Diastereoselective Radical Hydrogenation of α-(1-Hydroxyalkyl)vinyl Sulfoxides and Sulfones Controlled by Intramolecular Hydrogen Bonding

Article abstract of DOI:10.1021/jo005525o

The reaction of (S)-α-(1-hydroxyalkyl)vinyl sulfoxides (S)-5 with alkyl radicals and tributyltin hydride gave the addition-hydrogenation products with high diastereoselectivity, whereas the reaction with (R)-α-(1-hydroxyalkyl)vinyl sulfoxides (R)-5 resulted in complete recovery of the starting sulfoxides. Stereoselective intramolecular hydrogen bonding between the hydroxy group and the diastereotopic sulfonyl oxygen led to high diastereoselectivity in the radical reaction of α-(1-hydroxyethyl)vinyl sulfone 12. An important role of intramolecular hydrogen bonding on the diastereoselectivity as well as the reactivity toward alkyl radicals is discussed.

Full text of DOI:10.1021/jo005525o

J . Org. Chem. 2000, 65, 7083-7090
7083
Dia ster eoselective Ra d ica l Hyd r ogen a tion of
r-(1-Hyd r oxya lk yl)vin yl Su lfoxid es a n d Su lfon es Con tr olled by
In tr a m olecu la r Hyd r ogen Bon d in g
Nobuyuki Mase,†,‡ Yoshihiko Watanabe,† Takeshi Toru,*,† Terumitsu Kakumoto,§ and
Tsuneo Hagiwara|
Department of Applied Chemistry, Nagoya Institute of Technology, Gokiso, Showa-ku, Nagoya 466-8555,
J apan, Osaka Gas Co., Ltd., 17 Chuodori-minami-machi, Shimogyou-ku, Kyoto 600-8813, J apan, and
Teijinseiki Co., Ltd., 3-2-1 Sakato, Takatsu-ku, Kaswasaki 213-0012, J apan
toru@ach.nitech.ac.jp
Received May 25, 2000
The reaction of (S)-R-(1-hydroxyalkyl)vinyl sulfoxides (S)-5 with alkyl radicals and tributyltin
hydride gave the addition-hydrogenation products with high diastereoselectivity, whereas the
reaction with (R)-R-(1-hydroxyalkyl)vinyl sulfoxides (R)-5 resulted in complete recovery of the
starting sulfoxides. Stereoselective intramolecular hydrogen bonding between the hydroxy group
and the diastereotopic sulfonyl oxygen led to high diastereoselectivity in the radical reaction of
R-(1-hydroxyethyl)vinyl sulfone 12. An important role of intramolecular hydrogen bonding on the
diastereoselectivity as well as the reactivity toward alkyl radicals is discussed.
In tr od u ction
between the hydroxy group and the sulfinyl oxygen in
reactivity as well as in diastereoselectivity (eq 1).6
There are a number of reports of stereochemical studies
on the radical-mediated allylation, hydrogenation, cy-
clization, and addition reactions.1 Intramolecular hydro-
gen bonding is known to effectively stabilize the preferred
conformation of the intermediate radical in the reaction
of â-hydroxy-radicals R to the carbonyl group, and to
induce high stereoselectivity.1,2 The 1,2- and 1,3-asym-
metric inductions3,4,5 effected by the sulfinyl group, where
intramolecular hydrogen bonding does not effectively
work to stabilize the conformation of â-hydroxy-R-sulfinyl
radicals.3d On the other hand, we recently communicated
an excellent stereocontrol achieved in the radical reaction
of R-(1-hydroxyalkyl)vinyl sulfoxides, in which we showed
the significant role of intramolecular hydrogen bonding
The sulfonyl group is a synthetically useful functional
group.7 We preliminarily reported a new version of the
function of the sulfonyl group as a stereo-inducer.8,9
Stereoselective hydrogen bonding to one of the diaste-
reotopic sulfonyl oxygens would newly form a chiral
* To whom correspondence should be addressed. Phone: +81-52-
735-5217. Fax: +81-52-735-5217.
† Nagoya Institute of Technology.
‡ Present address: Department of Molecular Science, Faculty of
Engineering, Shizuoka University, 3-5-1 J ohoku, Hamamatsu 432-
8561, J apan.
(4) For 1,3-asymmetric induction using the sulfinyl group, see: (a)
Toru, T.; Watanabe, Y.; Tsusaka, M.; Ueno, Y. J . Am. Chem. Soc. 1993,
115, 10464. (b) Mase, N.; Watanabe, Y.; Ueno, Y.; Toru, T. J . Org.
Chem. 1997, 62, 7794. (c) Mase, N.; Watanabe, Y.; Toru, T. J . Org.
Chem. 1998, 63, 3899. (d) Mase, N.; Watanabe, Y.; Toru, T. Bull. Chem.
Soc. J pn. 1998, 71, 2957. (e) Toru, T.; Watanabe, Y.; Mase, N.; Tsusaka,
M.; Hayakawa, T.; Ueno, Y. Pure Appl. Chem. 1996, 68, 711. (f) Mase,
N.; Watanabe, Y.; Ueno, Y.; Toru, T. J . Chem. Soc., Perkin Trans 1
1998, 10, 1613.
§ Osaka Gas Co., Ltd.
| Teijinseiki Co., Ltd.
(1) (a) Curran, D. P.; Porter, N. A.; Giese, B. Stereochemistry of
radical reactions; VCH: Weinheim, 1995. (b) Giese, B. Radicals in
Organic Synthesis: Formation of Carbon-Carbon Bonds; Pergamon
Press: Oxford, 1986.
(2) Smadja, W. Synlett 1994, 1.
(5) For cyclization using the sulfinyl group, see: (a) Imboden, C.;
Bourquard, T.; Corminboeuf, O.; Renaud, P.; Schenk, K.; Zahouily, M.
Tetrahedron Lett. 1999, 40, 495. (b) Ke, B.-W.; Lin, C.-H.; Tsai, Y.-M.
Tetrahedron 1997, 53, 7805. (c) Zahouily, M.; J ournet, M.; Malacria,
M. Synlett 1994, 366. (d) Zhang, Q.; Mohan, R. M.; Cook, L.; Kazanis,
S.; Peisach, D.; Foxman, B. M.; Snider, B. B. J . Org. Chem. 1993, 58,
7640. (e) Snider, B. B.; Wan, B. Y.-F.; Buckman, B. O.; Foxman, B. M.
J . Org. Chem. 1991, 56, 328. (f) Tsai, Y.-M.; Ke, B.-W.; Lin, C.-H.
Tetrahedron Lett. 1990, 31, 6047. (g) Renaud, P. Tetrahedron Lett.
1990, 31, 4601. Others: (h) Delouvrie, B.; Lacoˆte, E.; Fensterbank,
L.; Malacria, M. Tetrahedron Lett. 1999, 40, 3565. (i) Lacoˆte, E.;
Delouvrie, B.; Fensterbank, L.; Malacria, M. Angew. Chem., Int. Ed.
Engl. 1998, 37, 2116. (j) Crandall, J . K.; Ayers, T. A. Tetrahedron Lett.
1991, 32, 3659.
(3) For 1,2-asymmetric induction using the sulfinyl group, see: (a)
Renaud, P.; Bourquard, T.; Carrupt, P.-A.; Gerster, M. Helv. Chim.
