Novel bi- and tridentate phosphane and thioether ligands derived from chiral α-hydroxy acids

Article abstract of DOI:10.1016/S0957-4166(99)00103-2

Novel bi- and tridentate ligands with phosphane and thioether moieties have been prepared in enantiomerically pure form in good to excellent yields by substitution reactions with phosphorus and sulfur nucleophiles of easily available tosylates derived from natural chiral α-hydroxy acids.

Full text of DOI:10.1016/S0957-4166(99)00103-2

Pergamon
Tetrahedron: Asymmetry 10 (1999) 1207–1215
Novel bi- and tridentate phosphane and thioether ligands derived
from chiral α-hydroxy acids
Jens Christoffers ∗ and Ulrich Rößler
Technische Universität Berlin, Institut für Organische Chemie, Sekretariat C 3, Straße des 17. Juni 135, D-10623 Berlin,
Germany
Received 2 March 1999; accepted 17 March 1999
Abstract
Novel bi- and tridentate ligands with phosphane and thioether moieties have been prepared in enantiomerically
pure form in good to excellent yields by substitution reactions with phosphorus and sulfur nucleophiles of easily
available tosylates derived from natural chiral α-hydroxy acids. © 1999 Elsevier Science Ltd. All rights reserved.
1. Introduction
We are interested in the development of new chiral multidentate ligands,1,2 e.g. tridentate ligands of the
general type 1 and bidentate ligands 2 (Scheme 1) with different donor moieties, such as phosphane and
thioether groups, for transition metal catalyzed asymmetric C–C bond formations, with special interest
in the transition metal catalyzed asymmetric Michael reaction.3
In this paper we report in continuation of our previous work1 the synthesis of three new enantiome-
rically pure C2-symmetric tridentate ligands with P,O,P- and S,O,S-donor sets (1a–1c) and an improved
route to the enantiopure hydroxyalkyl phosphanes and thioethers 2a–2f (Scheme 1). The hydroxy
compounds 2a–2f have already been prepared in racemic form as well as — in some cases — enantiopure
materials by either epoxide opening or substitution of hydroxy alkyl halides with phosphorus or sulfur
nucleophiles.4–10 The route we present herein is an improvement on the reported procedures, since
regioselectivity problems in epoxide opening reactions or stereoselectivity problems in the introduction
of chirality by an asymmetric reaction are avoided. In our approach the stereo information is derived from
natural, non-racemic α-hydroxy acids. Unlike 1a–1c, secondary alcohols 2a–2f can not only be applied
as chiral ligands, but play an important role as enantiopure building blocks or chiral auxiliaries.
∗
Corresponding author. Tel: +49 30/314-23189; fax: +49 30/723-1233; e-mail: jchr@wap0105.chem.tu-berlin.de
0957-4166/99/$ - see front matter © 1999 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(99)00103-2

1208
J. Christoffers, U. Rößler / Tetrahedron: Asymmetry 10 (1999) 1207–1215
Scheme 1. Tri- and bidentate ligands derived from natural α-hydroxy acids
2. Synthesis
The synthesis of the tridentate ligands 1a–1c starts from the recently published diol 3 (Scheme 2),
which is easily prepared from (S)-(−)-ethyl lactate.1 Compound 3 is tosylated with TosCl in pyridine to
give the bistosylate 4 in 51% yield. Intermediate 4 can be easily substituted by KPPh2 in DMF/THF or
NaSR in DMF to give compounds 1a–1c in good to excellent yields with an inversion of configuration
(Table 1). It is important to mention that by NMR or GC no other diastereoisomers of 1a–1c are
detectable, which means that the substitution is stereospecific and no epimerization takes place. The
13C spectrum of 1a shows the expected phosphorus coupling and that the two Ph groups of each Ph2P
moiety are diastereotopic.
Scheme 2. Ligand synthesis: (a) TosCl, pyridine, 51%; (b) see Table 1
It is remarkable, that — in our hands — bisphosphane 1a shows only a very low tendency to oxidize in
air at room temperature, although at elevated temperatures, especially in solution, formation of phosphane
oxides is detectable by 31P NMR.
