Ir(III) complexes of diamine ligands for asymmetric ketone hydrogenation

Article abstract of DOI:10.1016/j.tet.2009.05.012

The use of a combination of IrCl₃ with a series of ligands derived from the C2-symmetric diamine diphenylethanediamine (DPEN) forms a catalyst capable of the asymmetric hydrogenation of ketones in up to 85% ee.

Full text of DOI:10.1016/j.tet.2009.05.012

Tetrahedron 65 (2009) 5782–5786
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Ir(III) complexes of diamine ligands for asymmetric ketone hydrogenation
*
´
Jose E.D. Martins, Martin Wills
Department of Chemistry, The University of Warwick, Coventry CV4 7AL, UK
a r t i c l e i n f o
a b s t r a c t
Article history:
The use of a combination of IrCl3 with a series of ligands derived from the C2-symmetric diamine di-
phenylethanediamine (DPEN) forms a catalyst capable of the asymmetric hydrogenation of ketones in up
to 85% ee.
Received 11 February 2009
Received in revised form 29 April 2009
Accepted 7 May 2009
Ó 2009 Elsevier Ltd. All rights reserved.
Available online 13 May 2009
Ph
Ph
Ph
Ph
1. Introduction
H2N
NH2
TsHN
NH2
H2N
NH2
Relatively few organometallic complexes derived from amine
ligands have been reported to be effective at the control of asym-
metric hydrogenation reactions,1–10 particularly in comparison to
the large numbers of diphosphine11,12 and mixed amine/phos-
phine13,14 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 reactions and oxidation. Of the di-
amine-containing systems, which have been reported, a number
have been applied to the catalysis of the reduction of ketones in
high ee. In most cases, the complexes are of ruthenium, rhodium or
iridium metals, whilst the ligands are frequently derived from the
C2-symmetric 1,2-diphenylethylene-1,2-diamine 1 (R,R- or S,S-
DPEN) or 1,2-diaminocyclohexane 2 (R,R- or S,S-DACH).
(R,R)-DPEN 1
(R,R)-DACH 2
(R,R)-TsDPEN 3
Ru
M
H
H
H
NTs
NTs
NH
Ph
Ph
NH
H
4a M=Rh,
4b M=Ir
Ph
5
Ph
Ru
Ru
N
N
H
H
NH
NH
H
H
6
7
H
H
An iridium–diamine complex has been prepared in situ through
the combination of N,N0-dimethyl-DPEN (DiMeDPEN) with
[Ir(COD)2]BF4. This gave products in up to 80% ee in hydrogenations
highly effective.6 Ruthenium complexes 6 and 7 have also proved
to be very enantioselective catalysts in ketone hydrogenation.7,8
In recently reported preliminary studies, we reported that
N0-alkylated derivatives of TsDPEN 3 can be combined with IrCl3 to
form a competent catalyst for the reduction of acetophenone de-
rivatives in ees of up to 84% (Scheme 1).15 Although the activity of
these catalysts is lower than that of phosphine-derived catalysts,
their ease of preparation from stable materials and a simple Ir(III)
complex makes them attractive as a simple system for the re-
duction of selected ketones. The use of iridium was also shown to
be important; ruthenium or rhodium complexes formed catalysts,
of
a
-keto esters and 68% ee for acetophenone.1b,c Water soluble
DiMeDPEN complexes of Ir(I) salts gave better results than Ru or Rh
and 84% ee for the reduction of PhCOtBu.2 Complexes of R,R-DACH 2
and DiMeDPEN with [Ir(COD)2]BF4 have been used in the hydro-
genation of a
-keto esters1a (up to 72% and 31% ee, respectively). The
combination of (R,R)-N-tosyl-DPEN 3 (R,R-TsDPEN) and [Ir(cod)Cl]2
in MeOH/toluene has been reported to be effective in the reduction
of b
-keto esters.3
A number of amine-containing isolated complexes for ketone
hydrogenation have been reported.5–10 The pentamethylcyclo-
pentadienyl rhodium(III) and iridium(III) catalysts 4a and 4b, re-
spectively, derived from TsDPEN 3 have given excellent results.5 A
closely related Ru(II)/arene complex 5 has also been reported to be
Ph
Ph
HN
1 mol%
H
R'
OH
R
O
Ts NH
1 mol% Ir(III)Cl3
R
MeOH, NaOH,
50 bar H2, 40 °C, 24h.
100% conversion
up to 84% ee
X
X
* Corresponding author. Tel.: þ44 24 7652 3260; fax: þ44 24 7652 4112.
E-mail address: m.wills@warwick.ac.uk (M. Wills).
Scheme 1. Asymmetric ketone reduction using a combination of IrCl3 and a diamine
ligand.15
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.05.012

J.E.D. Martins, M. Wills / Tetrahedron 65 (2009) 5782–5786
5783
Table 1
which also reduced the arene ring of the substrate. In this paper, we
report the synthesis and screening of a diverse series of TsDPEN
derived ligands in ketone hydrogenation.
