Dynamic kinetic resolution-asymmetric transfer hydrogenation of 1-aryl-substituted cyclic ketones

Article abstract of DOI:10.1016/S0957-4166(02)00648-1

A range of 1-aryl-2-tetranols, and 1-phenyl-2-indanol, have been generated in high yield and enantiomeric excess from the corresponding racemic ketones, via a dynamic kinetic resolution-transfer hydrogenation process, using Ru(II)-TsDPEN in formic acid/triethylamine (5:2). This provides a potential entry to an asymmetric total synthesis of benzazepines such as Sch 39166.

Full text of DOI:10.1016/S0957-4166(02)00648-1

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 13 (2002) 2485–2490
Dynamic kinetic resolution–asymmetric transfer hydrogenation of
1-aryl-substituted cyclic ketones
Nathaniel J. Alcock,a Inderjit Mann,b Philip Peacha and Martin Willsa,*
aDepartment of Chemistry, University of Warwick, Coventry CV4 7AL, UK
bGlaxoSmithKline Pharmaceuticals, New Frontiers Science Park (North), Third Avenue, Harlow, Essex CM19 5AW, UK
Received 24 September 2002; accepted 10 October 2002
Abstract—A range of 1-aryl-2-tetranols, and 1-phenyl-2-indanol, have been generated in high yield and enantiomeric excess from
the corresponding racemic ketones, via a dynamic kinetic resolution–transfer hydrogenation process, using Ru(II)-TsDPEN in
formic acid/triethylamine (5:2). This provides a potential entry to an asymmetric total synthesis of benzazepines such as Sch
39166. © 2002 Elsevier Science Ltd. All rights reserved.
1. Introduction
strong possibility that this would be the case. The
synthesis could then be completed by tosylation of the
alcohol and deprotection of the amine in the product 3
to give 4, followed by intramolecular cyclisation and
deprotection. The sequence could also be modified, if
required to incorporate introduction of the 2-amino
group through azide displacement of the tosylate fol-
lowed by an alternative cyclisation sequence.2
The benzazepine dopamine D1 antagonist Sch 39166 1
has been the subject of several recent synthetic studies
due to its potential as a treatment for Parkinson’s
disease and other neurological disorders.1 Several
efficient syntheses of this material, and related com-
pounds, have been published. However, in most of the
known routes, the absolute stereochemistry is intro-
duced by the use of enantiomerically pure starting
materials, or through the use of chiral auxiliaries. The
favoured route involves the use of a Jacobsen epoxida-
tion coupled with resolution.1
In order to develop the underlying methodology for the
synthesis of Sch 39166 and related compounds, we
chose to investigate the use of asymmetric transfer
hydrogenation for the dynamic kinetic resolution–
reduction of 1-aryl-b-tetralones. This methodology has
been the subject of ongoing studies in this research
group.3 Although we have focused primarily on the use
of amino alcohol ligands for this application, catalytic
transfer hydrogenation in 5:2 formic acid/triethylamine,
using Noyori’s catalyst, [Ru(II)(p-cymene)-TsDPEN],
2. Results and discussion
The structure of the benzazepine core suggests that a
viable synthetic approach to the material might be via a
dynamic kinetic resolution (DKR) process based upon
asymmetric reduction of the carbonyl group of an
appropriate ketone (2, Scheme 1). For such an
approach to be successful, the rate of epimerisation at
the benzylic centre would have to be much faster than
that of the asymmetric reduction. Given the stabilisa-
tion of the enolic form of the substrate 2 by the two
adjacent aromatic rings, we considered that there was a
(TsDPEN=N-tosyl-1,2-diphenylethylenediamine
5),
has become one of the most important methods for the
enantioselective reduction of ketones.4,5 In particular
the method benefits from practical simplicity and cost
effectiveness due to the low catalyst loading.
* Corresponding author. Tel.: +44-024-76523260; fax: +44-024-
76524112; e-mail: m.wills@warwick.ac.uk
0957-4166/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(02)00648-1

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N. J. Alcock et al. / Tetrahedron: Asymmetry 13 (2002) 2485–2490
Scheme 1. Dynamic kinetic resolution approach to Sch 39166 1.