Acta 1998, 81, 1048. (b) Angelaud, R.; Landais, Y. Tetrahedron Lett.
1997, 38, 233. (c) Zahouily, M.; Caron, G.; Carrupt, P.-A.; Knouzi, N.;
Renaud, P. Tetrahedron Lett. 1996, 37, 8387. (d) Renaud, P.; Bourquard,
T. Synlett 1995, 1021. (e) Curran, D. P.; Kuo, L. H. J . Org. Chem. 1994,
59, 3259. (f) Renaud, P.; Moufid, N.; Kuo, L. H.; Curran, D. P. J . Org.
Chem. 1994, 59, 3547. (g) Renaud, P.; Bourquard, T. Tetrahedron Lett.
1994, 35, 1707. (h) Renaud, P.; Bourquard, T.; Gerster, M.; Moufid,
N. Angew. Chem., Int. Ed. Engl. 1994, 33, 1601. (i) Renaud, P.; Carrupt,
P.-A.; Gerster, M.; Schenk, K. Tetrahedron Lett. 1994, 35, 1703. (j)
Mesmaeker, A. D.; Waldner, A.; Hoffmann, P.; Mindt, T. Synlett 1993,
871. (k) Renaud, P.; Ribezzo, M. J . Am. Chem. Soc. 1991, 113, 7803.
(l) Renaud, P. Helv. Chim. Acta 1991, 74, 1305. (m) Waldner, A.;
Mesmaeker, A. D.; Hoffmann, P.; Mindt, T.; Winkler, T. Synlett 1991,
101. (n) Beckwith, A. L. J .; Hersperger, R.; White, J . M. J . Chem. Soc.,
Chem. Commun. 1991, 1151.
(6) Mase, N.; Wake, S.; Watanabe, Y.; Toru, T. Tetrahedron Lett.
1998, 39, 5553.
(7) Simpkins, N. S. Sulphones in Organic Synthesis; Pergamon
Press: Oxford, 1993.
10.1021/jo005525o CCC: $19.00 © 2000 American Chemical Society
Published on Web 09/16/2000

7084 J . Org. Chem., Vol. 65, No. 21, 2000
Sch em e 1. P r ep a r a tion of th e r-(1-Hyd r oxya lk yl)vin yl Su lfoxid esa
Mase et al.
a
Key: (a) EtMgI, Et2O/THF, 0 °C; (b) LDA, R1CHO, THF, -78 °C; (c) MeLi, (PhSe)2, THF, 0 °C; (d) (i) m-CPBA, CH2Cl2, 0 °C; (ii) flash
column chromatography; (e) (i) Ph3P, PhCOOH, diethyl azodicarboxylate, THF, rt; (ii) MeONa, MeOH, rt; (f) Ph3SiCl, pyridine, rt.
sulfur center which affects the diastereoselectivity in the
reaction of â-hydroxy-radicals R to the sulfonyl group (eq
2). We now report in detail a stereoselective radical
hydrogenation of â-hydroxy-radicals R to the sulfinyl and
sulfonyl groups.
F igu r e 1. View (ORTEP) of the (SS,2R)-3-(p-tolylsulfinyl)-3-
buten-2-ol ((R)-5b).
oxidation15 gave a diastereomeric mixture of the R-(1-
hydroxyalkyl)vinyl sulfoxides (R)-5 and (S)-5, which were
separable by flash column chromatography.10b A single
Resu lts a n d Discu ssion
crystal of the less polar diastereomer-5b ((R)-5b) was
subjected to X-ray crystallographic analysis (Figure 1).
Rea ction of r-(1-Hyd r oxya lk yl)vin yl Su lfoxid es.
The absolute configuration of the less polar diastereomer
(R)-5b was determined to be (SS,2R), and the hydroxy
group was found to form hydrogen bonding intermolecu-
larly with a sulfinyl oxygen of the neighboring molecule.
The Mitsunobu reaction of (R)-5 gave (S)-5. The absolute
Optically pure (SS)-1-phenyl-2-(p-tolylsulfinyl)-2-propen-
1-ol (5a ) and (SS)-3-(p-tolylsulfinyl)-3-buten-2-ol (5b) were
prepared in four steps as shown in Scheme 1.10,11 Opti-
cally pure (R)-ethyl p-tolyl sulfoxide12 (2), prepared from
(SS)-l-menthyl p-toluenesulfinate13 (1), was treated with
1.2 equiv of LDA at -78 °C and subsequently with
aldehyde to afford the â-hydroxy sulfoxide 3. The â-hy-
droxy sulfoxide 3 was treated with 3 equiv of methyl-
lithium at 0 °C, and the resulting anion was reacted with
diphenyl diselenide to give the selenide 4.14 Selective
1
configuration of 5a was deduced from H NMR analyses
as mentioned below. The hydroxy group, when required,
was silylated with triphenylsilyl chloride in pyridine.16
Radical addition-hydrogenation reactions were carried
out as follows. A solution of the R-(1-hydroxyalkyl)vinyl
sulfoxide 5 in CH2Cl2 (0.01 mol/L) was reacted with an
alkyl iodide (3 equiv), tributyltin hydride (3 equiv), and
triethylborane (3 equiv) as a radical initiator17 at -78
°C. For the reaction in the presence of a Lewis acid, a
mixture of 5 and a Lewis acid (1.1 equiv) was stirred for
30 min before addition of other reagents. The results are
shown in Table 1. The reaction of (SS,1S)-1-phenyl-2-(p-
tolylsulfinyl)-2-propen-1-ol ((S)-5a ) with tert-butyl radical
gave the addition-hydrogenation product 7a in 98% yield
but with low diastereoselectivity (entry 1). On the other
hand, the reaction of (SS,1R)-1-phenyl-2-(p-tolylsulfinyl)-
2-propen-1-ol ((R)-5a ) resulted in recovery of the starting
(R)-5a after 24 h, and no formation of the addition-
hydrogenation product was observed (entry 2). Diaste-
reoselectivity dramatically changed in the reaction of (S)-
(8) Recently, suggestive results of the utilization of the sulfonyl
group as a stereo-inducer were reported. For diastereoselective reac-
tions: (a) Marcantoni, E.; Cingolani, S.; Bartoli, G.; Bosco, M.; Sambri,
L. J . Org. Chem. 1998, 63, 3624. (b) Marino, J . P.; Viso, A.; Lee, J .-D.
J . Org. Chem. 1997, 62, 645. For enantioselective reactions: (c) Wada,
E.; Pei, W.; Kanemasa, S. Chem Lett. 1994, 2345. (d) Wada, E.;
Yasuoka, H.; Kanemasa, S. Chem Lett. 1994, 1637. (e) Wada, E.;
Yasuoka, H.; Kanemasa, S. Chem Lett. 1994, 145.
(9) Mase, N.; Watanabe, Y.; Toru, T. Tetrahedron Lett. 1999, 40,
2797-2800.
(10) The R-(1-hydroxyalkyl)vinyl sulfoxides 5 could not be obtained
in good total yield from (SS)-l-menthyl p-toluenesulfinate (1) by the
procedure reported in the literature: (a) Hiroi, K.; Arinaga, Y. Chem.
