Phosphine-free chiral iridium catalysts for asymmetric catalytic hydrogenation of simple ketones

Article abstract of DOI:10.1039/c6ra04524c

Novel pyridylalkylamine and aminopyridinato ligand stabilized iridium complexes with no P ligand are introduced. These complexes have been investigated as catalysts for asymmetric hydrogenation of simple ketones, resulting in an active catalyst for bulky alkyl aryl ketones that is α-methylpropiophenone. The ligands were synthesized from inexpensive starting materials and their modular design allows for the introduction of a broad variety of substitution patterns. Additionally, better activity and selectivity was observed at 20 °C and 20 bar H₂ pressure with a catalyst loading as low as 0.05 mol% iridium. These phosphorus free catalysts have always been a central issue in both academic and industrial research.

Full text of DOI:10.1039/c6ra04524c

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Phosphine-free Chiral Iridium Catalysts for Asymmetric
Catalytic Hydrogenation of Simple Ketones
Prashant Kumar,*a,b Torsten Irrgang,b George E. Kostakisa and Rhett Kempe*b
Received 00th January 20xx,
Accepted 00th January 20xx
Novel pyridylalkylamine and aminopyridinato ligands stabilized iridium complexes with no P ligand are introduced. These
complexes have been investigated as catalysts for asymmetric hydrogenation of simple ketones, resulting in an active
catalyst for bulky alkyl aryl ketones that is α- methylpropiophenone. The ligands were synthesized from inexpensive
starting materials and their modular design allows for the introduction of a broad variety of substitution patterns.
Additionally, better activity and selectivity was observed at 20 °C and 20 bar H2 pressure with a catalyst loading as low as
0.05 mol% iridium. These phosphorus free catalysts have always been a central issue in both academic and industrial
research.
DOI: 10.1039/x0xx00000x
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(Wilkinson’s
catalyst)8
and
the
most
widely
used
[Ir(cod)(py)(PCy3)]PF6 [py = pyridine, cod = 1,5-cyclooctadiene,
Crabtree’s catalyst9]. In contrast, iridium phosphorus-free catalysts
are extensively less efficient and/or enantioselective in this
asymmetric hydrogenation.10 Relatively, few organometallic
complexes derived from amine based ligands have been reported to
be effective at the control of asymmetric hydrogenation
reactions,10,11 particularly in comparison to the large numbers of
diphosphine12,13 and mixed amine/phosphine14,15 ligands, which
have been reported. In principle, amine-based ligands possess a
potential advantage over phosphorus because they are relatively
simple to prepare and less prone to decomposition and oxidation
reactions. Furthermore, Iridium(I) complexes of cycloocta-1,5-diene
(cod) are of interest because the coordinated cod can be replaced
by other ligands. Cod can also be hydrogenated to provide vacant
coordination sites around Iridium and thus increase the catalytic
activities of the complexes.16 In this paper, we report the synthesis
and structure of phosphorus-free iridium catalysts containing
aminopyridinato and pyridylalkylamine (Scheme 1) and cod ligands
for the hydrogenation of simple ketones.
1. Introduction
The catalytic reduction of polar multiple bonds-mainly carbonyl (-
C=O) functionalities into corresponding hydroxyl (-CH-OH)
functionalities by molecular hydrogen has great significance in
modern synthetic chemistry. The stereoselective hydrogenation of
ketones to yield enatiomerically pure alcohols is a key step, in the
synthesis of fine chemicals, perfumes, and pharmaceuticals. This
reaction is normally performed by complexes of precious metals
(e.g. Ru, Rh, Ir) using either H2 or iPrOH being the hydrogen
source.1 In particular, the reduction of ketones with gaseous
hydrogen provides an atom-economical synthetic method. High
enantioselectivity, low catalyst loadings, quantitative yields, atom
economy and mild conditions are attractive features of this
transformation as evident in the ever growing list of research
articles that use these methods. The importance of this topic was
recognized when Knowles and Noyori 3,4 were awarded the 2001
2,3
Nobel prize for their instrumental contributions to this field. The
development of highly enantioselective chemocatalyst based on
their low toxicity and lower price ligands could drastically increase
the importance of asymmetric homogeneous catalysis.5 Therefore,
it has been well established that organometallic complexes of
ruthenium have been well-employed in this scenario, recently in
particular by the groups of Noyori6 and Braunstein.7 Iridium and
rhodium complexes have long been known to be highly effective
homogeneous hydrogenation catalysts, with RhCl(PPh3)3
a.Department of Chemistry, School of Life Sciences, University of Sussex, Brighton
BN1 9QJ, UK. E-mail: pbhukumar@gmail.com.
b.Inorganic Chemistry II, University of Bayreuth, 95440-Bayreuth, Germany. Email:
kempe@uni-bayreuth.de.
Scheme 1. Aminopyridinato (a, b) and pyridylalkylamine (c-h)
Electronic Supplementary Information (ESI) available: [details of any
supplementary information available should be included here]. See
DOI: 10.1039/x0xx00000x
ligands.
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2. Experiment Section
4-methyl-2-(pyridin-2-ylamino)-pentan-1-ol (b)
White solid, 40% yield. C11H18N2O (194.14): calcd. C 68.01, H 9.34, N
14.42; found C 67.86, H 9.21, N 14.41. 1H NMR (250MHz, CDCl3, 298
K): δ = 7.99 (d, J = 5.4 Hz, 1H, Ar); 6.95 (t, J = 7.4 Hz, 1H, Ar); 6.23 (t,
J = 5.5 Hz, 1H, Ar); 5.94 (d, J = 7.4 Hz, 1H, Ar); 3.66-3.61 (m, 2H,
CH2-OH); 3.48-3.47 (m, 1H, CH-NH); 1.48-1.46 (m, 1H, CH-(CH3)2);
1.14-1.08 (m, 2H, CH2-CH-(CH3)2); 0.78-0.74 (dd, J = 5.2 Hz, 6 H, CH-
(CH3)2) ppm. 13C NMR (62.90 MHz, CDCl3, 298 K): δ = 158.94 (C5,
pyridine); 147.88 (C1, pyridine); 137.03 (C3, pyridine); 112.71 (C2,
pyridine); 108.38 (C4, pyridine); 52.23 (CH2, CH2OH); 44.99 (CH,
CHNH); 41.07(CH2, CH2CH(CH3)2); 24.99 (CH-(CH3)2); 22.18, 23.05
(CH-(CH3)2) ppm.
2.1. General method
All reactions and manipulations which are sensitive to moisture or
air were performed in argon-filled glove box or using standard
Schlenk techniques. Non-halogenated solvents were distilled from
sodium benzophenone ketyl and halogenated solvents from P2O5.