Asymmetric hydrogenation of 2-methylacetophenone using IrCl3 with diamine
ligands 9a–9qa
Ph
Ph
1 mol%
RO2SHN
1 mol% Ir(III)Cl3
H
OH
Me
O
2. Results and discussion
HN
Me
In previous studies,15 we had examined only the tosylated de-
rivatives of DPEN 1. In order to understand the importance of the
structure of the sulfonamide part, a series of sulfonamides were
selected for further studies.
MeOH, NaOH,
50 bar H2, 40 °C, 24 h.
Entry
Ligand
Conv./%
ee/% (R/S)
The ligands were prepared (Scheme 2) by the reaction of (S,S)-
DPEN 1 with the appropriate sulfonylhalide in DCM at 0 ꢀC, using
triethylamine as a base, to give sulfonamides 8a–8q. Reductive
amination of each with propanal resulted in formation of ligands
9a–9q in good isolated yields. The incorporation of an N0-propyl
group was selected as this had given the highest selectivity when
used in the tosylated catalyst series.15 In each case the (S,S) enan-
tiomers of diamines were prepared.
1
2
3
4
5
6
7
8
9a
9b
9c
9d
9e
9f
9g
9h
9i
9j
9k
9l
9m
9n
9o
9p
9q
100
100
100
100
99
100
100
100
100
100
93
100
100
100
100
29
79 (R) 90:10
55 (R)
79 (R) 90:10
81 (R) 90:10
62 (R)
82 (R)
40 (R)
55 (R)
73 (R)
77 (R)
65 (R)
81 (R)
80 (R)
76 (R)
83 (R)
4 (R)
61 (R)
9
10
11
12
13
14
15
16
17
Ph
Ph
Ph
Ph
RSO2Cl
O
O
Et3N, DCM, 0 °C
S NH NH2
8a-q
H2N
NH2
R
(S,S)-1
Ph
Ph
81
O
O
EtCHO
a
Conditions: 1 M 2-methylacetophenone in methanol (1 mL); 1% catalyst, 50 bar
S
NH HN
9a-q
NaBH3CN MeOH
hydrogen, NaOH:catalyst¼30:1, 40 ꢀC, 24 h.
R
R=
Table 2
Asymmetric hydrogenation of ketones using IrCl3 with diamine ligands 9o, 9d
F3C
(a)
and 9fa
(c)
(b)
(d)
H
OH
R
O
1 mol% ligand
1 mol% Ir(III)Cl3
R
X
X
F
MeOH, NaOH,
50 bar H2, 40 °C 24 h.
(e)
(f)
(j)
(h)
(g)
F
OMe
OMe
F
Entry
Ligand
Ketone
Conv./%
ee/% (R/S)
1
2
3
4
9o
9o
9o
9o
9o
9o
9o
9o
9o
9o
9o
9o
9o
9o
9o
9d
9d
9d
9f
10a
10b
10c
10d
10e
10f
10g
10h
10i
100
100
99
71 (R)
70 (R)
54 (R)
67 (R)
85 (R)
75 (R)
52 (R)
72 (R)
67 (R)
61 (R)
65 (R)
61 (R)
62 (R)
71 (R)
72 (R)
84 (R)
71 (R)
45 (R)
80 (R)
60 (R)
53 (R)
MeO
F
(k)
F
(i)
(l)
F
100
100
100
100
100
100
100
100
100
100
100
100
100
100
90
MeO
MeO
5
6
7
8
F3C
H3C
(q)
(p)
(n)
(o)
(m)
9
Scheme 2. Preparation of ligands 9a–9q.
10
11
12
13
14
15
16
17
18
19
20
21
10j
10k
10l
10m
10n
10o
10e
10d
10g
10e
10d
10g
Each of the ligands was employed in the asymmetric hydrogenation
of 2-methylacetophenone, using the conditions previously reported for
the reduction.15 The results are summarized in Table 1. 2-Methyl-
acetophenone was selected for study because it had given particularly
promising results in preliminary results, and because ortho-substituted
substrates can be challenging substrates to reduce in high ee.16
Of the ligands tested, the best results were obtained using those
with relatively unhindered aromatic rings containing electron-
withdrawing groups (entries 3, 4, 6,12,13,15). With the exception of
ligand 9l, diamines containing substituents at the ortho-position(s)
gave lower asymmetric inductions (entries 7–9), and those with two
ortho-substituents were particularly poor, possibly for steric rea-
sons. Electron-withdrawing groups on the aromatic ring provided
a reduction in the activity and the enantioselectivity, whilst both
non-aromatic rings gave incomplete conversions and correspond-
ingly reduced ees. Of the ligands examined, the best was the 2-
naphthalene sulfonyl derivative 9o, therefore, this was selected for
further tests on a series of ketones 10a–10o (Table 2).
98
100
99
9f
9f
a
Conditions: 1 M ketone in methanol (1 mL); 1% catalyst, 50 bar hydrogen,
NaOH:catalyst¼30:1, 40 ꢀC, 24 h.
The enantioselectivities of the reductions using ligand 9o are
reasonably similar to those obtained with the N-tosyl derivative,
although in some cases a marginally improved result was obtained
(e.g., entries 2, 3, 5, 6, 8, 10, 14). In the case of tetralone 10g and 2,5-
dimethoxyacetophenone 10d, ligand 9o was somewhat inferior.