Pharm. Bull. 1994, 42, 985. (b) Bonfand, E.; Gosselin, P.; Maignan, C.
Tetrahedron: Asymmetry 1993, 4, 1667. (c) Alexandre, C.; Belkadi, O.;
Maignan, C. Synthesis 1992, 547. (d) Cheng, H.-C.; Yan, T.-H.
Tetrahedron Lett. 1990, 31, 673. (e) Maignan, C.; Guessous, A.;
Rouessac, F. Tetrahedron Lett. 1986, 27, 2603.
(11) Optically pure 5 was obtained according to a similar procedure
to the preparation for 3-(p-tolylsulfinyl)acrylate without racemiza-
tion: Arai, Y.; Kuwayama, S.; Takeuchi, Y.; Koizumi, T. Tetrahedron
Lett. 1985, 26, 6205.
(15) Reich, H. J .; Renga, J . M.; Reich, I. L. J . Am. Chem. Soc. 1975,
97, 5434.
(12) Mislow, K.; Green, M. M.; Laur, P.; Melillo, J . T.; Simmons, T.;
Ternay, J . A. L. J . Am. Chem. Soc. 1965, 87, 1958.
(13) Solladie, G.; Hutt, J .; Girardin, A. Synthesis 1987, 173.
(14) Sato, T.; Itoh, T.; Fujisawa, T. Tetrahedron Lett. 1987, 28, 5677.
(16) Barker, S. A.; Brimacombe, J . S.; Harnden, M. R.; J arvis, J . A.
J . Chem. Soc. 1963, 3403.
(17) Nozaki, K.; Oshima, K.; Utimoto, K. Bull. Chem. Soc. J pn. 1991,
64, 403.

Hydrogenation of Vinyl Sulfoxides and Sulfones
J . Org. Chem., Vol. 65, No. 21, 2000 7085
Ta ble 1. Ra d ica l Hyd r ogen a tion of r-Su lfin yl Ra d ica l
Gen er a ted fr om Ad d ition of Alk yl Ra d ica ls to
r-(1-Hyd r oxya lk yl)vin yl Su lfoxid ea
Ta ble 2. Ch em ica l Sh ifts of th e Hyd r oxy P r oton a n d
Cou p lin g Con sta n ts J AB of th e r-(1-Hyd r oxya lk yl)vin yl
Su lfoxid es 5 a n d Su lfon es 12 a n d th e
â-Hyd r oxy-r-(p h en ylselen en yl) Su lfon es 22 in CDCl3
chemical shift (δ)
a
compd
0.1 M
0.05 M
0.01 M
J AB (Hz)
(S)-5a
(R)-5a
(S)-5b
(R)-5b
12a
12b
anti-22
syn-22
3.83
3.01
3.33
2.35
3.13
2.66
3.50
4.19
3.80
2.73
3.24
2.08
3.02
2.61
3.49
4.19
3.77
2.42
3.20
1.83
3.00
2.58
3.49
4.19
2.4
b
2.5
5.6
3.2
3.3
5.2
1.8
sub-
Lewis time
yield
(%)
entry strate
R
acidb
(h)
product
7a
syn/anti
60:40
a
b
Measured in 0.01 mol/L solution. The hydroxy proton in (R)-
5a is overlapped with methyl protons of the p-tolyl group.
1
2
(S)-5a t-Bu none
(R)-5a t-Bu none
3
98
24 no
reaction
3
(S)-5b t-Bu none
3
7b
89
81
>98:<2
>98:<2
results, reactivity toward tert-butyl radical is quite
different between (S)-5b and (R)-5b. This difference in
reactivity was further confirmed by the following results.
The reaction of a 51/49 diastereomeric mixture of (S)-5b
and (R)-5b afforded syn-7b derived only from (S)-5b in
48% yield (94% yield based on (S)-5b), and recovered the
starting 5b composed of only (R)-5b in 43% yield (88%
yield based on (R)-5b) (entry 16). Therefore, these dia-
stereomers 5b, which were rather difficult to separate
by chromatography, could be kinetically separated in the
radical reaction. Furthermore, the recovered (R)-5b could
be easily converted to (S)-5b by the Mitsunobu reaction
in 86% yield (Scheme 1). Since (S)-5b thus obtained can
be converted to syn-7b as mentioned above, the present
diastereomer-differentiating radical reaction efficiently
gives enantiomerically pure syn-7b. Neither (S)-6b nor
(R)-6b, the hydroxy group of which was protected with a
triphenylsilyl group, afforded the addition-hydrogenation
product (entries 17 and 18).
4c,d (S)-5b t-Bu none
24 7b
24 7b
12 8b
12 9b
5e,d (S)-5b t-Bu none
trace
6
7
8
9
(S)-5b c-Hex none
66f
93:7
93:7
79:21
(S)-5b i-Pr
(S)-5b Et
none
none
72f
12 10b
7b
24 7b
38f
(S)-5b t-Bu EtAlCl2
3
75
>98:<2
10d (S)-5b t-Bu EtAlCl2
19f >98:<2
g
11
12
(S)-5b t-Bu Et2AlCl
(S)-5b t-Bu Et3Al
6
6
7b
7b
68
70
>98:<2
>98:<2
13d (R)-5b t-Bu none
14d (R)-5b t-Bu EtAlCl2
15d (R)-5b t-Bu EtAlCl2
72 no
24 no
24 no
reaction
reaction
reaction
g
16
5bh
t-Bu none
3
7b
48
(94)i,j
>98:<2
17d (S)-6b t-Bu none
18d (R)-6b t-Bu none
24 no
24 no
reaction
reaction
a
The reaction was carried out using Bu3SnH (3.0 equiv), RI
(3.0 equiv), and Et3B (3.0 equiv) in a 0.01 mol/L CH2Cl2 solution
b
at -78 °C unless otherwise noted. 1.1 equiv of Lewis acid was
used unless otherwise noted. c The reaction was carried out in
The above results show that the reactivity of the R-(1-
hydroxyalkyl)vinyl sulfoxides 5 toward radicals largely
depends on intramolecular hydrogen bonding which
significantly enhances the reactivity of 5. In addition,
hydrogen bonding also plays an important role for
increasing diastereoselectivity. Compounds (S)-5a and
(S)-5b showed intramolecular hydrogen bonding in their
1H NMR spectra, in which only a small upfield shift for
the hydroxy proton was observed upon dilution (Table
2). Furthermore, the values of J AB (2.4 Hz for (S)-5a , 2.5
Hz for (S)-5b) were in good accord with intramolecular
hydrogen bonding.18 The infrared spectra also showed a
band (3500-3200 cm-1) for hydrogen bonding in a dilute
toluene. The reaction was carried out at -78 °C f rt. e The
d
reaction was carried out in THF. f (S)-5b was recovered in 24%
g
(entry 6), 22% (entry 7), 55% (entry 8), and 76% (entry 10). 2.0
equiv of EtAlCl2 was used. A diastereomeric mixture of 5b in a
ratio of (S)-5b: (R)-5b ) 51:49 was used. Yield in parentheses is
the one based on the (S)-5b isomer. The starting material (R)-
5b was recovered in 43% yield (88% yield based on the (R)-5b
isomer).
