A New Approach to the Synthesis of Peptidomimetic Renin Inhibitors: Palladium-Catalyzed Asymmetric Allylation of Acyclic Alkyl Aryl Ketones

A new approach to the synthesis of Tekturna, a recently marketed drug for hypertension, takes advantage of a modified protocol of the Stoltz palladium-catalyzed asymmetric allylation with a <i>t</i>-BuPHOX ligand for the synthesis of allylated acyclic alkyl aryl ketones. The method led to an α-isopropyl α-allyl aryl ketone in 90% yield and 88 to 91% <i>ee</i>, which was used in the synthesis of an advanced intermediate toward Tekturna. A beneficial effect of protic additives, such as BHT (2,6-di-<i>tert</i>-butyl-<i>p</i>-cresol), on the time and enantioselectivity of the reaction was discovered.