Some of the best results were obtained with relatively hindered
ortho-substituted ketones (e.g., 10a, 10b, 10e and 10f). To complete
this series of tests, ligands 9d and 9f were also tested against the

5784
J.E.D. Martins, M. Wills / Tetrahedron 65 (2009) 5782–5786
OMe O
dried MgSO4 and evaporated under reduced pressure to afford the
Cl
O
OMe O
Br
O
crude product, which was purified by silica gel chromatography
(0/5% v/v methanol/DCM) to afford 8o as a white solid (0.47 g,
27
1.1 mmol, 84%). Mp 199–201 ꢀC; [
a
]
D
ꢁ34 (c 0.55, CH3OH); nmax
10d
10a
10b
10c
(neat)/cmꢁ1: 3386, 3330, 3059, 3029, 1589, 1495, 1455, 1417, 1311,
1151, 1129, 875, 853, 750, 696, 662. dH (300 MHz; CDCl3)/ppm:
8.00–6.90 (17H, m, Ar–H), 6.20 (1H, br s, NH), 4.46 (1H, d, J 5.0,
PhCHNHSO2R), 4.13 (1H, d, J 5.0, PhCHNH2), 1.44 (2H, br s, NH2). dC
(75 MHz; CDCl3)/ppm: 141.1, 139.1, 136.8, 134.4, 131.8, 129.1, 128.8,
128.3, 128.2, 128.1, 128.0, 127.6, 127.4, 126.8, 126.2 (Ar–C), 63.2 (CH),
60.3 (CH). HRMS calcd for C24H23N2O2S [MþH]þ 403.1472, found
403.1488.
OMe
Me
O
O
CF3
O
O
10h
10g
10e
10f
Me
O
O
O
O
MeO
Me
10j
10l
10k
10i
MeO
Me
O
O
O
4.3. General procedure for N0-propyl-N-sulfonyl DPEN
derivatives
10m
10n
10o
The N-propyl derivatives 9a–9q were obtained by reductive
amination of the mono sulfonylated derivative 8a–8q with propa-
nal. Below is a representative example; the other ligands are
described in Supplementary data.
more challenging ketones (also shown in Table 2). Competitive, but
not sharply improved, results were obtained with these ligands.
Finally, we tested the ability of the IrCl3/(R,R)-N-nPr-N0-Ts-DPEN
system in asymmetric transfer hydrogenation17 using both iso-
propanol and formic acid as hydrogen sources. However, no ketone
reduction was observed in either case.
4.3.1. Naphthalene-2-sulfonic acid (1,2-diphenyl-2-propylamino-
ethyl)-amide 9o
To a stirred solution of 8o (0.20 g, 0.5 mmol) and molecular
sieves (0.7 g) in dried methanol (10 cm3), was added propanal
(0.035 cm3, 0.50 mmol) followed by two drops of glacial acetic
acid. The reaction was followed by TLC until the imine was formed
(3 h) and then sodium cyanoborohydride (0.13 g, 2.0 mmol) was
added and the reaction left to stir overnight at rt. The molecular
sieves were filtered through filter paper and the solution was
concentrated under reduced pressure. The residue was dissolved
in chloroform (30 mL), washed with saturated NaHCO3 solution
(20 mL) and then dried over anhydrous MgSO4. The solvent was
removed to give a crude product, which was purified by silica gel
column chromatography (0/30% v/v ethyl acetate/hexane) to
3. Conclusions
In conclusion, a series of N0-alkyl-N-sulfonylated derivatives of the
readily available and inexpensive diamine DPEN have been prepared
and tested in asymmetric ketone hydrogenation reactions. In some
cases, notably those of relatively sterically congested ketones (ortho-
t
substituted arenas, Bu-substituted), the ees are high. Whilst not
competitive with the best hydrogenation systems in terms of activity
and ee, the simplicity of this hydrogenation system (i.e., it is com-
patible with the simple salt IrCl3) may in some cases provide an at-
tractive alternative. The novel ligands and intermediates to them may
find application in other asymmetric catalytic processes.
afford 9o as a white solid (0.12 g, 0.27 mmol, 57%). Mp 148–151 ꢀC.
27
[
a
]
ꢁ4 (c 0.37, CH3OH); nmax (neat)/cmꢁ1: 3291, 3058, 2953,
D
2928, 2807, 2325, 1593, 1494, 1453, 1330, 1158, 1149, 1072, 1053,
1021, 8914, 839, 744, 697, 665. dH (300 MHz; CDCl3)/ppm: 8.00–
6.85 (17H, m, Ar–H), 4.32 (1H, d, J 8.0, PhCHNHSO2R), 3.61 (1H, d, J
8.0, PhCHNHpropyl), 2.30 (2H, m, CH2), 1.35 (3H, m, CH2 and NH),
0.81 (3H, t, J 7.3, CH3). dC (75 MHz; CDCl3)/ppm: 139.2, 137.9, 136.8,
134.4, 131.8, 129.1, 128.7, 128.5, 128.3, 128.1, 127.7, 127.6, 127.5,
127.4, 127.3, 127.2, 126.9, 122.3 (Ar–C), 67.6 (CH), 63.1 (CH), 48.9
(CH2), 23.1 (CH2), 11.5 (CH3). HRMS calcd for C27H29N2O2S [MþH]þ
445.1940, found 445.1944.
