The role of the alcohol and carboxylic acid in directed ruthenium-catalyzed C(sp3)H α-alkylation of cyclic amines

Sheba D. Bergman, Thomas E. Storr, Hana Prokopcová, Karel Aelvoet, Gaston Diels, Lieven Meerpoel, Bert U. W. Maes

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48 Citations (Scopus)

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 languageEnglish
Pages (from-to)10393-10398
Number of pages6
JournalChemistry - A European Journal
Volume18
Issue number33
Early online date11 Jul 2012
DOIs
Publication statusPublished - 13 Aug 2012

Keywords

  • acid effects
  • C[BOND]H activation
  • piperidines
  • ruthenium
  • selectivity

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