The hydroxyalkyl phosphanes 2a and 2b and thioethers 2c–2f have been prepared from the corres-
ponding hydroxy tosylates 5a and 5b (Scheme 2), which are derived in enantiomerically pure form from
(S)-(−)-ethyl lactate and (S)-(+)-ethyl mandelate.1 Substitution with KPPh2 in DMF/THF or NaSR in
DMF proceeds in high yields (Table 1). In the case of the phosphanes 2a and 2b all expected phosphorus
couplings are observed in the NMR spectra. Moreover, the Ph groups of the Ph2P moieties appear to be

J. Christoffers, U. Rößler / Tetrahedron: Asymmetry 10 (1999) 1207–1215
1209
Table 1
Yields and reaction conditions
diastereotopic. Besides that, it is remarkable that the specific rotation of compound 2a shows a strong
20
dependence on the solvent and concentration: it has a positive sign ([α]D +21.5, c 12.1) in CHCl3,
while it is negative in AcOEt ([α]D20 −3.8, c 8.6).
Although there are already syntheses of compounds 2 reported in the literature, the presented route is
superior to the others: the regioselectivity problem of the epoxide opening is avoided as well as the need
for an asymmetric reaction to build up the stereogenic center, because the stereo information is derived
from the chiral pool.
3. Asymmetric Michael reactions
Recently, Shibasaki has introduced an excellent heterobimetallic catalyst for the Michael reaction of β-
dicarbonyl compounds with α,β-unsaturated ketones.11,12 However, the reaction conditions are strongly
basic, thus often causing a number of unwanted side- and subsequent processes. The need for a neutral
transition metal catalyst has been — more or less successfully — addressed by a number of groups in the
past years.13–17 As our contribution to this topic we screened all nine ligands 1a–1c and 2a–2f with 12
metal salts† (which we knew would catalyze the Michael reaction, shown in Scheme 3, at least to some
extent at room temperature) in a combinatorial approach: separately, 108 (9 ligands×12 metal salts)
catalytic systems were formed in situ and screened for enantioselectivity in the catalysis of the Michael
reaction of oxoester 6 with methyl vinyl ketone 7 (Scheme 3). Analysis of the product 8 was performed
by chiral GC. Details are given in the experimental section. Unfortunately, in none of our experiments
was an enantioselectivity of more than 10% ee detectable.
Scheme 3. Metal catalyzed Michael reaction, screening of ligands 1 and 2 with metal compounds MXn
†
List of applied metal salts: CrCl3·6H2O, Mn(OAc)2·4H2O, FeCl3·6H2O, Ni(OAc)2·4H2O, NiCl2·6H2O, CoCl2·6H2O,
RhCl3·3H2O, Cu(OAc)2·H2O, AgOAc, ZnCl2, SnCl2, Pb(OAc)2·3H2O.

1210
J. Christoffers, U. Rößler / Tetrahedron: Asymmetry 10 (1999) 1207–1215
4. Summary
Three new chiral tridentate ligands with P,O,P- and S,O,S-donor sets and six enantiopure hydroxyethyl
phosphanes and thioethers have been prepared from commercially available natural chiral α-hydroxy
acids and tested as ligands in the asymmetric catalysis of the Michael reaction.
5. Experimental
5.1. General
1
Column chromatography was accomplished with Merck silica gel (Type 60, 0.063–0.200 mm). H
NMR spectra were recorded on a Bruker AM 400 (400 MHz), and reported in parts per million (ppm)
using the residual proton solvent peak of CDCl3 at 7.26 ppm as an internal standard, with coupling
constants (J) in hertz (Hz). 13C NMR spectra were recorded on a Bruker AC 200 (50 MHz, 1H decoupled),
and reported in parts per million (ppm) using the solvent triplet of CDCl3 at 77.0 ppm as an internal
standard. Assignments were made using DEPT experiments. 31P NMR spectra were recorded on a Bruker
AC 200 (80 MHz) using PPh3 (−6 ppm) in CDCl3 as an external standard. MS spectra were obtained with
Varian MAT 711 and MAT 955Q (high resolution) instruments. IR spectra were recorded on a Nicolet
Magna IR 750. Elemental analyses were obtained with an Analytik Jena Vario EL. Optical rotations were
measured with a Perkin–Elmer polarimeter 341. Chiral GC analysis was performed on a Packard 437A
with FI detection, a Shimadzu C-R6A integrator and a Macherey–Nagel column FS-LIPODEX E (25 m,
0.25 mm) with nitrogen carrier gas.
Starting compounds 3, 5a and 5b were synthesized according to literature procedures.1 DMF (HPLC
grade), NaSEt (90% technical quality), NaSPh (90% technical quality) and KPPh2 (0.5 M solution in
THF) were purchased from the Aldrich Chemical Co. and used as received.
5.2. Abbreviations
ATR: attenuated total reflection; MTB: tert-butyl methyl ether; Tos: p-tolylsulfonyl.