Deuterated solvents were obtained from Cambridge Isotope
Laboratories and were degassed, dried and distilled prior to use.
[Ir(OMe)(cod)]2 (cod = 1, 5-cyclooctydiene, Me = methyl) was
prepared according to the literature.17 All chemicals were
purchased from commercial vendors. H and 13C NMR spectra were
1
obtained at room temperature on ARX 250 or Varian INNOVA 300
or 400 spectrometer using C6D6, and CDCl3 as a solvent and
chemical shifts are reported in ppm relative to the deuterated
solvent. Elemental analyses for C, H and N were performed on a
Vario elementary EL III apparatus.
2.2.2. Preparation of pyridylalkylamine ligands
General procedure: To ice-cooled solution of amino alcohol (1.00
mmol) (Y), pyridine-2-carbaldehyde or 6-methylpyridine-2-
carbaldehyde (1.00 mmol) (X') was added slowly in 20 mL of
methanol. The resulting solution was stirred at room temperature
2.2. Synthetic procedures
2.2.1. Preparation of aminopyridinato ligands
for 3 h and subsequently treated with sodiumtetrahydridoborate
(2.5 mmol) in small portions. After additional 2 h, water (50 mL) was
added and the reaction mixture was concentrated to about 10 mL
using rotovap. The remaining solution was extracted with
dichloromethane (2 X 20 mL), and the organic layer was separated
and subsequently dried with sodium sulphate and concentrated in
vacuum to afford the product (c-h) in good to high yield.
General procedure: A 25 mL medium-pressure tube charged with 2-
bromopyridine (1.00 mmol), or 6-methyl-2-bromopyridine (1.00
mmol) X, substituted amino alcohol (1.00 mmol) Y, N,N-diisopropyl
ethylamine (1.16 mmol) and a stir bar was flushed with nitrogen
several times, stoppered and heated at 160 ±5 °C for 2 days. The
tube was allowed to cool to room temperature, the contents was
diluted with a small amount of CH2Cl2 and chromatographed
(hexanes-EtOAc 2:1 → 1:1 → neat EtOAc) to afford the product (a,
b) in good yield.
3-phenyl-2-[(pyridin-2-ylmethyl)-amino]-propan-1-ol (c)
Yellow solid, 90% yield. mp. 65 °C. C15H18N2O (242.14): calcd. C
73.35, H 7.49, N 11.56; found C 74.43, H 7.31, N 11.32. 1H NMR
(250MHz, CDCl3, 298 K): δ = 8.46 (d, J = 1.4 Hz, 1H, Ar), 7.56 (t, J =
3.8 Hz, 1H, Ar), 7.24-7.08 (m, 5H, Ar), 3.97-3.82 (m, 3H, CH2-N, CH-
N), 3.63-3.58 (m, 2H, CH2-O), 2.73-2.95 (m, 2H, CH2-Ar) ppm. 13C
4-methyl-2-(6-methyl-pyridin-2-ylamino)-pentan-1-ol (a)
Yellow viscous liquid, 64% yield. C12H20N2O (208.16): calcd. C 69.19,
H 9.68, N 13.45; found C 68.73, H 10.01, N 12.97. 1H NMR (250MHz,
CDCl3, 298 K): δ = 7.26 (t, J = 3.6 Hz, 1H, Ar); 6.37 (d, J = 5.2 Hz, 1H,
Ar); 6.25 (d, J = 4.5 Hz, 1H, Ar); 3.78-3.70 (m, 2H, CH2-OH); 3.49-3.45
(m, 1H, CH-NH); 2.29 (s, 3H, CH3), 1.69-1.64 (m, 1H, CH-(CH3)2);
1.45-1.30 (m, 2H, CH2-CH-(CH3)2); 0.88-0.83 (dd, J = 5.2 Hz, 6 H, CH-
(CH3)2) ppm. 13C NMR (62.90 MHz, CDCl3, 298 K): δ = 158.14 (C5,
pyridine), 155.81 (C1, pyridine), 137.96 (C3, pyridine), 111.93 (C4,
pyridine), 104.79 (C2, pyridine), 67.65 (CH2, CH2OH), 52.97(CH,
CHNH); 41.06(CH2, CH2CH(CH3)2); 24.87 (CH-(CH3)2); 23.69, 22.93
(CH-(CH3)2); 22.22(CH3) ppm.
NMR (62.90 MHz, CDCl3, 298 K):
δ = 160.11(C5, pyridine),
157.85(C1, pyridine), 139.68(C9, phenyl), 136.42(C3, pyridine),
129.65(C10, phenyl), 128.49(C11, phenyl), 126.21 (C12, phenyl),
121.11(C4, pyridine), 118.96 (C2, pyridine), 62.61 (CH2, CH2OH),
60.97(CH, CHNH), 52.31 (CH2,CH2NH), 38.66 (CH2, CH2C6H5) ppm.
2-[(pyridin-2-ylmethyl)-amino]-propan-1-ol (d)
Yellow solid, 90% yield. mp. 70 °C. C9H14N2O (166.11): calcd. C
65.03, H 8.49, N 16.85; found C 64.89, H 8.38, N 16.27. 1H NMR
(250MHz, CDCl3, 298 K): δ = 8.38 (d, J = 1.8 Hz, 1H); 7.06 (t, J = 5.2,
1H); 6.91 (d, J = 3.6, 1H); 6.60 (t, J = 6.5 Hz, 1H); 3.85-3.70 (m, 2H,
2 | J. Name., 2012, 00, 1-3
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CH2-N); 3.55-3.52 (m, 2H, CH2-O); 2.70-2.66 (m, 1H, CH-NH); 0.92 phenyl); 121.33(C4, pyridine); 119.39 (C2, pyridine); 67.62 (CH2,
(d, J = 3.2, 3H, CH3). 13C NMR (62.90 MHz, CDCl3, 298 K): δ = 160.53 CH2OH); 65.10 (CH, CHNH); 52.89 (CH2, CH2NH); 23.97 (CH3) ppm.
(C5, pyridine); 149.176 (C1, pyridine); 136.00 (C3, pyridine); 122.11
(C4, pyridine); 121.67 (C2, pyridine); 65.63 (CH2, CH2OH); 54.70 (CH, 2.2.3. Preparation of iridium complexes
CHNH); 52.33 (CH2, CH2NH); 17.16 (CH3, CH3CH) ppm.
