Rapid asymmetric access to β-hydroxysulfinic acids and allylsulfonic acids by chemoselective reduction of β-sultones

Article abstract of DOI:10.1055/s-2008-1078417

The reduction of readily available optically active β-sul-tones bearing a β-trichloromethyl substituent proceeds chemoselec-tively at three different sites via C-Cl, C-O or S-O bond cleavage and allows for the formation of highly enantioenriched β-hydroxy-sulfinic acids and allylsulfonic acids.

Full text of DOI:10.1055/s-2008-1078417

LETTER
1505
Rapid Asymmetric Access to b-Hydroxysulfinic Acids and Allylsulfonic Acids
by Chemoselective Reduction of b-Sultones
C
hemoselectiv
l
e
R
edu
o
ctionof
b
-S
r
Laboratory of Organic Chemistry, Department of Chemistry and Applied Biosciences, ETH Zürich, Hönggerberg HCI E 111, Wolfgang-
Pauli-Str. 10, , 8093 Zürich, Switzerland
Fax +41(44)6331226; E-mail: peters@org.chem.ethz.ch
Received 11 March 2008
(DHQ)2PYR (9 mol%),
M(OTf)3 (36 mol%),
PMP, CH2Cl2, –15 °C
Abstract: The reduction of readily available optically active b-sul-
tones bearing a b-trichloromethyl substituent proceeds chemoselec-
tively at three different sites via C–Cl, C–O or S–O bond cleavage
and allows for the formation of highly enantioenriched b-hydroxy-
sulfinic acids and allylsulfonic acids.
O
S
O
O
O
O
O
+
R
S
H
CCl3
Cl
yield = 36–87%
ee = 78 to >99%
dr = 20:1 to >100:1
R
CCl3
1
Key words: reduction, sulfinic acid, sulfonic acid, sultine, sultone
NuM = ROH, R2NH, RMgX, NaOH 54–92%
Functionalized enantiopure molecules are attractive syn-
thetic building blocks for the preparation of chemical li-
braries, if they are readily accessible and if reliable and
generally applicable methods exist for their transforma-
tion into diverse compound classes using defined
chemoselective reaction pathways occurring without ra-
cemization or epimerization.
OH
OH
Bu3SnH,
solvent, T
O
O
O O
S
S
Nu
CH3–nCln
Nu
CCl3
3: n = 1: 83%
4: n = 2: 70%
[Nu = O(CH2)2Ph]
R
R
2
Scheme 1 Catalytic asymmetric synthesis of b-sultones 1 and fur-
ther conversion into b-hydroxysulfonic acids, esters, amides or sulfo-
nes 2
As part of our program directed towards the development
of catalytic asymmetric methodologies providing chiral
sulfur containing building blocks, we have recently re-
ported the first enantioselective synthesis of b-sultones 1,
the sulfonyl analogues of b-lactones.1 A [2+2]-cyclocon-
densation of sulfonyl chlorides and electron-poor alde-
hydes such as chloral provides the strained four-
membered rings in a highly enantio- and syn-selective
process, which is catalyzed by a Lewis base–Lewis acid
combination of the dimeric cinchona alkaloid derivative
(DHQ)2PYR (dihydroquinine-2,5-diphenyl-4,6-pyrimi-
dinediyl diether) and either Bi(OTf)3 or In(OTf)3
(Scheme 1). We demonstrated that enantioenriched b-sul-
tones are attractive building blocks since regioselective
nucleophilic ring opening with hydroxide, alcohol, amine
or Grignard reagents provided almost enantio- and diaste-
reomerically pure b-hydroxysulfonic acids, sulfonates,
sulfonamides or sulfones 2 in a divergent manner. More-
over, a trichloromethyl group at the b-position could be
utilized to introduce additional functionalities. Depending
upon the reaction conditions, either mono or dichloro de-
rivatives 3 and 4, respectively, could be selectively
formed by dechlorination.
ids by S–O bond cleavage or generate allylsulfonic acids
by C–O bond fission, in both cases taking advantage from
the high ring strain of the four-membered heterocycle.
