Highly regio- and stereoselective halohydroxylation reaction of 1,2-allenyl phenyl sulfoxides. Reaction scope, mechanism, and the corresponding Pd- or Ni-catalyzed selective coupling reactions

Article abstract of DOI:10.1021/ja034039q

A highly regio- and stereoselective halohydroxylation of 1,2-allenyl sulfoxides with X⁺ and water was developed. The reaction shows E-stereoselectivity. In the iodohydroxylation reaction, I₂ was used to introduce the iodine atom. For

Full text of DOI:10.1021/ja034039q

Published on Web 03/26/2003
Highly Regio- and Stereoselective Halohydroxylation Reaction
of 1,2-Allenyl Phenyl Sulfoxides. Reaction Scope, Mechanism,
and the Corresponding Pd- or Ni-Catalyzed Selective
Coupling Reactions
Shengming Ma,* Hongjun Ren, and Qi Wei
Contribution from the State Key Laboratory of Organometallic Chemistry,
Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Lu,
Shanghai 200032, People’s Republic of China
Received January 4, 2003; E-mail: masm@pub.sioc.ac.cn
Abstract: A highly regio- and stereoselective halohydroxylation of 1,2-allenyl sulfoxides with X+ and water
was developed. The reaction shows E-stereoselectivity. In the iodohydroxylation reaction, I2 was used to
introduce the iodine atom. For bromohalohydroxylation, CuBr2, NBS, or Br2 can be used. When using I2,
NBS, or Br2, the addition of LiOAc‚2H2O is necessary for high yields of the halohydroxylation products.
The chlorohydroxylation reaction was preformed by milling 1,2-allenyl sulfoxides and CuCl2‚2H2O with silica
gel. Under the catalysis of a Pd(0) complex, the halohydroxylation products, that is, E-2-halo-1-phenylsulfinyl-
1-alken-3-ols, can undergo Sonogashira, Suzuki, and Negishi cross-coupling reactions leading to Z-2-
substituted-1-phenylsulfonyl-1-alken-3-ols. The C-S bond of the coupling product may undergo a further
coupling reaction with organozincs under the catalysis of an Ni catalyst. Here, the presence of a hydroxyl
group is important for a smooth coupling involving the C-S bond. Thus, optically active stereodefined
multisubstituted allylic alcohols can be prepared by the reaction of the easily available optically active
propargylic alcohols with sulfinyl chloride followed by E-halohydroxylation and a selective Pd- or Ni-coupling
reaction.
Scheme 1
Introduction
Stereodefined allylic alcohols are a class of compounds with
important synthetic potentials due to the presence of the hydroxy
group and carbon-carbon double bond. For their synthesis, there
are two challenges: (1) the control of the configuration of the
carbon-carbon double bonds and (2) the highly stereoselective
establishment of the chiral centers adjacent to the hydroxy group
(Scheme 1).1 Here, stereoselective halohydroxylation2 of 1,2-
allenyl sulfoxides was applied for such a purpose.
Recently, during the course of our systematic study of allene
chemistry,3 we observed that the hydrohalogenation4 of 1,2-
allenyl sulfones5 occurred smoothly with metallic halides, while
the corresponding reaction of 1,2-allenyl sulfoxides must be
mediated by certain Al(III) species.6 The simple reaction of 1,2-
propadienyl phenyl sulfoxide (1a) with NaI in HOAc at 80 °C
afforded 3-thiophenyl-2-iodo-2(Z)-propenyl acetate in 30%
yield, which can be further oxidized with H2O2/HOAc to afford
the corresponding sulfoxide Z-2aa′. The stereoselectivity was
established by the NOE study and the comparison with its
E-isomer, which was synthesized via the esterification of
corresponding E-3aa (Scheme 2).
(3) (a) Ma, S.; Shi, Z. J. Org. Chem. 1998, 63, 6387. (b) Ma, S.; Duan, D.;
Shi, Z. Org. Lett. 2000, 2, 1419. (c) Ma, S.; Zhao, S. J. Am. Chem. Soc.
1999, 121, 7943. (d) Ma, S.; Shi, Z.; Yu, Z. Tetrahedron Lett. 1999, 40,
2393. (e) Ma, S.; Wu, S. J. Org. Chem. 1999, 64, 9314. (f) Ma, S.; Zhang,
J. Chem. Commun. 2000, 117. (g) Ma, S.; Li, L. Org. Lett. 2000, 2, 941.
(h) Ma, S.; Wu, S. Tetrahedron Lett. 2001, 42, 4075. (i) Ma, S.; Shi, Z.;
Wu, S. Tetrahedron: Asymmetry 2001, 12, 193. (j) Ma, S.; Zhao, S. J. Am.
Chem. Soc. 2001, 123, 5578. (k) Ma, S.; Li, L. Synlett 2001, 1206. (l) Ma,
S.; Shi, Z. Chem. Commun. 2002, 540. (m) Ma, S.; Yin, S.; Tan, F. Org.
Lett. 2002, 4, 505. (n) Ma, S.; Jiao, N.; Zhao, S.; Hou, H. J. Org. Chem.
2002, 67, 2837. (o) Ma, S.; Duan, D.; Wang, Y. J. Comb. Chem. 2002, 4,
239-247. (p) Ma, S.; Yu, Z. Angew. Chem., Int. Ed. 2002, 1775-1778.
(4) (a) Ma, S.; Li, L.; Xie, H. J. Org. Chem. 1999, 64, 5325. (b) Ma, S.; Shi,
Z.; Li, L. J. Org. Chem. 1998, 63, 4522. (c) Ma, S.; Wang, G. Chin. J.
Chem. 1999, 17, 545. (d) Ma, S.; Li, L.; Xie, H.; Wei, Q.; Wang, G.; Shi,
Z.; Zhang, Z. Pure Appl. Chem. 2000, 72, 1739. (e) Ma, S.; Xie, H.; Wang,
G.; Zhang, J.; Shi, Z. Synthesis 2001, 5, 713.
(1) Bianchini, J.-P.; Cocordano, M. Tetrahedron 1970, 26, 3401.
(2) (a) Cabanal-Duvillard, I.; Berrien, J.; Royer, J.; Husson, H. Tetrahedron
Lett. 1998, 39, 5181. (b) Rossen, K.; Reamer, R. A.; Volante, R. P.; Reider,
P. J. Tetrahedron Lett. 1996, 37, 6843. (c) Mevellec, L.; Evers, M.; Huet,
F. Tetrahedron 1996, 52, 15103. (d) Crossley, M. J.; Davies, S. R.;
Hambley, T. W. Aust. J. Chem. 1994, 47, 2221. (e) Sawyer, D. T.; Hage,
J. P.; Sobkowiak, A. J. Am. Chem. Soc. 1995, 117, 106. (f) Hirosato, H.;
Kondo, F.; Ichikawa, Y.; Look, G. C.; Wong, C. J. Org. Chem. 1992, 57,
7265. (g) Lai, J.; Wang, F.; Guo, G.; Dai, L. J. Org. Chem. 1993, 58,
6944. (h) Rodebaugh, R.; Fraser-Reid, B. J. Am. Chem. Soc. 1994, 116,
3155. (i) Yamashita, M.; I´ida, A.; Ikai, K.; Oshikawa, T.; Hanaya, T.;
Yamamoto, H. Chem. Lett. 1992, 407. (j) Miljkovic, D.; Djurendic, E.;
Vukojevic, N.; Gasi, K.; Csanadi, J. Carbohydr. Res. 1992, 233, 251. (k)
Kato, T.; Hirukawa, T.; Namiki, K. Tetrahedron Lett. 1992, 33, 1475.
(5) Ma, S.; Wei, Q. J. Org. Chem. 1999, 64, 1026.
(6) Ma, S.; Wei, Q. Eur. J. Org. Chem. 2000, 1939.
9
10.1021/ja034039q CCC: $25.00 © 2003 American Chemical Society
J. AM. CHEM. SOC. 2003, 125, 4817-4830
4817

A R T I C L E S
Ma et al.
Scheme 2
Figure 1. ORTEP representation of E-3aa.
Scheme 3
Table 1. Reaction of 1,2-Allenic Sulfoxides with I2/H2O in
Aqueous MeCN
Scheme 4
1
1
2
3
entry
R
R
R
I2 (equiv) time (h)
yield (%)
1
2
3
4
5
6
7
8
9
H
H
H
H
H
H
H
CH3 (1b)
n-C4H9 (1c)
n-C8H17 (1d)
t-C4H9 (1e)
1.6
1.6
1.6
1.2
1.2
1.2
1.6
1.6
1.2
1.6
1.6
1.5 87 (E-3ab)
H
H
H
2
1
3.2
0.5
89 (E-3ac)
89 (E-3ad)
87 (E-3ae)
87 (E-3af)
CH3 CH3 (1f)
(CH2)5 (1g)
H (1h)
H (1i)
0.3 74 (E-3ag)
1.5 82 (E-3ah)
n-C4H9
Ph
n-C4H9 CH3 CH3 (1j)
H
H
H
H
2.2
1.3
1
79 (E-3ai)
88 (E-3aj)
82 (E-3ak)
92 (E-3al)
10
11
H
H
CH2dCHCH2CH2 (1k)
CH2dCHCH2 (1l)
1
With anhydrous HOAc, the reaction of 1a with NaI and LiBr
afforded Z-2aa and Z-2ab exclusively in relatively higher yields,
respectively (Scheme 3).
carried out in MeCN-H2O (7:1) at room temperature affording
E-iodo-3-(phenylsulfinyl)-2-alkenols in high yields and E-
stereoselectivity. The stereoselectivity of the product was
established by the X-ray diffraction study of E-3aa (Figure 1).8
The iodohydroxylation reactions of aryl or alkyl substituted 1,2-
allenic sulfoxides were faster than that of the unsubstituted 1a,
and the reactions finished in from 0.3 to 3.2 h at room
temperature to give the corresponding products E-3a in high
yields and excellent stereoselectivity (compare eq 1 with entries
1-11 of Table 1). Especially when the carbon atom of the
3-position of 1,2-allenic sulfoxides is substituted with two alkyl
groups, the reaction is the quickest and requires only 0.3-0.5
h at room temperature (entries 5, 6, and 9, Table 1). The butyl
and phenyl groups at the carbon atom of the 1-position of 1,2-
allenic sulfoxides can also accelerate the reaction (entries 8-9,
Table 1). When the carbon atom of the 3-position of 1,2-allenic
sulfoxides is substituted with allyl or homoallylic groups, the
iodohydroxylation occurs still in the â,γ-carbon-carbon double
bond of the allene moiety (entries 10 and 11, Table 1, and
Scheme 5), indicating a high chemoselectivity.
Furthermore, it is interesting to observe that the reaction of
1,2-allenyl phenyl sulfoxides with I2 and H2O in the presence
of LiOAc‚2H2O afforded the iodohydroxylation product E-2-
iodo-3-(phenylsulfinyl)-2-propen-1-ols (Scheme 4).7 We rea-
soned that this reaction may open up a new pathway for the
highly stereoselective synthesis of substituted allylic alcohols
(Scheme 4). In this paper, we wish to disclose our recent results
on the scope, mechanism, and synthetic application of this
reaction.
Results and Discussion
The iodohydroxylation reaction of 1,2-allenyl phenyl sulfox-
ide 1a with I2 and H2O was carried out in MeCN-H2O (7:1)
to afford E-2-iodo-3-(phenylsulfinyl)-2-propen-1-ol (E-3aa) in
high yield and stereoselectivity (eq 1).
Generally speaking, the direct iodohydroxylation of carbon-
The results in Table 1 show that the iodohydroxylation
reactions of 1,2-allenyl phenyl sulfoxides with I2 and H2O was
(8) Crystal data of E-3aa: C9H9IO2S, M ) 308.13, colorless, prismatic, triclinic,
space group P1 (#2), µ(Mo KR) ) 32.19 cm-1, R ) 0.035, Rw ) 0.049,
a ) 9.102(1), b ) 15.105(2), c ) 8.811(2) Å, V ) 1048.5(3) Å3, T ) 20.0
°C, Z ) 4; no. of reflections measured, total 3875; no. observations (I
>3.00σ(I)), 3141; no. variables, 236. CCDC 192876.
(7) Ma, S.; Wei, Q.; Wang, H. Org. Lett. 2000, 2, 3893.
9
4818 J. AM. CHEM. SOC. VOL. 125, NO. 16, 2003

Halohydroxylation of 1,2-Allenyl Phenyl Sulfoxides
A R T I C L E S
Scheme 5
Scheme 6
Figure 2.
Scheme 7
carbon double bonds using I2 and H2O is difficult.9 The reaction
of alkyl substituted allenes or 2,3-allenoates with halogens was
known to form dihalogenation products.10 Even under the current
reaction conditions for a halohydroxylation reaction, iodination
product 1,2-diiodo-2-decene (4) with a Z/E ratio of 88:12 was
formed (Scheme 6). It is interesting to observe that when 1,2-
allenic sulfone 5a was treated with iodine under the same
conditions, no reaction was observed and 80% of the starting
material was recovered, while under the same reaction condi-
tions, 96% of iodohydroxylation product E-3aa from 1,2-allenic
sulfoxide 1a was obtained. The introduction of the sulfinyl group
must be the key for the control of regio- and stereoselectivities.