DKR is attracting increasing levels of interest and
research.6 DKR has the advantage of a maximum 100%
theoretical yield, over a classical resolution in which the
yield is limited to 50%. The main drawback of such
processes is that since an efficient racemisation of the
stereogenic centre is needed, the substrate range is
limited. While there are many examples of DKR’s in
the literature, there are very few examples to our
knowledge where this process has been coupled to
transfer hydrogenation. Excellent known examples
include Noyori’s reduction of benzils to hydro-
benzoins (100% e.e.)7 Cossy’s reduction of 1,3-
diketones8 and Mioskowski’s reduction of b-(3,4-
dimethoxyphenyl)serine methyl ester derivatives
(quantitative conversions, >99% e.e. for the major
diastereoisomer).9
We wished to examine the use of transfer hydrogena-
tion–DKR to the 1-aryl-2-tetralone system, a novel
substrate for this application, in the belief that the
ketone substrate would be able to epimerise under these
conditions, and that transfer hydrogenation would (a)
react preferentially with one enantiomer of ketone 2
and (b) form the cis product with diastereoselectivity.
Towards this end, a range of 1-aryl-2-tetralones 7 were
prepared from 1-tetralone and the corresponding Grig-
nard reagents via the general method of Jensen (Scheme
2).10 This required an elimination reaction of tertiary
Scheme 2. Synthesis and dynamic kinetic resolution–transfer hydrogenation of cyclic ketones. Reagents and conditions: (i)
XC6H4MgBr, THF, 17 h; (ii) toluene p-TSA, 1 h; (iii) m-CPBA, DCM/water, 1 h, rt; (iv) ZnI2, 120°C, 1 h; (v) [Ru(p-
cymene)(S,S)-TsDPEN], HCO2H:Et3N 5:2, 92 h, rt.

N. J. Alcock et al. / Tetrahedron: Asymmetry 13 (2002) 2485–2490
2487
It should be noted that 1-phenyl-2-indanone appears to
be unstable, and even when stored at 4°C for more than
1 week, decomposition products appear to inhibit the
reaction, thus the reduction needs to be carried out
directly after isolation of the pure ketone.
The 1-phenyl-2-tetranol was converted to its tosylate 9
using p-toluenesulphonyl chloride in pyridine. An X-
ray crystal structural analysis of this confirmed that the
material has cis stereochemistry, with 1R,2S absolute
configuration (Fig. 1). This enantiomer is the one pre-
dicted on the basis of the known selectivity of reduc-
tions using (S,S)-TsDPEN/Ru(II) complexes.
Attempts were made to displace the tosylate with
phenyl magnesium bromide, phenyl magnesium bro-
mide/CeCl3, benzylamine and potassium diphenylphos-
phide. In all cases this only gave the elimination
product, probably via an E2 mechanism.
Figure 1. X-Ray crystal structure of 9.
3. Conclusion
alcohols which generally proceeded smoothly to give
intermediate alkenes 6. The conversion of the tertiary
alkenes to the 2-tetralones required the use of m-CPBA
followed by isomerisation to the ketones. Only poor to
moderate yields were obtained over the final two steps
for this process. 1-Phenyl-2-indanone was prepared by
the same general method however the last stage pro-
ceeded in very low yield. Although this would obvi-
ously preclude the use of the sequence in a synthetically
viable approach to the alcohol targets, we were able to
secure sufficient quantities of material to test the DKR-
reduction reaction.
In conclusion, we have demonstrated this DKR–trans-
fer hydrogenation to be an effective method for the
preparation of enantiomerically pure cis 1-aryl-2-tetra-
nols, paving the way for a synthetic approach to ben-
zazepines. Work in this area within our group is
ongoing and further results will be reported shortly.
4. Experimental
4.1. General procedure for synthesis of 1-aryl substi-
tuted cyclic alkenes
In the key step of this investigation, the racemic
ketones 7 were reduced in a 5:2 formic acid/triethyl-
amine system, using 0.5 mol% [Ru(II)(p-cymene)-
(S,S)TsDPEN]. The reactions of the three six-mem-
bered ketones proceeded cleanly to yield the corre-
sponding alcohols 8 in high yield and e.e. (Scheme 2).
Conversions, measured by NMR of crude mixtures,
were almost quantitative, whilst isolated yields were
also high. All of the reduction products appeared (by
300 MHz NMR) to be single diastereoisomers, suggest-
ing that the reduction was highly stereoselective. More
gratifyingly, the enantiomeric excesses of the products
were uniformly high, confirming that one enantiomer of
ketone had been predominantly reduced over the other.
