Pd-Catalyzed Redox Divergent Coupling of Ketones with Terpenols

Redox diversity is a common and important feature of nature. Herein, a Pd-catalyzed redox divergent coupling of ketones with terpenols has been developed to access a-substituted ketones with varying degrees of unsaturation. The control of oxidation states of the product is facilitated by employing different additives. With the aid of BnOH as an external hydrogen source, a reductive coupling pathway is thermodynamically favored. The use of LiBr as the additive will reduce the reactivity of Pd-H to divert the selectivity toward alpha,beta-unsatuated ketones. By switching the solvent from toluene to chlorobenzene, the active species Pd-H will be fully quenched to enable oxidative coupling. Gram-scale reaction with lower catalyst loading (0.5 mol %) was also accomplished to highlight the practicability of this protocol. Furthermore, detailed experimental studies were carried out to elucidate the reaction mechanism and the factors enabling manipulation of the redox selectivity. This redox divergent coupling protocol provides an important complement for known precedents on Tsuji-Trost allylation of ketones.

Automated summary

This study developed a Pd-catalyzed redox divergent coupling of ketones with terpenols, controlling the oxidation states of the product by employing different additives and highlighting the practicality of the protocol with gram-scale reactions and low catalyst loading. Detailed experimental studies were also conducted to elucidate the reaction mechanism and factors influencing redox selectivity. This coupling protocol provides an important complement to known precedents in Tsuji-Trost allylation of ketones.