Based on these results, a mechanism involving the participa-
tion of the sulfinyl group is proposed. First, the reaction of the
electron-rich carbon-carbon double bonds with I+ forms
iodonium intermediate 6. Intramolecular attack of the sulfinyl
oxygen at the 3-position affording a five-membered cyclic
intermediate 7 accounts for the stereospecificity of this reaction.
Subsequent hydrolysis of 7 afforded the product E-3am ste-
reospecifically with the inversion of the chiral sulfur center
(Scheme 7).
2,3-Allenic alcohols and 2,3-allenoic acid esters can react
individually with halogens, and the hydroxyl group and carbonyl
group participates the reactions as an intramolecular nucleo-
phile.13 To compare the participation ability of the sulfinyl group
with that of these groups, we synthesized 1-hydroxymethyl-
1,2-propadienyl sulfoxide 1n and 1-(methoxycarbonyl)-3-meth-
yl-1,2-butadienyl sulfoxide 1o. The control experiment shows
that the hydroxyl or carbonyl group did not participate in the
iodohydroxylation reaction. The products of iodohydroxylation
of the allene moiety were formed exclusively in high yields
(Scheme 8), indicating that the sulfinyl group has a much
stronger participation ability in these electrophilic addition
reactions.
To study the mechanism of the iodohydroxylation reaction
of 1,2-allenic sulfoxides, diastereoisomerically pure allenic
sulfoxide (1m) was synthesized.11 The structures of the optically
active 1,2-allenyl sulfoxide 1m and the corresponding iodohy-
droxylation product E-3am were identified respectively by
means of X-ray diffraction studies, which showed that the
configuration of the chiral sulfur centers in two compounds are
just the opposite. The absolute configurations of 1m and E-3am
were determined based on the stereochemistry of the (+)-
camphor part (Figure 2).12
(9) (a) Asensio, G.; Andreu, C.; Boix-Bernardini, C.; Mello, R.; Gonza´lez-
Nun˜ez, M. E. Org. Lett. 1999, 1, 2125. (b) Masuda, H.; Takase, K.; Nishio,
M.; Hasegawa, A.; Nishiyama, Y.; Ishii, Y. J. Org. Chem. 1994, 59, 5550.
(c) Friesen, R. W.; Giroux, A. Tetrahedron Lett. 1993, 34, 1867. (d) Cambie,
R. C.; Noall, W. I.; Potter, G. J.; Rutledge, P. S.; Woodgate, P. D. J. Chem.
Soc., Perkin Trans. 1 1977, 226. (e) Maligres, P. E.; Upadhyay, V.; Rossen,
K.; Cianciosi, S. J.; Purick, R. M.; Eng, K. K.; Reamer, R. A.; Askin, D.;
Volante, R. P.; Reider, P. J. Tetrahedron Lett. 1995, 36, 2195. (f) Dolenc,
D. Synlett 2000, 544.
(10) (a) Tendil, J.; Verny, M.; Vessiere, R. Bull. Soc. Chim. Fr. 1972, 4027.
(b) Natsias, K.; Hopf, H. Tetrahedron Lett. 1982, 23, 3673. (c) Georgoulis,
C.; Smadja, W.; Valery, J. M. Synthesis 1981, 572. (d) Coulomb, F.;
Roumestant, M.; Gore, J. Bull. Soc. Chim. Fr. 1973, 3352.
Bromohydroxylations of 1,2-Allenyl Sulfoxides.14 When
NBS was chosen as the halogen source, the bromohydroxylation
reactions also proceeded smoothly at room temperature with
good to excellent yields (entries 2, 3, and 5 of Table 2).
Recently, our group also developed a CuX2-mediated halolac-
tonization of 2,3-allenoic acids.15 We tested the reaction of 1,2-
(11) Mattay, J.; Conrads, M.; Runsink, J. Synthesis 1988, 595.
(12) Crystal data of 1m: C18H22OS, M ) 286.43, orthorhombic, space group
P212121 (#19), µ(MoKR) ) 2.14 cm-1, R ) 0.044, Rw ) 0.047, a ) 10.705-
(4), b ) 21.283(3), c ) 6.981(3) Å, V ) 1590(1) Å3, T ) 20.0 °C, Z ) 4;
no. of reflections measured, total 2122; no. observations (I > 2.00σ(I)),
1479; no. variables, 182. CCDC 192 875. Crystal data of E-3am: C18H23
-
OSI, M ) 430.34, prismatic, space group P212121 (#19), µ(MoKR ) )
18.70 cm-1, R ) 0.041, Rw ) 0.049, a ) 7.576(4), b ) 37.003(7), c )
6.523(4) Å, V ) 1828(1) Å3, T ) 20.0 °C, Z ) 4; no. of reflections
measured, total 2487; no. observations (I > 2.00σ(I)), 1953; no. variables,
200. CCDC 192 877. The supplementary crystallographic data for this paper.
These data can be obtained free of charge via www.ccdc.cam.ac.uk/conts/
retrieving.html (or from the Cambridge Crystallographic Data Centre, 12,
Union Road, Cambridge CB2 1Ez, UK; fax (+44) 1223-336-033; or
deposit@ccdc.cam.ac.uk).
(13) (a) Marshall, J. A.; Wang, X.-J. J. Org. Chem. 1990, 55, 2995. (b). Marshall,
J. A.; Wang, X.-J. J. Org. Chem. 1991, 56, 4913. (b) Florio, S.; Ronzini,
L.; Epifani, E.; Sgarra, R. Tetrahedron 1993, 49, 10413. (c) Gill, G. B.;
Idris, M. S. H. Tetrahedron Lett. 1985, 26, 4811. (d) Marshall, J. A.; Wolf,
M. A.; Wallace, E. M. J. Org. Chem. 1997, 62, 367.
(14) For a brief study of bromohydroxylation of 1,2-allenyl sulfoxides with Br2,
see: Horner, L.; Binder, V. Liebigs Ann. Chem. 1972, 757, 33.
9
J. AM. CHEM. SOC. VOL. 125, NO. 16, 2003 4819

A R T I C L E S
Ma et al.
Scheme 8
Table 3. Solventless Chlorohydroxylations of 1,2-Allenic
Sulfoxides with CuCl2‚2H2O
1,2-allenic sulfoxides 1
product
E-3c
yield
(%)
1
2
3
entry
R
R
R
1
2
3
4
5
H
H
H
CH3
H
H (1a)
t-Bu (1e)
CH3 (1f)
(CH2)5 (1g)
H (1h)
E-3ca
E-3ce
E-3cf
E-3cg
E-3ch
49
84
61
73
51
H
H
H
Table 2. Bromohydroxylation of 1,2-Allenic Sulfoxides with CuBr2
or NBS
n-Bu
Table 4. Halohydroxylation of Optically Active 1,2-Allenic
Sulfoxides
1
time/temp
(h/°C)
yield of
E-3b (%)
1
2
3
entry
R
R
R
reagent
1
2
3
4
5
6
7
8
H
H
H
H
H
H
H (1a) CuBr2 1.5/40-45 88 (E-3ba)
H
H
H
CH3
H
n-C4H9 (1c) NBS
n-C8H17 (1d) NBS
2
2
90 (E-3bc)
98 (E-3bd)
87 (E-3be)
68 (E-3bf)
86 (E-3bh)
92 (E-3bj)
95 (E-3bm)
1,2-allenic sulfoxides 1
1 (ee)
(%)
halogen
source
yield of 2a
(%)
2 (ee)
(%)
t-C4H9 (1e) CuBr2 2.5
CH3 (1f) NBS 0.5
H (1h) CuBr2 3.5
CH3 (1j) CuBr2
CuBr2 1.5
2
3
entry
R
R
n-C4H9
n-C4H9 CH3
1
2
3
4
5
6
7
8
9b
n-C4H9
n-C4H9
H (R-1c)
H (R-1c)
96 I2
96 Br2
96 CuBr2
96 Br2
98 (R-3ac)
96 (R-3bc)
92 (R-3bc)
99 (S-3bd)
97 (S-3bd)
88 (S-3ae) >99
85 (S-3be) >99
69 (S-3be) >99
95
96
97
97
96
1
1m
n-C4H9
H (R-1c)
H
H
H
H
H
H
n-C8H17(S-1d)
n-C8H17(S-1d)
96 CuBr2
Scheme 9
t-C4H9 (S-1e) >99 I2
t-C4H9 (S-1e) >99 Br2
t-C4H9 (S-1e) >99 CuBr2
t-C4H9 (S-1e) >99 CuCl2‚2H2O 82 (S-3ce) >99
a Isolated yield. b Solventless reaction.
Scheme 10 a
allenic sulfoxides with CuBr2 in acetone/water and successfully
obtained the bromohydroxylation products of 1,2-allenic sul-
foxides with good yields and excellent stereoselectivity (entries
1, 4, and 6-8 of Table 2). The reaction can also proceed with
NBS.
a Referred to the allene moiety.
surprise, when allenic sulfoxide 1g was mixed and milled with
CuCl2‚2H2O together with some silica gel 4 times from room
temperature to 65°C, the chlorohydroxylation reaction occurred
smoothly to afford product E-3cg in 73% yield. Some typical
results are listed in Table 3.
Halohydroxylation Reaction of Optically Active 1,2-
Allenyl Sulfoxides. Using optically active propargyl alcohols
as starting materials, we obtained optically active 1,2-allenic
sulfoxides whose configurations in the allene part are definite
(Table 4). The chirality of the optically active propargylic
alcohols were efficiently transferred to the allene moiety of
sulfoxides, as determined by HPLC. The ratio of the two
diastereoisomers of 1,2-allenic sulfoxides due to the presence
of the sulfinyl group may change with time (Scheme 10). The
absolute configurations of the allene moiety in 1c, 1d, and 1e
were assigned based on the mechanism.17
Chlorohydroxylation of 1,2-Allenyl Sulfoxides. At the
beginning, the chlorohydroxylation met some difficulty. Cl2/
H2O was a strong oxidant and, thus, cannot be used directly.
NCS did not give a chlorohydroxylation product. When 1,2-
allenic sulfoxides reacted with CuCl2‚2H2O in acetone/water,
the reaction proceeded extremely slowly to afford the product
with only 20% yield of E-3cg after 48 h at room temperature
(Scheme 9). At a higher reaction temperature, no chlorohy-
droxylation product could be isolated.
Recently, solvent-free reactions were developed rapidly.16 As
they occur on the surface of crystals of reactants, solvent-free
reactions sometimes are clean and the yields are high. To our
(15) Ma, S.; Wu, S. J. Org. Chem. 1999, 64, 9314.
(16) Rajagopal, D.; Rajagopalan, K.; Swaminathan, S. Tetrahedron: Asymmetry
1996, 7, 2189.
9
4820 J. AM. CHEM. SOC. VOL. 125, NO. 16, 2003

Halohydroxylation of 1,2-Allenyl Phenyl Sulfoxides
A R T I C L E S
Scheme 11
According to the halohydroxylation mechanism (Scheme 7),
if the optically active 1,2-allenic sulfoxides with a definite
configuration in the allene part react with halogen and H2O,
the chirality of the allene moiety can be transferred into the
chiral center of the allylic alcohol. The absolute configurations
of the chiral center connecting with the hydroxy group are
assigned based on the halohydroxylation result of 1m, and the
ee value of halohydroxylation product is equal to that of the
corresponding reactants (Table 4).
Synthetic Application of Pd- or Ni-Catalyzed Selective
Coupling Reactions. Transition metal-catalyzed cross-coupling
reaction has been becoming one of the most efficient methods
for the formation of C-C bonds and C-X bonds.18 The
transformation of halohydroxylation products is challenging.19
Generally, it is easy to convert the sulfinyl group to hydrogen20
but difficult to convert it to useful organic functional groups.21
Thus, various kinds of cross-coupling reactions of the iodohy-
droxylation products were studied.
Table 5. Pd(0)-Catalyzed Mono Coupling Reaction of the C-X
Bond of 4-Phenylsulfinyl-2-iodo-2(E)-alkenols with Organic Zincs
1. Coupling Reactions of the C-I bond. 1.1. Sonogashira
Coupling. Usually the coupling reaction of 1-alkenyl iodide
with terminal alkyne was carried out in Et3N under the catalysis
of Pd(PPh3)2Cl2 and CuI.22 However, due to the low solubility
of E-3aa, DMSO should be added as the cosolvent; the
corresponding reaction afforded 1-en-3-ynyl sulfoxide Z-4g in
92% yield (eq 2).
