CR(COOH)=CH$\sb2,$ 1, and (E)-CHR=CH(COOH), 2. The combined yields of 1 and 2 for various R's range from 60 to 90%. The regioselectivity is approximately 90:10 in favour of 1 when R is a phenyl or a straight chain alkyl group; 2 is the favoured product when R is t-Bu and the exclusive one when R is SiMe$\sb3.$ Under similar conditions, internal alkynes react with formic acid to produce the unsaturated carboxylic acids (E)-CR(COOH)=CHR$\sp\prime$, 3, and (E)-CHR=CR$\sp\prime$(COOH), 4, also in 60-90% combined yields. The regioselectivity of this reaction, however, is not as high as for terminal alkynes. Oxalic acid can be used instead of formic acid in both of these reactions. The most suitable phosphine ligands for alkyne hydrocarboxylation in the present system are PPh$\sb3$ and dppb (1,4-bis(diphenylphosphino)butane). In some cases, using a mixture of these two ligands remarkably improves the reaction yields; the implications of such ligand synergism are discussed. On the basis of deuterium labelling studies and other experimental results, a reaction mechanism has been proposed which involves the addition of the O-H bond of formic acid to form a cationic hydrido(alkyne) intermediate. This intermediate is thought to undergo a sequence of reactions, including hydride and CO insertions, to give the acid product and regenerate the active catalyst. Terminal alkynes undergo dicarbonylation upon reacting with formic acid and/or water in a catalytic system consisting of $\rm PdCl\sb2/CuCl\sb2/O\sb2/CO$ (room temperature, atmospheric pressure); the products are monosubstituted maleic anhydrides and the corresponding maleic and fumaric acids in 30-75% combined yields. The product distribution is influenced by both the steric bulk of the alkyne substituent and the amount of water present in the reaction medium. Internal alkynes are unreactive in this system. Among the solvents tested, THF is the most suitable one. Phosphines and phosphites completely inhibit the reaction. In contrast to most systems in which CuCl$\sb2$ acts as the principal oxidant for converting Pd(0) to Pd(II), the role of CuCl$\sb2$ in the present system seems to be secondary to that of oxygen. For instance, modest catalytic turnovers are observed in the absence of CuCl$\sb2$, whereas no catalysis occurs if oxygen is excluded from the system, even in the presence of excess CuCl$\sb2$. These and other observation are rationalized by invoking various oxidation schemes involving oxygen as the main oxidant. The role of CuCl$\sb2$ is thought to be one of facilitating the catalysis by forming a heterometallic Cu/Pd complex.