4. Experimental section
4.1. General
General experimental details, and the procedure for the hy-
drogenation reaction, have been described in
a previous
publication.15
4.2. General procedure for synthesis of sulfonated DPEN
derivatives
4.4. Analysis of reduction products
Compounds 8a–8q were obtained by reaction between (S,S)-
DPEN 1 and the correspondent sulfonylchloride (1:1) in DCM and
Et3N overnight. With the exception of 8p all reactions were per-
formed at 0 ꢀC. Although some of the monotosylated ligands have
been described in the literature, only a few references contain
experimental data, hence most were fully characterized. Below is
a representative example; the other ligands are described in
Supplementary data.
4.4.1. 1-(2-Methylphenyl)ethanol
Enantiomeric excess and conversion determined by GC analysis
(Chrompac cyclodextrin-
b
-236M-19 50 m, gas He, T¼150 ꢀC,
P¼15 psi, ketone 10.8 min, R isomer 15.6 min, S isomer 16.3 min);
[a
]
þ68.5 (c 0.54, CHCl3) 83% ee (R) (lit.18
[a
]
ꢁ72.1 (c 0.53,
32
29
D
D
CHCl3) for 91% ee (S)). dH (300 MHz; CDCl3)/ppm: 7.49–7.06 (4H, m,
Ar–H), 5.05 (1H, q, J 6.4, PHCHOH), 2.30 (3H, s, ArCH3), 1.41 (3H, d, J
6.4, CH3). dC (75 MHz; CDCl3)/ppm: 143.9, 134.2, 130.3, 127.1, 126.3,
124.5 (Ar–C), 66.7, (CH), 23.9 (CH3), 18.9 (CH3).
4.2.1. Naphthalene-2-sulfonic acid (2-amino-1,2-diphenyl-ethyl)-
amide 8o
4.4.2. 1-(20-Methoxyphenyl)ethanol
(S,S)-DPEN 1 (0.3 g, 1.4 mmol) was dissolved in DCM (20 cm3)
and cooled to 0 ꢀC, then Et3N (0.21 cm3, 1.5 mmol) was added fol-
lowed by a solution of 2-naphthalenesulfonyl chloride (0.31 g,
1.4 mmol) in DCM (5 cm3). The system was allowed to stay at rt and
it was stirred overnight. The mixture was washed with water
(10 cm3) and then the organic phase was separated, dried over
Enantiomeric excess and conversion determined by GC analysis
(Chrompac cyclodextrin-
b
-236M-19 50 m, gas He, T¼140 ꢀC,
P¼15 psi, ketone 31.3 min, S isomer 37.5 min, R isomer 39.0 min);
33
23
[a
]
þ37 (c 0.67, toluene) 71% ee (R) (lit.19
[
a]
ꢁ63.0 (c 1.10, tol-
D
D
uene) >99% ee (S)). dH (400 MHz; CDCl3)/ppm: 7.34 (1H, dd, J 7.4
and 1.6, Ar–H), 7.25 (1H, td, J 7.8 and 1.8, Ar–H), 6.96 (1H, t, J 7.4, Ar–

J.E.D. Martins, M. Wills / Tetrahedron 65 (2009) 5782–5786
5785
H), 6.88 (1H, d, J 8.3, Ar–H), 5.09 (1H, q, J 6.5, PhCHCH3), 3.86 (3H, s,
OCH3), 2.72 (1H, br s, OH), 1.50 (3H, d, J 6.5, CH3). dC (100.6 MHz;
CDCl3)/ppm: 156.6 (next to OCH3), 133.4, 128.3, 126.1, 120.8, 110.4
(Ar–C), 66.6 (CH), 55.3 (OCH3), 22.9 (CH3).
4.33 (1H, s, PhCHOH), 0.88 (9H, s, 3CH3). dC (75 MHz; CDCl3)/
ppm: 141.5, 127.0, 126.9, 126.6 (Ar–C), 81.7 (CH), 35.0 (C), 25.3
(3CH3).
4.4.9. 1-Tetralol
4.4.3. 1-(20-Chlorophenyl)ethanol
Enantiomeric excess and conversion determined by GC analysis
Enantiomeric excess and conversion determined by GC analysis
through its acetate derivative (Chrompac cyclodextrin-b-236M-19
(Chrompac cyclodextrin-
b
-236M-19 50 m, gas He, T¼150 ꢀC,
50 m, gas He, T¼140 ꢀC, P¼15 psi, ketone 47.2 min, R isomer (ace-
35
P¼15 psi, ketone 13.7 min, R isomer 20.7 min, S isomer 22.4 min);
tate) 62.9 min, S isomer (acetate) 64.2 min); [
a
]
D
ꢁ15 (c 0.37, CHCl3)
33
20
27
[
a]
þ44.5 (c 0.7, CHCl3) 70% ee (R) (lit.20
[a
]
þ41 (c 1.0, CHCl3)
53% ee (R) (lit.25
[
a]
D
ꢁ32.3 (c 1.00, CHCl3) 98% ee (R)). dH (400 MHz;
D
D
67% ee (R)). dH (400 MHz; CDCl3)/ppm: 7.56 (1H, dd, J 7.8 and 1.8,
Ar–H), 7.32–7.25 (2H, m, Ar–H), 7.18 (1H, td, J 7.7 and 1.8, Ar–H),
5.26 (1H, dq, J 6.3 and 2.8, PhCHCH3), 2.33 (1H, br d, J 3.0, OH), 1.46
(3H, d, J 6.5, CH3). dC (100.6 MHz; CDCl3)/ppm: 143.1, 131.6, 129.4,
128.4, 127.2, 126.4 (Ar–C), 66.9 (CH), 23.5 (CH3).