3
temp/
time (h)
yield
(%)
1
2
3
entry
R
R
R
RZnX
solvent
THF
1
2
3
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H (E-3aa)
H (E-3aa)
PhZnBr
PhZnBr
rt/3
rt/1
rt/2
rt/1
rt/1
rt/2
rt/2
rt/2
rt/1
rt/7
0 (Z-4a)
THF/DMF
THF/DMF
THF/DMF
THF/DMF
THF/DMF
THF/DMF
THF/DMF
THF/DMF
94 (Z-4a)
82 (Z-4b)
71 (Z-4c)
74 (Z-4c)
76 (Z-4d)
78 (Z-4d)
77 (Z-4d)
86 (Z-4e)
0 (Z-4f)
nBu (E-3ah) PhZnBr
4
n-Bu H (E-3ac)
n-Bu H (E-3ac)
n-Oct H (E-3ad)
n-Oct H (E-3ad)
n-Oct H (E-3ad)
PhZnBr
PhZnBr
PhZnBr
PhZnBr
PhZnBr
EtZnBr
5a
6
7b
8c
9
H
H
H
H
H (E-3aa)
H (E-3aa)
H (E-3aa)
H (E-3ba)
10
11
12
PhC2ZnBr THF/DMF
PhC2ZnBr THF/HMPA rt/1.5 94 (Z-4f)
PhC2ZnBr THF/HMPA rt/1.5 92 (Z-4f)
1.2. Suzuki Coupling.23 The Pd(0)-catalyzed coupling reac-
tion of E-3aa with phenyl boronic acid using K2CO3 as the base
in THF afforded 4a in 70% yield with an E/Z ratio of 20:80,
indicating the partial isomerization of the CdC bond, which
makes it synthetically useless. However, with the addition of
10 mol % of TBAB, the reaction was finished within 3 h to
afford 4a in an E/Z ratio of 3:97. With E-1-hexenyl boronic
acid, the reaction also afforded Z-4h in 90% yield highly
stereoselectively (Scheme 11).
1.3. Negishi Coupling.24 The Negishi coupling of E-3aa with
phenyl zinc bromide in THF did not afford the corresponding
coupling Z-4a (entry 1 of Table 5). When DMF was added as
the cosolvent, the reaction afforded Z-4a in 94% yield ste-
reospecifically. With ethyl zinc bromide, the reaction afforded
Z-4e in 86% yield (entry 9 of Table 5). Similarly, the reaction
with phenylacetylenic zinc bromide in THF did not work, while,
a (R)-E-3ac (97.1% ee); (R)-Z-4c (99.1% ee). b The starting (R)-prop-
argylic alcohol (94.0% ee), (R)-Z-4d (98.1% ee). c The starting (S)-
propargylic alcohol (95.7% ee), (S)-Z-4d (94.7% ee).
with the addition of HMPA as the cosolvent, the reaction went
smoothly to afford Z-4f in high yields (compare entry 10 with
entry 11 of Table 5). The reaction of E-3aa-TBS, in which the
hydroxyl group was protected, in THF can afford the coupling
product Z-4f-TBS in 94% yield (eq 3).
(17) Smith, G.; Stirling, C. J. M. J. Chem. Soc. C 1971, 1530.
(18) Metal-Catalyzed Cross-Coupling Reaction; Stang, P., Diederich, F., Eds.;
VCH: Weiheim, Germany, 1998.
2. Coupling Reaction of the C-I Bond and the C-S Bond.
Under the catalysis of Pd(PPh3)4, the coupling reaction stopped
at the stage of iodide coupling affording Z-4a. However, when
a Ni complex was added after the first coupling with the C-I
bond, the C-S bond was reacted further to produce Z-2,3-
diphenyl-2-propenyl alcohol (Z-5c) (Scheme 12). Among the
catalysts tested, Ni(acac)2 gave the best results (entry 3 of Table
6). Z-5e was formed in 54% yield at 40 °C (entry 6 of Table 6).
Under the catalysis of Ni(acac)2 alone, the reaction of E-3aa
and excess amount of phenyl zinc bromide in THF/DMF
afforded a mixture of Z-4a and Z-5c together with some
byproducts (Scheme 13).
(19) Negishi, E.; Ay, M.; Gulevich, V.; Noda, Y. Tetrahedron Lett. 1993, 34,
1437.
(20) (a) Holton, R. A.; Crouse, D. J.; Williams, A. D.; Kennedy, R. M. J. Org.
Chem. 1987, 52, 2317. (b) Julia, M.; Fabre, J. L. Tetrahedron Lett. 1983,
24, 4311.
(21) (a) Okamura, H.; Miura, M.; Takei, H. Tetrahedron Lett. 1979, 43. (b)
Srogl, J.; Liu, W.; Marshall, D.; Liebeskind, L. S. J. Am. Chem. Soc. 1999,
121, 9449. (c) Liebeskind, L. S.; Srogl, J. J. Am. Chem. Soc. 2000, 122,
11260. (d) Liebeskind, L. S.; Srogl, J. Org. Lett. 2002, 4, 979.
(22) Sonogashira, K. ComprehensiVe Organic Synthesis; Pergamon: Oxford,
1990; Vol. 3, pp 521-549.
(23) (a) Suzuki, A. Pure Appl. Chem. 1985, 57, 1749. (b) Suzuki, A. Pure Appl.
Chem. 1991, 63, 419. (c) Suzuki, A. Pure Appl. Chem. 1994, 66, 213.
(24) (a) King, A. O.; Okukado, N.; Negishi, E. J. Chem. Soc., Chem. Commun.
1977, 683. (b) Pour, M.; Negishi, E. Tetrahedron Lett. 1996, 37, 4679. (c)
Pour, M.; Negishi, E. Tetrahedron Lett. 1997, 38, 525.
9
J. AM. CHEM. SOC. VOL. 125, NO. 16, 2003 4821

A R T I C L E S
Ma et al.
Scheme 12
Table 7. Ni(0)-Catalyzed Coupling Reaction of C-S(O)Ph Bond
with Aryl Zincs
Z-4
R
ArZnBr
R
temp
(°C)
time
(h)
yield
(%)
1
2
entry
1
2
3
4
H (Z-4a)
H (Z-4a)
H (Z-4a)
H (Z-4a)
p-Cl
p-OMe
H
o-OMe
H
H
p-OMe
p-OMe
p-N(CH3)2
p-N(CH3)2
80
80
40
40
40
40
40
40
40
40
1.5
3
15.5
15
15
12
19
19
12
12
68 (Z-5a)
73 (Z-5b)
84 (Z-5c)
68 (Z-5d)
69 (Z-5e)
64 (Z-5e)
60 (Z-5f)
57 (Z-5f)
76 (Z-5g)
73 (Z-5g)
5
6a
7
n-C8H17 (Z-4d)
n-C8H17 (Z-4d)
n-C8H17 (Z-4d)
n-C8H17 (Z-4d)
n-C4H9 (Z-4c)
n-C4H9 (Z-4c)
8b
9
10c
a (S)-Z-4d (94.7% ee); (S)-Z-5e (95.6% ee). b (S)-Z-4d (94.7% ee); (S)-
Z-5f (95.8% ee). c (R)-Z-4c (99.1% ee); (R)-Z-5g (94.0% ee).
Table 6. Pd(0)- and Ni-Catalyzed Double Coupling Reaction of
4-Phenylsulfinyl-2-iodo-2(E)-alkenols with Organic Zincs
Table 8. Ni(0)-Catalyzed Couling Reaction of C-SO2Ph Bond
with Aryl Zincs
step one step two
yield
(%)
entry
NiCl2L2
R
time (h)
time (h)
time
(h)
yield
(%)
1
1
2
3
NiCl2(PPh3)2 H (E-3aa)
NiCl2 (dppe) H (E-3aa)
Ni(acac)2
Ni(acac)2
Ni(acac)2
Ni(acac)2
1
1
1
1.2
1
1.3
2
4.5
11
4
77 (Z-5c)
40 (Z-5c)
84 (Z-5c)
44 (Z-5e)
34 (Z-5e)
54 (Z-5e)
entry
R
1
m-Me
m-Me
19
19
12
12
11
12
63 (Z-5h)
57 (Z-5h)
66 (Z-5i)
65 (Z-5i)
60 (Z-5f)
70 (Z-5j)
H (E-3aa)
2a
3
4
n-C8H17 (E-3ad)
n-C8H17 (E-3ad)
n-C8H17 (E-3ad)
p-Me
p-Me
5a
6b
4b
5
1.6
12
p-OMe
p-N(CH3)2
6
a The starting (S)-propargylic alcohol (95.7% ee); (S)-Z-5e (95.4% ee).
b The Ni-catalyzed second coupling reaction was carried out at 40 °C.
a (S)-Z-6e (96.0% ee); (S)-Z-5h (94.5% ee). b (S)-Z-6e (96.0% ee), (S)-
Z-5i (96.6% ee).
Scheme 13
Some typical examples of this coupling reaction are listed in
Table 7. With optically active Z-4c and Z-4d, the reaction gave
the corresponding products without loss of enantiopurity (entries
6, 8, and 10 of Table 7).
Sulfoxide Z-4e can be easily oxidized to the corresponding
sulfone Z-6e (eq 5). Under the catalysis of Ni(acac)2, its coupling
reaction with aryl zinc bromide afforded Z-5 with reasonable
yield (Table 8). With optically active starting compounds, the
loss of enantiopurity was not observed.
A control experiment showed that the hydroxy group in E-3aa
played an important role in the coupling reaction, since the
coupling reaction of a 1:1 mixture of E-3aa and 2-phenylethenyl
phenylsulfoxide with PhZnBr afforded Z-5c in 85% yield and
stilbene in only 24% yield (eq 4).
In conclusion, we have observed the unique regio- and
stereoselectivity in the halohydroxylation reaction of 1,2-allenic
sulfoxides, which provides an efficient entry to (E)-2-halo-3-
hydroxy-1-alkenyl sulfoxides. With optically active 1,2-allenic
sulfoxides, the efficiency for the chirality transfer is excellent.
9
4822 J. AM. CHEM. SOC. VOL. 125, NO. 16, 2003

Halohydroxylation of 1,2-Allenyl Phenyl Sulfoxides
A R T I C L E S
MS m/z 277 (M+ + 1, 65.27), 126 (100). HRMS calcd for C17H24OS:
276.1548. Found: 276.1543.
Based on the reaction of 1m, it was found that the absolute
configuration of the sulfur center is inverted after the halohy-
droxylation reaction. Due to the easy availability of the starting
materials, simple/convenient operation, and the ready elaboration
of the functional groups in the products, the reaction will show
its broad utility in organic synthesis. In addition, with different
nucleophiles and the search for different groups, which are
capable of controlling the pertinent selectivities, this protocol
will open up a new area for the highly selective synthesis of
stereodefined alkenes with functionality. Further study in this
area is being carried out in our laboratory.
(f) (S)-1,2-Undecadienyl Phenyl Sulfoxide ((S)-1d): The reaction
of (S)-undec-1-yn-3-ol (840 mg, 5 mmol, 95.7% ee), Et3N (505 mg, 5
mmol), and sulfenyl chloride (723 mg, 5 mmol) afforded 1.18 g (86%)
of (S)-1d, ee% ) 95.7%, dr ) 61:39 (HPLC conditions: Chiralcel
OD column (0.46 cm φ × 25 cm); λ 254 nm; rate, 0.7 mL/min; eluent,
hexane/i-PrOH ) 95:5). 1H NMR (300 MHz, CDCl3) δ 7.57-7.70 (m,
2H), 7.38-7.57 (m, 3H), 5.96-6.07 (m, 1H), 5.63-5.70 (m, 1H), 2.00-
2.20 (m, 2H), 1.12-1.50 (m, 12H), 0.86 (t, J ) 6.2 Hz, 3H).
(g) 4,4-Dimethylpenta-1,2-dienyl Phenyl Sulfoxide (1e): The
reaction of 4,4-dimethylpent-1-yn-3-ol (2.24 g, 20 mmol), Et3N (2.22
g, 22 mmol), and sulfenyl chloride (3.18 g, 22 mmol) afforded 3.68 g
Experimental Section
1
(84%) of the product as solid, mp 48-50 °C (CH2Cl2/n-hexane). H
NMR (300 MHz, CDCl3) δ 7.33-7.50 (m, 2H), 7.15-7.33 (m, 3H),
5.85 (d, J ) 5.82 Hz, 1H), 5.46 (d, J ) 5.82 Hz, 1H), 0.78 (s, 9H); IR
(KBr) 1942, 1050 cm-1; MS m/z 221 (M+ + 1, 100). Anal. Calcd for
C13H16OS: C, 70.90%; H, 7.30%. Found: C, 71.15%; H, 7.50%.
Synthesis of Starting Materials. General Procedure for the
Synthesis of Sulfinyl Allene Preparation: An oven-dried three-neck
round-bottom flask was charged with propargyl alcohol in methylene
chloride. After the mixture was cooled to -85 °C, 1 equiv of
triethylamine was added. After 10 min with stirring, a solution of
sulfenyl chloride (1 equiv) in methylene chloride was added dropwise.
After the reaction was stirred at -85 °C for another 10 min, it was
allowed to warm to room temperature following quenching with water.
The organic layer was separated, and the aqueous layer was extracted
with methylene chloride. The combined organic extracts were washed
with water and brine and dried over anhydrous magnesium sulfate. The
concentration of the solution reduced under pressure and afforded the
appropriate allene.
