The kinetics and mechanism of the organo-iridium-catalysed enantioselective reduction of imines

Matthew J. Stirling, Gemma Sweeney, Kerry Macrory, A. John Blacker, Michael I. Page

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

The iridium complex of pentamethylcyclopentadiene and (S,S)-1,2-diphenyl-N′-tosylethane-1,2-diamine is an effective catalyst for the asymmetric transfer hydrogenation of imine substrates under acidic conditions. Using the Ir catalyst and a 5 : 2 ratio of formic acid : triethylamine as the hydride source for the asymmetric transfer hydrogenation of 1-methyl-3,4-dihydroisoquinoline and its 6,7-dimethoxy substituted derivative, in either acetonitrile or dichloromethane, shows unusual enantiomeric excess (ee) profiles for the product amines. The reactions initially give predominantly the (R) enantiomer of the chiral amine products with >90% ee but which then decreases significantly during the reaction. The decrease in ee is not due to racemisation of the product amine, but because the rate of formation of the (R)-enantiomer follows first-order kinetics whereas that for the (S)-enantiomer is zero-order. This difference in reaction order explains the change in selectivity as the reaction proceeds - the rate formation of the (R)-enantiomer decreases exponentially with time while that for the (S)-enantiomer remains constant. A reaction scheme is proposed which requires rate-limiting hydride transfer from the iridium hydride to the iminium ion for the first-order rate of formation of the (R)-enantiomer amine and rate-limiting dissociation of the product for the zero-order rate of formation of the (S)-enantiomer.
Original languageEnglish
Pages (from-to)3614-3622
Number of pages9
JournalOrganic and Biomolecular Chemistry
Volume14
Issue number14
Early online date10 Mar 2016
DOIs
Publication statusPublished - 14 Apr 2016

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Iridium
Imines
Enantiomers
enantiomers
iridium
imines
Amines
formic acid
Kinetics
Hydrogenation
kinetics
amines
Hydrides
hydrides
Diamines
products
Methylene Chloride
hydrogenation
catalysts
Ions

Cite this

Stirling, Matthew J. ; Sweeney, Gemma ; Macrory, Kerry ; Blacker, A. John ; Page, Michael I. / The kinetics and mechanism of the organo-iridium-catalysed enantioselective reduction of imines. In: Organic and Biomolecular Chemistry. 2016 ; Vol. 14, No. 14. pp. 3614-3622.
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abstract = "The iridium complex of pentamethylcyclopentadiene and (S,S)-1,2-diphenyl-N′-tosylethane-1,2-diamine is an effective catalyst for the asymmetric transfer hydrogenation of imine substrates under acidic conditions. Using the Ir catalyst and a 5 : 2 ratio of formic acid : triethylamine as the hydride source for the asymmetric transfer hydrogenation of 1-methyl-3,4-dihydroisoquinoline and its 6,7-dimethoxy substituted derivative, in either acetonitrile or dichloromethane, shows unusual enantiomeric excess (ee) profiles for the product amines. The reactions initially give predominantly the (R) enantiomer of the chiral amine products with >90{\%} ee but which then decreases significantly during the reaction. The decrease in ee is not due to racemisation of the product amine, but because the rate of formation of the (R)-enantiomer follows first-order kinetics whereas that for the (S)-enantiomer is zero-order. This difference in reaction order explains the change in selectivity as the reaction proceeds - the rate formation of the (R)-enantiomer decreases exponentially with time while that for the (S)-enantiomer remains constant. A reaction scheme is proposed which requires rate-limiting hydride transfer from the iridium hydride to the iminium ion for the first-order rate of formation of the (R)-enantiomer amine and rate-limiting dissociation of the product for the zero-order rate of formation of the (S)-enantiomer.",
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The kinetics and mechanism of the organo-iridium-catalysed enantioselective reduction of imines. / Stirling, Matthew J.; Sweeney, Gemma; Macrory, Kerry; Blacker, A. John; Page, Michael I.

In: Organic and Biomolecular Chemistry, Vol. 14, No. 14, 14.04.2016, p. 3614-3622.

Research output: Contribution to journalArticle

TY - JOUR

T1 - The kinetics and mechanism of the organo-iridium-catalysed enantioselective reduction of imines

AU - Stirling, Matthew J.

AU - Sweeney, Gemma

AU - Macrory, Kerry

AU - Blacker, A. John

AU - Page, Michael I.

N1 - Accepted and published March 2016. HN 31/10/2017

PY - 2016/4/14

Y1 - 2016/4/14

N2 - The iridium complex of pentamethylcyclopentadiene and (S,S)-1,2-diphenyl-N′-tosylethane-1,2-diamine is an effective catalyst for the asymmetric transfer hydrogenation of imine substrates under acidic conditions. Using the Ir catalyst and a 5 : 2 ratio of formic acid : triethylamine as the hydride source for the asymmetric transfer hydrogenation of 1-methyl-3,4-dihydroisoquinoline and its 6,7-dimethoxy substituted derivative, in either acetonitrile or dichloromethane, shows unusual enantiomeric excess (ee) profiles for the product amines. The reactions initially give predominantly the (R) enantiomer of the chiral amine products with >90% ee but which then decreases significantly during the reaction. The decrease in ee is not due to racemisation of the product amine, but because the rate of formation of the (R)-enantiomer follows first-order kinetics whereas that for the (S)-enantiomer is zero-order. This difference in reaction order explains the change in selectivity as the reaction proceeds - the rate formation of the (R)-enantiomer decreases exponentially with time while that for the (S)-enantiomer remains constant. A reaction scheme is proposed which requires rate-limiting hydride transfer from the iridium hydride to the iminium ion for the first-order rate of formation of the (R)-enantiomer amine and rate-limiting dissociation of the product for the zero-order rate of formation of the (S)-enantiomer.

AB - The iridium complex of pentamethylcyclopentadiene and (S,S)-1,2-diphenyl-N′-tosylethane-1,2-diamine is an effective catalyst for the asymmetric transfer hydrogenation of imine substrates under acidic conditions. Using the Ir catalyst and a 5 : 2 ratio of formic acid : triethylamine as the hydride source for the asymmetric transfer hydrogenation of 1-methyl-3,4-dihydroisoquinoline and its 6,7-dimethoxy substituted derivative, in either acetonitrile or dichloromethane, shows unusual enantiomeric excess (ee) profiles for the product amines. The reactions initially give predominantly the (R) enantiomer of the chiral amine products with >90% ee but which then decreases significantly during the reaction. The decrease in ee is not due to racemisation of the product amine, but because the rate of formation of the (R)-enantiomer follows first-order kinetics whereas that for the (S)-enantiomer is zero-order. This difference in reaction order explains the change in selectivity as the reaction proceeds - the rate formation of the (R)-enantiomer decreases exponentially with time while that for the (S)-enantiomer remains constant. A reaction scheme is proposed which requires rate-limiting hydride transfer from the iridium hydride to the iminium ion for the first-order rate of formation of the (R)-enantiomer amine and rate-limiting dissociation of the product for the zero-order rate of formation of the (S)-enantiomer.

U2 - 10.1039/C6OB00245E

DO - 10.1039/C6OB00245E

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EP - 3622

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JF - Organic and Biomolecular Chemistry

SN - 1477-0520

IS - 14

ER -