Abstract
A general directed Ru-catalyzed C(sp3)[BOND]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).
Original language | English |
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Pages (from-to) | 10393-10398 |
Number of pages | 6 |
Journal | Chemistry - A European Journal |
Volume | 18 |
Issue number | 33 |
Early online date | 11 Jul 2012 |
DOIs | |
Publication status | Published - 13 Aug 2012 |
Keywords
- acid effects
- C[BOND]H activation
- piperidines
- ruthenium
- selectivity