In contrast, reduction of the five-membered ketone
substrate gave the product in low yield and e.e., sug-
gesting that the method is particularly appropriate for
six-membered rings.
Magnesium shavings (2.13 g, 8.75×10−2 mol) were
stirred in THF (100 mL) and I2 (trace) was added.
Bromobenzene (8.6 mL, 8.21×10−2 mol) was added
dropwise to the mixture; the reaction was exothermic,
and the mixture was stirred for 20 min. 1-Tetralone (7.3
mL, 5.47×10−2 mol) was then added, (exothermic), the
reaction was stirred for 17 h. Water (30 mL) was slowly
added, (exothermic), the product was extracted with
DCM (2×100 mL), dried over magnesium sulphate and
the solvent removed to yield the tertiary alcohol as a
red-brown oil (11.85 g, 5.47×10−2 mol). This alcohol
was dissolved in toluene (100 mL) and p-toluenesul-
phonic acid (1.04 g, 5.47×10−3 mol) was added. The
reaction was heated under reflux for 1 h after which
time it was cooled to ambient temperature and washed
with water (2×20 mL), dried over magnesium sulphate
and the solvent removed to give a brown oil. This was
then purified by column chromatography on silica,
using ethyl acetate/hexane (3%) to yield the product.
4.1.1. 3,4-Dihydro-1-phenylnaphthalene 6 (n=1, X=H).
1
White solid (8.12 g, 72%, two steps); mp 38–39°C; H
NMR (300 MHz, CDCl3, Me4Si): l 2.4 (2H, m,
CH2CH2CH), 2.8 (2H, t, J=7.6 Hz, CH2CH2CH), 6.0
(1H, t, J=4.7 Hz, CH), 7.0 (1H, d, J=7.2 Hz, ArH),

2488
N. J. Alcock et al. / Tetrahedron: Asymmetry 13 (2002) 2485–2490
7.0–7.2 (3H, m, ArH), 7.3–7.4 (4H, m, ArH); 13C NMR
(75.5 MHz, CDCl3, Me4Si): l 23.9 (t), 28.7 (t), 125.8
(d), 126.3 (d), 126.6 (d), 127.4 (d), 128.0 (d), 128.6 (d),
129.2 (d), 135.5 (s), 137.2 (s), 140.3 (s), 141.2 (s).
Matches authentic material purchased from Lancaster.
mL), dried over magnesium sulphate, and evaporated
to yield a brown oil. Purification by column chro-
matography on silica using ethyl acetate (1%) in hexane
yielded the product.
4.2.1. 1-Phenyl-2-tetralone 7 (n=1, X=H). Pale yellow
oil (1.42 g, 50%, two steps); wmax (neat): 30.24, 1709,
4.1.2. 3,4-Dihydro-1-(p-chlorophenyl)naphthalene 6 (n=
1, X=Cl). Yellow solid (62%, two steps); mp 90–92°C;
wmax (neat): 2921, 2882, 2828, 2359, 1484, 1085, 811,
1
1661, 1596, 1491, 1447, 1267, 1145, 741, 697 cm−1; H
NMR (300 MHz, CDCl3, Me4Si): l 2.6 (1H, m,
CH2CHHCO), 2.7 (1H, m, CH2CHHCO), 3.1 (2H, m,
CH2CH2CHO), 4.8 (1H, s, COCHPh), 7.0–7.4 (9H, m,
ArH); 13C NMR (300 MHz, CDCl3, Me4Si): l 28.6 (t),
37.4 (t), 60.2 (d), 129.2 (d), 129.1 (d), 128.9 (d), 128.6
(d), 127.9 (d), 127.6 (d), 127.5 (d); MS (EI): m/z
222.103699 (C16H14O requires 222.104465), 222 (100%,
M+), 194 (70%), 179 (45%), 165 (30%).
1
766, 736 cm−1; H NMR (300 MHz, CDCl3, Me4Si): l
2.4 (2H, m, CH2CH2CH), 2.9 (2H, m, CH2CH2CH), 6.1
(1H, t, J=4.7 Hz, CH), 6.9–7.0 (8H, m, ArH); 13C
NMR (75.5 MHz, CDCl3, Me4Si): l 23.9 (t), 28.6 (t),
125.6 (d), 126.7 (d), 127.2 (d), 127.6 (d), 128.1 (d), 128.3
(d), 128.8 (d), 130.5 (d), 133.3 (s), 135.1 (s), 137.2 (s),
139.3 (s); MS (EI): m/z 240 (100%, M+), 205 (75%,
M+−Cl). Anal. found: C, 79.45; H, 5.43. C16H13Cl
requires: C, 79.83; H, 5.44%.