CDCl3)/ppm: 7.43–7.38 (1H, m, Ar–H), 7.21–7.15 (2H, m, Ar–H), 7.10–
7.06 (1H, m, Ar–H), 4.74 (1H, br s, CHOH), 2.85–2.66 (2H, m, CH2
ortho to CHOH), 2.00–1.70 (5H, m, 2ꢂCH2þOH). dC (100.6 MHz;
CDCl3)/ppm: 138.9, 137.1, 129.0, 128.7, 127.6, 126.2 (Ar–C), 68.1 (CH),
32.3 (CH2), 29.3 (CH2), 18.9 (CH2).
4.4.4. 1-(20-Bromophenyl)ethanol
4.4.10. 1-(40-Methoxyphenyl)ethanol
Enantiomeric excess and conversion by GC analysis through its
Enantiomeric excess and conversion determined by GC analysis
acetate derivative (Chrompac cyclodextrin-
b
-236M-19 50 m, gas
(Chrompac cyclodextrin-
b
-236M-19 50 m, gas He, T¼130 ꢀC,
He, T¼160 ꢀC, P¼15 psi, ketone 15.4 min, R isomer 21.8 min, S iso-
P¼15 psi, ketone 65.96 min, R isomer 71.8 min, S isomer 74.3 min);
þ27 (c 0.6, CHCl3) 54% ee (R) (lit.21
[a
]
ꢁ39.5
33
20
3
2
2
7
mer 23.6 min); [
a]
[a
]
þ33.8 (c 0.54, CHCl3) 67% ee (R) (lit.25
[a]
D
þ32.3 (c 1.00,
D
D
D
(c 0.96, CHCl3) 81% ee (S)). dH (300 MHz; CDCl3)/ppm: 7.59–7.06
CHCl3) 90% ee (R)). dH (400 MHz; CDCl3)/ppm: 7.30–7.26 (2H, m,
Ar–H), 6.89–6.85 (2H, m, Ar–H), 4.83 (1H, q, J 6.3, PhCHCH3), 3.79
(3H, s, OCH3), 2.02 (1H, br s, OH), 1.46 (3H, d, J 6.3, CH3). dC
(100.6 MHz; CDCl3)/ppm: 159.0 (next to OCH3), 138.1, 126.7, 113.9
(Ar–C), 70.0 (CH), 55.3 (OCH3), 25.0 (CH3).
(4H, m, Ar–H), 5.20 (1H, q, J 6.3, CH a-OH), 1.44 (3H, d, J 6.3, CH3). dC
(75 MHz; CDCl3)/ppm: 144.0, 132.0, 128.1, 127.2, 126.0, 121.0 (Ar–C),
68.5 (CH), 22.9 (CH3).
4.4.5. 1-(2,5-Dimethoxyphenyl)ethanol
Enantiomeric excess and conversion by GC analysis (Chrompac
4.4.11. 1-(4-Methylphenyl)ethanol
cyclodextrin-
b
-236M-19 50 m, gas He, T¼155 ꢀC, P¼15 psi, ketone
Enantiomeric excess and conversion determined by GC analysis
33
40.7 min, R isomer 49.6 min, S isomer 51.6 min); [
a
]
D
þ18.6 (c 0.5,
(Chrompac cyclodextrin-
b
-236M-19 50 m, gas He, T¼125 ꢀC,
25
CHCl3) 71% ee (R) (lit.22
[a
]
þ23.8 (c 2.6, CHCl3) 91% ee (R)). dH
P¼15 psi, ketone 28.3 min, R isomer 35.2 min, S isomer 38.1 min);
D
33 26
(300 MHz; CDCl3)/ppm: 6.96–6.71 (3H, m, Ar–H), 5.05 (1H, m, CH
a
-
[a
]
þ38 (c 0.72, CHCl3) 61% ee (R) (lit.18
[
a
]
D
ꢁ53.0 (c 0.55, CHCl3)
D
OH), 3.81 (3H, s, OCH3), 3.76 (3H, s, OCH3), 1.48 (3H, d, J 6.5, CH3). dC
(75 MHz; CDCl3)/ppm: 153.7, 150.6, 134.6, 112.4, 112.2, 111.3 (Ar–C),
66.4 (CH), 55.8 (OCH3), 55.7 (OCH3), 22.9 (CH3).
for 92% ee (S)). dH (300 MHz; CDCl3)/ppm: 7.22–7.15 (2H, m, Ar–H),
7.12–7.06 (2H, m, Ar–H), 4.73 (1H, q, J 6.4, PHCHOH), 2.30 (3H, s,
CH3), 1.38 (3H, d, J 6.4). dC (75 MHz; CDCl3)/ppm: 143.0, 136.9, 129.1,
125.4 (Ar–C), 70.0 (CH), 25.1 (CH3), 21.1 (CH3).
