PALLADIUM-CATALYZED CARBONYLATIVE CYCLIZATION OF 1-IODO-2-ALKENYLBENZENES

The Pd-catalyzed carbonylation of omega-vinyl-substituted o-iodoalkeny lbenzenes 1-4 can provide up to modest yields (50-60%) of 5- and 6-mem bered Type I cyclic acylpalladation products, i.e., alpha,beta-unsatur ated cyclic ketones, in the absence of an external nucleophile and hig h yields of 5- and 6-membered Type II cyclic acylpalladation products, i.e., alpha- or beta-((alkoxycarbonyl)methyl)substituted cyclic keton es in the presence of an alcohol, e.g., MeOH. In cases where no such p rocesses are available, other side reactions, such as cyclic carbopall adation, polymeric acylpalladation, and trapping of acylpalladiums via esterification and other processes may become predominant. Neither sm aller, 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 ac ylpalladation of 3 proceeds exclusively via endo-mode cyclization to g ive 5-membered ketones. Substitution of one or more hydrogens in the o mega-vinyl group with carbon groups has significant effects on the rea ction 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 r esults represent a major deviation from those obtained with 1 and 2. I n the absence of an external nucleophile, formation of Type I cyclic a cylpalladation products is, in some cases, accompanied by Type III cyc lic acylpalladation involving trapping of acylpalladiums by internal e nolates. In the presence of MeOH or other alcohols, Type II acylpallad ation 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 us ing i-PrOH or t-BuOH in place of MeOH in combination with appropriate solvents, typically those of lower polarity. Heteroatom-containing sub stituents on the omega-vinyl groups also exert significant effects on cyclic acylpalladation. Electron-donating substituents tend to lead to high yields of cyclic acylpalladation products, while electron-withdr awing alkoxycarbonyl groups conjugated with the omega-alkenyl group te nd to give lower yields of cyclic acylpalladation products. With Me(3) Si and alkoxycarbonyl groups products of apparent endo-mode cyclic acy lpalladation, i.e., naphthols, have been obtained in significant yield s (25-50%). Free OH and other nucleophilic heteroatom groups can serio usly interfere with cyclic acylpalladation, and they must be appropria tely protected in most cases, although there are indications that acyl palladation-lactonization tandem processes similar to Type II cyclic a cylpalladation might be developed.