Sulfinic acid derivatives are of fundamental importance in
asymmetric synthesis2 and are very versatile synthetic in-
termediates.3 Chiral sulfinate esters have, for example,
been intensively used as the primary source for chiral sulf-
oxides.4 Moreover, they have elicited interest in medicinal
chemistry.5 Homochiral b-hydroxysulfinic acids were re-
cently reported by AstraZeneca as potent drug candidates
for the treatment of reflux disease.6
We found that exposure of syn-configured a,b-disubstitut-
ed b-sultones 1 to LiAlH4 in Et2O at ambient temperature
provides b-hydroxysulfinic acids 5 within a few minutes
in good yield and without epimerization (Table 1).7
To evade overreduction to the corresponding thiol, a large
excess of the hydride source and extended reaction times
had to be avoided. The free acids were obtained by purifi-
cation with an ion-exchange resin. Although sulfinic acids
have been reported to be unstable even in the absence of
oxygen due to disproportionation, the here reported b-hy-
droxysulfinic acids 5 are remarkably stable and do not
have to be stored as a salt. After several months at –18 °C
under N2 the material was basically unchanged.
In this letter we describe that b-sultones 1 can be
chemoselectively reduced at three different reaction sites.
In addition to partial dechlorination one can either reduce
the cyclic sulfonic esters to provide b-hydroxysulfinic ac-
The reduction conditions were also compatible with a 2-
chloroethyl substituent at the a-position. Sulfinic acid 5d
could either be isolated after acidic workup or cyclized to
SYNLETT 2008, No. 10, pp 1505–1509
Advanced online publication: 16.05.2008
DOI: 10.1055/s-2008-1078417; Art ID: G07608ST
x
x
.x
x
.2
0
0
8
© Georg Thieme Verlag Stuttgart · New York

1506
F. M. Koch, R. Peters
LETTER
Table 1 Chemoselective Reduction of b-Sultones 1 with LiAlH4
LiAlH4, Et2O,
then H+
LiAlH4, Et2O,
then H2O
O
S
O
S
OH
OH
CCl3
O
O
HO2S
O
CCl3
67%
71–90%
R
CCl3
R
for R =
(CH2)2Cl
6
1
5
ee = 87 to > 99%
dr = 20 to > 50 : 1
Entry
5
R
Yield (%)a
drb
1
2
3
4
5
5a
5b
5c
5d
5e
Me
Et
73
90
77
71
86
20:1
>50:1
>50:1
>50:1
>50:1
n-Pr
(CH2)2Cl
Bn
a Isolated yield.
b Determined by 1H NMR.
g-sultine 6 by quenching with water. To our knowledge
this is the first reported example for the formation of a g-
sultine by nucleophilic displacement of a halide with a
sulfinate oxygen.8 g-Sultines were recently reported as a
new class of flavor compounds. 3-Propyl-g-sultine was,
for example, identified in the extracts of the yellow pas-
sion fruit as enantiomerically pure epimeric mixture with
respect to the configuration at S.9 In our case a 2.9:1 dia-
stereomeric mixture was formed, which was separable by
column chromatography. In the major epimer the S=O
bond adopts the axial position as determined by X-ray
crystal structure analysis (Figure 1).10,11 The five-mem-
bered ring adopts a distorted envelope conformation in the
solid state and the hydroxyl units form intermolecular
rather than intramolecular hydrogen bonds with the sulfi-
nyl moieties.12
Figure 1 X-ray crystal structure of the major g-sultine isomer 6
with an axial S=O group
Table 2 Chemoselective Hydrogenation of b-Sultones 17
If the reduction of b-sultones 1 was performed under hy-
drogenation conditions using a catalytic amount of Pd/C
(2 mol%) in EtOH [p(H2) = 1 atm], dichloroallylsulfonic
acids 7 were obtained without significant racemization of
the remaining stereocenter (Table 2). Only few enantiose-
lective methods for the synthesis of a-substituted sulfonic
acids have been reported so far,13 although enantiomeri-
cally pure sulfonic acid derivatives often display interest-
ing biological activities.14 While chloroethyl-substituted
acid 7d was formed in 80% yield (entry 4), all the other
examples proceeded in high yield. Further dechlorination,
hydrogenation or isomerization of the generated C=C
double bond were much slower under the described reac-
tion conditions than the initial reaction.