(h) 4,4-Dimethylpenta-1,2-dienyl Phenyl Sulfoxide ((S)-1e): The
reaction of (S)-4,4-dimethyl-pent-1-yn-3-ol (448 mg, 4 mmol, >99%
ee), Et3N (400 mg, 4 mmol), and sulfenyl chloride (578 mg, 4 mmol)
afforded 787 mg (89%) of (S)-1e, ee% > 99%, dr ) 92:8 (HPLC
conditions: Chiralcel OD column (0.46 cm φ × 25 cm); λ 254 nm;
rate, 0.7 mL/min; eluent, hexane/i-PrOH ) 100:2). 1H NMR (300 MHz,
CDCl3) δ 7.55-7.78 (m, 2H), 7.42-7.55 (m, 3H), 6.12 (d, J ) 5.88
Hz, 1H), 5.70 (d, J ) 5.88 Hz, 1H), 0.78 (s, 9H).
(i) 3-Methylbuta-1,2-dienyl Phenyl Sulfoxide (1f):14 The reaction
of 2-methyl-but-3-yn-2-ol (2.10 g, 25 mmol), Et3N (2.53 g, 25 mmol),
and sulfenyl chloride (3.62 g, 25 mmol) afforded 3.50 g (73%) of the
(a) 1,2-Propadienyl Phenyl Sulfoxide (1a):25 The reaction of
propargyl alcohol (3.08 g, 55 mmol), Et3N (5.05 g, 55 mmol), and
sulfenyl chloride (7.23 g, 50 mmol) afforded 6.75 g (82%) of the
1
product. H NMR (300 MHz, CDCl3) δ 7.56-7.60 (m, 2H), 7.42-
1
7.49 (m, 3H), 5.84-5.88 (m, 1H), 1.76 (d, J ) 2.40 Hz, 3H), 1.72 (d,
J ) 2.10 Hz, 3H); 13C NMR (75.4 MHz, CDCl3) δ 201.61, 144.83,
130.59, 128.94, 124.02, 104.65, 100.47, 19.89, 19.74.
product as oil. H NMR (300 MHz, CDCl3) δ 7.60-7.71 (m, 2H),
7.43-7.58 (m, 3H), 6.09 (t, J ) 9 Hz, 1H), 5.23-5.42 (m, 2H); 13C
NMR (75.4 MHz, CDCl3) δ 206.96, 144.09, 130.65, 128.80, 123.66,
101.67, 81.96; IR (neat) 1937 cm-1
.
(j) 2-(Cyclohexylideneethenyl)phenyl Sulfoxide (1g):14 The reac-
tion of 1-ethynylcyclohexanol (4.10 g, 33 mmol), Et3N (3.34 g, 33
mmol), and sulfenyl chloride (4.77 g, 33 mmol) afforded 6.72 g (88%)
(b) 1,2-Butadienyl Phenyl Sulfoxide (1b):26 The reaction of but-
3-yn-2-ol (4.97 g, 71 mmol), Et3N (7.2 g, 71 mmol), sulfenyl chloride
1
1
of the product. H NMR (300 MHz, CDCl3) δ 7.36-7.83 (m, 5H),
(9.35 g, 64.6 mmol) afforded 8.684 g (76%) of the product as oil. H
5.95 (s, 1H), 2.10-2.40 (m, 4H), 1.40-1.90 (m, 6H); 13C NMR (75.4
MHz, CDCl3) δ 201.50, 145.14, 130.67, 129.05, 124.13, 113.62, 102.99,
34.39, 34.34, 20.56, 20.54, 13.73; MS, m/z 215 (M+ -OH, 0.22), 79
(100).
NMR (300 MHz, CDCl3) δ 7.58-7.75 (m, 2H), 7.40-7.58 (m, 3H),
5.93-6.08 (m, 1H), 5.58-5.80 (m, 1H), 1.70-1.90 (m, 3H).
(c) 1,2-Heptadienyl Phenyl Sulfoxide (1c): The reaction of hept-
1-yn-3-ol (6.09 g, 54 mmol), Et3N (5.05 g, 50 mmol), and sulfenyl
chloride (7.23 g, 50 mmol) afforded 8.08 g (73%) of the product as an
oil. 1H NMR (300 MHz, CDCl3) δ 7.60-7.72 (m, 2H), 7.40-7.60 (m,
3H), 5.96-6.08 (m, 1H), 5.65 (m, 1H), 2.00-2.23 (m, 2H), 1.22-
(k) 1,2-heptadien-3-yl Phenyl Sulfoxide (1h): The reaction of hept-
2-yn-1-ol (5.68 g, 51 mmol), Et3N (5.13 g, 51 mmol), and sulfenyl
1
chloride (7.33 g, 51 mmol) afforded 9.42 g (85%) of the product. H
1.52 (m, 4H), 0.89 (t, J ) 7.0 Hz, 3H); IR (neat) 1946, 1046 cm-1
;
NMR (300 MHz, CDCl3) δ 7.58-7.61 (m, 2H), 7.44-7.51 (m, 3H),
5.18-5.29 (m, 2H), 2.11-2.16 (m, 1H), 1.77-1.81 (m, 1H), 1.17-
1.40 (m, 4H), 0.77 (t, J ) 7.2 Hz, 3H); 13C NMR (75.4 MHz, CDCl3)
δ 205.38, 143.37, 130.68, 128.86, 124.36, 113.01, 82.05, 29.26, 22.15,
21.88, 13.57; IR (neat) 1946, 1443 cm-1; MS m/z 220 (M+, 16.88),
126 (100). HRMS calcd for C13H16OS: 220.0918. Found: 220.0942.
MS m/z 221 (M+ + 1, 100). HRMS calcd for C13H16OS: 220.0918.
Found: 220.0890.
(d) (R)-1,2-Heptadienyl Phenyl Sulfoxide ((R)-1c): The reaction
of (R)-hept-1-yn-3-ol (240 mg, 2 mmol, 96% ee), 0.27 mL Et3N (200
mg, 2 mmol), and sulfenyl chloride (290 mg, 2 mmol) afforded (R)-
1c, 370 mg (84%), ee% ) 95.5%, dr ) 70:30 (HPLC conditions:
Chiralcel OD column (0.46 cm φ × 25 cm); λ 254 nm; rate, 0.7 mL/
(l) 1-Phenylpropadienyl Phenyl Sulfoxide (1i): The reaction of
3-phenylprop-2-yn-1-ol (3.68 g, 28 mmol), Et3N (2.83 g, 28 mmol),
and sulfenyl chloride (4.05 g, 28 mmol) afforded 5.76g (86%) of the
product. 1H NMR (300 MHz, CDCl3) δ 7.18-7.62 (m, 10H), 5.55 (d,
1
min; eluent, hexane/i-PrOH ) 95:5). H NMR (300 MHz, CDCl3) δ
7.56-7.73 (m, 2H), 7.40-7.56 (m, 3H), 5.93-6.06 (m, 1H), 5.60-
5.77 (m, 1H), 2.00-2.23 (m, 2H), 1.20-1.52 (m, 4H), 0.84-1.00 (m,
3H).
J ) 9 Hz, 1H), 5.47 (d, J ) 9 Hz, 1H); IR (neat) 1931, 1050 cm-1
;
MS m/z 240 (M+, 13.74), 115 (100). HRMS calcd for C15H12OS:
240.0606. Found: 240.0602.
(e) 1,2-Undecadienyl Phenyl Sulfoxide (1d): The reaction of undec-
(m) 2-Methylocta-2,3-dien-4-yl Phenyl Sulfoxide (1j): The reaction
of 2-methyl-oct-3-yn-2-ol (2.53 g, 18 mmol), Et3N (1.99 g, 20 mmol),
and sulfenyl chloride (2.86 g, 20 mmol) afforded 4.04 g (90%) of the
1-yn-3-ol (5.04 g, 30 mmol), Et3N (3.34 g, 33 mmol), and sulfenyl
chloride (4.77 g, 33 mmol) afforded 7.03 g (85%) of the product. H
1
NMR (300 MHz, CDCl3) δ 7.52-7.64 (m, 2H), 7.47-7.52 (m, 3H),
5.92-6.00 (m, 1H), 5.58-5.73 (m, 1H), 1.98-2.15 (m, 2H), 1.12-
1
product. H NMR (300 MHz, CDCl3) δ 7.57-7.63 (m, 2H), 7.43-
1.50 (m, 12H), 0.80 (t, J ) 6.71 Hz, 3H); IR (neat) 1941, 1051 cm-1
;
7.57 (m, 3H), 2.18-2.30 (m, 1H), 1.75-1.92 (m, 1H), 1.82 (s, 3H),
1.80 (s, 3H), 1.17-1.40 (m, 4H), 0.81 (t, J ) 7.21 Hz, 3H); 13C NMR
(75.4 MHz, CDCl3) δ 199.21, 143.82, 130.10, 128.52, 124.09, 111.17,
104.18, 29.35, 22.55, 21.66, 20.14, 19.95, 13.48; IR (neat) 1959, 1048
(25) Altenbach, H.; Soicke, H. Liebigs Ann. Chem. 1982, 1096.
(26) Bandin, J. B.; Julia, S. A.; Lorne, R. Bull. Soc. Chim. Fr. 1992, 440.
9
J. AM. CHEM. SOC. VOL. 125, NO. 16, 2003 4823

A R T I C L E S
Ma et al.
cm-1; MS m/z 248 (M+, 21.50), 81 (100). HRMS calcd for C15H20OS:
248.1230. Found: 248.1209.
(hexane/ethyl acetate (2:1)) afforded 42 mg (86%) of Z-2aa′ as oil. 1H
NMR (400 MHz, CDCl3) δ 7.75-7.77 (m, 2H), 7.53-7.55 (m, 3H),
6.97 (s, 1H), 4.85 (dd, J1 ) 15.60 Hz, J2 ) 1.5 Hz, 1H), 4.75 (dd, J1
) 15.60 Hz, J2 ) 1.5 Hz, 1H), 2.08 (s, 3H); 13C NMR (75.4 MHz,
CDCl3) δ 169.22, 143.40, 142.65, 131.42, 129.51, 124.20, 107.59,
70.05, 20.55; MS m/z 351 (M+ + 1, 75.08), 43 (100); IR (neat) 1743,
1223, 1041 cm-1. HRMS calcd for C11H11O3S (M+ - I): 223.0426.
Found: 223.0414.
(n) Hepta-1,2,6-trien-1-yl Phenyl Sulfoxide (1k): The reaction of
hept-6-en-1-yn-3-ol (2.59 g, 23 mmol), Et3N (2.29 g, 23 mmol), and
sulfenyl chloride (3.28 g, 23 mmol) afforded 3.13 g (63%) of the
1
product. H NMR (300 MHz, CDCl3) δ 7.58-7.73 (m, 2H), 7.45-
7.58 (m, 3H), 6.00-6.07 (m, 1H), 5.64-5.88 (m, 2H), 4.95-5.11 (m,
2H), 2.07-2.33 (m, 4H); IR (neat) 1949, 1641, 1047 cm-1; MS m/z
218 (M+, 3.24), 126 (100). HRMS calcd for C13H14OS: 218.0762.
Found: 218.0767.
(E)-2-Iodo-3-(phenylsulfinyl)-2-propenyl Acetate (E-2aa′). To a
dried reaction tube were added anhydrous NaOAc (82 mg, 1 mmol),
(E)-3aa (154 mg, 0.5 mmol), Ac2O (0.1 mL), and THF (1 mL) under
N2, and then the mixture was stirred at room temperature for 6 h. After
the reaction was complete, 1 mL of water and 10 mL of ethyl acetate
were added and the reaction mixture was neutralized with saturated
aqueous NaHCO3 and extracted with ethyl acetate. The combined
organic layer was dried over MgSO4 and purified by chromatography
on silica gel (hexane/ethyl acetate (4:1 to 2:1)) to afford 151 mg (86%)
(o) Hexa-1,2,5-trien-1-yl Phenyl Sulfoxide (1l): The reaction of
hex-5-en-1-yn-3-ol (2.88 g, 30 mmol), Et3N (3.0 g, 30 mmol), and
sulfenyl chloride (4.34 g, 30 mmol) afforded 3.54 g (58%) of the
1
product. H NMR (300 MHz, CDCl3) δ 7.56-7.70 (m, 2H), 7.40-
7.56 (m, 3H), 6.00-6.12 (m, 1H), 5.63-5.86 (m, 2H), 5.00-5.18 (m,
2H), 2.74-2.96 (m, 2H); IR (neat) 1948, 1638, 1082 cm-1; MS m/z
204 (M+, 1.66), 77 (100). HRMS calcd for C12H12OS: 204.0606.
Found: 204.0612.
