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 t-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% ee, which was used in the synthesis of an advanced intermediate toward Tekturna. A beneficial effect of protic additives, such as BHT (2,6-di-tert-butyl-p-cresol), on the time and enantioselectivity of the reaction was discovered.
Department of Chemistry, Université de Montréal, C.P. 6128, Succ. Centre-Ville, Montréal, Québec H3C 3J7, Canada. stephen.hanessian@umontreal.ca
Stephen
S
Hanessian
Etienne
E
Chénard
D000478:Alkylation; D002384:Catalysis; D007659:Ketones / Q000138:chemical synthesis*; D015394:Molecular Structure; D010165:Palladium / Q000737:chemistry*; D011480:Protease Inhibitors / Q000138:chemical synthesis*; D013237:Stereoisomerism; D000092502:Renin Inhibitors
D007659:Ketones; D010165:Palladium; D011480:Protease Inhibitors; D000092502:Renin Inhibitors