H2, Pd/C (2 mol%)
EtOH
O
S
O
O
HO3S
Cl
80–99%
R
Cl
R
CCl3
1
7
ee = 87 to >99%
ee = 85 to >99%
Entry
7
R
Yield 1: ee 7: ee
(%)a
(%)b (%)b
1
2
3
4
5
6
7a
7b
7c
7d
7e
7f
Me
97
87
85
Et
97
>99
89
>99
86
n-Pr
95
(CH2)2Cl
80
94
94
Two mechanistic scenarios might account for the product
formation which are depicted in Scheme 2: the reaction
could either proceed by oxidative addition of Pd(0) to the
trichloromethyl group followed by b-elimination (path A)
or alternatively oxidative addition might involve the four-
membered ring system providing an oxypalladacycle in-
termediate (path B). In both cases Pd(II) would be formed
Bn
88
99
99
(CH2)2O-p-MeOC6H4
99
>99
>99
a Isolated yield.
b Determined by chiral column HPLC (Daicel OD-H) after esterifica-
tion with TMS-diazomethane.
Synlett 2008, No. 10, 1505–1509 © Thieme Stuttgart · New York

LETTER
Chemoselective Reduction of b-Sultones
1507
O
S
References and Notes
O
path A
path B
O
(1) (a) Koch, F. M.; Peters, R. Angew. Chem. Int. Ed. 2007, 46,
2685. (b) For b-sultams, see: Zajac, M.; Peters, R. Org. Lett.
2007, 9, 2007.
Pd(0)
Pd(0)
R
CCl3
O
O
O
1
(2) (a) Solladié, G.; Hutt, J.; Girardin, A. Synthesis 1987, 173.
(b) Davis, F. A.; Reddy, R. E.; Szewczyk, J. M.; Reddy, G.
V.; Portonovo, P. S.; Zhang, H.; Fanelli, D.; Reddy, T.;
Zhou, P.; Carroll, P. J. J. Org. Chem. 1997, 62, 2555.
(c) Cogan, D. A.; Liu, G.; Kim, K.; Backes, B. J.; Ellman, J.
A. J. Am. Chem. Soc. 1998, 120, 8011. (d) Zhou, P.; Chen,
B.-C.; Davis, F. A. Tetrahedron 2004, 60, 8003. (e) Evans,
J. W.; Fierman, M. B.; Miller, S. J.; Ellman, J. A. J. Am.
Chem. Soc. 2004, 126, 8134.
O
S
O
O
S
Pd(L)n
H2
H2
Cl
Cl
R
R
Cl
Cl
(L)nPdCl
Cl
Pd(II)
Pd(II)
9
8
HO3S
Cl
R
Cl
(3) (a) The Chemistry of Sulfinic Acids, Esters, and Their
Derivatives; Patai, S., Ed.; Wiley: Chichester, 1990.
(b) Krauthausen, E. Sulfinsäuren und ihre Derivate, In
Houben-Weyl, Methoden der Organischen Chemie, 4th ed.,
Vol. E11; Klamann, D., Ed.; Thieme: Stuttgart, 1985, 614–
664.
(4) Fernández, I.; Khiar, N. Chem. Rev. 2003, 103, 3651.
(5) For example, analysis to steroid receptor binding: Doré, J.-
C.; Gilbert, J.; Ojasoo, T.; Raynaud, J.-P. J. Med. Chem.
1986, 29, 54.
7
Scheme 2 Mechanistic alternatives for the formation of dichloro-
allylsulfonic acids 7
Zn (5 equiv),
AcOH (5 equiv),
THF, 60 °C
Bu3SnH,
toluene,
60 °C, 1 h
O
S
O
S
O
O
O
O
HO3S
Cl
R
R
CCl3
R
CHCl2
(6) Fitzpatrick, K.; Geiss, W.; Lehmann, A.; Sanden, G.;
von Unge, S. WO2002100823, 2002.