4.2.2. 1-(p-Chlorophenyl)-2-tetralone 7 (n=1, X=Cl).
Yellow solid which turned green in the fridge overnight
(39%, two steps); wmax (neat): 2944, 2360, 1708, 1653,
4.1.3. 3,4-Dihydro-1-(p-methoxyphenyl)naphthalene
6
1
(n=1, X=OMe). White solid (77%, two steps); mp
39–40°C; wmax (neat): 2921, 1604, 1507, 1439, 1243,
1173, 815, 738 cm−1; 1H NMR (300 MHz, CDCl3,
Me4Si): l 2.4 (2H, m, CH2CH2CH), 2.8 (2H, m,
CH2CH2CH), 3.8 (3H, s, OCH3), 6.0 (1H, t, J=4.7 Hz,
CH), 6.9–7.3 (8H, m, ArH); 13C NMR (75.5 MHz,
CDCl3, Me4Si): l 23.9 (t), 29.8 (t), 55.7 (q), 114.0 (d),
125.8 (d), 126.6 (d), 127.3 (d), 128.0 (d), 130.2 (d), 133.6
(s), 135.7 (s), 137.3 (s), 139.7 (s), 159.2 (s); MS (EI): m/z
236.119645 (C17H16O requires 236.120115), 236 (100%,
M+), 221 (45%), 205 (35%), 178 (27%), 165 (23%), 128
(23%), 121 (28%).
1487, 1455, 1397, 1085, 1014, 811, 741 cm−1; H NMR
(300 MHz, CDCl3, Me4Si):
l 2.5–2.7 (2H, m,
CH2CH2CO), 3.0–3.1 (2H, m, CH2CH2CO), 4.7 (1H, s,
CHPh), 6.9–7.3 (8H, m, ArH); 13C NMR (300 MHz,
CDCl3, Me4Si): l 28.9 (t), 35.9 (t), 59.5 (d), 128.1 (d),
128.9 (d), 129.3 (d), 130.1 (d), 130.7 (d), 133.1 (s), 134.5
(s), 136.9 (s), 209.3 (s); MS (EI): m/z 256.057281
(C16H13ClO requires 256.065493), 256 (95%, M+), 228
(100%), 193 (85%), 179 (92%).
4.2.3. 1-(p-Methoxyphenyl)-2-tetralone 7 (n=1, X=
OMe). Yellow oil (23%, two steps); wmax (neat): 2953,
1704, 1609, 1509, 1440, 1302, 1246, 1775, 1147, 1106,
1027, 813, 786 cm−1; 1H NMR (300 MHz, CDCl3,
Me4Si): l 2.5–2.6 (1H, m, CHHCH2CO), 2.7–2.8 (1H,
m, CHHCH2CO), 2.9–3.1 (2H, m, CH2CH2CO), 3.7
(3H, s, CH3), 4.7 (1H, s, CHPh), 6.9–7.3 (8H, m, ArH);
13C NMR (300 MHz, CDCl3, Me4Si): l 28.6 (t), 37.3
(t), 55.7 (q), 59.4 (d), 114.5 (d), 127.6 (d), 127.7 (d),
128.3 (d), 130.1 (d), 137.1 (s), 137.2 (s), 137.3 (s), 159.2
(s), 210.0 (s); MS (EI): m/z 252.113672 (C17H16O2
requires 252.115030), 252 (100%, M+), 223 (54%), 209
(27%), 193 (55%), 178 (24%), 165 (22%), 155 (32%), 138
(32%), 115 (24%).
4.1.4. 1-Phenylindene 6 (n=0, X=H). Yellow oil (74%
yield, two steps); wmax (neat): 3024, 2880, 2359, 2339,
1
1723, 1658, 1488, 1444, 1388, 1267, 764 cm−1; H NMR
(400 MHz, CDCl3, Me4Si): l 3.5 (2H, d, J=2.0 Hz,
CH2), 6.6 (1H, t, J=2.0 Hz, CH), 7.3–7.6 (9H, m,
ArH); 13C NMR (400 MHz, CDCl3, Me4Si): l 38.6 (t),
120.8 (d), 124.6 (d), 125.3 (d), 126.6 (d), 128.0 (d), 128.2
(d), 129.0 (d), 131.4 (d), 136.6 (s), 144.3 (s), 145.2 (s),
145.6 (s); MS (EI): m/z 192.0936 (C15H12 requires
192.0939), 192 (100%, M+), 179 (41%), 165 (43%).