4.4.6. 1-(2-Trifluoromethylphenyl)ethanol
Enantiomeric excess and conversion determined by GC analysis
4.4.12. 1-Phenylpropan-1-ol
Enantiomeric excess and conversion determined by GC anal-
ysis (Chrompac cyclodextrin-
(Chrompac cyclodextrin-
b
-236M-19 50 m, gas He, T¼120 ꢀC,
P¼15 psi, ketone 18.1 min, R isomer 31.8 min, S isomer 34.1 min).
b
-236M-19 50 m, gas He, T¼115 ꢀC,
33
22
[
a]
þ33 (c 0.16, CH3OH) 75% ee (R) (lit.19
[a
]
ꢁ45.5 (c 0.66,
P¼15 psi, ketone 29.3 min,
R
isomer 45.8 min,
S
isomer
D
D
33
20
D
CH3OH) 97% ee (S)). dH (400 MHz; CDCl3)/ppm: 7.84 (1H, d, J 7.8,
ArH), 7.64–7.58 (2H, m, ArH), 7.38 (1H, t, J 7.7, ArH), 5.34 (1H, q, J 6.3,
CH(OH)CH3), 1.98 (1H, br s, OH), 1.50 (3H, d, J 6.3, CH3). dC
(100.6 MHz; CDCl3)/ppm: 145.0, 132.4, 127.4, 127.2, 125.4, 125.3,
(Ar–C), 124.1 (F3C, q, J 273.8 Hz), 65.7 (CH), 25.5 (CH3).
47.9 min); [
a
]
þ33 (c 1, CHCl3) 62% ee (R) (lit.26
[
a
]
þ47.0 (c
D
1.4, CHCl3) 95% ee (R)). dH (400 MHz; CDCl3)/ppm: 7.36–7.24 (5H,
m, Ar–H), 4.57 (1H, t, J 6.5, PhCH(OH)CH2), 2.00 (1H, br s, OH),
1.86–1.68 (2H, m, CH2), 0.90 (3H, t, J 7.4, CH3). dC (100.6 MHz;
CDCl3)/ppm: 144.6, 128.4, 127.5, 126.0 (Ar–C), 76.0 (CH), 31.9
(CH2), 10.2 (CH3).
4.4.7. 1-(10-Naphthyl)ethanol
Enantiomeric excess and conversion determined by GC analysis
4.4.13. 1-(3-Methylphenyl)ethanol
(Chrompac cyclodextrin-
b
-236M-19 50 m, gas He, T¼170 ꢀC,
Enantiomeric excess and conversion determined by GC analysis
P¼10 psi, ketone 49.1 min, S isomer 70.6 min, R isomer 72.8 min);
(Chrompac cyclodextrin-
b
-236M-19 50 m, gas He, T¼125 ꢀC,
33
28
[
a]
þ65 (c 0.8, Et2O) 72% ee (R) (lit.23
[
a]
þ77.2 (c 0.67, Et2O) 99%
P¼15 psi, ketone 26.1 min, R isomer 37.7 min, S isomer 38.8 min);
D
D
33 26
ee (R)). dH (300 MHz; CDCl3)/ppm: 8.09 (1H, d, J 8.0, Ar–H), 7.87–
7.83 (1H, m, Ar–H), 7.76 (1H, d, J 8.3, Ar–H), 7.65 (1H, d, J 7.0, Ar–H),
7.53–7.43 (3H, m, Ar–H), 5.64 (1H, q, J 6.4, CH(OH)CH3), 2.05 (1H, br
s, OH), 1.65 (3H, d, J 6.5, CH3). dC (75 MHz; CDCl3)/ppm: 141.5, 133.8,
130.3, 128.9, 127.9, 126.0, 125.6, 125.5, 123.2, 122.1 (Ar–C), 67.1 (CH),
24.4 (CH3).
[a
]
þ34.6 (c 0.8, CHCl3) 65% ee (R) (lit.18
[a
]
ꢁ42.6 (c 0.62, CHCl3)
D
D
for 84% ee (S)). dH (300 MHz; CDCl3)/ppm: 7.26–7.4 (4H, m, Ar–H),
4.80 (1H, q, J 6.4, PHCHOH), 2.34 (3H, s, CH3), 1.44 (3H, d, J 6.4). dC
(75 MHz; CDCl3)/ppm: 145.8, 138.1, 128.4, 128.2, 126.1, 122.4 (Ar–C),
70.3 (CH), 25.1 (CH3), 21.4 (CH3).