5.3. (S,S)-(−)-Bis[2-(p-tolylsulfonyloxy)propyl]ether 4
TosCl (1.49 g, 7.80 mmol) was added to a solution of the diol 3 (262 mg, 1.95 mmol) in pyridine
(1.5 ml), and stirred overnight at room temperature. Water (10 ml) and CH2Cl2 (10 ml) were added,
and the mixture was stirred for 30 min. The layers were separated, and the aqueous layer was extracted
three times with CH2Cl2 (each 30 ml). The combined organic layers were washed with hydrochloric acid
(18%, 50 ml), water (50 ml) and brine (50 ml). The solution was dried over MgSO4, evaporated, and the
crude product was chromatographed (SiO2, MTB:hexane 1:1, Rf=0.29) to give compound 4 (442 mg,
0.999 mmol, 51%) as a colorless oil. [α]D20 −9.9 (c 11.3, CHCl3). 1H NMR (400 MHz, CDCl3): δ 1.19
(6H, d, J=6.5 Hz), 2.44 (6H, s), 3.32 (2H, dd, J=4.4 Hz, J=10.8 Hz), 3.41 (2H, dd, J=5.7 Hz, J=10.8
Hz), 4.53–4.63 (2H, m), 7.30–7.35 (4H, m), 7.74–7.79 (4H, m). 13C NMR (50 MHz, CDCl3): δ 17.44 (2
CH3), 21.59 (2 CH3), 73.47 (2 CH2), 77.79 (2 CH), 127.73 (4 CH), 129.73 (4 CH), 134.25 (2 C), 144.60
(2 C). IR (ATR): 3066 (w), 2984 (w), 2936 (w), 2874 (w), 1597 (w), 1495 (w), 1451 (w), 1401 (w), 1381
(w), 1348 (s), 1307 (w), 1291 (w), 1211 (w), 1189 (s), 1173 (vs), 1120 (m), 1097 (m), 1045 (w), 1019
(w), 972 (w), 916 (s), 904 (s), 876 (s), 814 (s), 764 (s), 705 (w), 662 (s). MS (EI, 70 eV) m/z (%)=442

J. Christoffers, U. Rößler / Tetrahedron: Asymmetry 10 (1999) 1207–1215
1211
(1), 270 (6), 243 (10), 229 (1), 213 (22), 173 (5), 155 (100), 91 (55), 65 (6). HRMS: Mol. mass calcd
442.1120 (for C20H26O7S2), found 442.1121 (M+). Anal. calcd for C20H26O7S2 (442.55): C 54.28, H
5.92, found C 54.00, H 6.00.
5.4. (R,R)-(+)-Bis[2-(diphenylphosphanyl)propyl]ether 1a
KPPh2 (5.8 ml of a 0.5 M solution in THF, 2.9 mmol) was added to a degassed (three times) solution
of compound 4 (430 mg, 0.972 mmol) in DMF (5 ml) under an atmosphere of Ar at 0°C, stirred for 5 min
in the cold, and overnight at room temperature. The mixture was hydrolyzed with water (10 ml), diluted
with MTB (75 ml), and washed twice with water (each 50 ml). The organic layer was dried over MgSO4,
and evaporated to dryness. The crude product was chromatographed (SiO2, MTB:hexane 1:30, Rf=0.23)
20
to give compound 1a (213 mg, 0.453 mmol, 47%) as a colorless oil. [α]D +34.6 (c 14.8, CHCl3). 1H
NMR (400 MHz, CDCl3): δ 1.07 (6H, dd, J=6.9 Hz, J=14.6 Hz), 2.54–2.74 (2H, m), 3.17–3.30 (2H, m),
3.30–3.44 (2H, m), 7.22–7.40 (12H, m), 7.40–7.58 (8H, m). 13C NMR (50 MHz, CDCl3): δ 14.71 (2
CH3, d, J=14.9 Hz), 31.19 (2 CH3, d, J=10.9 Hz), 73.54 (2 CH2, d, J=23.7 Hz), 128.23 (8 CH, d, J=7.2
Hz), 128.60 (2 CH, s), 128.67 (2 CH, s), 133.27 (4 CH, d, J=19.2 Hz), 133.61 (4 CH, d, J=19.8 Hz),
136.39 (2 C, d, J=13.7 Hz), 136.86 (2 C, d, J=14.1 Hz). 31P NMR (80 MHz, CDCl3): δ −8 (br s). IR
(ATR): 3070 (m), 3052 (m), 3015 (w), 3000 (w), 2958 (m), 2924 (m), 2868 (m), 1585 (w), 1570 (w),
1480 (m), 1455 (w), 1433 (s), 1375 (w), 1354 (w), 1307 (w), 1269 (w), 1182 (w), 1157 (w), 1091 (s),
1071 (s), 1027 (m), 999 (m), 916 (w), 880 (w), 741 (s), 696 (vs). MS (EI, 70 eV) m/z (%)=470 (3), 285
(100), 262 (4), 227 (4), 185 (38), 183 (29), 109 (15), 108 (13), 77 (2). HRMS: Mol. mass calcd 470.1928
(for C30H32OP2), found 470.1922 (M+).