4-methyl-2-(6-methyl-pyridin-2-ylamino)-pent-1-oxy-iridium(I)-
cyclooctadiene (1a)
2-[(6-methyl-pyridin-2-ylmethyl)-amino]-3-phenyl-propan-1-ol (e)
[{IrOMe(cod)}2] 0.662 g (1.00 mmol) was dissolved in THF (20 mL)
Yellow solid, 91% yield. mp. 76 °C. C16H20N2O (256.16): calcd. C and a solution of 0.416 g (2.00 mmol) aminopyridinato ligands (a)
73.86, H 7.86, N 10.93; found C 73.96, H 7.69, N 10.68. 1H NMR dissolved in THF (5 mL) was subsequently added dropwise. A red
(250MHz, CDCl3, 298 K): δ = 7.44 (t, J = 1.4 Hz, 1H, Ar), 7.29-7.16 (m, solution was obtained after addition. The reaction solution was
5H, Ar), 6.92 (t, J = 3.8 Hz, 1H, Ar), 3.91-3.82 (m, 3H, CH2-N, CH-N), stirred overnight at room temperature. The resulting solution was
3.60-3.41 (m, 2H, CH2-O), 2.91-2.79 (m, 2H, CH2-Ar), 2.48 (s, 3H, removed in vacuo and the residue was recrystallised from toluene,
CH3) ppm. 13C NMR (62.90 MHz, CDCl3, 298 K): δ = 157.84(C5, yielding red crystals at -30°C, which were suitable for X-ray crystal
pyridine), 158.83(C1, pyridine), 138.88(C9, phenyl), 136.93(C3, structure analyses. Yield: 0.52 g (65%). C28H42Ir2N2O (807.04): calcd.
pyridine), 129.29(C10, phenyl), 128.43(C11, phenyl), 126.24 (C12, C = 41.67; H = 5.25; N = 3.47; found C = 41.92; H = 5.16; N = 3.86. 1H
phenyl), 121.63(C4, pyridine), 119.13(C2, pyridine), 62.57(CH2, NMR (250 MHz, C6D6, 296 K): δ = 7.43 (t, 1H,); 6.34 (dd, 2H, Ar);
CH2OH), 60.75(CH, CHNH), 51.93(CH2,CH2NH), 38.24(CH2, CH2C6H5), 4.45-4.36 (m, 4H, COD); 3.80-3.38 (m, 6H, CH2-OH, COD); 2.66-2.58
24.19 (CH3) ppm.
(m, 1H, CH-NH); 2.54-2.27 (m, 6H, CH-CH2-CH, COD); 2.07 (s, 3H,
CH3), 1.75-1.39 (m, 5H, CH-(CH3)2/CH2,COD); 0.96-0.78 (dd, 6H, CH-
(CH3)2) ppm. 13C (250 MHz, C6D6): 158.29, 157.02, 139.0, 114.96,
4-methyl-2-[(6-methyl-pyridin-2-ylmethyl)-amino]-propan-1-ol (f)
Pale yellow solid, 94% yield. mp. 60 °C. C13H22N2O (222.17): calcd. C 106.69 (C5H3N); 71.47 (CH2, CH2OH), 68.71, 64.63, 62.41, 60.28,
70.23, H 9.97, N 12.60; found C 70.44, H 10.20, N 12.51. 1H NMR 60.03 (COD); 53.95 (CH,CHNH); 41.77 (CH2, CH2CH(CH3)2); 41.56,
(250MHz, CDCl3, 298 K): δ = 7.23 (d, J = 2.4 Hz, 1H, Ar), 6.63 (d, J = 35.72, 34.07, 33.94, 32.82, 32.25, 32.06, 31.96, 30.57, 30.28, 25.42
4.3 Hz, 1H, Ar), 3.88-3.83 (d, J = 5.4, 2H, CH2-NH); 3.83-3.74 (dd, 1H, (COD); 24.88 (CH-(CH3)2); 23.60, 23.42, (CH-(CH3)2); 22.52(CH3) ppm.
CH-NH); 3.49-3.43 (dd, 1H, CH2-OH); 2.80-2.49 (m, 1H, CH2-OH);
2.72 (s, 3H, CH3), 1.78-1.67 (sept, 1H, CH-(CH3)2); 1.45-1.30 (m, 2H, 4-methyl-2-(pyridin-2-ylamino)-pent-1-oxy-iridium(I)-
CH2-CH-(CH3)2); 0.86-0.82 (t, J = 6.4 Hz, 6 H, CH-(CH3)2) ppm. 13C cyclooctadiene (1b)
NMR (62.90 MHz, CDCl3, 298 K): δ = 160.20 (C5, pyridine), Complex 1b was prepared using 0.388
g
(2.00 mmol)
157.91(C1, pyridine), 136.59(C3, pyridine), 121.26(C4, pyridine), aminopyridinato ligand (b), following the above procedure for 1a.
119.32(C2, pyridine), 63.62(CH2, CH2OH), 57.35(CH, CHNH), Red crystals were obtained in hexane at room temperature. Yield:
52.21(CH2,CH2NH); 41.61(CH2, CH2CH(CH3)2); 25.06 (CH-(CH3)2); 0.50 g (63%). C27H40Ir2N2O (793.01): calcd. C = 40.89; H = 5.08; N =
1
24.20, 23.15 (CH-(CH3)2); 22.91(CH3) ppm.
3.53; found C = 41.12; H = 4.98; N = 3.90. H NMR (250 MHz, C6D6,
296 K): δ = 7.06 (t, 1H,); 6.27 (dd, 2H, Ar); 4.50-4.34 (m, 4H, COD);
3.84-3.46 (m, 6H, CH2-OH, COD); 2.77-2.70 (m, 1H, CH-NH); 2.57-
2-[(6-methyl-pyridin-2-ylmethyl)-amino]-propan-1-ol (g)
Brown solid, 84% yield. mp. 75 °C. C10H16N2O (180.13): calcd. C 2.26 (m, 6H, CH-CH2-CH, COD); 1.49-1.25 (m, 5H, CH-(CH3)2 ,COD);
66.63, H 8.95, N 15.54; found C 66.38, H 8.64, N 15.09. 1H NMR 0.81-0.71 (dd, 6H, CH-(CH3)2) ppm. 13C (250 MHz, C6D6): 159.23,
(250MHz, CDCl3, 298 K): δ = 7.04 (t, J = 2.6 Hz, 1H); 6.79 (d, J = 3.6, 148.12, 139.79, 115.96, 108.40 (C5H4N); 76.16 (CH2, CH2OH), 66.42,
1H); 6.55 (d, J = 4.5 Hz, 1H); 3.85-3.70 (m, 2H, CH2-N); 3.37-3.35 (m, 66.12, 64.86, 64.56, 55.33 (COD); 51.17 (CH,CHNH); 44.99 (CH2,
2H, CH2-O); 2.71-2.69 (m, 1H, CH-NH); 2.35 (s, 3H, CH3); 0.94 (dd, CH2CH(CH3)2); 42.09, 41.24, 35.58, 34.34, 33.96, 32.41, 30.99, 28.09,
3H, CH3) ppm. 13C NMR (62.90 MHz, CDCl3, 298 K): δ = 159.91 (C5, 27.20, 25.19 (COD); 24.55 (CH-(CH3)2); 23.17, 22.63, (CH-(CH3)2)
pyridine); 157.98 (C1, pyridine); 136.45 (C3, pyridine); 121.14 (C4, ppm.
