1401997-72-5Relevant articles and documents
The role of the alcohol and carboxylic acid in directed ruthenium-catalyzed C(sp3)-H α-alkylation of cyclic amines
Bergman, Sheba D.,Storr, Thomas E.,Prokopcová, Hana,Aelvoet, Karel,Diels, Gaston,Meerpoel, Lieven,Maes, Bert U. W.
, p. 10393 - 10398 (2012)
A general directed Ru-catalyzed C(sp3)-H α-alkylation protocol for piperidines (less-reactive substrates than the corresponding five-membered cyclic amines) has been developed. The use of a hindered alcohol (2,4-dimethyl-3-pentanol) as the solvent and catalyst activator, and a catalytic amount of trans-1,2-cyclohexanedicarboxylic acid is necessary to achieve a high conversion to product. This protocol was used to effectively synthesize a number of 2-hexyl- and 2,6-dihexyl piperidines, as well as the alkaloid (±)-solenopsin A. Kinetic studies have revealed that the carboxylic acid additive has a significant effect on catalyst initiation, catalyst longevity, and reverses the reaction selectivity compared with the acid-free reaction (promotes alkylation versus competing alkene reduction). Acid makes the difference! A directed Ru-catalyzed C(sp3)-H α-alkylation protocol for cyclic amines has been developed (see scheme). Kinetic studies revealed that the carboxylic acid aids catalyst activation, increases catalyst longevity, and reverses the reaction selectivity. The alcohol selected as the solvent plays an active role in the catalysis. Copyright
