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

doi:10.1002/chem.201201072

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

Research output: Contribution to journal › Article › peer-review

60 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 language	English
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	https://doi.org/10.1002/chem.201201072
Publication status	Published - 13 Aug 2012

Keywords

acid effects
C[BOND]H activation
piperidines
ruthenium
selectivity

Access to Document

10.1002/chem.201201072

http://doi.wiley.com/10.1002/chem.201201072

Cite this

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

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).",

keywords = "acid effects, C[BOND]H activation, piperidines, ruthenium, selectivity",

author = "Bergman, \{Sheba D.\} and Storr, \{Thomas E.\} and Hana Prokopcov{\'a} and Karel Aelvoet and Gaston Diels and Lieven Meerpoel and Maes, \{Bert U. W.\}",

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doi = "10.1002/chem.201201072",

language = "English",

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pages = "10393--10398",

journal = "Chemistry - A European Journal",

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T1 - The role of the alcohol and carboxylic acid in directed ruthenium-catalyzed C(sp3)-H α-alkylation of cyclic amines

AU - Bergman, Sheba D.

AU - Storr, Thomas E.

AU - Prokopcová, Hana

AU - Aelvoet, Karel

AU - Diels, Gaston

AU - Meerpoel, Lieven

AU - Maes, Bert U. W.

PY - 2012/8/13

Y1 - 2012/8/13

N2 - 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).

AB - 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).

KW - acid effects

KW - C[BOND]H activation

KW - piperidines

KW - ruthenium

KW - selectivity

U2 - 10.1002/chem.201201072

DO - 10.1002/chem.201201072

M3 - Article

SN - 0947-6539

VL - 18

SP - 10393

EP - 10398

JO - Chemistry - A European Journal

JF - Chemistry - A European Journal

IS - 33

ER -