1
of E-2aa′. H NMR (300 MHz, CDCl3) δ 7.65-7.72 (m, 2H), 7.50-
7.60 (m, 3H), 7.03 (s, 1H), 5.33 (d, J ) 13.5 Hz, 1H), 5.02 (d, J )
(p) 2-(Benzenesulfinylvinylidene)-1,7,7-trimethylbicyclo[2.2.1]-
heptane (1m): The reaction of (1R,2S,4R)-2-ethynyl-1,7,7-trimethylbi-
cyclo[2.2.1]heptan-2-ol (1.4 g, 7.9 mmol), Et3N (0.8 g, 7.9 mmol), and
sulfenyl chloride (1.14 g, 7.9 mmol) afforded 1.35 g (60%) of the
product as solid, mp 89-90 °C (n-hexane), [R]D25 ) -54.9° (C ) 1.0,
EtOH). 1H NMR (300 MHz, CDCl3) δ 7.58-7.69 (m, 2H), 7.42-7.58
(m, 3H), 6.06 (t, J ) 3.5 Hz, 1H), 2.63-2.76 (m, 1H), 2.10-2.21 (m,
1H), 1.63-1.88 (m, 3H), 1.37-1.48 (m, 1H), 1.20-1.31 (m, 1H), 0.90
(s, 6H), 0.86 (s, 3H); 13C NMR (75.4 MHz, CDCl3) δ 197.09, 144.85,
130.40, 128.82, 124.25, 120.31, 104.48, 53.11, 48.35, 44.51, 35.09,
34.41, 27.25, 19.46, 18.31, 13.11; IR (KBr) 1937, 1044 cm-1; MS m/z
262 (M+, 1.39), 105 (100).
13.5 Hz, 1H), 2.19 (s, 3H); IR (neat) 1739, 1669, 1220, 1021 cm-1
;
MS m/z 351 (M+ + 1, 49.05), 43 (100). HRMS calcd for C11H11O3S
(M+ - I): 223.0426. Found: 223.0429.
Typical Procedure for Iodohydroxylation of 1,2-Alkadienyl
Phenyl Sulfoxides. (a) (E)-2-Iodo-3-(phenylsulfinyl)-2-propen-1-ol
(E-3aa): A solution of LiOAc‚2H2O (102 mg, 1.0 mmol), water (0.3
mL), and 1,2-propadienyl phenylsulfoxide 1a (82 mg, 0.5 mmol) in
MeCN (2 mL) was treated at 55 °C with I2 (305 mg, 1.2 mmol) with
stirring for 1 h. When the reaction was complete, it was quenched with
water (2 mL), neutralized with saturated NaHCO3 and washed with
saturated sodium thiosulfate to remove the excess I2. Then the mixture
was extracted with CH2Cl2 (2 × 10 mL), and the organic layer was
dried over MgSO4. Filtration, evaporation, and flash chromatography
on silica gel afforded 147 mg (96%) of E-3aa as solid, mp 115.5-
116.5 °C (dichloromethane/n-hexane). 1H NMR (300 MHz, CDCl3) δ
7.60-7.74 (m, 2H), 7.44-7.60 (m, 3H), 6.89 (s, 1H), 4.56 (d, J )
14.97 Hz, 1H), 4.69 (d, J ) 15.21 Hz, 1H), 3.98 (bs, 1H); 13C NMR
(75.4 MHz, CDCl3) δ 143.60, 142.51, 131.46, 129.70, 124.54, 115.79,
68.22; IR (KBr) 3219, 1589, 1473, 1012 cm-1; MS m/z 308 (M+, 100).
(b) (E)-3-Iodo-4-(phenylsulfinyl)-3-buten-2-ol (E-3ab): The reac-
tion of 1b (89 mg, 0.5 mmol), I2 (203 mg, 0.8 mmol), and LiOAc‚
2H2O (102 mg, 1.0 mmol) afforded 140 mg (87%) of E-3ab as solid,
mp 118-119 °C (dichloromethane/n-hexane), dr ) 66:34. Major
isomer: 1H NMR (300 MHz, CDCl3) δ 7.40-7.73 (m, 5H), 6.89 (s,
1H), 4.60-4.66 (m, 1H), 4.10 (bs, 1H), 1.28 (d, J ) 6.20 Hz, 3H).
Minor isomer: 1H NMR (300 MHz, CDCl3) δ 7.40-7.73 (m, 5H),
6.85 (s, 1H), 4.66-4.73 (m, 1H), 4.10 (bs, 1H), 1.38 (d, J ) 6.33 Hz,
3H); IR (KBr) 3392, 1646, 1580, 1009 cm-1; MS m/z 322 (M+, 5.61),
43 (100). Anal. Calcd. for C10H11IO2S: C, 37.28%; H, 3.44%. Found:
C, 37.22%; H, 3.41%.
(q) 2-Benzenesulfinylbuta-2,3-dien-1-ol (1n): The reaction of but-
2-yn-1,4-diol (5.16 g, 60 mmol), Et3N (3.01g, 30 mmol), and sulfenyl
1
chloride (4.34 g, 30 mmol) afforded 1.52 g (26%) of the product. H
NMR (300 MHz, CDCl3) δ 7.57-7.75 (m, 2H), 7.40-7.57 (m, 3H),
5.41 (d, J ) 7.77 Hz, 1H), 5.24 (d, J ) 7.77 Hz, 1H), 4.10-4.40 (m,
1H), 4.40-4.50 (m, 1H), 3.12 (t, J ) 5.02 Hz, 1H); IR (neat) 1944,
1042 cm-1; MS m/z 194 (M+, 15.74), 147 (100). HRMS calcd for
C10H10O2S: 194.0399. Found: 194.0412
(r) 2-Benzenesulfinyl-4-methylpenta-2,3-dienoic Acid (1o):27 The
reaction of 4-hydroxy-4-methyl-but-2-ynoic acid methyl ester (2.84 g,
20 mmol), Et3N (2.02 g, 20 mmol), and sulfenyl chloride (2.89 g, 20
mmol) afforded 3.66 g (72%) of the product. 1H NMR (300 MHz,
CDCl3) δ 7.63-7.82 (m, 2H), 7.42-7.60 (m, 3H), 3.81 (s, 3H), 1.89
(s, 3H), 1.76 (s, 3H).
(Z)-2-Iodo-3-(thiophenyl)-2-propenyl Acetate (Z-2aa). A solution
of NaI (300 mg, 2 mmol) and 1a (82 mg, 0.5 mmol) in HOAc (1.5
mL) was heated at 80 °C with stirring for 5 h. When the reaction was
complete, 2 mL of water was added, and the reaction mixture was
extracted with ether (2 × 10 mL). The combined organic layer was
washed with saturated NaHCO3 until pH ) 7 and dried over MgSO4.
Filtration, evaporation, and chromatography on silica gel (n-hexane/
ethyl acetate (20:1)) afforded 69 mg (41%) of Z-2aa as oil.1H NMR
(300 MHz, CDCl3) δ 7.40-7.49 (m, 2H), 7.28-7.40 (m, 3H), 7.12 (s,
1H), 4.80 (s, 2H), 2.11 (s, 3H); 13C NMR (75.48 MHz, CDCl3) δ
170.13, 139.09, 133.25, 131.04, 129.39, 128.02, 92.66, 71.40, 20.94;
(c) (E)-2-Iodo-1-(phenylsulfinyl)-1-hepten-3-ol (E-3ac): The reac-
tion of 1c (110 mg, 0.5 mmol), I2 (203 mg, 0.8 mmol), and LiOAc‚
2H2O (102 mg, 1.0 mmol) afforded 161 mg (89%) of E-3ac as solid,
mp 107-108 °C (dichloromethane/n-hexane), dr ) 63:37. IR (KBr)
3285, 1578 cm-1; MS m/z 365 (M+ + 1, 29.7), 109 (100). Anal. Calcd
for C13H17IO2S: C, 42.87%; H, 4.70%. Found: C, 42.70%; H, 4.59%.
The two isomers can be separated by repeated chromatography on silica
gel. Less polar isomer: 1H NMR (300 MHz, CDCl3) δ 7.63-7.67 (m,
2H), 7.49-7.53 (m, 3H), 6.92 (s, 1H), 4.42 (dd, J1 ) 12.9 Hz, J2 )
6.3 Hz, 1H), 3.31-4.33 (bs, 1H), 1.64 (q, J ) 6.9 Hz, 2H), 1.31-1.46
(m, 4H), 0.92 (t, J ) 7.2 Hz, 3H); 13C NMR (75.4 MHz, CDCl3) δ
143.83, 143.22, 131.26, 129.51, 125.15, 124.25, 73.18, 37.26, 27.01,
22.43, 13.89. More polar isomer: 1H NMR (300 MHz, CDCl3) δ 7.58-
7.62 (m, 2H), 7.51-7.58 (m, 3H), 6.98 (s, 1H), 5.07 (d, J ) 3.3 Hz,
1H), 4.36-4.42 (m, 1H), 1.69-1.73 (m, 1H), 1.21-1.46 (m, 5H), 0.89
(t, J ) 7.2 Hz, 3H); 13C NMR (75.4 MHz, CDCl3) δ 142.46, 142.08,
131.49, 129.61, 128.89, 124.34, 71.33, 36.46, 27.27, 22.46, 13.91.
MS m/z 334 (M+, 1.69), 207 (100); IR (neat) 1737, 1650, 1232 cm-1
.
HRMS calcd for C11H11IO2S: 333.9521. Found: 333.9510.
(Z)-2-Iodo-3-(phenylsulfinyl)-2-propenyl Acetate (Z-2aa′). A solu-
tion of Z-2aa (40 mg, 0.14 mmol), HOAc (0.5 mL), and H2O2 (30%,
0.05 mL, 0.44 mmol) was stirred at room temperature for 18 h. When
the reaction was over, 2 mL of water was added, and reaction mixture
was extracted with ether (2 × 10 mL). The combined organic layer
was washed with saturated NaHCO3 until pH ) 7 and dried over
MgSO4. Filtration, evaporation, and chromatography on silica gel
(27) Conrads, M.; Mattay, J. Synthesis 1991, 11.
9
4824 J. AM. CHEM. SOC. VOL. 125, NO. 16, 2003

Halohydroxylation of 1,2-Allenyl Phenyl Sulfoxides
A R T I C L E S
(d) (E)-2-Iodo-1-(phenylsulfinyl)-1-undecen-3-ol (E-3ad): The
reaction of 1d (110 mg, 0.4 mmol), I2 (163 mg, 0.64 mmol), and LiOAc‚
2H2O (60 mg, 0.60 mmol) afforded 150 mg (89%) of E-3ad, dr )
72:28. 1H NMR (300 MHz, CDCl3) δ 7.59-7.70 (m, 2H), 7.48-7.59
(m, 3H), 6.97 (s, 1H), 4.38-4.48 (m, 1H), 2.66 (bs, 1H), 1.62-1.80
(m, 2H), 1.14-1.62 (m, 12H), 0.81-0.96 (m, 3H). The following signal
is discernible for the minor isomer: 6.90 (s, 1H); IR (KBr) 3330, 1582,
1034 cm-1; MS m/z 421 (M+ + 1, 37.29), 403 (100); HRMS calcd for
C17H26IO2S (M ++ 1): 421.0691. Found: 421.0722.
(e) (E)-2-Iodo-4,4-dimethyl-1-(phenylsulfinyl)-1-penten-3-ol (E-
3ae): The reaction of 1e (110 mg, 0.4 mmol), I2 (153 mg, 0.60 mmol),
and LiOAc‚2H2O (102 mg, 1.0 mmol) afforded 158 mg (87%) of E-3ae
as solid, mp 163.5-164.5 °C (dichloromethane/n-hexane), dr ) 92:8.
1H NMR (300 MHz, CDCl3) δ 7.65-7.73 (m, 2H), 7.47-7.59 (m,
3H), 7.21 (s, 1H), 4.36 (s, 1H), 3.70-4.20 (s, 1H), 1.07 (s, 9H). The
following signal is discernible for the minor isomer: 7.10 (s, 1H), 4.40
(s, 1H); IR (KBr) 3422, 1626, 1032 cm-1; MS m/z 365 (M+ + 1, 11.7),
57 (100). Anal. Calcd for C13H17IO2S: C, 42.87%; H, 4.70%. Found:
C, 42.72%; H, 4.82%.
(f) (E)-3-Iodo-2-methyl-4-(phenylsulfinyl)-3-buten-2-ol (E-3af):
The reaction of 1f (96 mg, 0.5 mmol), I2 (152 mg, 0.60 mmol), and
LiOAc‚2H2O (102 mg, 1.0 mmol) afforded 146 mg (87%) of E-3af as
solid, mp 147.5-148.5 °C (ethyl acetate/n-hexane). 1H NMR (300 MHz,
CDCl3) δ 7.73-7.87 (m, 2H), 7.42-7.60 (m, 3H), 6.73 (s, 1H), 3.40-
2.50 (bs, 1H), 1.66 (s, 3H), 1.44 (s, 3H); 13C NMR (75.4 MHz, CDCl3)
δ 144.31, 143.90, 130.99, 129.26, 125.03, 120.99, 77.78, 30.16, 29.62;
IR (KBr) 3262, 1626, 1576 cm-1; MS m/z 336 (M+, 0.71), 43 (100).
Anal. Calcd for C11H13IO2S: C, 39.30%; H, 3.90%. Found: C, 39.69%;
H, 3.63%.