4.2. General procedure for the synthesis of ketones
4.2.4. 1-Phenylindan-2-one 7 (n=0, X=H). Purified
three times by chromatography on silica 1% EtOAc/
hexane to yield a yellow oil (4%); wmax (neat): 3024,
m-CPBA (6.8 g, 3.94×10−2 mol) and sodium bicarbon-
ate (3.64 g, 4.33×10−2 mol) were dissolved in DCM/
water (1:1, 200 mL) and stirred for 20 min.
2,4-Dihydro-1-phenylnaphthalene (8.12 g, 3.94×10−2
mol) in DCM/water (1:1, 120 mL) was added and the
reaction was stirred for 1 h. The organic layer was
separated, and the aqueous layer extracted with DCM
(30 mL). The combined organic layers were dried over
magnesium sulphate, and evaporated to yield the epox-
ide as a brown oil (10.1 g). This was processed directly
to 1-phenyl-2-tetralone without full characterisation;
zinc iodide (1.21 g, 3.78×10−3 mol), was heated to
120°C under vacuum for 1 h, cooled to ambient tem-
perature, then the epoxide (2.80 g, 1.26×10−2 mol)
dissolved in toluene (150 mL) was added. The reaction
was heated to reflux for 1 h. The reaction was cooled to
ambient temperature then washed with water (2×50
1
2363, 1750, 1598, 1493, 1450, 1136, 1068, 737 cm−1; H
NMR (300 MHz, CDCl3, Me4Si): l 3.7 (2H, s, CH2),
4.7 (1H, s, CH), 7.1–7.4 (9H, m, ArH); 13C NMR (300
MHz, CDCl3, Me4Si): l 43.4 (t), 60.2 (d), 125.3 (d),
126.4 (d), 127.7 (d), 128.3 (d), 128.4 (d), 128.9 (d), 129.2
(d), 138.1 (s), 138.5 (s), 141.7 (s); MS (EI): m/z
208.0870 (C15H12O requires 208.0888), 207 (71%), 180
(100%, M+), 165 (28%).
4.3. General procedure for DKR-asymmetric reduction
Ruthenium p-cymene dimer (0.0103 g, 1.69×10−5 mol,
0.25%) and (S,S)-TsDPEN (0.0123 g, 3.38×10−5 mol,
0.50%) were stirred in formic acid/triethylamine (5:2,
3.4 mL) at 28°C, for 20 min. 1-Phenyl-2-tetralone (1.5

N. J. Alcock et al. / Tetrahedron: Asymmetry 13 (2002) 2485–2490
2489
g, 6.76×10−3 mol), was added and the reaction stirred at
28°C for 92 h; the reaction was followed by TLC on
silica. The reaction mixture was filtered through a plug
of silica and the product eluted with ethyl acetate
(2×100 mL). The solution was evaporated to yield a
brown oil (2.34 g) and purified by column chromatog-
raphy on silica using ethyl acetate/hexane (5%) to yield
the alcohol.
ane, 1.0 mL/min): Rt 10.9, 12.5 min, 99% e.e. Com-
pared with authentic racemic material.
4.3.4. (1R,2S)-1-Phenylindan-2-ol
8 (n=0, X=H).
Colourless oil (21% yield); [h]2D0=−49.7 (c 0.910,
CHCl3); wmax (neat): 3534, 3412, 3022, 2907, 2361, 2246,
1949, 1601, 1492, 1451, 1316, 1191, 1075, 1042, 980, 723
1
cm−1; H NMR (300 MHz, CDCl3, Me4Si): l 2.8 (1H,
4.3.1.