h
i
j
5b,in which thereaction in a solvent such as dichloromethane
or toluene gave the addition-hydrogenation product 7b
in a syn/anti ratio of >98:<2 (entries 3 and 4). The
reaction in THF resulted in recovery of the starting (S)-
5b together with the formation of a trace amount of 7b
(entry 5). Cyclohexyl, isopropyl, and ethyl radicals could
also add to (S)-5b to give a mixture of syn and anti
isomers in moderate yields (entries 6-8). The addition-
hydrogenation product syn-7b was also obtained in good
yield and with high diastereoselectivity when the reaction
was carried out in the presence of 1.1 equiv of a Lewis
acid such as EtAlCl2, Et2AlCl, or Et3Al (entries 9, 11, and
12), but only in 19% yield with 2 equiv of EtAlCl2 (entry
10). In contrast to the results of (S)-5b, no addition
products were obtained even after 72 h in the reaction
of (R)-5b, where the starting (R)-5b was quantitatively
recovered (entry 13). The addition of EtAlCl2 did not
improve the reactivity of (R)-5b for the addition of tert-
butyl radical (entries 14 and 15). Obviously from these
1
solution. On the other hand, the H NMR study of (R)-
5a and (R)-5b supported no intramolecular hydrogen
bonding in solution; upfield shift for the hydroxy proton
is observed upon dilution. The value of J AB (5.6 Hz for
(R)-5b) was bigger than that for (S)-5b and were in good
accord with the anticipated value given by the Karplus
equation. In addition, analysis of the infrared spectra
showed the existence of a free hydroxy group (3605 cm-1).
Nucleophilic radicals such as tert-butyl radical more
easily add to an olefin with lower LUMO energy.1b Table
3 shows LUMO energy and heat of formation of the R-(1-
hydroxyalkyl)vinyl sulfoxides 5 calculated by MOPAC 93/
(18) Kingsbury, C. A.; Auerbach, R. A. J . Org. Chem. 1971, 36, 1737.

7086 J . Org. Chem., Vol. 65, No. 21, 2000
Mase et al.
Ta ble 4. Ca lcu la tion of th e Dista n ce betw een th e
Hyd r oxy P r oton a n d th e Su lfin yl Oxygen , th e Rela tive
Hea t of F or m a tion , a n d Tota l En er gy for th e Ra d ica l
In ter m ed ia tes 5R Der ived fr om 5
Ta ble 3. Ca lcu la tion of th e Dista n ce betw een th e
Hyd r oxy P r oton a n d th e Su lfin yl Oxygen , th e Rela tive
LUMO En er gy, Hea t of F or m a tion , a n d Tota l En er gy for
th e r-(1-Hyd r oxya lk yl)vin yl Su lfoxid es 5
OH‚‚‚OdS (Å)
∆LUMOa (eV)
∆Eb (kcal/mol)
HF/
HF/
3-21G
HF/
conformer PM3 3-21G
PM3
PM3c 3-21Gd
(S)-5a -A
(S)-5a -B
(S)-5a -C
(R)-5a -A
(R)-5a -D
(R)-5a -E
(S)-5b-A
(S)-5b-B
(S)-5b-C
(R)-5b-A
(R)-5b-D
(R)-5b-E
5.23
1.81
1.81
4.86
1.81
1.80
4.89
1.82
1.82
4.94
1.82
1.80
e
e
e
e
e
e
0.000
-0.264
-0.233
0.000
-0.216
-0.243
0.000
e
e
e
e
e
e
0.000
+0.562
-1.272
0.000
+0.039
+1.656
0.000
e
e
e
e
e
e
4.83
1.77
1.80
4.57
1.72
1.75
0.000
0.000
-0.205 -0.400 -1.106 -3.889
OH‚‚‚OdS (Å)
∆Ea (kcal/mol)
PM3b HF/3-21Gc
-0.173 -0.210 -3.095 -4.065
conformer
PM3
HF/3-21G
0.000
0.000
0.000
0.000
-0.174 -0.359 +0.280 -0.073
-0.138 -0.271 +2.217 +0.011
(S)-5a -AR
5.17
1.81
1.81
1.81
1.82
5.20
1.82
1.81
1.80
1.83
d
d
d
d
0.000
+0.248
-0.502
-5.000
-2.571
0.000
-0.268
-1.268
-1.897
-3.721
d
d
d
d
(S)-5a -BR1
(S)-5a -BR2
(S)-5a -CR1
(S)-5a -CR2
(S)-5b-AR
(S)-5b-BR1
(S)-5b-BR2
(S)-5b-CR1
(S)-5b-CR2
a
∆LUMO ) LUMO (5-B, 5-C, 5-D, or 5-E) - LUMO (5-A). b ∆E
) E(5-B, 5-C, 5-D, or 5-E) - E(5-A). c Difference in heat of
d
d
formation. Difference in total energy. e Not optimized.
d
5.45
1.84
1.81
1.84
1.75
0.000
-5.068
-9.136
-5.625
-9.912
PM319 and GAUSSIAN 94/HF/3-21G.20 The distance
between the hydroxy proton and the sulfinyl oxygen is
approximately 1.8 Å in the optimized structures (S)-5a -
B,C and (S)-5b-B,C, showing the existence of intramo-
lecular hydrogen bonding in these optimized conformers.
LUMO energies of conformers (S)-5a -B,C and (S)-5b-B,C
with intramolecular hydrogen bonding are lower than
those of the corresponding conformers (S)-5-A without
intramolecular hydrogen bonding in the 5a and 5b series.
Therefore, (S)-5a and (S)-5b which form a large extent
of intramolecular hydrogen bonding, can easily react with
an alkyl radical. In addition, the results of the energy
differences (∆E) show that cyclic conformers (S)-5a -C,
(S)-5b-B, and (S)-5b-C are more stable than the acyclic
(S)-5a -A and (S)-5b-A, respectively; especially, the most
stable conformers are (S)-5a -C and (S)-5b-C. (R)-5a -D,E
and (R)-5b-D,E also show 1.8 Å for the distance between
the hydroxy proton and the sulfinyl oxygen, and lower
LUMO energies than the corresponding acyclic (R)-5a -A
and (R)-5b-A. In (R)-5a and (R)-5b, however, the most
stable conformers are (R)-5a -A and (R)-5b-A both of
which hardly form intramolecular hydrogen bonding, and
thus (R)-5a and (R)-5b without intramolecular hydrogen
bonding cannot be good substrates toward alkyl radicals
(Table 1). These calculation data are in good accord with
a
b
∆E ) E(5-BR or 5-CR) - E(5-AR). Difference in heat of
formation. c Difference in total energy. Not optimized.
d
Next, we calculated heat of formation and the distance
of the hydrogen bonding for the intermediate radicals
derived from the reactive vinyl sulfoxide (S)-5 and the
results are shown in Table 4. The cyclic radical interme-
diates (S)-5a - and (S)-5b-BR1, -BR2, -CR1, -CR2 were
found to be more stable than the noncyclic intermediates
(S)-5a - and (S)-5b-AR except (S)-5a -BR1. The distance
between the hydroxy proton and the sulfinyl oxygen was
approximately 1.8 Å in optimized structures 5-BR and
5-CR. The conformer (S)-5a -CR1 was the most stable
conformer derived from (S)-5a . In (S)-5a -CR1, both
radical faces are shielded to some extent by the tert-butyl,
p-tolyl, and phenyl groups, and hydrogenation with
tributyltin hydride resulted in low diastereoselectivity
(Table 1, entry 1). On the other hand, (S)-5b-CR2 was
the most stable among conformers derived from (S)-5b.