(g) 1-[(E)-1′-Iodo-2′-(phenylsulfinyl)ethenyl]-1-cyclohaxanol (E-
3ag): The reaction of 1g (232 mg, 1.0 mmol), I2 (304 mg, 1.2 mmol),
and LiOAc‚2H2O (204 mg, 2.0 mmol) afforded 277 mg (74%) of E-3ag
as solid, mp 173-174 °C (dichloromethane/n-hexane). 1H NMR (300
MHz, CDCl3) δ 7.72-7.87 (m, 2H), 7.42-7.58 (m, 3H), 6.77 (s, 1H),
4.12-4.31 (bs, 1H), 2.03-2.20 (m, 2H), 1.85-2.03 (m, 2H), 1.37-
1.85 (m, 4H), 1.13-1.23 (m, 2H); 13C NMR (75.4 MHz, CDCl3) δ
144.48, 144.14, 130.81, 129.15, 124.98, 123.66, 78.52, 36.25, 35.73,
24.84, 21.50, 21.04; MS m/z 377 (M+ + 1, 11.12), 359 (100); IR (KBr)
3235, 1591, 1029 cm-1. Anal. Calcd for C14H17IO2S: C, 44.69%; H,
4.55%. Found: C, 44.45%; H, 4.36%.
MHz, CDCl3) δ 7.84-7.87 (m, 2H), 7.74-7.50 (m, 3H), 3.8-4.2 (bs,
1H), 2.55-2.65 (m, 1H), 2.38-2.48 (m, 1H), 1.81 (s, 3H), 1.71 (s,
3H), 1.43-1.54 (m, 1H), 1.20-1.34 (m, 2H), 0.94-1.03 (m, 1H), 0.83
(t, J ) 7.3 Hz, 3H); 13C NMR (75.4 MHz, CDCl3) δ 146.85, 143.78,
130.63, 129.09, 125.71, 123.72, 79.16, 34.35, 33.18, 31.87, 31.36, 23.05,
13.90; MS, m/z 393 (M+ + 1, 27.84), 375 (100); IR (KBr) 3218, 1673,
1029 cm-1; Anal. Calcd for C15H21IO2S: C, 45.93%; H, 5.40%.
Found: C, 45.81%; H, 5. 23%.
(k) (E)-2-Iodo-1-(phenylsulfinyl)-1,6-heptadien-3-ol (E-3ak): The
reaction of 1k (436 mg, 1.0 mmol), I2 (305 mg, 1.20 mmol), and LiOAc‚
2H2O (408 mg, 4.0 mmol) afforded 594 mg (82%) of E-3ak as solid,
mp 86-94 °C (dichloromethane/n-hexane). 1H NMR (300 MHz,
CDCl3) δ 7.43-7.83 (m, 5H), 6.93 (s, 1H), 5.75-5.95 (m, 1H), 4.96-
5.23 (m, 2H), 4.35-4.60 (m, 1H), 3.37 (bs, 1H), 2.05-2.40 (m, 2H),
1.71-2.01 (m, 2H). The following signal is discernible for the minor
isomer: 6.97 (s, 1H); IR (KBr) 3402, 1635, 1016 cm-1; MS m/z 345
(M+ - 17, 40.7), 109 (100). HRMS calcd for C13H14IOS (M+ - OH):
344.9806. Found: 344.9824.
(l) (E)-2-Iodo-1-(phenylsulfinyl)-1,5-hexadien-3-ol (E-3al): The
reaction of 1l (102 mg, 0.5 mmol), I2 (203 mg, 0.80 mmol), and LiOAc‚
2H2O (102 mg, 1.0 mmol) afforded 160 mg (92%) of E-3al as solid,
mp 92-95 °C (dichloromethane/n-hexane). 1H NMR (300 MHz,
CDCl3) δ 7.60-7.78 (m, 2H), 7.42-7.60 (m, 3H), 6.99 (s, 1H), 5.65-
5.95 (m, 1H), 5.08-5.31 (m, 2H), 4.45-4.64 (m, 1H), 2.40-2.60 (m,
2H), 2.24-2.40 (m, 1H). The following signal is discernible for the
minor isomer: 6.94 (s, 1H); IR (KBr): 3350, 1637, 1028 cm-1; MS
m/z 348 (M+, 12.04), 109 (100). Anal. Calcd. for C12H13IO2S: C,
41.39%; H, 3.76%. Found: C, 41.37%; H, 3.64%.
(m) (1R,2R,4R)-2-Hydroxyl-2-[(E)-1′-iodo-2′-(phenylsulfinyl)ethe-
nyl]-1,7,7-trimethylbicyclo[2.2.1]heptane (E-3am): The reaction of 1m
(72 mg, 0.25 mmol), I2 (77 mg, 0.30 mmol), and LiOAc‚2H2O (51
mg, 0.50 mmol) afforded 105 mg (98%) of E-3am as solid, mp 141-
143 °C (dichloromethane/n-hexane), [R]20D ) -142.3° (C ) 1, ethanol).
1H NMR (300 MHz, CDCl3) δ 7.82-7.88 (m, 2H), 7.56-7.63 (m,
3H), 7.36 (s, 1H), 2.75 (d, J ) 14 Hz, 1H), 2.42-2.65 (s, 1H), 2.26-
2.37 (m, 1H), 1.99 (t, J ) 4 Hz, 1H), 1.57-1.95 (m, 4H), 1.36 (s, 3H),
1.24 (s, 3H), 1.01 (s, 3H); MS m/z 431 (M+ + 1, 0.57), 413 (100); IR
(KBr) 3394, 1626, 1220, 999 cm-1
.
(n) (E)-3-Iodo-2-(phenylsulfinyl)-2-buten-1,4-diol (E-3an): The
reaction of 1n (97 mg, 0.50 mmol), I2 (203 mg, 0.80 mmol), and LiOAc‚
2H2O (102 mg, 1.0 mmol) afforded 137 mg (81%) of E-3an as solid,
mp 97-98 °C (dichloromethane). 1H NMR (300 MHz, CDCl3) δ 7.60-
7.71 (m, 2H), 7.48-7.60 (m, 3H), 4.93 (d, J ) 14.97 Hz, 1H), 4.75 (d,
J ) 13.95 Hz, 1H), 4.47 (d, J ) 13.21 Hz, 1H), 4.37 (d, J ) 13.21 Hz,
1H), 2.85 (bs, 2H); IR (KBr) 3378, 1604, 1030 cm-1; MS m/z 338
(M+, 5.64), 127 (100). Anal. Calcd for C10H11IO3S: C, 35.52%; H,
3.28%. Found: C, 35.43%; H, 3.19%.
(h) (E)-2-Iodo-3-(phenylsulfinyl)-2-hepten-1-ol (E-3ah): The reac-
tion of 1h (110 mg, 0.50 mmol), I2 (203 mg, 0.8 mmol), and LiOAc‚
2H2O (102 mg, 1.0 mmol) afforded 149 mg (82%) of E-3ah: solid,
mp 83-84 °C (dichloromethane/n-hexane). 1H NMR (300 MHz,
CDCl3) δ 7.40-7.53 (m, 2H), 7.53-7.68 (m, 3H), 4.94 (d, J ) 13.4
Hz, 1H), 4.86 (d, J ) 13.4 Hz, 1H), 2.80-3.03 (bs, 1H), 2.37-2.52
(m, 1H), 2.08-2.22 (m, 1H), 1.33-1.53 (m, 1H), 1.09-1.33 (m, 3H),
0.77 (t, J ) 7.3 Hz, 3H); 13C NMR (75.4 MHz, CDCl3) δ 150.81,
141.55, 130.77, 129.19, 124.33, 117.55, 67.20, 32.05, 30.51, 22.74,
(o) Methyl (E)-4-Methyl-3-iodo-3-hydroxy-2-(phenylsulfinyl)-2-
pentenoate (E-3ao): The reaction of 1o (100 mg, 0.40 mmol), I2 (127
mg, 0.50 mmol), and LiOAc‚2H2O (102 mg, 1.0 mmol) afforded 134
mg (85%) of E-3ao as solid, mp 161-163 °C (dichloromethane/n-
13.47; MS m/z 365 (M+ + 1, 100); IR (KBr) 3324, 1615, 1042 cm-1
.
Anal. Calcd for C13H17IO2S: C, 42.87%; H, 4.70%. Found: C, 43.00%;
H, 4.68%.
1
hexane). H NMR (300 MHz, CDCl3) δ 7.87-8.00 (m, 2H), 7.35-
(i) (E)-2-Iodo-3-phenyl-3-(phenylsulfinyl)-2-propen-1-ol (E-3ai):
The reaction of 1i (120 mg, 0.50 mmol), I2 (203 mg, 0.8 mmol), and
LiOAc‚2H2O (102 mg, 1.0 mmol) afforded 151 mg (79%) of E-3ai as
solid, mp 147-148 °C (dichloromethane-hexane). 1H NMR (300 MHz,
CDCl3) δ 6.89-7.56 (m, 8H), 6.49-6.89 (bs, 2H), 5.13 (d, J ) 13.59
Hz, 1H), 5.02 (d, J ) 13.64 Hz, 1H), 3.22-3.55 (bs, 1H); 13C NMR
(75.4 MHz, CDCl3) δ 151.39, 140.95, 134.27, 130.94, 129.76, 128.81,
128.78, 127.60, 124.57, 120.00, 67.03; MS m/z 385 (M+ + 1, 56.04),
131 (100); IR (KBr) 3356, 1616, 1017 cm-1. Anal. Calcd for C15H13-
IO2S: C, 46.89%; H, 3.41%. Found: C, 46.71%; H, 3.27%.
(j) (E)-3-Iodo-2-methyl-4-(phenylsulfinyl)-3-octen-2-ol (E-3aj):
The reaction of 1j (248 mg, 1.0 mmol), I2 (305 mg, 1.20 mmol), and
LiOAc‚2H2O (204 mg, 2.0 mmol) afforded 345 mg (88%) of E-3aj as
solid, mp 150-152 °C (dichloromethane/n-hexane). 1H NMR (300
7.50 (m, 3H), 4.15-4.65 (bs, 1H), 3.76 (s, 3H), 1.62 (s, 3H), 1.17 (s,
3H); MS m/z 395 (M+ + 1, 100); IR (KBr) 3237, 1730, 1593, 1241,
1018 cm-1; Anal. Calcd for C13H15IO4S: C, 39.61%; H, 3.84; Found:
C, 39.32%; H, 3.84%.
Bromohydroxylation of 1,2-Alkadienyl Phenyl Sulfoxides. (a) (E)-
2-Bromo-3-(phenylsulfinyl)-2-propen-1-ol (E-3ba): The reaction of
CuBr2 (892 mg, 4.0 mmol), 1a (164 mg, 1.0 mmol), and water/acetone
(1:2 (v/v), 8 mL) was stirred at 40-45 °C for 1.5 h. After the reaction
was complete as monitored by TLC, it was extracted with CH2Cl2 (3
× 10 mL) and the combined layer was washed subsequently with
saturated aqueous NaHCO3 and distilled water and dried over MgSO4.
Filtration, evaporation, and flash chromatography on silica gel (elu-
ent: hexane/ethyl acetate (2:1)) afforded 230 mg (88%) of 3ba as solid,
mp 87-88 °C (dichloromethane/n-hexane). 1H NMR (300 MHz,
9
J. AM. CHEM. SOC. VOL. 125, NO. 16, 2003 4825

A R T I C L E S
Ma et al.
CDCl3) δ 7.67-7.70 (m, 2H), 7.52-7.57 (m, 3H), 6.67 (s, 1H), 4.70
(d, J ) 15.2 Hz, 1H), 4.64 (d, J ) 15.2 Hz, 1H), 4.41 (bs, 1H); 13C
NMR (75.4 MHz, CDCl3) δ 142.77, 137.39, 137.21, 131.42, 129.60,
7.60-7.69 (m, 2H), 7.47-7.59 (m, 3H), 6.70 (s, 1H), 4.94-5.04 (m,
1H), 4.08-4.12 (m, 1H), 1.71-1.92 (m, 2H), 1.31-1.55 (m, 4H), 0.83-
1.05 (m, 3H). Minor isomer: 1H NMR (300 MHz, CDCl3) δ 7.60-
7.69 (m, 2H), 7.47-7.59 (m, 3H), 6.67 (s, 1H), 4.90-5.00 (m, 1H),
3.10 (d, J ) 7.23 Hz, 1H), 1.71-1.92 (m, 2H), 1.31-1.55 (m, 4H),
0.83-1.05 (m, 3H); IR (KBr) 3378, 1694, 1601, 1046 cm-1; MS m/z
319 (M+ + 1 (81Br), 3.35), 317 (M+ + 1 (79Br), 3.71), 77 (100). Anal.
Calcd for C13H17BrO2S: C, 49.22%; H, 5.40%. Found: C, 49.07%; H,
5.40%.
124.38, 65.13; IR (KBr) 3278, 1607, 1027 cm-1; MS m/z 263 (M+
+
1 (81Br), 4.66), 261 (M+ + 1 (79Br), 4.62), 77 (100). Anal. Calcd for
C9H9BrO2S: C, 41.40%; H, 3.47%. Found: C, 41.42%; H, 3.44%.