(1R,2S)-1-Phenyl-2-hydroxy-1,2,3,4-tetrahydro-
dd, J=2.8, 13.4 Hz, CHH), 3.1 (1H, dd, J=5.5, 10.7
Hz, CHH), 4.3 (1H, d, J=5.5 Hz, CHPh), 4.5 (1H, m,
CHCHCH2), 7.0–7.4 (9H, m, ArH); 13C NMR (300
MHz, CDCl3, Me4Si): l 40.4 (t), 57.0 (d), 75.4 (d),
124.9 (d), 125.3 (d), 127.0 (d), 127.2 (d), 128.5 (d), 129.8
(d), 137.6 (d), 141.9 (d), 142.9 (d); MS (EI): m/z
210.1045 (C15H14O requires 210.1045), 210 (73%, M+),
192 (100%), 178 (53%), 165 (59%), 91 (37%); 28% e.e.
determined by conversion to Mosher’s ester. Compared
with authentic racemic material.
naphthalene 8 (n=1, X=H). Viscous colourless oil (1.40
g, 91%); [h]2D0=−91.75 (c 2.060, CHCl3); wmax (neat):
3239, 3024, 2931, 2880, 1735, 1601, 1488, 1242, 1051,
699 cm−1; H NMR (300 MHz, CDCl3, Me4Si): l 1.9
1
(2H, m, CH2CH2CHOH), 2.9 (1H, dt, J=6.7 Hz, 17.2,
CHHCHOH), 3.1 (1H, dt, J=6.0, 17.2 Hz, CHH-
CHOH), 4.2 (1H, m, CHOH), 4.4 (1H, d, J=4.9 Hz,
PhCHCHOH), 6.9 (1H, d, J=7.9 Hz, ArH), 7.0–7.4
(8H, m, ArH); 13C NMR (300 MHz, CDCl3, Me4Si): l
27.3 (t), 28.1 (t), 51.7 (d), 69.8 (d), 126.5 (d), 126.9 (d),
127.3 (d), 128.8 (d), 129.1 (d), 131.1 (d), 131.2 (d), 136.6
(s), 138.3 (s), 143.6 (s); MS (EI): m/z 224 (13%, M+),
206 (100%), 179 (84%), 165 (30%), 152 (8%), 128 (8%),
115 (9%), 91 (10%); chiral HPLC (5% IPA/hexane, 0.5
mL/min): Rt 20.2, 24.5 min, 94% e.e. Compared with
authentic racemic material. Anal. found: C, 85.49; H,
7.02. C16H16O requires: C, 85.67; H, 7.19%.
4.3.5.
(1R,2S)-1-Phenyl-2-hydroxy-1,2,3,4-tetrahydro-
naphthalene p-toluenesulphonyl ester, 9. 1-Phenyl-2-tet-
ranol (0.25 g, 1.123×10−3 mol) and p-toluenesulphonyl
chloride (0.24 g, 1.225×10−3 mol) was dissolved in pyri-
dine (5.4 mL) and stirred for 16 h. Hydrochloric acid
(1.5 mL, 5 M), and water (10 mL) was added and a
white precipitate formed. The product was extracted
with DCM (2×20 mL), evaporated to yield a brown oil
(0.4085 g) and purified by column chromatography on
silica using ethyl acetate/hexane (15%) to yield a
colourless crystalline solid (0.3332 g, 78%); mp 118–
120°C; [h]2D0=−80.4 (c 1.035, CHCl3); wmax (neat): 2941,
1330, 1168, 937, 897 cm−1; 1H NMR (300 MHz, CDCl3,
Me4Si): l 1.9 (1H, m, CHHCH2CHOH), 2.3 (1H, m,
CHHCH2CHOH), 2.4 (3H, s, CH3), 2.8–2.9 (1H, dt,
J=17.1, 7.0 Hz, CHHCHOTs), 3.1–3.2 (1H, dt, J=
17.3, 6.6 Hz, CHHCHOH), 4.4 (1H, d, J=4.9 Hz,
CHPh), 5.0 (1H, m, CHOTs), 6.8–7.2 (11H, m, ArH),
7.6 (2H, d, J=8.5 Hz, ArH); 13C NMR (300 MHz,
CDCl3, Me4Si): l 22.0 (q), 26.2 (d), 26.7 (d), 49.9 (d),
80.9 (d), 126.6 (d), 126.8 (d), 127.2 (d), 127.2 (d), 128.0
(d), 128.9 (d), 130.0 (d), 130.7 (d), 131.2 (d), 134.2 (s),
136.0 (s), 136.4 (s), 140.6 (s), 144.7 (s); MS (EI): m/z
378 (20%, M+), 270 (59%), 207 (87%), 179 (72%), 165
(68%), 91 (100%). Anal. found: C, 72.83; H, 5.81.
C23H22O3S requires: C, 72.99; H, 5.86%.
