Palladium-Catalyzed Carbonylative Cyclization of 1-Iodo-2-alkenylbenzenes

Abstract

The Pd-catalyzed carbonylation of ω-vinyl-substituted o-iodoalkenylbenzenes 1−4 can provide up to modest yields (50−60%) of 5- and 6-membered Type I cyclic acylpalladation products, i.e., α,β-unsaturated cyclic ketones, in the absence of an external nucleophile and high yields of 5- and 6-membered Type II cyclic acylpalladation products, i.e., α- or β-((alkoxycarbonyl)methyl)substituted cyclic ketones in the presence of an alcohol, e.g., MeOH. In cases where no such processes are available, other side reactions, such as cyclic carbopalladation, polymeric acylpalladation, and trapping of acylpalladiums via esterification and other processes may become predominant. Neither smaller, i.e., 3- or 4-membered, nor 7-membered or larger cyclic ketones appear to be accessible by the reaction. In most cases, the exo-mode cyclic acylpalladation takes place exclusively. However, the cyclic acylpalladation of 3 proceeds exclusively via endo-mode cyclization to give 5-membered ketones. Substitution of one or more hydrogens in the ω-vinyl group with carbon groups has significant effects on the reaction course. Those substrates containing a 1,2-disubstituted alkenyl group in place of a vinyl group, i.e., 19−22 and 24 excluding 25, can give monomeric cyclic acylpalladation products in high yields. These results represent a major deviation from those obtained with 1 and 2. In the absence of an external nucleophile, formation of Type I cyclic acylpalladation products is, in some cases, accompanied by Type III cyclic acylpalladation involving trapping of acylpalladiums by internal enolates. In the presence of MeOH or other alcohols, Type II acylpalladation products have been obtained in respectable yields from 19−20, 23, and 24. In the presence of an alcohol, premature esterification can be a serious side reaction. However, this problem can be alleviated using i-PrOH or t-BuOH in place of MeOH in combination with appropriate solvents, typically those of lower polarity. Heteroatom-containing substituents on the ω-vinyl groups also exert significant effects on cyclic acylpalladation. Electron-donating substituents tend to lead to high yields of cyclic acylpalladation products, while electron-withdrawing alkoxycarbonyl groups conjugated with the ω-alkenyl group tend to give lower yields of cyclic acylpalladation products. With Me3Si and alkoxycarbonyl groups products of apparent endo-mode cyclic acylpalladation, i.e., naphthols, have been obtained in significant yields (25−50%). Free OH and other nucleophilic heteroatom groups can seriously interfere with cyclic acylpalladation, and they must be appropriately protected in most cases, although there are indications that acylpalladation−lactonization tandem processes similar to Type II cyclic acylpalladation might be developed.