pyridine); 119.39 (C2, pyridine); 65.49 (CH2, CH2OH); 55.02 (CH,
CHNH); 52.50 (CH2, CH2NH); 23.99 (CH3); 17.21 (CH3, CH3CH) ppm.
3-phenyl-2-[(pyridin-2-ylmethyl)-amino]-prop-1-oxy-iridium(I)-
cyclooctadiene (2c)
2-[(6-methyl-pyridin-2-ylmethyl)-amino]-2-phenyl-ethanol (h)
To an yellow solution of 0.484 g (2.00 mmol) pyridylalkylamine
Yellow solid, 84% yield. mp. 60 °C. C15H18N2O (242.14): calcd. C ligand (c) in 20 mL of THF, 0.662 g (1.00 mmol) [{IrOMe(cod)}2]
1
74.35, H 7.49, N 11.56; found C 74.23, H 7.07, N 11.56. . H NMR dimer was added, accompanied by a color change to dark red. The
(250MHz, CDCl3, 298 K): δ = 7.44 (t, J = 1.4 Hz, 1H, Ar), 7.29-7.16 (m, reaction solution was stirred at room temperature for 16 h. The
5H, Ar), 6.92 (t, J = 3.8 Hz, 1H, Ar), 3.91-3.82 (m, 3H, CH2-N, CH-N), resulting solution was filtered and the filtrate concentrated to
3.60-3.41 (m, 2H, CH2-O), 2.91-2.79 (m, 2H, CH2-Ar), 2.48 (s, 3H, dryness under vacuum. The remaining solid was washed with 15 mL
CH3) ppm. 13C NMR (62.90 MHz, CDCl3, 298 K): δ = 159.72 (C5, hexane and subsequently re-crystallized from toluene. Yellow
pyridine); 157.98(C1, pyridine); 141.69 (C9, phenyl); 136.45 (C3, crystals were grown at -30°C, which were suitable for X-ray crystal
pyridine); 129.29 (C10, phenyl); 128.89 (C11, phenyl); 126.38 (C12, structure analyses. Yield: 0.64 g (68%). C38H48Ir2N2O (933.18): calcd.
C = 48.91; H = 5.18; N = 3.00; found C = 48.45; H = 5.26; N = 2.86. 1H
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exclusion of oxygen and moisture. Stock solutions of the pre-
catalysts were prepared in THF via alcohol elimination reaction of
the ligand (stock solution in THF) and 0.5 equiv. of [IrOCH3(cod)]2.
The solutions were prepared and stored in a glove box. A high
pressure steel autoclave (Parr Instruments; 300 mL, 200bar, 350 °C)
with an aluminium insert for multiple reaction tubes (5 or 20) was
taken into a glove box. Then the reaction tube (placed in a 20- or 5-
well insert for the autoclave, equipped with a magnetic stir bar) was
loaded with additive (base if required), the pre-catalyst solution
(e.g. 100μL = 0.05 mol%) and 350 μL (2.29 mmol) of the substrate
solution. Then the autoclave was sealed and taken out of the glove
box. The autoclave was attached to a high-pressure hydrogen line
and purged with H2. The autoclave was sealed under the
appropriate H2 pressure and the mixture was stirred for e.g. 48 h at
the appropriate pressure at room temperature or at the
appropriate temperature (external heating mantle). In order to stop
the hydrogenation reaction, the pressure was released and water
and dodecane (standard for GC) were added to the reaction.
NMR (250 MHz, C6D6, 296 K): δ = 7.90 (d, 1H); 7.75 (d, 1H); 7.68 (d,
1H); 7.52 (d, 1H); 7.33-6.99 (m, 5H, C6H5); 5.49 ( br, 1H, NH); 4.55-
4.40 (m, 4H, COD); 3.60-3.36 (m, 4H, COD); 3.12 ( s, 2H, CH2NH);
3.00 (d, CH, CH2O); 2.69-2.62 (m, CH, CHNH); 2.27-2.16 (m, 10H,
CH2C6H5, COD); 1.64-1.48 (m, 8H, COD) ppm. 13C (250 MHz, C6D6):
δ = 165.16, 147.14, 135.79, 134.99, 129.59 (C5H3N); 129.34, 126.30,
124.78, 122.50 (C6H5); 68.08 (CH, -CH2O); 67.18 (CH, CHN); 66.24,
65.16, 61.06, 59.86 (COD); 55.0 (CH2, CH2NH); 40.73, 35.67, 33.05,
32.14, 31.68, 31.29, 31.03, 30.74, 30.70, 28.14, 28.74, 22.76 (COD)
ppm.
2-[(pyridin-2-ylmethyl)-amino]-prop-1-oxy-iridium(I)-
cyclooctadiene (2d)
Complex 2d was prepared using 0.332
pyridylalkylamine ligand (d), following the above procedure for 2c.
At -30°C red crystals were obtained. Yield: 0.49 (57%).
g
(2.00 mmol)
g
C32H44Ir2N2O (857.09): calcd. C = 44.84; H = 5.17; N = 3.27; found C =
44.80; H = 4.96; N = 3.01. 1H NMR (250 MHz, C6D6, 296 K): δ = 7.82
(d, 1H); 7.55 (d, 1H); 7.27 (d, 1H); 7.25 (d, 1H); 5.25 ( br, 1H, NH);
4.42-4.29 (m, 4H, COD); 4.20-4.14 (m, 4H, COD); 3.94-3.90 ( m, 2H,
CH2NH); 3.40 (d, CH, CH2O); 2.91-2.88 (m, CH, CHNH); 2.05-1.93 (m,
8H, COD); 1.54-1.34 (m, 8H, COD); 0.89 (d, 3H, CH3) ppm. 13C (250
MHz, C6D6): δ = 165.56, 147.39, 140.72, 124.91, 122.62 (C5H4N);
76.91, 68.02, 67.57 (COD); 66.82 (CH2, CH2OH); 54.34 (CH, CHNH);
51.33 (CH2, CH2NH); 49.0, 31.62, 30.87, 30.70, 30.55, 30.12, 29.82,
28.55, 28.14, 28.02, 25.71, 23.21, 22.70 (COD); 16.16 (CH3, CH3CH)
ppm.