5.5. (R,R)-(+)-Bis[2-(ethylsulfanyl)propyl]ether 1b
A solution of compound 4 (1.64 g, 3.71 mmol) in DMF (7.5 ml) was added to a solution of NaSEt
(1.25 g, 14.8 mmol) in DMF (7.5 ml), stirred overnight at room temperature in a tightly closed reaction
flask, and diluted with MTB (50 ml). The mixture was washed three times with water (each 35 ml), dried
over MgSO4, and evaporated to dryness. The crude product was chromatographed (SiO2, MTB:hexane
20
1:10, Rf=0.50) to give compound 1b (656 mg, 2.95 mmol, 80%) as a colorless oil. [α]D +59 (c 7.1,
1
CHCl3). H NMR (400 MHz, CDCl3): δ 1.25 (6H, t, J=7.4 Hz), 1.28 (6H, d, J=7.0 Hz), 2.60 (2H, q,
J=7.4 Hz), 2.61 (2H, q, J=7.4 Hz), 2.91–3.02 (2H, m), 3.40 (2H, dd, J=7.8 Hz, J=9.6 Hz), 3.54 (2H, dd,
J=5.5 Hz, J=9.6 Hz). 13C NMR (50 MHz, CDCl3): δ 15.04 (2 CH3), 18.44 (2 CH3), 24.83 (2 CH2), 39.04
(2 CH), 76.12 (2 CH2). IR (ATR): 2964 (vs), 2927 (vs), 2869 (s), 2792 (w), 1728 (w), 1451 (s), 1375
(m), 1355 (w), 1295 (w), 1265 (m), 1210 (w), 1086 (vs), 1011 (w), 971 (w), 926 (w), 785 (w), 763 (w),
723 (w), 664 (w). MS (EI, 70 eV) m/z (%)=222 (1), 193 (1), 133 (6), 103 (100), 102 (79), 89 (75), 74
(23), 61 (26). HRMS: Mol. mass calcd 222.1112 (for C10H22OS2), found 222.1117 (M+). Anal. calcd for
C10H22OS2 (222.42): C 54.01, H 9.97, found C 54.01, H 10.02.
5.6. (R,R)-(+)-Bis[2-(phenylsulfanyl)propyl]ether 1c
A solution of compound 4 (453 mg, 1.02 mmol) in DMF (3 ml) was added to NaSPh (404 mg, 3.06
mmol), stirred overnight at room temperature in a tightly closed reaction flask, and diluted with MTB
(30 ml). The mixture was washed twice with water (each 20 ml), dried over MgSO4, and evaporated to
dryness. The crude product was chromatographed (SiO2, MTB:hexane 1:50, Rf=0.11) to give compound
20
1
1c (213 mg, 0.669 mmol, 66%) as a colorless oil. [α]D +50 (c 6.4, CHCl3). H NMR (400 MHz,

1212
J. Christoffers, U. Rößler / Tetrahedron: Asymmetry 10 (1999) 1207–1215
CDCl3): δ 1.24–1.30 (6H, m), 3.28–3.47 (4H, m), 3.47–3.59 (2H, m), 7.19–7.37 (6H, m), 7.37–7.49 (4H,
m). 13C NMR (50 MHz, CDCl3): δ 18.01 (2 CH3), 42.21 (2 CH3), 74.86 (2 CH2), 126.84 (2 CH), 128.76
(4 CH), 131.87 (4 CH), 134.46 (2 C). IR (ATR): 3073 (w), 3056 (w), 2966 (w), 2925 (w), 2864 (w),
2791 (w), 1583 (w), 1572 (w), 1474 (m), 1438 (m), 1374 (w), 1354 (w), 1291 (w), 1268 (w), 1208 (w),
1088 (s), 1067 (s), 1024 (m), 1014 (m), 911 (w), 737 (vs), 689 (vs). MS (EI, 70 eV) m/z (%)=318 (12),
181 (5), 168 (39), 151 (100), 137 (86), 123 (28), 109 (69), 77 (13). HRMS: Mol. mass calcd 318.1112
(for C18H22OS2), found 318.1113 (M+). Anal. calcd for C18H22OS2 (318.50): C 67.88, H 6.96, found C
68.03, H 7.21.