4.3.2. (1R,2S)-1-(p-Chlorophenyl)-2-hydroxy-1,2,3,4-tet-
rahydronaphthalene 8 (n=1, X=Cl). Viscous colourless
oil (91%); [h]2D0=−124.7 (c 1.650, EtOH); wmax (neat):
3377, 2931, 2359, 1907, 1487, 1406, 1087, 1054, 1013,
963, 917 cm−1; H NMR (300 MHz, CDCl3, Me4Si): l
1
1.9 (2H, m, CH2CH2CHOH), 2.9 (1H, m,
CH2CHHCHOH), 3.1 (1H, m, CH2CHHCHOH), 4.1–
4.2 (1H, m, CHOH), 4.3 (1H, d, J=4.8 Hz,
CHCHOH), 6.9–7.3 (8H, m, ArH); 13C NMR (300
MHz, CDCl3, Me4Si): l 27.2 (t), 28.2 (t), 51.0 (d), 69.7
(d), 126.6 (d), 127.1 (d), 128.8 (d), 129.1 (d), 131.0 (d),
132.3 (d), 133.2 (s), 136.8 (s), 137.2 (s), 140.3 (s); MS
(EI): m/z 258.079932 (C16H15OCl requires 258.081143),
258 (5%, M+), 239 (7%), 179 (19%), 117 (15%), 87
(79%), 85 (98%), 83 (100%); 95% e.e. determined with
8%
europium
tris[3-(heprafluropropylhydroxy-
methylene)-(+)-camphorate]. Compared with authentic
racemic material.
4.3.3. (1R,2S)-1-(p-Methoxyphenyl)-2-hydroxy-1,2,3,4-
tetrahydronaphthalene
8 (n=1, X=OMe). Viscous
colourless oil (88%); [h]2D0=−96.1 (C=3.905 EtOH);
wmax (neat): 3419, 2932, 2833, 1607, 1507, 1457, 1240,
1176, 1034, 823 cm−1; 1H NMR (300 MHz, CDCl3,
Acknowledgements
Me4Si):
l 1.8 (1H, br s, OH), 1.9 (2H, m,
CH2CH2CHOH), 2.8–2.9 (1H, m, CH2CHHCHOH),
3.0–3.1 (1H, m, CH2CHHCHOH), 3.7 (3H, s, OCH3),
4.1 (1H, m, CHOH), 4.3 (1H, d, J=4.8 Hz,
CHCHOH), 6.8–7.2 (8H, m, ArH); 13C NMR (300
MHz, CDCl3, Me4Si): l 27.4 (t), 28.1 (t), 50.8 (d), 55.7
(d), 69.9 (q), 114.2 (d), 126.4 (d), 126.8 (d), 129.0 (d),
131.1 (d), 132.0 (d), 133.7 (s), 136.9 (s), 138.1 (s), 159.0
(s); MS (EI): m/z 254.129942 (C17H18O2 requires
254.130680), 254 (64%), 209 (83%), 179 (100%), 165
(85%), 115 (56%), 77 (42%); chiral HPLC (5% IPA/hex-
We thank the EPSRC and GlaxoSmithKline for sup-
port of a CASE studentships (to P.P.). Professor D.
Games and Dr. B. Stein of the EPSRC National Mass
Spectroscopic Service (Swansea) are thanked for
HRMS analysis of certain compounds. We also
acknowledge the generous loan of ruthenium and
rhodium salts by Johnson-Mathey Limited, a personal
communication from J. Clader and G. Wu (Schering-
Plough) and the use of the EPSRC’s Chemical Data-
base Service at Daresbury.11

2490
N. J. Alcock et al. / Tetrahedron: Asymmetry 13 (2002) 2485–2490
4. For monotosylated diamines with Ru(II) in iPrOH or
References
HCO2H/TEA, see: (a) Hashiguchi, S.; Fujii, A.; Take-
hara, J.; Ikariya, T.; Noyori, R. J. Am. Chem. Soc. 1995,
117, 7562; (b) Fujii, A.; Hashiguchi, S.; Uematsu, N.;
Ikariya, T.; Noyori, R. J. Am. Chem. Soc. 1996, 118,
2521; (c) Pu¨ntener, K.; Schwink, L.; Knochel, P. Tetra-
hedron Lett. 1996, 37, 8165. For monotosylated diamines
with Rh(III) in iPrOH, see: (d) Mashima, K.; Abe, T.;
Tani, K. Chem. Lett. 1998, 1199; (e) Mashima, K.; Abe,
T.; Tani, K. Chem. Lett. 1998, 1201; (f) Murata, K.;
Ikariya, T.; Noyori, R. J. Org. Chem. 1999, 64, 2186. For
imines, see: (g) Uematsu, N.; Fujii, A.; Hashiguchi, S.;
Ikariya, T.; Noyori, R. J. Am. Chem. Soc. 1996, 118,
4916.