2.2.5. Single crystal X-ray structure determinations
Crystals suitable for single crystal X-ray diffraction analyses for 1a,
1b, 2c, 2d and 2e contained toluene as a solvate. Preliminary data
on the space group and unit cell dimensions as well as intensity
data were collected by using a STOE-IPDS II equipped with an
Oxford Cryostream low temperature unit using graphite
monochromatized Mo-Kα radiation. Structure solution and
refinement were accomplished using SIR9718, SHELXL-9719 and
WinGX20.The non-hydrogen atoms were refined with anisotropic
thermal parameters. Hydrogen atoms were geometrically fixed and
allowed to refine using riding model. CCDC deposition numbers
1437480-1437485 contain supplementary crystallographic data in
CIF format for this paper. These data can be obtained free of charge
via http//www.ccdc.ac.uk/conts/retriving.html (or from the CCDC,
12 Union Road, Cambridge CB2 IEZ, UK; Fax: + 44-1223-336033; E-
mail: deposit@ccdc.cam.ac.uk).
2-[(6-methyl-pyridin-2-ylmethyl)-amino]-3-phenyl-prop-1-oxy-
iridium(I)-cyclooctadiene (2e)
Complex 2e was prepared using 0.512
g
(2.00 mmol)
pyridylalkylamine ligand (e) following the above procedure for 2c.
Yellow crystals were grown at room temperature, which were
suitable for X-ray crystal structure analyses.Yield: 0.38 g (69%).
C24H31IrN2O (555.71): calcd. C = 51.86; H = 6.12; N = 5.13; found C =
51.96; H = 6.16; N = 5.17. 1H NMR (250 MHz, C6D6, 296 K): δ = 7.34
(d, 1H); 7.27 (d, 1H); 7.23 (d, 1H); 7.20 - 6.35 (m, 5H, C6H5); 4.16-
4.15 (m, 1H, COD); 4.09- 4.04 (m, 2H, COD); 3.91-3.90 (m, 1H,COD);
3.88 ( s, 2H, CH2NH); 3.61 (d, CH, CH2O); 3.52-3.46 (m, CH, CHNH);
2.94 (d, CH, CH2C6H5); 2.52 (s, 3H, CH3), 2.39-2.27 (m, 4H, COD);
2.23-1.89 (m, 4H, COD) ppm. 13C (250 MHz, C6D6): δ = 158.8, 155.95,
138.79, 136.57, 130.00 (C5H3N); 129.28, 126.91, 122.37, 118.50
(C6H5); 74.2 (CH, -CH2O); 70.5 (CH, CHN); 61.38, 58.03, (CH, COD);
55.9 (CH2, CH2NH); 52.07, 51.7 (CH, COD); 38.9 (CH, CH2-C6H5);
33.85, 32.44, 31.35, 31.14 (CH2, COD); 25.5 (CH3) ppm.
3. Results and Discussion
3.1. Ligand Synthesis
The targeted ligands were obtained from commercially available
reactants in one or two steps based on previous studies.20 The
ligand precursors 4-methyl-2-(6-methyl-pyridin-2-ylamino)-pentan-
1-ol (a) and 4-methyl-2-(pyridin-2-ylamino)-pentan-1-ol (b) were
synthesized in
a one-pot reaction starting from 6-methyl 2-
bromopyridines and 2-bromopyridines with enantiopure amino
alcohols using N,N-diisopropylethyl amine as a base at 165 °C for 3
days (Scheme 2) in quantitative yields.22 Ligands (c-h) were
prepared by reductive amination of heteroaromatic aldehydes
(pyridine-2-carbaldehyde or 6-methylpyridine-2-carbaldehyde) with
enantiopure aminoalcohols over two steps including the formation
of the corresponding ketimine and further reduction with sodium
borohydride (Scheme 3). Both methodologies allowed us to prepare
Complexes 2f-h: not isolated, pre-catalyst-solution prepared via
alcohol elimination in situ.
2.2.4. General Procedure for the Asymmetric Hydrogenation
All catalytic hydrogenation experiments were carried out in
stainless steel autoclaves (parr instrument N-MT5 300 mL) and in a
mmol scale. All experiments were carried out in a glove box under
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a family of substituted ligands based on a pyridylalkylamine and shorter than the Ir–N bond indicating the localization of the
aminopyridinato core. All the synthesized ligands are air stable and negative charge of the alkoxy (-CH2OH) at the oxygen atom. The
soluble in polar as well as non-polar solvents and characterized by bite angle N1–Ir1–O1 (80.6°) is almost equal to 2c, but significantly
1H, 13C NMR and elemental analysis.
smaller than 2e. While in 2c and 2d, the two iridium atoms (Ir1 and
Ir2) are stabilized by the formation of a five membered chelate (Ir1,
N2, C9, C10, O1, and Ir2, N1, N2, C19, C18 2c; Ir2, N1, C15, C16, O1,
and Ir1, N1, N2, C9, C10 2d). Again, the Ir–O bond [2.021(6) Å] is
significantly shorter than the Ir–N bond [2.151(6) Å] and Ir–N bond
[2.103(7) Å] and Ir–N bond [2.106(6) Å] are almost equal in 2c and
2d (Fig 3 and 4).
3.2. Synthesis and Structure of the Complexes
The dinuclear iridium complexes 1a, b and 2c, d can be obtained via
alcohol elimination route with [IrOCH3(cod)]223(Schemes 2 and 3).
Addition of 0.5 equiv. of the metal precursor to a solution of a-d in
THF gives rise to 1a, b and 2c, d which is accompanied by a color
change to yellow/reddish-brown. While under the same reaction
condition mononuclear iridium complexes 2e-h can be synthesized
by reaction with [IrOCH3(cod)]2 (Scheme 3). This synthetic approach
shows the presence of the methyl group, at sixth position of
pyridine ring, and the methylene (-CH2NH) group, favour the
formation of mononuclear iridium complex.