4.4.14. 1-(30-Methoxyphenyl)ethanol
4.4.8. 1-Phenyl-2,2-dimethyl-1-propanol
Enantiomeric excess and conversion determined by GC analysis
Enantiomeric excess and conversion determined by GC anal-
(Chrompac cyclodextrin-
b
-236M-19 50 m, gas He, T¼140 ꢀC,
ysis through its acetate derivative (Chrompac cyclodextrin-
b
-
P¼15 psi, ketone 33.4 min, R isomer 48.8 min, S isomer 51.0 min);
3
3
2
2
236M-19 50 m, gas He, T¼125 ꢀC, P¼10 psi, ketone 39.6 min, R
[a
]
þ21.6 (c 0.74, MeOH) 61% ee (R) (lit.19
[a
]
ꢁ34.9 (c 0.849,
D
D
33
isomer (acetate) 59.7 min, S isomer (acetate) 58.2 min); [
a
]
þ28
MeOH) >99% ee (S)). dH (400 MHz; CDCl3)/ppm: 7.26 (1H, dd, J1¼J2
8.0, Ar–H), 6.96–6.92 (2H, m, Ar–H), 6.83–6.79 (1H, m, Ar–H), 4.86
(1H, q, J 6.4, CH(OH)CH3), 3.81 (3H, s, ArOCH3), 1.94 (1H, br s, OH),
D
20
(c 0.55, acetone) 72% ee (R) (lit.24
[
a
]
ꢁ30.3 (c 0.3, acetone)
D
100% ee (S)). dH (300 MHz; CDCl3)/ppm: 7.28–7.19 (5H, m, Ar–H),

5786
J.E.D. Martins, M. Wills / Tetrahedron 65 (2009) 5782–5786
729–733; (h) Furegati, M.; Rippert, A. J. Tetrahedron: Asymmetry 2005, 16,
3947–3950.
5. Ohkuma, T.; Utsumi, N.; Watanabe, M.; Tsutsumi, K.; Arai, N.; Murata, K. Org.
Lett. 2007, 9, 2565–2567.
1.48 (3H, d, J 6.5, CH3). dC (100.6 MHz; CDCl3)/ppm: 159.8 (ArC–
OMe), 147.6, 129.6, 117.7, 112.9, 110.9 (Ar–C), 70.4 (CH), 55.2 (OCH3),
25.2 (CH3).
6. (a) Ohkuma, T.; Utsumi, N.; Tsutsumi, K.; Murata, K.; Sandoval, C. A.; Noyori, R.
J. Am. Chem. Soc. 2006, 128, 8724–8725; (b) Ohkuma, T.; Tsutsumi, K.; Utsumi,
N.; Arai, N.; Noyori, R.; Murata, K. Org. Lett. 2007, 9, 255–257; (c) Sandoval, C. A.;
Ohkuma, T.; Utsumi, N.; Tsutsumi, K.; Murata, K.; Noyori, R. Chem. Asian J. 2006,
1-2, 102–110; (d) Ito, M.; Endo, Y.; Ikariya, T. Organometallics 2008, 27,
6053–6055.
7. Ito, M.; Hirakawa, M.; Murata, K.; Ikariya, T. Organometallics 2001, 20, 379–
381.
8. (a) Hedberg, C.; Kallstrom, K.; Arvidsson, P. I.; Brandt, P.; Andersson, P. G. J. Am.
Chem. Soc. 2005, 127, 15083–15090; (b) Samec, J. S. M.; Ba¨ckvall, J.-E.; Andersson,
P. G.; Brandt, P. Chem. Soc. Rev. 2006, 35, 237–248;(c)Paptchikhine, A.;Kaellstroem,
K.; Andersson, P. G. C.R. Chim. 2007, 10, 213–219.
9. (a) Jones, M. D.; Raja, R.; Thomas, J. M.; Johnson, B. F. G.; Lewis, D. W.; Rouzard,
J.; Harris, K. D. M. Angew. Chem., Int. Ed. 2003, 42, 4326–4331; (b) Raja, R.;
Thomas, J. M.; Jones, M. D.; Johnson, B. F. G.; Vaughan, D. E. W. J. Am. Chem. Soc.
2003, 125, 14982–14983.
10. Haung, H.; Okuno, T.; Tsuda, K.; Yoshimura, M.; Kitamura, M. J. Am. Chem. Soc.
2006, 128, 8716–8717.
11. (a) Noyori, R. Adv. Synth. Catal. 2003, 345, 15–32; (b) Noyori, R.; Sandoval, C. A.;
Muniz, K.; Ohkuma, T. Philos. Trans. R. Soc. London, Ser. A 2005, 363, 901–912; (c)
Hedberg, C. In Modern Reduction Methods; Andersson, P. G., Munslow, I. J., Eds.;
Wiley-VCH: 2008; Chapter 5; (d) Noyori, R.; Ohkuma, T. Angew. Chem., Int. Ed.
2006, 40, 40–73.
12. (a) Doucet, H.; Ohkuma, T.; Murata, K.; Yokozawa, T.; Katayama, E.; England,
A. F.; Ikariya, T.; Noyori, R. Angew. Chem., Int. Ed. 1998, 37, 1703–1707; (b)
Ohkuma, T.; Ooka, H.; Hashiguchi, S.; Ikariya, T.; Noyori, R. J. Am. Chem. Soc.
1995, 117, 2675–2676; (c) Sandoval, C. A.; Ohkuma, T.; Muniz, K.; Noyori, R.