1b (R = Et, ee = 93%)
1d (R = (CH2)2Cl,
ee = 95%)
10b (83%)
10d (69%)
11b (91%, ee = 93%
E/Z = 3.2:1)
11d (90%, ee = 95%
(7) General Procedure for b-Hydroxysulfinic Acids 5: To a
stirred solution of the corresponding b-sultone 1 in Et2O (10
mL/mmol) a solution of LiAlH4 (1 M in THF, 0.5 equiv) in
Et2O (2.5 mL/mmol 1) was added dropwise at r.t. After 10
min the reaction mixture was quenched with ice and HCl (1
M, 1 mL/mmol 1). Et2O was removed in a stream of N2 and
the remaining aqueous solution was filtrated over Amberlite
IR-120 (acidic form). The resin was washed with H2O until
the eluate was no longer acidic. Concentration in vacuo
yielded the corresponding sulfinic acids 5. For 1d and 1e the
quenched, acidified reaction mixture was not purified by
ion-exchange resin, but extracted with CHCl3 (4 ×). In the
case of 1d quenching the reaction mixture with H2O
followed by extraction with CHCl3 yielded the
E/Z = 2.5:1)
Scheme 3 Formation of monochloroallylsulfonic acid 11
which is then reduced with H2 to regenerate Pd(0). HCl
generated during this process protonates the correspond-
ing Pd-sulfonate intermediates. At this point we cannot
exclude one of these two mechanisms.
Monochloroallylsulfonic acids 11 were not available by
hydrogenation of the dichloromethyl-substituted b-sul-
tones 10, which were prepared from 1 by selective partial
dechlorination with Bu3SnH (Scheme 3), due to overre-
duction of the generated C=C double bond. However,
treatment of 10 with Zn and HOAc in THF at 60 °C fur-
nished 11 without racemization of the remaining stereo-
center as a mixture of the E- and Z-isomer (2.5–3.2:1).7
corresponding g-sultine 6.
General Procedure for g,g-Dichloroallylsulfonic Acids 7:
The corresponding b-sultone 1 was dissolved in EtOH (1
mL/5 mg 1) and Pd (10% on activated charcoal, 0.02 equiv)
was added. The suspension was stirred for 21 h under a
positive pressure (1 atm) of H2. The reaction mixture was
then filtrated over Celite, repeatedly washed with EtOH and
the filtrate was concentrated in vacuo. H2O (1 mL/5 mg) was
added to the dark oily residue and the solids were removed
by filtration. Concentration of the colorless filtrate yielded
the corresponding sulfonic acids 7.
In conclusion, we have shown that the reduction of opti-
cally active b-sultones bearing a trichloromethyl group at
the b-position can proceed chemoselectively at three dif-
ferent sites and without significant racemization or
epimerization. In addition to the dechlorination with
Bu3SnH, b-hydroxysulfinic acids15 and allylsulfonic
acids16 are now readily available in highly enantioen-
riched form by a direct operationally simple synthetic ap-
proach. These compounds would be difficult to access by
alternative routes.
General Procedure for g-Monochloroallylsulfonic Acids
11: To a stirred solution of the corresponding b-sultone 10 in
THF (1 mL/7 mg) AcOH (5 equiv) was added, followed by
Zn dust (5 equiv). The flask was subsequently closed and
stirring was continued at 60 °C for 12 h. The reaction
mixture was filtrated over Celite and the filter cake was
washed with EtOH. The filtrate was concentrated in vacuo
and the residue was dissolved in H2O. To remove unreacted
sultone the aqueous layer was washed with MTBE (2 × 25
mL). To remove Zn salts the aqueous layer was subsequently
filtrated over Amberlite IR-120 (acidic form) and the resin
was washed with H2O until the eluate was no longer acidic.
Concentration in vacuo yielded the corresponding
monochloroallylsulfonic acids 11.
Acknowledgment
This work was financially supported by the Swiss National Science
Foundation (SNF; PhD fellowship to F.M.K.) and F. Hoffmann-La
Roche. We thank Paul Seiler for determining the X-ray crystal
structure.
Synlett 2008, No. 10, 1505–1509 © Thieme Stuttgart · New York

1508
F. M. Koch, R. Peters
LETTER
(8) Previous methodologies (selected examples):
(a) Rearrangement of thietane dioxides: Dodson, R. M.;
Hammen, P. D.; Davis, R. A. J. Org. Chem. 1971, 36, 2693.