The lower face is shielded so efficiently by both the
methyl and tert-butyl groups in (S)-5b-CR2 that tribu-
tyltin hydride attacks predominantly from the upper face
to give syn-7b with high diastereoselectivity (Figure 2,
Table 1, entry 3).
1
the observation of their H NMR and IR spectra (Table
2).
Rea ction of r-(1-Hyd r oxya lk yl)vin yl Su lfon es. In-
tramolecular hydrogen bonding was demonstrated to
enhance the radical addition-hydrogenation reaction of
the R-(1-hydroxyalkyl)vinyl sulfoxides 5 and fix the
conformation of the radical intermediates to allow the
reaction to proceed with high stereoselectivity. These
results encouraged us to examine the sulfonyl group as
a new stereo-inducer in the radical reaction, even though
the sulfonyl group had been recognized as an inefficient
(19) Stewart, J . J . P. J . Comput. Chem. 1989, 10, 210.
(20) Frisch, M. J .; Trucks, G. W.; Schlegel, H. B.; Gill, P. M. W.;
J ohnson, B. G.; Robb, M. A.; Cheeseman, J . R.; Keith, T.; Petersson,
G. A.; Montgomery, J . A.; Raghavachari, K.; Al-Laham, M. A.;
Zakrzewski, V. G.; Ortiz, J . V.; Foresman, J . B.; Cioslowski, J .;
Stefanov, B. B.; Nanayakkara, A.; Challacombe, M.; Peng, C. Y.; Ayala,
P. Y.; Chen, W.; Wong, M. W.; Andres, J . L.; Replogle, E. S.; Gomperts,
R.; Martin, R. L.; Fox, D. J .; Binkley, J . S.; Defrees, D. J .; Baker, J .;
Stewart, J . P.; Head-Gordon, M.; Gonzalez, C.; Pople, J . A.; Gaussian,
Inc.: Pittsburgh, PA, 1995.

Hydrogenation of Vinyl Sulfoxides and Sulfones
J . Org. Chem., Vol. 65, No. 21, 2000 7087
Ta ble 5. Hyd r ogen a tion of th e r-Su lfon yl Ra d ica l
Gen er a ted fr om th e Ad d ition of ter t-Bu tyl Ra d ica l to th e
r-(1-Hyd r oxya lk yl)vin yl Su lfon es 12a
entry substrate T (°C) solvent time (h) yield (%) syn/anti
F igu r e 2. Proposed model for hydrogenation of the R-sulfinyl
1b
2c
3
12a
12a
12a
12a
12a
12a
12a
12b
12b
12b
12b
12b
rt
rt
rt
CH2Cl2
CH2Cl2
CH2Cl2
PhH
1
1
1
98
98
91
95
88
94
94
95
98
93
91
84
63:37
63:37
69:31
66:34
70:30
80:20
68:32
86:14
87:13
74:26
98:2
radical with tributyltin hydride.
Sch em e 2. P r ep a r a tion of th e
4d
5
6
80
0
-78
-78
rt
0.5
1
2
2
1
2
0.5
2
r-(1-Hyd r oxya lk yl)vin yl Su lfon esa
CH2Cl2
CH2Cl2
THF
CH2Cl2
CH2Cl2
PhH
7
8b
9
rt
10d
11
12
80
-78
-78
CH2Cl2
THF
2
81:19
a
The reaction was carried out in 0.01 mol/L solution unless
b
otherwise noted. The reaction was carried out in 0.1 mol/L
solution. c The reaction was carried out in 0.05 mol/L solution.
d
AIBN was used as a radical initiator.
a
Key: (a) R1CHO, DABCO; (b) Ac2O, BF3‚OEt2; (c) Ph3SiCl,
Ta ble 6. Hyd r ogen a tion of th e r-Su lfon yl Ra d ica l
Gen er a ted fr om th e Ad d ition of Va r iou s Alk yl Ra d ica ls
to th e r-(1-Hyd r oxya lk yl)vin yl Su lfon es 12
pyridine.
1,2-stereo-inducer in the hydrogenation of the â-oxy-R-
sulfonyl radicals.21 Since the stereochemistry of the R-(1-
hydroxyalkyl)vinyl sulfoxides 5 had considerable influ-
ence on the formation of an intramolecular hydrogen
bonding, intramolecular hydrogen bonding was expected
to be formed stereoselectively between the hydroxy
proton and the specific diastereotopic sulfonyl oxygen in
the R-(1-hydroxyalkyl)vinyl sulfones 12 (eq 2). The vinyl
sulfones 12a ,b were prepared by the reaction of phenyl
vinyl sulfone22 11 with benzaldehyde and acetaldehyde,
respectively, in the presence of a catalytic amount of 1,4-
diazabicyclo[2.2.2]octane (DABCO) as shown in Scheme
2.23 The acetoxy- and triphenylsilyl-protected derivatives
were also prepared.
Radical reaction of the R-(1-hydroxyalkyl)vinyl sulfones
12 was carried out in a manner similar to the reaction
of the R-(1-hydroxyalkyl)vinyl sulfoxides 5. The results
are shown in Table 5. Treatment of 1-phenyl-2-(phenyl-
sulfonyl)-2-propen-1-ol (12a ) with tert-butyl iodide, tribu-
tyltin hydride, and triethylborane furnished the expected
products 15 in high yields, with diastereoselectivity
variously changed by the reaction conditions used. The
reaction of 12a in 0.01 mol/L CH2Cl2 solution gave the
addition-hydrogenation product 15a with slightly better
diastereoselectivity than that in the reaction performed
in 0.1 and 0.05 mol/L solutions (entries 1-3). Higher
diastereoselectivity was obtained when the reaction was
carried out at lower temperature (entries 5 and 6). The
reaction of 12b proceeded with higher diastereoselectiv-
ity, favoring the syn-isomer 15b, than in the reaction of
12a . A polar solvent such as THF lowered the diastereo-
selectivity in both cases (entries 7 and 12). Notably, the
reaction of 12b in 0.01 mol/L CH2Cl2 solution at -78 °C
time
(h)
yield
(%)
entry substrate
R2
product
15a
16a
17a
19a
15b
16b
17b
syn/anti
1
2
3
4
5
12a
12a
12a
12a
12b
12b
12b
12b
12b
12b
t-Bu
c-Hex
i-Pr
Et
t-Bu
c-Hex
i-Pr
Bu
2
1
1
3
2
1
1
3
8
94
94
96
91
91
93
91
88
95
80:20
79:21
81:19
80:20
98:2
76:24
69:31
62:38
60:40
6
7
8a
9a
10a
18b
19b
no reaction
Et
Me
24
a
The reaction was carried out at -78 °C f rt.
gave the addition-hydrogenation product 15b in a syn/
anti ratio of 98:2 (entry 11).