5.7. (S)-(+)-(2-Hydroxy-1-propyl)-diphenylphosphane 2a
KPPh2 (3.0 ml of a 0.5 M solution in THF, 1.5 mmol) was added to a degassed (three times) solution
of tosylate 5a (230 mg, 1.00 mmol) in DMF (2 ml) under an atmosphere of Ar at 0°C, stirred for 5 min
in the cold, and overnight at room temperature. The mixture was hydrolyzed with water (10 ml), diluted
with MTB (75 ml), and washed twice with water (each 50 ml). The organic layer was dried over MgSO4,
and evaporated to dryness. The crude product was chromatographed (SiO2, MTB:hexane 1:1, Rf=0.40)
20
20
to give 2a (93.0 mg, 0.381 mmol, 38%) as a colorless oil. [α]D +21.5 (c 12.1, CHCl3), [α]D −3.8
(c 8.6, AcOEt; lit.5 −7.2, c 2, AcOEt). H NMR (400 MHz, CDCl3): δ 1.32 (3H, d, J=6.1 Hz), 2.02
1
(1H, br s), 2.27–2.43 (2H, m), 3.87–3.97 (1H, m), 7.28–7.60 (10H, m). 13C NMR (50 MHz, CDCl3): δ
24.51 (CH3, d, J=6.3 Hz), 39.17 (CH2, d, J=12.1 Hz), 65.67 (CH, d, J=16.5 Hz), 128.1–128.7 (6 CH, m),
132.49 (2 CH, d, J=18.4 Hz), 132.72 (2 CH, d, J=18.6 Hz), 137.6–138.4 (2 C, m). 31P NMR (80 MHz,
CDCl3): δ −24 (br s). IR (ATR): 3383 (s), 3070 (w), 3053 (w), 2966 (m), 2928 (w), 2898 (w), 1585 (w),
1481 (m), 1454 (w), 1433 (s), 1405 (w), 1375 (w), 1306 (w), 1273 (w), 1213 (w), 1183 (w), 1157 (w),
1118 (m), 1098 (m), 1063 (m), 1018 (m), 1000 (w), 936 (m), 861 (w), 810 (w), 738 (s), 696 (vs). MS
(EI, 70 eV) m/z (%)=244 (89), 227 (8), 202 (26), 199 (100), 186 (54), 183 (57), 121 (95), 108 (57), 91
(18), 77 (9). HRMS: Mol. mass calcd 244.1017 (for C15H17OP), found 244.1019 (M+). Anal. calcd for
C15H17OP (244.27): C 73.76, H 7.01, found C 73.19, H 7.04.
5.8. (S)-(+)-(2-Hydroxy-2-phenyl-1-ethyl)-diphenylphosphane 2b
KPPh2 (3.0 ml of a 0.5 M solution in THF, 1.5 mmol) was added to a degassed (three times) solution
of tosylate 5b (292 mg, 1.00 mmol) in DMF (2 ml) under an atmosphere of Ar at 0°C, stirred for 5 min
in the cold, and overnight at room temperature. The mixture was hydrolyzed with water (10 ml), diluted
with MTB (75 ml), and washed twice with water (each 50 ml). The organic layer was dried over MgSO4,
and evaporated to dryness. The crude product was chromatographed (SiO2, MTB:hexane 1:3, Rf=0.26)
to give compound 2b (134 mg, 0.437 mmol, 44%) as a colorless oil. [α]D +43.8 [c 10.7, CHCl3; lit.6
20
−36 for (R)-2b, no concentration and solvent given]. 1H NMR (400 MHz, CDCl3): δ 2.33 (1H, br s), 2.57
(1H, ddd, J=1.6 Hz, J=4.9 Hz, J=13.9 Hz), 2.63 (1H, ddd, J=1.5 Hz, J=8.8 Hz, J=13.9 Hz), 4.79 (1H,
ddd, J=4.9 Hz, J=7.1 Hz, J=8.8 Hz), 7.22–7.58 (15H, m). 13C NMR (50 MHz, CDCl3): δ 39.63 (CH2,
d, J=13.9 Hz), 71.90 (CH, d, J=16.9 Hz), 125.63 (2 CH), 127.54 (CH), 128.1–128.6 (7 CH, m), 128.71
(CH), 132.49 (2 CH, d, J=18.5 Hz), 132.94 (2 CH, d, J=19.2 Hz), 137.79 (C, d, J=12.3 Hz), 138.26
(C, d, J=11.5 Hz), 144.44 (C, d, J=6.1 Hz). 31P NMR (80 MHz, CDCl3): δ −23 (br s). IR (ATR): 3559
(m), 3385 (vs), 3068 (m), 3053 (m), 3029 (w), 3001 (w), 2938 (w), 2901 (w), 1953 (w), 1884 (w), 1812
(w), 1601 (w), 1585 (w), 1571 (w), 1492 (w), 1481 (m), 1454 (m), 1433 (s), 1406 (w), 1329 (w), 1306
(w), 1273 (w), 1183 (w), 1157 (w), 1095 (w), 1046 (m), 1026 (s), 1000 (m), 969 (w), 914 (w), 878 (w),
846 (w), 807 (w), 770 (m), 739 (s), 723 (s), 696 (vs). MS (EI, 70 eV) m/z (%)=306 (17), 262 (63), 199

J. Christoffers, U. Rößler / Tetrahedron: Asymmetry 10 (1999) 1207–1215
1213
(100), 186 (13), 183 (26), 121 (77), 108 (15), 91 (13), 77 (22). HRMS: Mol. mass calcd 306.1174 (for
C20H19OP), found 306.1174 (M+). Anal. calcd for C20H19OP (306.34): C 78.42, H 6.25, found C 78.08,
H 6.20.