(b) (E)-2-Bromo-4,4-dimethyl-1-(phenylsulfinyl)-1-penten-3-ol (E-
3be): The reaction of 1e (55 mg, 0.25 mmol), CuBr2 (223 mg, 1.00
mmol), and H2O/acetone (1:2, 3 mL) afforded 69 mg (87%) of E-3be
1
as solid, mp 144 °C-145 °C (dichloromethane/n-hexane). H NMR
(g) (E)-2-Bromo-1-(phenylsulfinyl)-1-undec-3-ol (E-3bd): The
reaction of 1d (138 mg, 0.50 mmol), NBS (110 mg, 0.60 mmol), and
LiOAc‚2H2O (60 mg, 0.60 mmol) afforded 182 mg (98%) of E-3bd
as solid, mp 84-85 °C (dichloromethane/n-hexane). Major isomer: 1H
NMR (300 MHz, CDCl3) δ 7.61-7.69 (m, 2H), 7.52-7.55 (m, 3H),
6.70 (s, 1H), 4.91-5.06 (m, 1H), 4.06 (d, J ) 4.71 Hz, 1H), 1.70-
1.86 (m, 2H), 1.10-1.55 (m, 12H), 0.88 (t, J ) 6.64 Hz, 3H). Minor
isomer: 1H NMR (300 MHz, CDCl3) δ 7.61-7.69 (m, 2H), 7.52-
7.55 (m, 3H), 4.85-5.05 (m, 1H), 3.02 (d, J ) 7.46 Hz, 1H), 1.70-
1.86 (m, 2H), 1.10-1.55 (m, 12H), 0.88 (t, J ) 6.64 Hz, 3H); IR (KBr)
3394, 1595, 1034 cm-1; MS m/z 375 (M+ + 1 (81Br), 19.20), 373 (M+
(300 MHz, CDCl3) δ 7.63-7.76 (m, 2H), 7.51-7.63 (m, 3H), 6.89 (s,
1H), 4.85 (m, 1H), 2.97 (m, 1H), 1.12 (s, 9H). The following signal is
discernible for the minor isomer: 6.80 (s, 1H), 1.19 (s, 9H). 13C NMR
(75.4 MHz, CDCl3) δ 142.75, 142.53, 137.65, 131.68, 129.66, 124.87,
77.51, 36.33, 27.06; MS m/z 319 (M+ + 1 (81Br), 31.46), 317 (M+
+
1 (79Br), 31.11), 243 (100); IR (KBr) 3362, 1578, 1034 cm-1. Anal.
Calcd for C13H17BrO2S: C, 49.22%; H, 5.40%. Found: C, 49.02%; H,
5.35%.
(c) (E)-2-Bromo-3-(phenylsulfinyl)-2-hepten-1-ol (E-3bh): The
reaction of 1h (55 mg, 0.25 mmol), CuBr2 (223 mg, 1.00 mmol), and
H2O/acetone (1:2, 3 mL) afforded 68 mg (86%) of E-3bh as solid, mp
71 °C-72 °C (dichloromethane/n-hexane).1H NMR (300 MHz, CDCl3)
δ 7.61-7.64 (m, 2H), 7.26-7.53 (m, 3H), 4.87-4.93 (m, 2H), 3.08
(t, J ) 6.60 Hz, 1H), 2.33-2.38 (m, 1H), 2.14-2.18 (m, 1H), 1.25-
1.50 (m, 1H), 1.15-1.25 (m, 2H), 0.70-0.90 (m, 1H), 0.76 (t, J )
6.90 Hz, 3H); 13C NMR (75.4 MHz, CDCl3) δ 146.95, 141.35, 135.52,
130.80, 129.14, 124.38, 64.40, 30.28, 27.62, 22.72, 13.41; IR (KBr)
3348, 1616, 1030 cm-1; MS m/z 319 (M+ + 1 (81Br), 80.63), 317 (M+
+ 1 (79Br), 79.39), 299 (100). Anal. Calcd for C13H17BrO2S: C, 49.22%;
H, 5.40%. Found: C, 49.27%; H, 5.30%.
(d) (E)-3-Bromo-2-methyl-4-(phenylsulfinyl)-3-octen-2-ol (E-
3bj): The reaction of 1j (62 mg, 0.25 mmol), CuBr2 (223 mg, 1.00
mmol), and H2O/acetone (1:2, 3 mL) afforded 79 mg (92%) of E-3bj
as solid, mp 126-127 °C (dichloromethane/n-hexane). 1H NMR (400
MHz, CDCl3) δ 7.85-7.88 (m, 2H), 7.47-7.50 (m, 3H), 3.60-4.80
(bs, 1H), 2.36-2.50 (m, 2H), 1.77 (s, 3H), 1.63 (s, 3H), 1.37-1.56
(m, 1H), 1.21-1.31 (m, 2H), 0.91-1.03 (m, 1H), 0.82 (t, J ) 7.3 Hz,
3H); 13C NMR (75.4 MHz, CDCl3) δ 143.66, 142.78, 140.85, 130.62,
129.07, 125.60, 78.28, 31.30, 31.26, 30.74, 28.98, 23.12, 13.93; IR
(KBr) 3241, 1593, 1032 cm-1; MS m/z 347 (M+ + 1 (81Br), 23.39),
345 (M+ + 1 (79Br), 23.79), 329 (100); Anal. Calcd for C15H21BrO2S:
C, 52.18%; H, 6.13%. Found: C, 52.39%; H, 5.98%.
(e) (1R,2R,4R)-2-hydroxy-2-[(E)-1′-bromo-2′-(phenylsulfinylethe-
nyl)]-1,7,7-trimethylbicyclo[2.2.1]heptane (E-3bm): The reaction of
1m (72 mg, 0.25 mmol), CuBr2 (223 mg, 1.00 mmol), and H2O/acetone
(1:2, 3 mL) afforded 38 mg of E-3bm (94.5%) as solids, mp 170 -172
°C (dichloromethane/n-hexane), [R]20D ) -208.1° (C ) 1.0, alcohol).
1H NMR (300 MHz, CDCl3) δ 7.70-7.73 (m, 2H), 7.42-7.45 (m,
3H), 6.72 (s, 1H), 3.02 (s, 1H), 2.62 (d, J ) 14.10 Hz, 1H), 2.02-2.09
(m, 1H), 1.85 (t, J ) 4.20 Hz, 1H), 1.60-1.70 (m, 2H),1.40-1.52 (m,
2H), 1.21 (s, 3H), 1.15 (s, 3H), 0.89 (s, 3H); 13C NMR (75.4 MHz,
CDCl3) δ 144.52, 142.69, 140.06, 130.82, 129.18, 125.12, 87.49, 56.43,
50.33, 46.57, 45.56, 30.84, 25.57, 21.10, 20.63, 11.26. IR (KBr) 3394,
1626, 1021 cm-1; MS m/z 385 (M+ + 1 (81Br), 10.46), 383 (M+ + 1
(79Br), 10.37), 367 (100), 365 (96.16). Anal. Calcd for C18H23BrO2S:
C, 56.40%; H, 6.05%. Found: C, 56.34%; H, 6.02%. In this reaction,
42 mg of the starting material was recovered.
(f) (E)-2-Bromo-1-(phenylsulfinyl)-1-hepten-3-ol (E-3bc): The
reaction of 1c (110 mg, 0.50 mmol), NBS (110 mg, 0.60 mmol), LiOAc‚
2H2O (60 mg, 0.60 mmol), and H2O/CH3CN (1:7, 2.5 mL) was stirred
at room temperature for 2 h. After the reaction was complete as
monitored by TLC, it was subsequently extracted with CH2Cl2 (3 ×
10 mL) and the combined layer was washed with brine and dried over
MgSO4. Filtration, evaporation, and flash chromatography on silica gel
afforded 143 mg (90%) of E-3bc as solid, mp 70-71 °C (dichlo-
romethane/n-hexane). Major isomer: 1H NMR (300 MHz, CDCl3) δ
+ 1 (79Br), 19.11), 357 (100). HRMS calcd for C17H2681BrO2S (M+
+
1): 375.0810. Found: 375.0815. HRMS calcd for C17H2679BrO2S (M+
+ 1): 373.0830. Found: 373.0825.
(h) (E)-3-Bromo-2-methyl-4-(phenylsulfinyl)-3-buten-2-ol (E-
3bf): The reaction of 1f (96 mg, 0.50 mmol), NBS (110 mg, 0.60
mmol), and LiOAc‚2H2O (60 mg, 0.60 mmol) afforded 98 mg (68%)
of E-3bf as solid, mp 112.5-113.5 °C (dichloromethane/n-hexane).
1H NMR (300 MHz, CDCl3) δ 7.79-7.81 (m, 2H), 7.48-7.50 (m,
3H), 6.47 (s, 1H), 1.63 (s, 3H), 1.40-1.60 (bs, 1H), 1.41 (s, 3H); 13C
NMR (75.4 MHz, CDCl3) δ 144.22, 141.73, 136.93, 130.95, 129.21,
124.88, 77.45, 29.00, 28.93; IR (KBr) 3265, 1628, 1591, 1023 cm-1
;
MS m/z 290 (M+ (81Br), 1.22), 288 (M+ (79Br), 1.09), 43 (100). Anal.
Calcd for C11H13BrO2S: C, 45.69%; H, 4.53%. Found: C, 45.44%; H,
4.45%.
Chlorohydroxylation of 1,2-Alkadienyl Phenyl Sulfoxides. (a) (E)-
2-Chloro-3-(phenylsulfinyl)-2-propen-1-ol (E-3ca): To a pestle were
added 400 mg of silica gel (200 mesh) and 1a (180 mg, 1.1 mmol).
After these were mixed thoroughly, CuCl2‚2H2O (748 mg, 4.4 mmol)
was added and the mixture was milled for a couple of minutes followed
by heating at 65 °C (under an IR lamp) for 5 min. This process was
repeated 4 times until the complete disappearance of the starting
sulfoxide. Chromatography on silica gel (eluent: petroleum ether/ethyl
acetate (1:1 to 1:2)) afforded 105 mg (49%) of 3ca as an oil. 1H NMR
(400 MHz, CDCl3) δ 7.67-7.69 (m, 2H), 7.48-7.55 (m, 3H), 6.47 (s,
1H), 4.80-5.40 (bs, 1H), 4.69 (d, J ) 14.90 Hz, 1H), 4.59 (d, J )
14.90 Hz, 1H); 13C NMR (75.4 MHz, CDCl3) δ 146.27, 142.76, 134.18,
131.36, 129.54, 124.29, 63.38; IR (neat) 3338, 1614, 1030 cm-1; MS
m/z 219 (M+ + 1 (37Cl), 16.90, 217 (M+ + 1 (35Cl), 42.64)), 77 (100).
HRMS calcd for C9H8ClOS (M+ - OH): 198.9980. Found: 198.9977.
(b) (E)-2-Chloro-4,4-dimethyl-1-(phenylsulfinyl)-1-penten-3-ol (E-
3ce): The reaction of 200 mg of silica gel (200 mesh), 1e (110 mg,
0.50 mmol), and CuCl2‚2H2O (340 mg, 2.0 mmol) afforded 114 mg
(84%) of E-3ce as solid, mp 146-148°C (CH2Cl2/n-hexane). 1H NMR
(300 MHz, CDCl3) δ 7.68-7.71 (m, 2H), 7.52-7.56 (m, 3H), 6.60 (s,
1H), 4.88 (d, J ) 5.4 Hz, 1H), 3.60 (d, J ) 6.0 Hz, 1H), 1.08 (s, 9H).
The following signal is discernible for the minor isomer: 6.56 (s, 1H),
1.17 (s, 3H). MS m/z 254 (M+ - H2O (35Cl), 31.93), 199 (100); IR
(KBr) 3387, 1623, 1576, 1036 cm-1; Anal. Calcd for C13H17ClO2S:
C, 57.24%; H, 6.28%. Found: C, 57.15%; H, 6.11%.
(c) (E)-3-Chloro-2-methyl-4-(phenylsulfinyl)-3-buten-2-ol (E-
3cf): The reaction of 400 mg of silica gel (200 mesh), 1f (96 mg, 0.50
mmol), and CuCl2‚2H2O (340 mg, 2.0 mmol) afforded 74 mg (61%)
of E-3cf with the recovery of 11 mg (12%) of 1f. E-3cf: solid, mp
1
133-134 °C (CH2Cl2/n-hexane); H NMR (300 MHz, CDCl3) δ )
7.65-7.78 (m, 2H), 7.40-7.50 (m, 3H), 6.23 (s, 1H), 1.56 (s, 3H),
1.39 (s, 3H); IR (KBr) 3235, 1600, 1020 cm-1 13C NMR (75.4 MHz,
;
9
4826 J. AM. CHEM. SOC. VOL. 125, NO. 16, 2003

Halohydroxylation of 1,2-Allenyl Phenyl Sulfoxides
A R T I C L E S
CDCl3) δ 150.06, 144.39, 133.74, 130.94, 129.23, 124.79, 76.15, 28.53,
28.47; MS m/z 247 (M+ + 1(37Cl), 245 (M+ + 1(35Cl), 12.82), 4.78),
43 (100). Anal. Calcd for C11H13ClO2S: C, 53.98%; H, 5.35%.