Furthermore, in complexes 2e (Fig 5) the monoanionic ligand
coordinates the Ir-atom via a five membered chelate (Ir1, N1, C9,
C10, and O1). The Ir1-O1 bond [1.995(3) Å] is significantly shorter
than the Ir1–N1 bond [2.127(3) Å], simply indicating the localization
of the anionic charge of the alkoxy at the oxygen atom. The 6-
methylpyridyl moiety is bent out of the pyridine plane (N1-C18-C19
110.4°) and coordination by the pyridine nitrogen does not occur.
However, the bite angle of complex 1a (N1–Ir1–O1, 80.6°), 1b (N1–
Ir1–O1, 80.3), 2c (N2–Ir1–O1, 80.9°), and 2d (N1–Ir1–O1, 80.6°) are
almost same but slightly smaller than 2e (N1–Ir1– O1, 82.67°). The
increased angle brought the Ir atom, the reaction center of the
catalyst, closer to the ligand backbone and created a chiral
environment around the Ir atom that permitted more efficient
catalysis.
Scheme 2. Synthesis of iridium complexes 1 (a: R1 = CH3, R2 = CH2-
(CH3)2, b: R1 = H, R2 = CH2-CH(CH3)2).
Fig 1. Molecular structure of 1a. [Thermal Ellipsoid Diagram (50 %)
for all non-carbon atoms] without H atoms. Selected bond length
[Å] and angles [°]: Ir1–O1 1.979(8), Ir1–N1 2.144(10), Ir2–N1
2.145(10), Ir2–N2 2.020(10), O1–C9 1.413(15), N1–C10 1.490(15),
N1–C15 1.388(15); N1–Ir1–O1 80.6(4), N1–Ir2–N2 63.5(4), Ir2–N1–
Ir1 94.0(4), Ir1–O1–C9 114.9(7), C10–N1–Ir2 130.7(7), C10–N1–Ir1
106.0(7).
Scheme 3. Synthesis of iridium complexes 2 (c: R1 = H, R2 = CH2-
C6H5, d: R1 = H, R2 = CH3, e: R1= CH3, R2 = CH2-C6H5, f: R1 = CH3, R2 =
CH2-CH(CH3)2, g: R1 = CH3, R2 = CH3, h: R1 = CH3, R2 = C6H5)
X-ray crystal structure analyses of the dinuclear complexes (1a,
b and 2c, d) and the mononuclear (2e) were performed to
determine the molecular structures (Fig 1-5). Selected
crystallographic data and geometrical parameters are summarized
in the Fig 1-5, respectively and details about the data collection,
solution, and refinement are summarized in the Supporting
Information (Table S1). In complexes 1a and 1b (Fig 1 and 2) the Ir1-
atoms are stabilized by the formation of a five membered chelate
(Ir1, N1, C9, C10, O1) and Ir2-atom is stabilized by the formation of
a four membered chelate (Ir2, N1, N2, C15). It was observed that Ir–
Namido bond [Ir2–N1 2.145(10) 1a, Ir2– N1 2.202(5), Å] is significantly
longer than Ir–Npyridine bond [Ir2–N2 2.020(10) 1a, N2–Ir2 2.062(6),
Å 1b]. These simply suggest that the anionic charge of the ligand is
not localized at the amido-N-atom. The Ir-O bond is significantly
Fig 2. Molecular structure of 1b. [Thermal Ellipsoid Diagram for all
non-carbon atoms] without H atoms. Selected bond length [Å] and
angles [°]: Ir1–O1 1.998(5), Ir1–N1 2.086(6), Ir2–N1 2.202(5), Ir2–N2
2.062(6), O1–C9 1.401(9), N1–C10 1.491(9), N1–C15 1.414(11); N1–
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Ir1–O1 80.3(2), N1–Ir2–N2 63.5(2), Ir2–N1–Ir1 82.73(16), Ir1–O1–C9 3.3. Catalytic Studies
Journal Name
115.2(5), C10–N1–Ir2 108.1(14) 128.4(4), C10–N1–Ir1 109.9(4).
Based on the pioneering work of Kempe et al. group.24 where amido
Iridium complexes were employed as a catalyst for the asymmetric
hydrogenation of the simple ketones, we have chosen to determine
the catalytic potential of iridium-N^N^O complexes for such
reactions. In general, the screening reactions were performed using
2.29 mmol of the substrate at 20° C for 48 h and the catalyst was
prepared in situ from stock solutions of [IrOCH3(cod)]2 and N^N^O
ligand.
First of all, mononuclear iridium complexes 2e-h (Scheme 3)
were used to determine the effect of substitution at the amino
skeleton of the ligands on the asymmetric hydrogenation of simple
ketones (Table 3). Evidently, the catalysts 2e and 2f containing
benzyl and isopropyl substituents on the nitrogen (Table 1, entries
2 and 4) gave better results than those containing the methyl (2g)
or phenyl (2h) substituent (Table 1, entries 6 and 8). The best
catalyst for this reaction seems to be compound 2e (Table 1, entry
2), which achieved a >99% conversion and 89% ee at a very low
catalyst loading (0.05 mol% iridium) and excess KOtBu.
Fig 3. Molecular structure of 2c. [Thermal Ellipsoid Diagram for all
non-carbon atoms] without H atoms. Selected bond length [Å] and
angles [°]: Ir1–O1 2.021(6), Ir1–N2 2.151(6), Ir2–N1 2.103(7), Ir2–N2
2.106(6), O1–C9 1.356(9), N2–C10 1.452(10); N2–Ir1–O1 80.9(2),
N1–Ir2–N2 79.7(2), Ir2–N2–Ir1 89.7(2), Ir1–O1–C9 112.4(5), C10–
N2–Ir2 119.0(5), C18–N2–Ir1 119.1(5), C18–N2–Ir2 109.8(5), C10–
N2–Ir1 107.1(5), N2-C18-C19 112.2(6)
Table 1. Asymmetric hydrogenation of (α−methylpropiophenone)
with 2e-h.a
Entry Pre-catalyst Base Conv.b (%) eeb (%)
1
2
3
4
5
6
7
8
2e
2e
2f
-
55
>99
46
10
89
8
KOtBu
-
2f
KOtBu
>99
16
74
5
2g
2g
2h
2h
-
KOtBu
-
64
82
10
68
Fig 4. Molecular structure of 2d. [Thermal Ellipsoid Diagram for all
non-carbon atoms] without H atoms. Selected bond length [Å] and
angles [°]: Ir2–O1 2.017(12), Ir1–N1 2.145(14), Ir2–N1 2.150(18),
Ir1–N2 2.089(16), O1–C16 1.39(2), N1–C15 1.47(3); N1–Ir2–O1
80.6(6), N1–Ir1–N2 80.6(7), Ir2–N1–Ir1 88.7(6), Ir2–O1–C16
114.4(11), C15–N1–Ir2 108.1(14), C15–N1–Ir1 125.6(13), C9–N1–Ir1
109.6(11), C9–N1–Ir2 118.3(13), C10–N2–Ir1 116.1(13), N1-C9-C10
112.3(15).