The reaction with various alkyl radicals was also
examined. The results are shown in Table 6. Cyclohexyl,
isopropyl, and ethyl radicals successfully added to 12a
and 12b. It should be noted that no steric influence of
alkyl radicals on the diastereoselectivity was observed
in the reaction of 12a , the syn/anti ratio being always
approximately 80:20 (entries 1-4). On the other hand,
the stereoselection was lowered in the reaction of 12b,
as the size of alkyl radicals was sterically smaller (entries
5-9).
Results in the reaction of 12 in the presence of Lewis
acids are shown in Table 7. Addition of a Lewis acid such
as Et2Zn, Me3Al, and Et2AlCl did not improve the
diastereoselectivity (entries 2-4), whereas EtAlCl2 in-
creased the diastereoselectivity in reactions of both 12a
and 12b (entries 5 and 10). Especially, the reaction of
12b proceeded with high diastereoselectivity in a ratio
(21) Giese, B.; Bulliard, M.; Dickhaut, J .; Halbach, R.; Hassler, C.;
Hoffmann, U.; Hinzen, B.; Senn, M. Synlett 1995, 116.
(22) Paquette, L. A.; Carr, R. V. C. Org. Synth. 1986, 64, 157.
(23) (a) Weichert, A.; Martin, H.; Hoffmann, R. J . Org. Chem. 1991,
56, 4098. (b) Auvray, P.; Knochel, P.; Normant, J . F. Tetrahedron 1988,
44, 6095.

7088 J . Org. Chem., Vol. 65, No. 21, 2000
Mase et al.
Ta ble 7. Hyd r ogen a tion of th e r-Su lfon yl Ra d ica l
Gen er a ted fr om th e Ad d ition of ter t-Bu tyl Ra d ica l to th e
r-(1-Hyd r oxya lk yl)vin yl Su lfon es 12-14 in th e P r esen ce
of Lew is Acid s
Lewis time
yield
entry substrate
P
acid (h) product (%) syn/anti
1
12a
12a
12a
12a
12a
12a
12a
12a
12b
12b
12b
12b
12b
12b
13a
13a
13b
13b
14a
14b
H
H
H
H
H
H
H
H
H
H
H
H
H
H
none
2
2
10
3
3
24
4
4
2
5
2
24
7
5
2
1
2
1
2
2
15a
15a
15a
15a
15a
15a
15a
15a
15b
15b
15b
15b
15b
15b
20a
20a
20b
20b
21a
21b
94
94
81
83
94
98
92
98
91
64
76
93
93
91
87
99
92
97
88
99
80:20
81:19
79:21
81:19
85:15
68:32
58:42
80:20
98:2
2
Et2Zn
Me3Al
Et2AlCl
EtAlCl2
MAD
3a
4
F igu r e 3. Optimized conformers for the R-(1-hydroxyalkyl)-
vinyl sulfones 12 (see the Supporting Information for the
calculation data).
5
6
7
MADb
none
none
nyl oxygen is approximately 1.8 Å in cyclic optimized
structures 12a -B,C,D,E and 12b-B,C,E except for 12b-
D, showing that intramolecular hydrogen bonding is
formed in these conformers (Figure 3). Calculation by
PM3 showed that LUMO energies of cyclic conformers
12a - and 12b-B,C,D,E with intramolecular hydrogen
bonding are lower than those of 12a -A and 12b-A without
intramolecular hydrogen bonding. Although the LUMO
difference (∆LUMO) of these cyclic conformers relative
to the respective acyclic conformers 12a -A and 12b-A,
does not remarkably decrease in comparison with that
of the R-(1-hydroxyalkyl)vinyl sulfoxides 5 (Table 3), the
R-(1-hydroxyalkyl)vinyl sulfones 12 can easily react with
nucleophilic alkyl radicals, since the value of LUMO of
the sulfone 12 is lower than that of the sulfoxide 5 (for
example, ∆LUMO ) LUMO (12b-A) - LUMO ((S)-5b-
A) ) -0.787 (eV) obtained by HF/3-21G calculation).
Diastereoselectivity in hydrogenation of the radical R
to the sulfonyl group is possibly ascribed to conforma-
tionally and configurationally different radical intermedi-
ates. We performed the calculation of the hydrogen
bonding length and the relative LUMO energy, heat of
formation and total energy for the cyclic radical inter-
mediates relative to the acyclic intermediates 12-AR
(Figure 4). In the case of 12a , the radical intermediate
12a -CR2 was found to be the most stable conformer and
the hydrogen bonding length was 2.51 Å, indicating that
considerably weak intramolecular hydrogen bonding
exists between the hydroxy group and the anti-sulfonyl
oxygen. It would be ascribed to this loosely bound radical
intermediate 12a -CR2 that 12a gave the products 15a ,
16a , 17a , and 19a with moderate diastereoselectivity
(syn/anti ) 80:20) irrespective of the bulkiness of the
alkyl radicals (Table 6, entries 1-4). On the other hand,
the most stable conformer among the radical intermedi-
ates 12b-R was 12b-CR2 in which strong intramolecular
hydrogen bonding exists between the hydroxy group and
the anti-sulfonyl oxygen. The structure of 12b-CR2 fully
corresponds with that of the most stable R-sulfinyl radical
intermediate (S)-5b-CR2 in Table 4. The upper face is
more widely open in 12b-CR2 to the attack of tributyltin
hydride, and the hydride approaches from the upper face
opposite to the methyl and tert-butyl groups, leading to
the addition-hydrogenation product with syn stereochem-
istry (Figure 5). As the alkyl radical is sterically bulkier,
the lower face is more shielded by the newly formed alkyl
group to cause higher diastereoselectivity (Table 6,
8c
9
10
EtAlCl2
EtAlCl2
MAD
99:1
99:1
11d
12a
13
88:12
68:32
99:1
77:23
79:21
90:10
92:8
MADb
none
14c
15
Ac
Ac
Ac
Ac
none
EtAlCl2
none
16
17
18
19
EtAlCl2
SiPh3 none
SiPh3 none
31:69
67:33
20
a
b
The reaction was carried out at -78 °C f rt. MAD (5 equiv)
was used. c Ph3SnH was used instead of Bu3SnH. The reaction
was carried out at room temperature.
d
of 99:1 even at room temperature, favoring the same syn-
isomer 15b as that obtained in the reaction without a
Lewis acid (entry 11). These results show that high
diastereoselectivity obtained with EtAlCl2 can be ascribed
to the formation of the rigid chelated structure in the
intermediate radical derived from the addition of tert-
butyl radical to 12. The diastereoselectivity decreased in
the presence of the bulky methylaluminum bis(2,6-di-tert-
butyl-4-methylphenoxide) (MAD), probably due to forma-
tion of the nonchelated intermediate (entries 6-7, 12-
13). The diastereoselectivity increased when triphenyltin
hydride was used as a hydrogen donor in the reaction of
12b (entry 14). The acetyl or triphenylsilyl protection of
the hydroxy group decreased the diastereoselectivity
(entries 15-20).