1. (a) Draper, R. W.; Hou, D.; Iyer, R.; Lee, G. M.; Liang,
J. T.; Mas, J. L.; Tormas, W.; Vater, E. J. Org. Process
Res. Dev. 1998, 2, 175; (b) Draper, R. W.; Hou, D.; Iyer,
R.; Lee, G. M.; Liang, J. T.; Mas, J. L.; Vater, E. J. Org.
Process Res. Dev. 1998, 2, 186; (c) Wu, G.; Wong, Y.;
Tormos, W.; Schmacher, D. P.; Love, G. M.; Shutts, B.
Org. Process Res. Dev. 1997, 1, 359; (d) Hou, D.;
Schmacher, D. Curr. Opin. Drug Dis. Dev. 2001, 41, 792.
2. (a) Wyrick, S. D.; Booth, R. G.; Myers, A. M.; Owens,
C. E.; Kula, N. S.; Baldessarini, R. J.; McPhail, A. T.;
Mailman, R. B. J. Med. Chem. 1993, 36, 2542; (b)
Wyrick, S. D.; Booth, R. G.; Myers, A. M.; Owens, C.
E.; Bucholtz, E. C.; Hooper, P. C.; Kula, N. S.;
Baldessarini, R. J.; Mailman, R. B. J. Med. Chem. 1995,
38, 3857.
3. (a) Palmer, M. J.; Wills, M. Tetrahedron: Asymmetry
1999, 10, 2045–2061; (b) Palmer, M.; Walsgrove, T.;
Wills, M. J. Org. Chem. 1997, 62, 5226; (c) Wills, M.;
Gamble, M.; Palmer, M.; Smith, A. R. C.; Studley, J. R.;
Kenny, J. A. J. Mol. Catal. A; Chem. 1999, 146, 139–148;
(d) Kenny, J. A.; Palmer, M. J.; Smith, A. R. C.; Wals-
grove, T.; Wills, M. Synlett 1999, 1615; (e) Smith, A. R.
C.; Kenny, J. A.; Heck, A. J. R.; Kettenes-van der Bosch,
J. J.; Wills, M. Tetrahedron: Asymmetry 1999, 10, 3267–
3270; (f) Wills, M.; Palmer, M. J.; Smith, A. R. C.;
Kenny, J. A.; Walsgrove, T. Molecules 2000, 5, 1–15; (g)
Kenny, J. A.; Versluis, K.; Heck, A. J. R.; Walsgrove, T.;
Wills, M. Chem. Commun 2000, 99–100; (h) Kawamoto,
A.; Wills, M. Tetrahedron: Asymmetry 2000, 11, 3257–
3261.
5. For a review, see: Palmer, M.; Wills, M. Tetrahedron:
Asymmetry 1999, 10, 2045.
6. For reviews, see: (a) Ba¨ckvall, J.-E.; Huerta, F.; Minidis,
A. Chem. Soc. Rev. 2001, 30, 321–331; (b) Ward, R.
Tetrahedron: Asymmetry 1995, 7, 1475–1490; (c) Noyori,
R. Bull. Chem. Soc. Jpn. 1995, 68, 36–56.
7. Murata, K.; Okano, K.; Miyagi, M.; Iwane, H.; Ikariya,
T.; Noyori, R. Org. Lett. 1999, 1, 1119.
8. (a) Dalko, P.; Eustache, F.; Cossy, J. Tetrahedron Lett.
2001, 42, 5005–5007; (b) Eustache, F.; Dalko, P.; Cossy,
J. Org. Lett. 2002, 8, 1263–1265.
9. Mohar, B.; Valleix, A.; Desmurs, J.-R.; Felemez, M.;
Wagner, A.; Mioskowski, C. Chem. Commun. 2001,
2572–2573.
10. Slobodzian, S.; Jensen, B. Tetrahedron Lett. 2000, 41,
6029–6033.
11. Fletcher, D. A.; McMeeking, R. F.; Parkin, D. J. Chem.
Inf. Comput. Sci. 1996, 36, 746–749.