5.9. (S)-(+)-Ethyl-(2-hydroxy-1-propyl)thioether 2c
Attention: Due to the high volatility of the product 2c all evaporation processes should be done
carefully. A solution of the tosylate 5a (461 mg, 2.00 mmol) in DMF (3 ml) was added to NaSEt (336
mg, 4.00 mmol), and stirred overnight at room temperature in a tightly closed reaction flask, and diluted
with MTB (75 ml). The mixture was washed twice with water (each 50 ml), dried over MgSO4, and
evaporated to dryness. The crude product was chromatographed (SiO2, MTB:hexane 1:1, Rf=0.31) to
20
1
give compound 2c (194 mg, 1.61 mmol, 81%) as a yellowish oil. [α]D +78.7 (c 13.8, CHCl3). H
NMR (400 MHz, CDCl3): δ 1.25 (3H, d, J=6.2 Hz), 1.27 (3H, t, J=7.4 Hz), 2.44 (1H, dd, J=9.0 Hz,
J=13.7 Hz), 2.56 (2H, q, J=7.4 Hz), 2.57 (1H, br s), 2.74 (1H, dd, J=3.5 Hz, J=13.7 Hz), 3.78–3.88 (1H,
m). 13C NMR (50 MHz, CDCl3): δ 14.59 (CH3), 21.77 (CH3), 25.89 (CH2), 40.82 (CH2), 65.39 (CH).
IR (ATR): 3396 (s), 2970 (s), 2926 (vs), 2875 (m), 2855 (m), 1733 (m), 1496 (w), 1454 (m), 1375 (m),
1355 (w), 1266 (m), 1205 (w), 1177 (m), 1129 (m), 1079 (s), 1059 (s), 1029 (m), 938 (w), 730 (w), 702
(w). MS (EI, 70 eV) m/z (%)=120 (100), 105 (11), 77 (13), 76 (81), 75 (41), 61 (57), 59 (17). HRMS:
Mol. mass calcd 120.0609 (for C5H12OS), found 120.0610 (M+).
5.10. (S)-(+)-(2-Hydroxy-1-propyl)-phenyl thioether 2d
A solution of the tosylate 5a (461 mg, 2.00 mmol) in DMF (3 ml) was added to NaSPh (529 mg, 4.00
mmol), stirred overnight at room temperature in a tightly closed reaction flask, and diluted with MTB
(75 ml). The mixture was washed twice with water (each 50 ml), dried over MgSO4, and evaporated to
dryness. The crude product was chromatographed (SiO2, MTB:hexane 1:1, Rf=0.40) to give compound
2d (302 mg, 1.79 mmol, 90%) as a yellowish oil. [α]D20 +60.1 [c 12.2, CHCl3; lit.9 +54.7, c 1, CHCl3].
1H NMR (400 MHz, CDCl3): δ 1.27 (3H, d, J=6.2 Hz), 2.33 (1H, br s), 2.84 (1H, dd, J=8.6 Hz, J=13.7
Hz), 3.12 (1H, dd, J=3.6 Hz, J=13.7 Hz), 3.80–3.89 (1H, m), 7.18–7.41 (5H, m). 13C NMR (50 MHz,
CDCl3): δ 21.83 (CH3), 43.28 (CH2), 65.54 (CH), 126.39 (CH), 128.90 (2 CH), 129.81 (2 CH), 135.26
(C). IR (ATR): 3378 (s), 3075 (w), 3058 (w), 2970 (m), 2918 (w), 1584 (m), 1480 (m), 1438 (m), 1409
(w), 1372 (w), 1302 (w), 1264 (w), 1239 (w), 1186 (w), 1123 (m), 1068 (m), 1036 (m), 1025 (s), 934
(m), 874 (w), 816 (w), 736 (vs), 689 (vs). MS (EI, 70 eV) m/z (%)=168 (72), 135 (4), 124 (100), 123 (36),
110 (15), 109 (20), 91 (31), 78 (26), 65 (10), 51 (14). HRMS: Mol. mass calcd 168.0609 (for C9H12OS),
found 168.0612 (M+).