J. Am. Chem. Soc. 2003, 125, 13490–13503; (d) Abbel, R.; Abdur-Rashid, K.;
Faatz, M.; Hadzovic, A.; Lough, A. J.; Morris, R. H. J. Am. Chem. Soc. 2005, 127,
1870–1882; (e) Leysson, T.; Peters, D.; Harvey, J. N. Organometallics 2008, 27,
1514–1523.
4.4.15. 2-Methyl-1-phenylpropan-1-ol
Enantiomeric excess and conversion by GC analysis (Chrompac
cyclodextrin-
b
-236M-19 50 m, gas He, T¼115 ꢀC, P¼10 psi, ketone
33
45.8 min, R isomer 90.7 min, S isomer 92.1 min); [
a
]
þ33 (c 0.47,
D
25
ether) 71% ee (R) (lit.19
(400 MHz; CDCl3)/ppm: 7.37–7.22 (5H, m, Ar–H), 4.33 (1H, d, J 6.9,
CH -OH), 2.00–1.88 (1H, m, CH), 0.99 (3H, d, J 6.6, CH3), 0.78 (3H, d,
[
a
]
ꢁ49.1 (c 0.85, ether) 99% ee (S)). dH
D
a
J 6.8, CH3). dC (100.6 MHz; CDCl3)/ppm: 143.0, 127.5, 126.8, 125.9
(Ar–C), 79.4 (CH), 34.6 (CH), 18.3 (CH3), 17.6 (CH3).
4.4.16. 1-(2,5-Dimethylphenyl)ethanol
Enantiomeric excess and conversion by GC analysis (Chrompac
cyclodextrin-
b
-236M-19 50 m, gas He, T¼140 ꢀC, P¼15 psi, ketone
33
21.8 min, R isomer 36.5 min, S isomer 39.9 min); [
a
]
þ64 (c 0.5,
D
27
CHCl3) 85% ee (R) (lit.15
(300 MHz; CDCl3)/ppm: 7.32–6.92 (3H, m, Ar–H), 5.03 (1H, q, J 6.4, CH
-OH), 2.31 (3H, s, CH3), 2.26 (3H, s, CH3), 1.41 (3H, d, J 6.4, CH3). dC
[a]
ꢁ61.7 (c 0.6, CHCl3) 83% ee (S)). dH
D
a
(75 MHz; CDCl3)/ppm: 143.7, 135.8, 131.0, 130.3, 127.8, 125.1 (Ar–C),
66.7 (CH), 23.9 (CH3), 21.1 (CH3), 18.4 (CH3).
Acknowledgements
We thank the EPSRC for financial support of JEDM (EPSRC pro-
ject grant no. EP/F019424/1 since 1/4/08), and Coordenaça˜o de
Aperfeiçoamento de Pessoal de Ensinol Superior (CAPES, Brazil) for
a scholarship to JEDM (2007). Dr. B. Stein and colleagues of the
EPSRC National Mass Spectroscopic service (Swansea) are thanked
for HRMS analysis of certain compounds. We acknowledge the use
of the EPSRC Chemical Database Service at Daresbury.27
13. (a) Rautenstrauch, V.; Hoang-Cong, X.; Churland, R.; Abdur-Rashid, K.;
Morris, R. H. Chem.dEur. J. 2003, 9, 4954–4967; (b) Gao, J.-X.; Ikariya, T.;
Noyori, R. Organometallics 1996, 15, 1087–1089; (c) Gao, J.-X.; Zhang, H.; Yi,
X.-D.; Xu, P.-P.; Tang, C.-L.; Wan, H.-L.; Tsai, K.-R.; Ikariya, T. Chirality 2000,
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14. (a) Li, T.; Churland, R.; Lough, A. J.; Abdur-Rashid, K.; Morris, R. H. Or-
ganometallics 2004, 23, 6239–6247; (b) Hamilton, R. J.; Bergens, S. H. J. Am.
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8898–8903.
Supplementary data
15. Martins, J. E. D.; Morris, D. J.; Wills, M. Tetrahedron Lett. 2009, 50, 688–692.
16. (a) Clarke, M. L.; Diaz-Valenzuela, M. B.; Slawin, A. M. Z. Organometallics 2007, 26,
16–19; (b) Ohkuma, T.; Sandoval, C. A.; Srinivasan, R.; Lin, Q.; Wei, Y.; Muniz, K.;
Noyori, R. J. Am. Chem. Soc. 2005, 127, 8288–8289; (c) Morris, D. J.; Hayes, A. M.;
Wills, M. J. Org. Chem. 2006, 71, 7035–7044.
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2237; (b) Zassinovich, G.; Mestroni, G.; Gladiali, S. Chem. Rev. 1992, 92, 1051–
1069; (c) Gladiali, S.; Alberico, E. Chem. Soc. Rev. 2006, 35, 226–236; (d) Ikariya,
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Blacker, A. J. Acc. Chem. Res. 2007, 40, 1300–1308.
Procedures for preparation of, and characterization data for,
ligands not described above, and 1H and 13C NMR of all new com-
pounds. Supplementary data associated with this article can be
found in the online version, at doi:10.1016/j.tet.2009.05.012.
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