(b) Oxidative cyclization of tert-butyl-3-
+53.18 0.12 (c = 0.6, H2O; sample with ee >99%). 5c: 1H
NMR (300 MHz, D2O): d = 4.72 (m, 1 H, CHOH), 2.94–3.06
(m, 1 H, CHS), 1.94–2.14 (m, 1 H, CHHCHS), 1.41–1.81
(m, 3 H, CHHCHS, CH2CH3), 0.83–1.01 (m, 3 H, Me). 13
NMR (75 MHz, D2O): d = 102.4 (CCl3), 76.1 (CHCCl3),
65.5 (CSO2H), 25.1 (CH2Et), 20.8 (CH2CH2CH3), 13.4
(Me). IR (ATR): 3402, 1352, 1139 cm–1. [a]D24.0 +30.32
C
hydroxyalkylsulfoxides: Sharma, N. K.; de Reinach-
Hirtzbach, F.; Durst, T. Can. J. Chem. 1976, 54, 3012. (c)
insertion of SO2 into cyclopropane: Bondarenko, O. B.;
Voevodskaya, T. I.; Saginova, L. G.; Tafeenko, V. A.;
Shabarov, Y. S. Zh. Org. Khim. 1987, 23, 1736.
(d) Oxidative cyclization of sulfanyl alcohols: King, J. F.;
Rathore, R. Tetrahedron Lett. 1989, 30, 2763. (e) Yolka, S.;
Fellous, R.; Lizzani-Cuvelier, L.; Loiseau, M. Tetrahedron
Lett. 1998, 39, 991. (f) Radical cyclization: Coulomb, J.;
Certal, V.; Fensterbank, L.; Lacôte, E.; Malacria, M. Angew.
Chem. Int. Ed. 2006, 45, 633.
0.93 (c = 0.55, H2O; sample with ee = 85%). 5d: 1H NMR
(300 MHz, CDCl3): d = 5.02 (m, 1 H, CHOH), 2.74–3.82 (m,
2 H, CHHCl, CHS), 2.54–3.61 (m, 1 H, CHHCl), 2.74–2.86
(m, 1 H, CHHCHS), 2.28–2.41 (m, 1 H, CHHCHS). 13
C
NMR (75 MHz, CDCl3): d = 101.5 (CCl3), 77.2 (CHCCl3),
61.7 (CSO2H), 42.2 (CH2Cl), 26.0 (CH2CHS). IR (ATR):
3386, 2923, 1111 cm–1. [a]D22.0 +31.93 0.49 (c = 1.00,
CHCl3; sample with ee = 96%). 5e: 1H NMR (300 MHz,
CDCl3): d = 7.25–7.35 (m, 5 H, CHPh), 5.23 (br, 2 H, OH,
SO2H), 5.15 (m, 1 H, CHOH), 2.60–3.78 (m, 2 H, CHHPh,
CHS), 3.12 (dd, J = 11.5, 15.3 Hz, 1 H, CHHPh). 13C NMR
(75 MHz, CDCl3): d = 129.2 (2 × CPh), 128.8 (2 × CPh), 128.7
(CPh,q), 127.2 (CPh), 101.8 (CCl3), 76.0 (CHCCl3), 65.5
(CSO2H), 29.7 (CH2Ph). IR (ATR): 3383, 1496, 1454, 1106
cm–1. [a]D21.5 +41.51 0.44 (c = 1.15, CHCl3; sample with
ee = 99%). g-Sultine 6: HRMS (EI): m/z [M]+ calcd for
C5H7O3SCl3: 251.9176; found: 251.9175. Anal. Calcd for
C5H7Cl3O3S: C, 23.69; H, 2.78. Found: C, 23.90; H, 2.88.
(2S)-6: Rf 0.39 (EtOAc–cyclohexane, 1:1); mp 123.5–124.4
°C. 1H NMR (300 MHz, CDCl3): d = 4.88 (ddd, J = 4.0, 8.7,
12.8 Hz, 1 H, CHHO), 4.70 (m, 1 H, CHOH), 4.48–4.57 (m,
1 H, CHHO), 3.76 (d, J = 4.4 Hz, 1 H, OH), 3.72 (ddd, J =
4.4, 8.4, 10.6 Hz, 1 H, CHS), 2.76–2.90 (m, 1 H,
(9) (a) Yolka, S.; Dunach, E.; Loiseau, M.; Lizzani-Cuvelier, L.;
Fellous, R.; Rochard, S.; Schippa, C.; George, G. Flavour
Frag. J. 2002, 17, 425. (b) A biosynthesis has been
proposed which proceeds via oxidation of 3-mercaptohexan-
1-ol, which is mainly responsible for the flavor of the yellow
passion fruit and which has also been detected to
considerably contribute to the bouquet of Sauvignon blanc
wines (see ref. 9a).