5.11. (S)-(+)-Ethyl-(2-hydroxy-2-phenyl-1-ethyl)thioether 2e
A solution of the tosylate 5b (585 mg, 2.00 mmol) in DMF (3 ml) was added to NaSEt (336 mg, 4.00
mmol), stirred overnight at room temperature in a tightly closed reaction flask, and diluted with MTB
(75 ml). The mixture was washed twice with water (each 50 ml), dried over MgSO4, and evaporated to
dryness. The crude product was chromatographed (SiO2, MTB:hexane 1:2, Rf=0.38) to give compound
2e (313 mg, 1.72 mmol, 86%) as a yellowish oil. [α]D20 +81 [c 6.4, CHCl3; lit.10 −75.8 for (R)-2e, c 2.19,
1
CHCl3]. H NMR (400 MHz, CDCl3): δ 1.28 (3H, t, J=7.4 Hz), 2.58 (2H, q, J=7.4 Hz), 2.73 (1H, dd,
J=9.6 Hz, J=13.8 Hz), 2.95 (1H, dd, J=3.6 Hz, J=13.8 Hz), 3.03 (1H, br s), 4.71–4.77 (1H, m), 7.25–7.41
(5H, m). 13C NMR (50 MHz, CDCl3): δ 14.51 (CH3), 25.81 (CH2), 41.12 (CH2), 71.65 (CH), 125.56 (2

1214
J. Christoffers, U. Rößler / Tetrahedron: Asymmetry 10 (1999) 1207–1215
CH), 127.46 (CH), 128.14 (2 CH), 142.48 (C). IR (ATR): 3423 (vs), 3085 (w), 3062 (w), 3029 (w), 2925
(m), 2871 (w), 1952 (w), 1882 (w), 1809 (w), 1756 (w), 1602 (w), 1585 (w), 1493 (m), 1453 (s), 1409
(m), 1376 (m), 1332 (w), 1266 (m), 1231 (w), 1194 (m), 1081 (w), 1058 (s), 1028 (s), 1002 (w), 980 (m),
915 (w), 860 (w), 769 (m), 758 (m), 730 (s), 699 (vs). MS (EI, 70 eV) m/z (%)=182 (4), 107 (58), 91 (6),
79 (44), 77 (31), 76 (100), 61 (11). HRMS: Mol. mass calcd 182.0765 (for C10H14OS), found 182.0761
(M+). Anal. calcd for C10H14OS (182.29): C 65.89, H 7.74, found C 65.58, H 7.90.
5.12. (S)-(−)-(2-Hydroxy-2-phenyl-1-ethyl)-phenyl thioether 2f
A solution of the tosylate 5b (585 mg, 2.00 mmol) in DMF (3 ml) was added to NaSPh (529 mg, 4.00
mmol), stirred overnight at room temperature in a tightly closed reaction flask, and diluted with MTB
(75 ml). The mixture was washed twice with water (each 50 ml), dried over MgSO4, and evaporated to
dryness. The crude product was chromatographed (SiO2, MTB:hexane 1:3, Rf=0.35) to give compound
20
2f (420 mg, 1.82 mmol, 91%) as a yellowish oil. [α]D −12.5 [c 13.9, CHCl3; lit.10 +8.6 for (R)-2f, c
1.07, CHCl3]. 1H NMR (400 MHz, CDCl3): δ 2.85 (1H, br s), 3.10 (1H, dd, J=9.5 Hz, J=13.8 Hz), 3.34
(1H, dd, J=3.4 Hz, J=13.8 Hz), 4.73 (1H, dd, J=3.4 Hz, J=9.5 Hz), 7.21–7.46 (10H, m). 13C NMR (50
MHz, CDCl3): δ 43.75 (CH2), 71.61 (CH), 125.76 (2 CH), 126.59 (CH), 127.85 (CH), 128.42 (2 CH),
129.00 (2 CH), 130.00 (2 CH), 134.93 (C), 142.09 (C). IR (ATR): 3394 (s), 3059 (w), 3029 (w), 3003
(w), 2919 (w), 2886 (w), 1601 (w), 1582 (m), 1493 (w), 1480 (m), 1453 (m), 1438 (m), 1408 (w), 1332
(w), 1302 (w), 1230 (w), 1192 (w), 1156 (w), 1086 (w), 1053 (m), 1025 (s), 1001 (w), 989 (w), 914 (w),
858 (w), 768 (w), 737 (vs), 698 (vs), 689 (vs). MS (EI, 70 eV) m/z (%)=230 (9), 124 (100), 107 (29), 91
(8), 79 (21), 77 (15), 65 (3), 51 (7). HRMS: Mol. mass calcd 230.0765 (for C14H14OS), found 230.0763
(M+). Anal. calcd for C14H14OS (230.33): C 73.01, H 6.13, found C 73.12, H 6.25.
