Access to Substituted Indenol Ethers via a Regioselective Intermolecular Carbopalladation Cascade

Abstract

Alkyne carbopalladation reactions represent a powerful approach to generating multiple new C–C bonds and substituted alkenes, however regioselectivity is often challenging for intermolecular variants. By utilizing ynol ethers as polarized alkynes we observe complete regiocontrol of migratory insertion with Pd–Ar species. A Heck reaction was used to turn-over the catalytic cycle by intercepting the vinyl-Pd adduct of carbopalladation with a pendant alkene. When using <i>o</i>-iodo styrenes substrates the resulting products are oligosubstituted 1-indenol ethers with defined stereochemistry based on the initial alkene geometry. By blocking β-hydride elimination we demonstrated C–H and C–C reductive elimination steps for catalyst turnover. Herein we report the optimization of reaction conditions, scope, and alternative termination steps.

Access to Substituted Indenol Ethers via a Regioselective Intermolecular Carbopalladation Cascade

“…Herein, we report the regioselective palladium-catalyzed synthesis of oligosubstituted 1-indenol ethers with the catalytic cycle turned over via a Heck reaction along with examples of C−H and C−C reductive eliminations (Figure 1E). 27 ■ RESULTS AND DISCUSSION Initial optimization efforts utilized o-iodosytyrene 1a and trimethyl(phenoxyethynyl)silane 2a to evaluate a variety of bases in dioxane with Ph 3 P as the ligand (entries 1−4, Table 1).…”