(10) For a previous X-ray crystal structure analysis of a g-sultine,
see ref. 8c.
(11) Inconsistency exists in literature with regard to the relative
stability of g-sultines possessing either an axial or equatorial
S=O entity. While isomerization of axial S=O into equatorial
S=O on storage at room temperature for several weeks has
been reported (ref. 8b), isomerization to an axial S=O with I2
has been described later: lka, S.; Fellous, R.; Lizzani-
Cuvelier, L.; Loiseau, M. Tetrahedron Lett. 1999, 40, 3159.
(12) Each unit cell contains two independent molecules with the
same configuration, but with slightly different
conformations. The second conformer not depicted in
Figure 1 shows a stronger distortion of the envelope
resembling a half-chair conformation. Supplementary
crystallographic data have been deposited with the
Cambridge Crystallographic Data Centre as deposition
676601. This material is available free of charge via the In-
ternet at http://www.ccdc.cam.ac.uk/products/csd/request/.
(13) See ref 1 and for example: (a) Corey, E. J.; Cimprich, K. A.
Tetrahedron Lett. 1992, 33, 4099. (b) Lawrence, R. M.;
Biller, S. A.; Dickson, J. K.; Logan, J. V. H.; Magnin, D. R.;
Sulsky, R. B.; DiMarco, J. D.; Gougoutas, J. Z.; Beyer, B.
D.; Taylor, S. C.; Lan, S.; Ciosek, C. P. Jr.; Harrity, T. W.;
Jolibois, K. G.; Kunselman, L. K.; Slusarchyk, D. A. J. Am.
Chem. Soc. 1996, 118, 11668. (c) Enders, D.; Vignola, N.;
Berner, O. M.; Bats, J. W. Angew. Chem. Int. Ed. 2002, 41,
109. (d) Harnying, W.; Kitisriworaphan, W.; Pohmakotr,
M.; Enders, D. Synlett 2007, 2529.
CH2CHHCH), 2.39–2.49 (m, 1 H, CH2CHHCH). 13C NMR
(75 MHz, CDCl3): d = 101.4 (CCl3), 78.6 (Cl3CCHO), 76.0
(CH2CH2O), 68.5 (CHS), 24.1 (CH2CH2CH). IR (ATR):
3292, 1082, 1075 cm–1. [a]D23.9 –92.33 0.21 (c = 1.05,
CHCl3; sample with ee = 96%). (2R)-6: Rf: 0.50 (EtOAc–
cyclohexane, 1:1); mp 108.1–110.0 °C. 1H NMR (300 MHz,
CDCl3): d = 4.89 (dt, J = 7.2, 8.4 Hz, 1 H, CHHO), 4.70–4.78
(m, 1 H, CHHO), 4.58 (m, 1 H, CHOH), 3.78–3.85 (m, 1 H,
CHS), 3.38 (br, 1 H, OH), 2.52–2.73 (m, 2 H, CH2CH2CH).
13C NMR (75 MHz, CDCl3): d = 102.0 (CCl3), 78.1
(Cl3CCHO), 77.2 (CHS), 75.7 (CH2CH2O), 24.6
23.6
(CH2CH2CH). IR (ATR): 3289, 1088, 1051 cm–1. [a]D
+4.24 1.1 (c = 0.20, CHCl3; sample with ee = 96%).
