The role of the alcohol and carboxylic acid in directed ruthenium-catalyzed C(sp3)-H α-alkylation of cyclic amines.
A general directed Ru-catalyzed C(sp(3))-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).
Organic Synthesis, Department of Chemistry, University of Antwerp, Groenenborgerlaan 171, 2020 Antwerp, Belgium.
Sheba D
SD
Bergman
Thomas E
TE
Storr
Hana
H
Prokopcová
Karel
K
Aelvoet
Gaston
G
Diels
Lieven
L
Meerpoel
Bert U W
BU
Maes
D000433:1-Propanol / Q000737:chemistry*; D000438:Alcohols / Q000737:chemistry*; D000478:Alkylation; D000588:Amines / Q000737:chemistry*; D002264:Carboxylic Acids / Q000737:chemistry*; D002384:Catalysis; D015394:Molecular Structure; D010880:Piperidines / Q000737:chemistry*; D012428:Ruthenium / Q000737:chemistry*; D013237:Stereoisomerism
D000438:Alcohols; D000588:Amines; D002264:Carboxylic Acids; D010880:Piperidines; D012428:Ruthenium; D000433:1-Propanol