28
KOtBu
55
aReaction conditions: 0.05 mol% 2e-h, THF, KOtBu/2e-h 500:1, 48 h,
20 °C, 20 bar H2. bDetermined via GC.
In this catalytic work, all optimization studies were carried out
with α-methyl propiophenone as model substrates. As can be seen
from Table 2, KOtBu appears to be the most suitable base, because
complete conversion and a good ee (89%) could only be achieved
by using this base (Table 2, entry 6). This result shows that KOtBu is
needed as an additive for better enantioselectivity during
hydrogenation. Presence of base KOtBu is essential for catalysis,
because base itself act as a catalyst for the hydrogenation of simple
ketones under drastic conditions,25 its potassium cations accelerate
the reaction rate of phosphane–ruthenium–diamine complexes.26
Fig 5. Molecular structure of 2e. [Thermal Ellipsoid Diagram for all
non-carbon atoms] without H atoms. Selected bond length [Å] and
angles [°]: Ir1–O1 1.995(3), Ir1–N1 2.127(3), O1–C9 1.425(5), C9–
C10 1.530(6), N1–C18 1.492(6); N1–Ir1–O1 82.67(13), C9–O1–Ir1
112.7(3), C9–C10–N1 106.1(4), C10–N1–Ir1 105.9(3), N1-C18-C19
110.4(4).
After these optimisations, we examined the addition of excess
amounts of base was needed to allow complete conversion or
whether catalytic quantities of base are sufficient. Therefore, the
influence of the base/catalyst ratio was investigated (Table 3,
entries 1–5). The results shown in Table 3, entries 1–5, suggest that
it is necessary to use a base/catalyst ratio of 500:1, because only in
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this case (Table 3, entry 5) was it possible to obtain complete
conversion and a better ee (96%) within 48 h in the presence of
catalytic amount of acetone (acetone:α-methylpropiophenone 2:1).
Table 2. Base Screening, Base/pre-catalyst 500:1, 48 h, 0.05 mol%
2e, 20° C, and H2 (20 bar)
Entry
Base
-
Conv.[%]
55
ee[%]
10
1
2
3
4
5
6
7
NaNH2
KOSiMe3
KOH
NaOtBu
KOtBu
KN(SiMe3)2
25
65
40
34
64
30
46
74
>99
69
89
80
However, at a base loading of only 5 mol%, it was possible to
achieve a conversion (> 99%) and ee (90%) (Table 3, entry 4), which Fig 6. Hydrogenation of α-methylpropiophenone with 2e in the
contradicts the aforementioned excess requirement for base. For presence of KOtBu and acetone
this reason, we investigated whether it is possible to bring the
reaction to complete conversion or better ee by the use of 25 mol%
of KOtBu. To this end, the reaction time was 48 h an ee of 96% were
obtained.
Table 4. Asymmetric hydrogenation of (α-methylpropiophenone)
with 2e-h.a
–
Amount of KOtBu, acetone:α-methyl-
Entry
Pre-catalyst
Conv.b (%) eeb(%)
Acetone/α−methyl-
Table 3. Screening
propiophenone
propiophenone 2:1, THF, 48 h, 0.05 mol% 2e, 20 °C, 20 bar
1
2
3
4
5
6
7
8
2e
2e
2f
-
2:1
-
>99
>99
>99
>99
64
89
96
74
94
82
88
68
82
Entry Base: pre-catalyst Conv.(%) ee (%)
1
2
3
4
5
1:1 (0.05 mol%)
10:1(0.5 mol%)
50:1(2.5 mol%)
100:1(5 mol%)
500:1(25 mol%)
60
32
60
82
90
96
2f
2:1
-
78
2g
2g
2h
2h
96
2:1
-
68
>99
>99
55
2:1
70
The final screening was performed on the catalyst loading to find
the minimum catalyst loading necessary to achieve full conversion
and good ee (Fig 6). As shown in Fig 6, it was sufficient to use a
catalyst loading of 0.05 mol% to obtain a very good ee (96%) for this
reaction (Fig 6). It was observed the addition of KOtBu and acetone
leads to quantitative conversion with 2e as a pre-catalyst with
catalyst loadings of 1, 0.5, 0.2, 0.1, and 0.05 mol% (Fig 6). It was
examined that without KOtBu and acetone with 1.0 mol% of 2e a
conversion of 55% and 10% ee is obtained (Fig 6, Table 1, and entry
1). The catalytic performance for hydrogenation of α- methylpropio
phenone of 2e–h with KOtBu and acetone was examined (Table 4).
Upon addition of acetone in the presence of KOtBu, 96% ee could
be achieved under same reaction condition with 0.05 mol% catalyst
loading (Table 4, entry 2). The increase in enantioselectivity could
result from the fact that the more enantioselective catalyst species
is formed during catalysis, the addition of (non-prochiral) ketones,
which is hydrogenated in parallel and preferentially faster, should
support the formation of a more enantioselective catalyst.
A Reaction conditions: 0.05 mol% 2e-h, KOtBu/pre-catalyst 500:1, 48
h, 20 °C, 20 bar H2. b Determined via GC.
As it can be seen in Table 4, catalyst 2e and 2f are active catalyst for
asymmetric hydrogenation of α-methylpropiophenone. Further, we
were interested to examine the effect of acetone on the reaction. It
was observed that acetone/pre-catalyst 2e ratio of 2:1 was use to
obtain complete conversion (> 99%) and good ee (96%). It was also
observed that if we changed the acetone/catalyst ratio (1:1 and
3:1), considerably affect on the conversion (86% and 90%) and ee
(80% and 86%).
To confirm the results we achieved for the hydrogenation α-
methylpropiophenone with catalyst 2e, different simple aromatic
ketones were further examined (Fig 7). These results show that the
reduction of the hindered aromatic ketones proceeded with
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Journal Name
excellent enantioselectivity, although the expected trend of a selectivity combined with the novel structural motif opens up new
decrease in conversion and enantioselectivity for the more bulky t- prospects for the enantioselective hydrogenation of ketones.
butyl substituent was also observed (Fig 7). Also with the increase
of the α-carbon chain (-CH2CH2CH3) (Fig 7, VIII), the selectivity and
activity of the reaction drops significantly. This result illustrates the
importance of bulky groups next to the carbonyl for obtaining high
enantioselectivity. The aromatic ketones (Fig 7, VII) with a strong σ-
electron withdrawing and weak π-electron donating chloro group
and with the π-electron donating methoxy and methyl group in the
Acknowledgements
Financial support from Deutsche Forschungsgemeinschaft is
gratefully acknowledged. P. Kumar is thankful to the Deutscher
Akademischer Austausch Dienst (DAAD) for a fellowship.