(16) Analytical data for sulfonic acids 7 and 11: 7a: 1H NMR
(300 MHz, D2O): d = 5.83 (d, J = 10.1 Hz, 1 H, CH=CCl2),
3.78–3.88 (m, 1 H, CHS), 1.26 (d, J = 6.9 Hz, 3 H, Me). 13
C
NMR (75 MHz, D2O): d = 126.0 (C=C), 123.8 (C=C), 56.6
(CSO3H), 14.8 (Me). IR (ATR): 2941, 1621, 1141, 1007
cm–1. HRMS (ESI): m/z [M – H]– calcd for C4H6O3SCl2:
202.9332; found: 202.9343. [a]D22.9 –75.46 0.42 (c = 1.30,
H2O; sample with ee = 85%). 7b: 1H NMR (300 MHz, D2O):
d = 5.77 (d, J = 10.4 Hz, 1 H, CH=CCl2), 3.57–3.67 (m, 1 H,
CHS), 1.79–1.95 (m, 1 H, CHHCHS), 1.41–1.57 (m, 1 H,
CHHCHS), 0.79 (t, J = 7.3 Hz, 3 H, Me). 13C NMR (75
MHz, D2O): d = 125.1 (C=C), 124.9 (C=C), 63.1 (CSO3H),
23.1 (CH2CHS), 10.2 (Me). IR (ATR): 3412, 1663, 1621,
1178, 1039 cm–1. HRMS (ESI): m/z [M – H]– calcd for
C5H8O3SCl2: 216.9498; found: 216.9495. [a]D28.0 –87.32
0.10 (c = 0.95, H2O; sample with ee >99%). 7c: 1H NMR
(300 MHz, D2O): d = 5.77 (d, J = 10.4 Hz, 1 H, CH=CCl2),
3.66–3.77 (m, 1 H, CHS), 1.70–1.85 (m, 1 H, CHHCHS),
1.42–1.59 (m, 1 H, CHHCHS), 1.07–1.36 (m, 2 H,
(14) The Chemistry of Sulfonic Acids, Esters and Their
Derivatives; Patai, S.; Rappoport, Z., Eds.; Wiley:
Chichester, New York, 1991.
(15) Analytical data for sulfinic acids 5: 5a: 1H NMR (300 MHz,
D2O): d = 4.66 (d, J = 1.6 Hz, 1 H, CHOH), 3.19 (dq, J = 1.6,
7.2 Hz, 1 H, CHS), 1.36 (dd, J = 7.2 Hz, 3 H, Me). 13C NMR
(75 MHz, D2O): d = 101.8 (CCl3), 76.9 (CHCCl3), 61.6
(CSO2H), 6.3 (Me). IR (ATR): 2970, 2497, 1454, 1365,
1216 cm–1. [a]D23.6 +37.68 0.12 (c = 1.25, H2O; sample
with ee = 87%). 5b: 1H NMR (300 MHz, D2O): d = 4.57 (d,
J = 1.3 Hz, 1 H, CHOH), 2.91 (ddd, J = 1.3, 4.4, 9.3 Hz, 1 H,
CHS), 2.00 (tdd, J = 3.4, 7.8, 15.6 Hz, 1 H, CHHCHS), 1.60
(tdd, J = 7.5, 9.3, 15.6 Hz, 1 H, CHHCHS), 0.96 (dd, J = 7.5,
7.8 Hz, 3 H, Me). 13C NMR (75 MHz, D2O): d = 102.2
(CCl3), 75.8 (CHCCl3), 67.1 (CSO2H), 16.6 (CH2CH3), 11.9
CH2CH3), 0.75 (t, J = 7.3 Hz, 3 H, Me). 13C NMR (75 MHz,
D2O): d = 125.4 (C=C), 124.7 (C=C), 61.3 (CSO3H), 31.5
(CH2CHS), 19.1 (CH2CH3), 12.8 (Me). IR (ATR): 2958,
1622, 1198, 1080 cm–1. HRMS (ESI): m/z [M – H]– calcd for
C6H10O3SCl2: 230.9655; found: 230.9654. [a]D26.4 –79.53
27.9
(Me). IR (ATR): 3356, 2970, 1365, 1228 cm–1. [a]D
Synlett 2008, No. 10, 1505–1509 © Thieme Stuttgart · New York

LETTER
0.14 (c = 1.20, H2O; sample with ee = 86%). 7d: 1H NMR
Chemoselective Reduction of b-Sultones
1509
H, CH2CHS), 1.81–1.97 (m, 1 H, CH2CHS). 13C NMR (75