According to the results of the reaction of the vinyl
sulfones 12 shown in Tables 5-7, intramolecular hydrogen
bonding seems to be strongly related to the stereochem-
ical outcome as in the reaction of R-(1-hydroxyalkyl)vinyl
sulfoxide 5. Actually, significant intramolecular hydrogen
bonding was shown to exist in both of 12a and 12b, since
only a small upfield shift of the chemical shift of the
hydroxy proton was observed upon dilution and the
values of J AB (3.2 Hz for 12a , 3.3 Hz for 12b) were in
good accord with those of the conformer having an
intramolecular hydrogen bonding (Table 2). The infrared
spectra also support the existence of intramolecular
hydrogen bonding (3575-3400 cm-1).
We performed the calculation of the LUMO energy and
heat of formation of the R-(1-hydroxyalkyl)vinyl sulfones
12 by MOPAC 93/PM3 and GAUSSIAN 94/HF/3-21G.
The distance between the hydroxy proton and the sulfo-

Hydrogenation of Vinyl Sulfoxides and Sulfones
J . Org. Chem., Vol. 65, No. 21, 2000 7089
F igu r e 4. Conformers of the radical intermediates derived from 12 (see the Supporting Information for the calculation data).
upfield shift upon dilution in the 1H NMR spectra,
suggesting the existence of intramolecular hydrogen
bonding (see, Table 2). However, from the coupling
1
constant (J AB ) 5.2 Hz) in the H NMR spectrum anti-
22 appears not to form an intramolecular hydrogen
bonding. Precursors anti- and syn-22 were reduced
separately with tributyltin hydride in the presence of
Et3B at -78 °C to give the reduction product 23 with the
same diastereoselectivity in a ratio of 47:53, indicating
that both radical reductions of anti- and syn-22 proceeded
F igu r e 5. Proposed model for hydrogenation of the R-sulfonyl
via conformationally the same radical intermediates, i.e.,
radical with tributyltin hydride.
a rapidly equilibrated or sp2 carbon radical intermediate
Sch em e 3. Ra d ica l Hyd r ogen a tion of
â-Hyd r oxy-r-(p h en ylselen en yl) Su lfon es 22
was formed.
In conclusion, we have shown an important role of
intramolecular hydrogen bonding in diastereoselectivity
at the carbon R to the sulfinyl and sulfonyl groups as
well as in reactivity toward alkyl radicals in the reaction
of R-(1-hydroxyalkyl)vinyl sulfoxides and sulfones. In this
reaction, a diastereotopic sulfonyl oxygen was success-
fully discriminated by stereoselective intramolecular
hydrogen bonding or by chelating coordination with a
Lewis acid to a specific sulfonyl oxygen which cor-
responded to the hydrogen-bonded sulfinyl oxygen in the
radical intermediate. This new version of the use of a
sulfonyl group as a stereo-inducer would open a way to
various useful stereoselective reactions.
entries 5-9). These results were quite different from
those reported in the radical reaction of the â-hydroxy
R,â-unsaturated esters24 or â-amino R,â-unsaturated
esters,25 in which the diastereoselectivity decreases as
the alkyl radicals become sterically bulkier. The substit-
uents on the ester have little influence on the stereose-
lectivity due to the trigonal planar structure of the ester,
whereas the substituents on the sulfonyl group in the
present reaction have significant influence on the ste-
reoselectivity definitely due to the tetrahedral sulfur
structure of the sulfone.
The planar radical intermediates have been assumed
through the above discussion. To confirm the planarity
of the carbon radical R to the sulfonyl group, the stere-
ochemical outcome in the radical reduction of the â-hy-
droxy-R-(phenylselenenyl) sulfones anti- and syn-22 was
studied (Scheme 3). The radical precursors syn- and anti-
22 were prepared by aldol reaction of the carbanion
derived from the corresponding R-(phenylselenenyl) sul-
fone with acetaldehyde. Both precursors showed a small
Exp er im en ta l Section
Gen er a l P r oced u r e for th e Ra d ica l Rea ction of th e
r-(1-Hyd r oxya lk yl)vin yl Su lfoxid es 5 a n d th e r-(1-Hy-
d r oxya lk yl)vin yl Su lfon es 12. To a degassed solution of 5
or 12 in CH2Cl2 (0.01 mol/L) were added an alkyl iodide (3
equiv), tributyltin hydride (3 equiv), and triethylborane (3
equiv). For the reaction using a Lewis acid, the Lewis acid
(1.1 equiv) was added to a CH2Cl2 solution of 5 or 12 and the
mixture was stirred for 30 min before the addition of other
reagents. After the mixture was stirred for the appropriate
time, the mixture was poured into saturated NaH2PO4, and
extracted with Et2O. The combined organic extracts were
washed with brine, dried over Na2SO4, and concentrated to
give the crude product, which was purified by column chro-
matography to give the addition-hydrogenation products.
(SS,1S,2R)-4,4-Dim et h yl-2-(p -t olylsu lfin yl)-1-h exa n ol
(syn -7a ): Rf ) 0.33 (hexane/ethyl acetate ) 50/50); 1H NMR δ
0.69 (s, 3H), 1.86 (dd, J ) 1.7, 15.9 Hz, 1H), 2.10 (dd, J ) 7.8,
15.9 Hz, 1H), 2.38-2.47 (m, 1H), 2.49 (s, 3H), 4.71 (s, 1H),
5.30 (s, 1H), 6.81-7.30 (m, 5H), 7.45 (d, J ) 8.2 Hz, 2H), 7.62
(d, J ) 8.2 Hz, 2H); IR (neat) 3120-3600, 2970, 1470, 1010,
730 cm-1; MS (EI) m/e 330 (M+, 2), 315 (5), 92 (100). Anal.
Calcd for C20H26O2S: C, 72.69; H, 7.93. Found: C, 72.94; H,
8.16.
(24) Urabe, H.; Yamashita, K.; Suzuki, K.; Kobayashi, K.; Sato, F.
J . Org. Chem. 1995, 60, 3576.
(25) Ku¨ndig, E. P.; Xu, L.-H.; Romanens, P. Tetrahedron Lett. 1995,
36, 4047.

7090 J . Org. Chem., Vol. 65, No. 21, 2000
Mase et al.
(SS,1S,2S)-4,4-Dim et h yl-2-(p -t olylsu lfin yl)-1-h exa n ol
(a n ti-7a ): Rf ) 0.53 (hexane/ethyl acetate ) 50/50); 1H NMR
δ 0.60 (s, 9H), 1.22-1.38 (m, 2H), 2.32-2.42 (m, 1H), 2.44 (s,
3H), 4.96 (dd, J ) 2.3, 6.8 Hz, 1H), 5.44-5.51 (m, 1H), 6.97-
a n ti-5,5-Dim eth yl-3-(p h en ylsu lfon yl)-2-h exa n ol (a n ti-
) 0.60 (hexane/ethyl acetate ) 60/40); 1H NMR δ 0.78
15b): Rf
(s, 9H), 1.39 (d, J ) 6.6 Hz, 3H), 1.63 (dd, J ) 5.2, 15.5 Hz,
1H), 1.87 (dd, J ) 3.1, 15.5 Hz, 1H), 3.09 (ddd, J ) 3.1, 5.2,
5.6 Hz, 1H), 3.31 (d, J ) 6.2 Hz, 1H), 4.14 (ddq, J ) 5.6, 6.2,
6.6 Hz, 1H), 7.48-7.75 (m, 3H), 7.82-7.97 (m, 2H); IR (neat)
3600-3200, 2965, 1480, 1450, 1410, 1375, 1280, 1145, 740
cm-1; MS (EI) m/e 270 (M+, 0.9), 255 (9), 226 (22), 169 (96),
143 (52), 129 (100).