5.13. Asymmetric catalysis: ethyl 2-(3-oxobutyl)cyclopentanone-2-carboxylate 8
Metal compound (0.05 mmol, 5 mol%), chiral ligand 1 (0.075 mmol, 7.5 mol%) or 2 (0.1 mmol, 10
mol%) and oxoester 6 (156 mg, 1.0 mmol) were dissolved in CH2Cl2 (1 ml). After stirring for 1 h at room
temperature methyl vinyl ketone 7 (84 mg, 1.2 mmol) was added and the mixture was stirred overnight at
room temperature. Subsequently, all volatile materials were removed in vacuo and the residue was filtered
through SiO2 (MTB:hexane 1:1, Rf=0.25). The product mixture was analyzed by chiral GC, isothermal
elution (130°C).
Acknowledgements
This work was supported by the Fonds der Chemischen Industrie and the Deutsche Forschungs-
gemeinschaft. We are also grateful to Prof. S. Blechert and the Institut für Organische Chemie der
Technischen Universität Berlin for support. J. C. also thanks the Deutsche Forschungsgemeinschaft for a
fellowship.
References
1. Christoffers, J.; Rößler, U. Tetrahedron: Asymmetry 1998, 9, 2349–2357.
2. Christoffers, J. Liebigs Ann./Recueil 1997, 1353–1358.
3. Christoffers, J. Eur. J. Org. Chem. 1998, 1259–1266.

J. Christoffers, U. Rößler / Tetrahedron: Asymmetry 10 (1999) 1207–1215
1215
4. rac-2a and rac-2b: Issleib, K.; Roloff, H.-R. Chem. Ber. 1965, 98, 2091–2098.
5. (S)-2a: Kagan, H. B.; Tahar, M.; Fiaud, J.-C. Tetrahedron Lett. 1991, 32, 5959–5962.
6. (R)-2b: Muller, G.; Sainz, D. J. Organomet. Chem. 1995, 495, 103–111.
7. rac-2c: Takeuchi, H.; Kitajima, K.; Yamamoto, Y.; Mizuno, K. J. Chem. Soc., Perkin Trans. 2 1993, 199–203.
8. rac-2d: Iqbal, J.; Pandey, A.; Shukla, A.; Srivastava, R. R.; Tripathi, S. Tetrahedron 1990, 46, 6423–6432.
9. (S)-2d: Crumbie, R. L.; Deol, B. S.; Nemorin, J. E.; Ridley, D. D. Aust. J. Chem. 1978, 31, 1965–1980.
10. (R)-2e and (R)-2f: Node, M.; Nishide, K.; Shigeta, Y.; Obata, K.; Shiraki, H.; Kunishige, H. Tetrahedron 1997, 53,
12883–12894.
11. Yamada, K.; Arai, T.; Sasai, H.; Shibasaki, M. J. Org. Chem. 1998, 63, 3666–3672.
12. Review: Shibasaki, M.; Sasai, H.; Arai, T. Angew. Chem. 1997, 109, 1290–1311; Angew. Chem., Int. Ed. Engl. 1997, 36,
1236–1256.
13. End, N.; Macko, L.; Zehnder, M.; Pfaltz, A. Chem. Eur. J. 1998, 4, 818–824.
14. Brunner, H.; Hammer, B. Angew. Chem. 1984, 96, 305–306; Angew. Chem., Int. Ed. Engl. 1984, 23, 312–313.
15. Sawamura, M.; Hamashima, H.; Ito, Y. Tetrahedron: Asymmetry 1991, 2, 593–596.
16. Desimoni, G.; Dusi, G.; Faita, G.; Quadrelli, P.; Righetti, P. Tetrahedron 1995, 51, 4131–4144.
17. Leonard, J.; Diez-Barra, E.; Merino, S. Eur. J. Org. Chem. 1998, 2051–2061.