MHz, D2O): d = 153.2 (CPh), 151.9 (CPh), 125.2 (C=C), 124.4
(C=C), 116.4 (2 × CHPh), 114.8 (2 × CHPh), 65.9 (CH2O),
58.9 (CSO3H), 55.7 (OMe), 29.5 (CH2CHS). IR (ATR):
3422, 1621, 1509, 1216, 1167, 1032 cm–1. HRMS (ESI):
m/z [M – H]– calcd for C12H14O5SCl2: 338.9866; found:
338.9866. [a]D20.3 –80.63 0.26 (c = 0.55, MeOH; sample
with ee >99%). 11b: 1H NMR (300 MHz, D2O; E-isomer):
d = 6.34 (d, J = 13.4 Hz, 1 H, CH=CHCl), 5.81 (dd, J = 10.3,
13.4 Hz, 1 H, CH=CHCl), 3.38 (dt, J = 3.7, 10.3 Hz, 1 H,
CHS), 1.88–2.04 (m, 1 H, CHHCHS), 1.50–1.66 (m, 1 H,
CHHCHS), 0.86 (t, J = 7.5 Hz, 3 H, Me). 1H NMR (300
MHz, D2O; Z-isomer): d = 6.45 (d, J = 7.2 Hz, 1 H,
(300 MHz, D2O): d = 5.83 (d, J = 10.4 Hz, 1 H, CH=CCl2),
3.99 (td, J = 3.7, 10.4 Hz, 1 H, CHS), 3.64 (td, J = 5.4, 10.9
Hz, 1 H, CHHCl), 3.37–3.38 (m, 1 H, CHHCl), 2.23–2.36
(m, 1 H, CHHCHS), 1.96–2.28 (m, 1 H, CHHCHS). 13
C
NMR (75 MHz, D2O): d = 126.0 (C=C), 124.0 (C=C), 59.0
(CSO3H), 41.7 (CH2Cl), 32.5 (CH2CHS). IR (ATR): 2539,
1621, 1193, 1060 cm–1. HRMS (ESI): m/z [M – H]– calcd for
C5H7O3SCl3: 250.9109; found: 250.9109. [a]D28.5 –134.18
0.07 (c = 1.37, MeOH; sample with ee = 94%). 7e: 1H NMR
(300 MHz, D2O): d = 7.20–7.35 (m, 5 H, CHPh), 5.94 (d, J =
10.3 Hz, 1 H, CH=CCl2), 4.09 (m, 1 H, CHS), 3.37 (dd, J =
3.1, 13.7 Hz, 1 H, CHHPh), 2.82 (m, 1 H, CHHPh). 13
C
NMR (75 MHz, D2O): d = 139.7 (CPh,q), 131.7 (2 × CPh),
131.1 (2 × CPh), 129.3, 127.9, 127.2 (C=C), 65.5 (CSO3H),
38.5 (CH2Ph). IR (ATR): 3029, 1621, 1216, 1154, 1038
cm–1. HRMS (ESI): m/z [M – H]– calcd for C10H10O3SCl2:
278.9655; found: 278.9654. [a]D23.8 –75.97 0.13 (c = 0.95,
MeOH; sample with ee = 99%). 7f: 1H NMR (300 MHz,
D2O): d = 6.75–6.85 (m, 4 H, CHPh), 5.84 (d, J = 10.6 Hz, 1
H, CH=CCl2), 3.90–4.05 (m, 2 H, CHS, CH2OAr), 3.75–
3.87 (m, 1 H, CH2Cring), 3.63 (s, 3 H, OMe), 2.23–2.39 (m, 1
CH=CHCl), 5.74 (dd, J = 7.2, 10.3 Hz, 1 H, CH=CHCl),
3.95 (dt, J = 3.2, 10.3 Hz, 1 H, CHS), 1.88–2.04 (m, 1 H,
CHHCHS), 1.50–1.66 (m, 1 H, CHHCHS), 0.87 (t, J = 7.5
Hz, 3 H, Me). 13C NMR (75 MHz, D2O; E-isomer): d = 127.9
(C=C), 123.0 (C=C), 64.1 (CSO3H), 22.7 (CH2CHS), 10.6
(Me). 13C NMR (75 MHz, D2O; Z-isomer): d = 126.3 (C=C),
123.6 (C=C), 60.5 (CSO3H), 23.2 (CH2CHS), 10.4 (Me). IR
(ATR): 2973, 1694, 1115 cm–1. HRMS (ESI): m/z [M – H]–
calcd for C5H9O3SCl: 182.9888; found: 182.9889.
Synlett 2008, No. 10, 1505–1509 © Thieme Stuttgart · New York

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