7.67 (m, 9H); IR (neat) 3600-3100, 2970, 1470, 1030 cm-1
;
MS (EI) m/e 330 (M+, 1), 140 (100). Anal. Calcd for
C20H26O2S: C, 72.69; H, 7.93. Found: C, 72.71; H, 8.22.
(SS,2S,3R)-5,5-Dim et h yl-3-(p -t olylsu lfin yl)-2-h exa n ol
(syn -7b): Rf ) 0.61(hexane/ethyl acetate ) 30/70); [R]26
)
D
+213 (c 0.137, CHCl3); 1H NMR δ 0.97 (s, 9H), 1.09 (d, J ) 7.2
Hz, 3H), 1.87 (dd, J ) 3.1, 15.9 Hz, 1H), 1.98 (dd, J ) 6.5,
15.9 Hz, 1H), 2.29 (ddd, J ) 1.2, 3.1, 6.5 Hz, 1H), 2.44 (s, 3H),
4.25-4.50 (m, 1H), 4.36 (s, 1H), 7.37 (d, J ) 8.1 Hz, 2H), 7.53
(d, J ) 8.1 Hz, 2H); 13C NMR δ 20.6, 21.4, 29.6, 30.6, 36.5,
63.1, 66.3, 124.6, 130.0, 138.2, 141.7; IR (neat) 3600-3200,
2950, 1470, 1040, 810 cm-1; MS (EI) m/e 268 (M+, 1), 252 (11),
151 (45), 140(100). Anal. Calcd for C15H24O2S: C, 67.12; H,
9.01. Found: C, 67.36; H, 9.24.
syn -4,4-Dim et h yl-1-p h en yl-2-(p h en ylsu lfon yl)-1-p en -
ta n ol (syn -15a ): Rf ) 0.61 (hexane/ethyl acetate ) 60/40); 1H
NMR δ 0.44 (s, 9H), 1.93 (d, J ) 3.6 Hz, 2H), 3.08 (dt, J ) 0.9,
3.6 Hz, 1H), 3.80 (s, 1H), 5.24 (s, 1H), 7.10-7.35 (m, 5H), 7.60-
7.80 (m, 3H), 7.98-8.09 (m, 2H); IR (neat) 3600-3300, 2950,
1450, 1295, 1245, 1140, 740 cm-1; MS (EI) m/e 332 (M+, 6),
275 (20), 226 (16), 190 (18), 169 (100). Anal. Calcd for
Ra d ica l Hyd r ogen a tion of th e â-Hyd r oxy-r-(p h en ylse-
len en yl) Su lfon e 22. To a solution of 22 in CH2Cl2 (0.01 mol/
L) were added tributyltin hydride (2 equiv) and triethylborane
(1 equiv) at -78 °C. The mixture was concentrated to give the
crude product, which was purified by column chromatography
(silica gel, hexane/ethyl acetate ) 85/15) to give the reduction
product 23.
3-(P h en ylsu lfon yl)-2-bu ta n ol (23): Rf ) 0.10 (hexane/
ethyl acetate ) 70/30); 1H NMR δ 1.14 (d, J ) 7.1 Hz, 3H,
anti-isomer) and 1.21 (d, J ) 6.5 Hz, 3H, syn-isomer), 1.25 (d,
J ) 6.4 Hz, 3H, anti-isomer) and 1.34 (d, J ) 7.2 Hz, 3H, syn-
isomer), 3.01 (dq, J ) 1.3, 7.2 Hz, 1H, syn-isomer) and 3.14
(dq, J ) 7.1, 8.2 Hz, 1H, anti-isomer), 2.99 (s, 1H, anti-isomer)
and 3.93 (s, 1H, syn-isomer), 4.15-4.25 (m, 1H, anti-isomer)
and 4.40-4.55 (m, 1H, syn-isomer), 7.45-7.80 (m, 3H), 7.80-
8.05 (m, 2H); IR (neat) 3600-3300, 2980, 2930, 1445, 1300,
C
19H24O3S: C, 68.64; H, 7.28. Found: C, 68.86; H, 7.35.
1140, 1080 cm-1
.
a n ti-4,4-Dim eth yl-1-p h en yl-2-(p h en ylsu lfon yl)-1-p en -
ta n ol (a n ti-15a ): Rf ) 0.56 (hexane/ethyl acetate ) 60/40);
1H NMR δ 0.68 (s, 9H), 1.71 (dd, J ) 4.6, 15.5 Hz, 1H), 2.15
(dd, J ) 3.6, 15.5 Hz, 1H), 3.46 (ddd, J ) 3.6, 4.6, 6.0 Hz, 1H),
4.36 (d, J ) 6.3 Hz, 1H), 4.99 (dd, J ) 6.0, 6.3 Hz, 1H), 7.15-
7.35 (m, 5H), 7.37-7.60 (m, 3H), 7.65-7.73 (m, 2H); IR (neat)
3600-3200, 2960, 1475, 1450, 1300, 1140 cm-1; MS (EI) m/e
332 (M+, 6), 275 (23), 226 (19), 190 (25), 169 (100).
syn -5,5-Dim et h yl-3-(p h en ylsu lfon yl)-2-h exa n ol (syn -
15b): Rf ) 0.60 (hexane/ethyl acetate ) 60/40); 1H NMR δ 0.82
(s, 9H), 1.29 (d, J ) 6.3 Hz, 3H), 1.73 (dd, J ) 4.3, 15.8 Hz,
1H), 1.91 (dd, J ) 3.6, 15.8 Hz, 1H), 3.00 (ddd, J ) 1.5, 3.6,
4.3 Hz, 1H), 3.57 (d, J ) 4.9 Hz, 1H), 4.16 (ddq, J ) 1.5, 4.9,
6.3 Hz, 1H), 7.52-7.75 (m, 3H), 7.88-8.00 (m, 2H); 13C NMR
δ 20.0, 29.4, 30.2, 34.2, 66.2, 66.3, 128.6, 129.3, 133.9, 138.3;
IR (KBr) 3650-3150, 2970, 1480, 1450, 1420, 1375, 1280, 1150,
750, 690 cm-1; MS (EI) m/e 255 (M+-15, 4), 226 (28), 169 (99),
143 (54), 129 (100). Anal. Calcd for C14H22O3S: C, 62.19; H,
8.20. Found: C, 62.38; H, 8.45.
Ack n ow led gm en t. Thanks to Dr. Shinya Kusuda,
Ono Pharmaceutical Co., Ltd., for X-ray crystallographic
analysis. This work was supported by a Grant-in-Aid
for Scientific Research (07750950, 09750932, 12650853)
from the Ministry of Education, Science, Sports and
Culture of J apan.
Su p p or tin g In for m a tion Ava ila ble: Spectroscopic data
and experimental details of 3-6, 8-10, 12-14, and 16-22.
Determination of the absolute configuration of the addition
product 7b. Determination of the relative configuration of the
addition products 15-19 and 23. Calculations data for 12 and
radical intermediates 12R derived from 12. This material is
available via the Internet at http://pubs.acs.org.
J O005525O