Notes and references
para position showed
a higher selectivity and lower activity
1
(a) R. M. Bullock, Chem. Eur. J. 2004, 10, 2366; R. M. Bullock in
Handbook of Homogeneous hydrogenation (Eds.: J. G. de Vries,
C. J. Elsevier), Wiley-VCH, Weinheim, 2007, chap. 7, (b) R.
Noyori and T. Ohkuma, Angew. Chem. 2001, 113, 40, (c) Angew.
Chem. Int. Ed. 2001, 40, 40, (d) N. B. Johnson, I. C. Lennon, P. H.
Moran and J. A. Ramsden, Acc. Chem. Res. 2007, 40, 1291.
W. S. Knowles, Angew. Chem., Int. Ed, 2002, 41, 1998.
W. S. Knowles and R. Noyori, Acc. Chem. Res, 2007, 40, 1238.
R. Noyori, Angew. Chem., Int. Ed, 2002, 41, 2008.
compared to that with propiophenone. These results indicate that
the para substituted ketones have major effect on the catalytic
hydrogenation of ketones.
2
3
4
5
(a) N. B. Johnson, I. C. Lennon, P. H. Moran and J. A. Ramsden,
Acc.Chem. Res. 2007, 40, 1291, (b) C. S. Schultz and S.W. Krska,
Acc. Chem. Res. 2007, 40, 1320, (c) H. Shimizu, I. Nagasaki, K.
Matsumura, N. Sayo and T. Saito, Acc. Chem. Res. 2007, 40,
1385.
6
(a) R. Noyori, Asymmetric Catalysis in Organic Synthesis; Wiley:
New York, 1994,(b) R. Noyori, Chem. Soc. Rev. 1989, 18, 187; R.
Noyori and S. Hashiguchi, Acc. Chem. Res. 1997, 30, 97.
(a) P. Braunstein, F. Naud and S. J. Rettig, New J. Chem. 2001,
25, 32, (b) P. Braunstein, M. D. Fryzuk, F. Naud and S. J. Rettig, J.
Chem. Soc., Dalton Trans. 1999, 589, (c) P. Braunstein, F. Naud,
C. Graiff and A. Tiripicchio, Chem. Commun. 2000, 897.
W. A. Herrmann and B. Cornils, Angew. Chem., Int. Ed. 1997, 36,
1049.
7
8
9
Fig 7. Asymmetric Hydrogenation of Ketones Catalyzed by 2e.
(a) R. H. Crabtree, H. Felkin and G. E. Morris, J. Organomet.
Chem. 1977, 135, 205, (b) R. H. Crabtree and G. E. Morris, J.
Organomet. Chem. 1977, 135, 395 (c) R. H. Crabtree, Acc.Chem.
Res. 1979, 12, 331, (d) R. H. Crabtree, H. Felkin, T. Fillebeen-
Khan and G. E. Morris, J. Organomet. Chem. 1979, 168, 183.
In contrast, the dinuclear iridium complexes 1a, b and 2c, d
show lower catalytic activity and selectivity for the hydrogenation
of simple ketones. For example asymmetric hydrogenation of
-
methylpropiophenone catalyzed by 1a and 2c (0.05 mol %) in the
presence of excess KOtBu and acetone under same reaction
condition (see Table S2) gave corresponding alcohol in 40% and
35% yield and 24% and 8% ee. While 1b and 2d gave 23% and 16%
yield and 11% and 2.0 % ee. Needless to say, no reaction occurred
in the absence of KOtBu. This may suggest that dinuclear iridium
complexes act as catalyst precursor to promote enantioselective
asymmetric hydrogenation under the influence of base and
acetone.
10 Examples of phosphorus-free ruthenium catalysts: (a) M. Ito, M.
Hirakawa, K. Murata and T. Ikariya, Organometallics. 2001, 20,
379, (b) I. Karame, M. Jahjah, A. Messaoudi, M. L. Tommasino
and M. Lemaire, Tetrahedron: Asymmetry. 2004, 15, 1569, (c) T.
Ohkuma,N. Utsumi, K. Tsutsumi, K. Murata, C. A. Sandoval and
R. Noyori, J. Am. Chem. Soc. 2006, 128, 8724, (d) C. A. Sandoval,
T. Ohkuma, N. Utsumi, K. Tsutsumi, K. Murata and R. Noyori,
Chem. Asian J. 2006, 1–2, 102, (e) M. L. Tommasino, C.
Thomazeau, F. Touchard and M. Lemaire, Tetrahedron:
Asymmetry. 1999, 10, 1813, (f) M. L. Tommasino, M. Casalata,
J. A. Breuzard, M. C. Bonnet, M. Lemaire, Stud. Surf. Sci. Catal.
2000, 130D, 3369, (g) C. Maillet, T. Praveen, P. Janvier, S.
Minguet, M. Evain, C. Saluzzo, M. L. Tommasino and B. Bujoli, J.
Org. Chem. 2002, 67, 8191, (h) J. Liu, X. Wu, X. Wu, J. A. Iggo
and J. Xiao, Coord. Chem. Rev. 2008, 252, 782, (i) J. E. D.
Martins, D. J. Morris, M. Wills, Tetrahedron Lett. 2009, 50, 688.
11 (a) X. Wu, C. Corcoran, S. Yang and J. Xiao, ChemSusChem. 2008,
4. Conclusions
In conclusion the reported pyridylalkylamine mononuclear iridium
complexes 2e-h represents a novel class of efficient and easily
accessible catalysts for the asymmetric hydrogenation of simple
ketones. Due to the modular ligand design, broad substitution
patterns can be realized. The moderate to high efficiency and good
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Graphical Abstract
Phosphine-free Chiral Iridium Catalysts for Asymmetric Catalytic
Hydrogenation of Simple Ketones
Prashant Kumar,*a,b Torsten Irrgang,b George E. Kostakisa and Rhett Kempe*b
Phosphine free iridium catalysts with simple structures show efficient enantioselectivities and activities in the
asymmetric hydrogenation of simple ketones by using chiral iridium catalysts (see scheme; C yellow, N green,
O blue, Ir red) a bulky alkyl aryl ketones were hydrogenated to chiral alcohols with up to 96% ee.