Found: C, 54.01%; H, 5.34%.
mmol), and LiOAc‚2H2O (102 mg, 1.0 mmol) afforded 160 mg (88%)
of (S)-E-3ae, ee% > 99%, dr ) 99:1(HPLC conditions: Chiralcel OD
column (0.46 cm φ × 25 cm); λ 254 nm; rate, 0.7 mL/min; eluent,
hexane/i-PrOH ) 95:5). 1H NMR (300 MHz, CDCl3) δ 7.65-7.73 (m,
2H), 7.47-7.59 (m, 3H), 7.20 (s, 1H), 4.36 (s, 1H), 1.50-1.85 (s, 1H),
1.06 (s, 9H).
(d) 1-[(E)-1′-Chloro-2′-(phenylsulfinylethenyl)]-1-cyclohexanol
(E-3cg): The reaction of 200 mg of silica gel (200 mesh), 1g (58 mg,
0.25 mmol), and CuCl2‚2H2O (170 mg, 1.0 mmol) afforded 52 mg
(73%) of E-3cg as solid, mp 142 °C-143 °C(CH2Cl2/hexane). 1H NMR
(300 MHz, CDCl3) δ 7.66-7.80 (m, 2H), 7.40-7.55 (m, 3H), 6.29 (s,
1H), 3.74-3.85 (s, 1H), 1.47-2.18 (m, 8H), 1.07-1.27 (m, 2H); 13C
NMR (75.4 MHz, CDCl3) δ 150.95, 144.53, 134.03, 130.80, 129.17,
124.77, 77.58, 34.68, 34.54, 24.86, 21.03, 20.69; IR (KBr) 3429, 3226,
1594, 1023 cm-1; MS m/z 286 (M+ (37Cl), 2.08), 284 (M+ (35Cl), 3.56),
110 (100). Anal. Calcd for C14H17ClO2S: C, 59.04%; H, 6.02%.
Found: C, 58.99%; H, 5.88%.
(e) (E)-2-Chloro-3-(phenylsulfinyl)-2-hepten-1-ol (E-3ch): The
reaction of 200 mg of silica gel (200 mesh), 1h (55 mg, 0.25 mmol),
and CuCl2‚2H2O (170 mg, 1.0 mmol) afforded 35 mg (51%) of E-3ch
as solid, mp 74 -75 °C (CH2Cl2/n-hexane). 1H NMR (300 MHz,
CDCl3) δ 7.50-7.60 (m, 2H), 7.35-7.50 (m, 3H), 4.63-4.82 (m, 2H),
2.80-3.10 (s, 1H), 2.20-2.32 (m, 1H), 1.95-2.15 (m, 1H), 1.20-
1.28 (m, 1H), 1.00-1.10 (m, 2H), 0.70-0.85 (m, 1H), 0.67 (t, J )
7.31 Hz, 3H); 13C NMR (75.4 MHz, CDCl3) δ 144.89, 142.12, 141.33,
130.80, 129.12, 124.40, 62.83, 30.27, 25.16, 22.73, 13.42; IR (KBr)
3343, 1622, 1030 cm-1; MS m/z 257 (M+ - OH (37Cl), 0.05), 255
(M+ - OH (35Cl), 0.94), 121 (100). Anal. Calcd for C13H17ClO2S: C,
57.24%; H, 6.28%. Found: C, 57.25%; H, 6.22%.
(e) 2-Bromo-4,4-dimethyl-1-(phenylsulfinyl)-1(E)-penten-3(S)-ol
((S)-E-3be). Method A: The reaction of (S)-1e (110 mg, 0.50 mmol),
Br2 (0.50 M in MeCN, 1.2 mL, 0.6 mmol), and LiOAc‚2H2O (102
mg, 1.0 mmol) afforded 135 mg (85%) of (S)-E-3be, ee > 99%, dr )
92:8 (HPLC conditions: Chiralcel OD column (0.46 cm φ × 25 cm);
1
λ 254 nm; rate, 0.9 mL/min; eluent, hexane/i-PrOH ) 100:1.5). H
NMR (300 MHz, CDCl3) δ 7.60-7.73 (m, 2H), 7.48-7.60 (m, 3H),
6.84 (s, 1H), 4.80 (d, J ) 5.7 Hz, 1H), 3.16 (d, J ) 5.8 Hz, 1H), 1.08
(s, 9H). The following signal is discernible for the minor isomer: 6.80
(s, 1H), 1.18 (s, 3H).
Method B: The reaction of (S)-1e (110 mg, 0.5 mmol), CuBr2 (446
mg, 2 mmol), and water/acetone (1:2, 2 mL) at room temperature
afforded 109 mg (69%) of (S)-E-3be, ee% > 99%, dr ) 98:2 (HPLC
conditions: Chiralcel OD column (0.46 cm φ × 25 cm); λ 254 nm;
rate, 0.8 mL/min; eluent, hexane/i-PrOH ) 97:3.
(f) 2-Chloro-4,4-dimethyl-1-(phenylsulfinyl)-1(E)-penten-3(S)-ol
((S)-E-3ce). Method C: The reaction of 245 mg of silica gel, (S)-1e
(67 mg, 0.3 mmol), and CuCl2‚2H2O (204 mg, 1.2 mmol) afforded 67
mg (82%) of (S)-E-3ce, ee% > 99%, dr ) 89:11 (HPLC conditionss:
Chiralcel OD column (0.46 cm φ × 25 cm); λ 254 nm; rate, 0.9 mL/
1
min; eluent, hexane/i-PrOH ) 100:1.5). H NMR (300 MHz, CDCl3)
Halohydroxylation of Optically Active 1,2-Alkadienyl Phenyl
Sulfoxides. (a) 2-Iodo-1-(phenylsulfinyl)-1(E)-hepten-(R)-3-ol ((R)-
E-3ac): The reaction of (R)-1c (110 mg, 0.5 mmol), I2(153 mg, 0.6
mmol), and LiOAc‚2H2O (102 mg, 1.0 mmol) afforded 179 mg (98%)
of (R)-E-3ac, ee% ) 95%, dr ) 73:27 (HPLC conditions: Chiralpak
AS column (0.46 cm φ × 25 cm); λ 254 nm; rate, 0.7 mL/min; eluent,
δ 7.60-7.68 (m, 2H), 7.41-7.55 (m, 3H), 6.52 (s, 1H), 4.81 (s, 1H),
1.50-1.70 (s, 1H), 1.02 (s, 9H).
Coupling Reaction of the Carbon-Halogen Bond. (a) Z-2-
(Benzenesulfinylmethylene)oct-3-yn-1-ol (Z-4g): A mixture of E-3aa
(77 mg, 0.25 mmol), Et3N (1 mL), 1-hexyne (41 mg, 0.5 mmol), Pd-
(PPh3)2Cl2 (0.9 mg, 0.001 25 mmol), CuI (0.5 mg, 0.0026 mmol), and
DMSO (1 mL) were heated at 40-45 °C over a period of 5 h under
nitrogen. After the reaction mixture was cooled to room temperature,
1 mL of water was added. The organic layer was separated. The aqueous
layer was extracted with three 5 mL portions of ether. The combined
organic layer was dried over MgSO4. Evaporation and column
chromatography on silica gel (eluent: hexane/ethyl acetate ) 2:1) gave
1
hexane/i-PrOH ) 65:35). H NMR (300 MHz, CDCl3) δ 7.60-7.75
(m, 2H), 7.46-7.60 (m, 3H), 6.98 (s, 1H), 4.40-4.51 (m, 1H), 2.50-
3.20 (bs, 1H), 1.59-1.80 (m, 2H), 1.15-1.59 (m, 4H), 0.74-1.06 (m,
3H). The following signal is discernible for the minor isomer: 6.93 (s,
1H).
(b) 2-Bromo-1-(phenylsulfinyl)-1(E) -hepten-3(R)-ol ((R)-E-3bc).
Method A: The reaction of (R)-1c (55 mg, 0.25 mmol), Br2 (0.5 M in
MeCN, 0.6 mL, 0.3 mmol), and LiOAc‚2H2O (60 mg, 0.6 mmol)
afforded 76 mg (96%) of (R)-E-3bc, ee% ) 96%, dr ) 50:50 (HPLC
conditions: Chiralcel OJ column (0.46 cm φ × 25 cm); λ 254 nm;
rate, 0.7 mL/min; eluent: hexane/i-PrOH ) 90:10). 1H NMR (300 MHz,
CDCl3) δ 7.40-7.71 (m, 5H), 6.69 (s, 1H), 4.91-5.01 (m, 1H), 2.80
(d, J ) 7.05 Hz, 1H), 1.62-1.88 (m, 2H), 1.23-1.62 (m, 4H), 0.83-
1.05 (m, 3H). The following signal is discernible for the minor
isomer: 6.66 (s, 1H), 4.91-5.01 (m, 1H), 3.75 (bs, 1H).
1
Z-4g (60 mg, 92%). H NMR (300 MHz, CDCl3) δ 7.64-7.67 (m,
2H), 7.44-7.51 (m, 3H), 6.37 (s, 1H), 4.54 (dd, J1 ) 14.10 Hz, J2 )
6.30 Hz, 1H), 4.45 (ddd, J1 ) 14.10 Hz, J2 ) 6.60 Hz, J3 ) 0.90 Hz,
1H), 4.26 (t, J ) 6.90 Hz, 1H), 2.29 (t, J ) 6.90 Hz, 2H), 1.30-1.48
(m, 4H), 0.84 (t, J ) 7.50 Hz, 3H); 13C NMR (75.4 MHz, CDCl3) δ
143.41, 139.52, 135.16, 130.89, 129.32, 124.46, 98.55, 77.53, 62.17,
30.18, 21.85, 19.16, 13.45; IR (neat) 1612, 1039 cm-1; MS m/z 263
(M+ + 1, 100). HRMS calcd for C15H18O2S: 262.1023. Found:
262.1005.
Method B: The reaction of CuBr2 (223 mg, 1 mmol), (R)-1c (55
mg, 0.25 mmol), and water/acetone (1:2, 2 mL) at room temperature
afforded 73 mg (92%) of (R)-E-3bc, ee% ) 97%, dr ) 51:49.
(c) 2-Bromo-1-(phenylsulfinyl)-1(E)-undecen-3(S)-ol ((S)-E-3bd).
Method A: The reaction of (S)-1d (69 mg, 0.25 mmol), Br2 (0.5 M in
MeCN, 0.7 mL, 0.35 mmol), and LiOAc‚2H2O (60 mg, 0.6 mmol)
afforded 92 mg (99%) of (S)-E-3bd, ee% ) 97%, dr ) 53:47 (HPLC
conditions: Chiralcel OD column (0.46 cm φ × 25 cm); λ 254 nm;
rate, 0.8 mL/min; eluent, hexane/i-PrOH ) 97:3). 1H NMR (300 MHz,
CDCl3) δ 7.41-7.70 (m, 5H), 6.68 (s, 1H), 4.90-5.05 (m, 1H), 3.30-
4.20 (bs, 1H), 1.53-1.87 (m, 2H), 1.14-1.53 (m, 12H), 0.73-0.94
(m, 3H). The following signal is discernible for the minor isomer: 6.66
(s, 1H).
(b) Z-2-(Benzenesulfinylmethylene)oct-3(E)-en-1-ol (Z-4h): A
mixture of E-3aa (27.2 mg, 0.09 mmol), E-1-hexenyl boronic acid (12.6
mg, 0.1 mmol), Pd(PPh3)4 (5.8 mg, 5% mmol), n-Bu4NBr (1.6 mg,
5mol %), K2CO3 (2 M in water, 0.15 mL, 0.3 mmol), and THF (1 mL)
was refluxed under nitrogen for 3 h. After the reaction mixture was
cooled to room temperature, 1 mL of water was added. The organic
layer was separated. The aqueous layer was extracted with three 5 mL
portions of CH2Cl2. The combined organic layer was dried over MgSO4.
Evaporation and column chromatography on silia gel (eluent: hexane/
1
ethyl acetate ) 2:1) gave Z-4h (21 mg, 90%). H NMR (300 MHz,
CDCl3) δ 7.58-7. 61 (m, 2H), 7.38-7.45 (m, 3H), 6.16 (dt, J1 ) 15.90
Hz, J2 ) 7.20 Hz, 1H), 6.04 (s, 1H), 5.86 (d, J ) 15.90 Hz, 1H), 4.68
(d, J ) 13.20 Hz, 1H), 4.54 (d, J ) 12.90 Hz, 1H), 3.89 (bs, 1H), 2.05
(q, J ) 6.90 Hz, 2H), 1.18-1.32 (m, 4H), 0.80 (t, J ) 6.90 Hz, 3H);
13C NMR (75.4 MHz, CDCl3) δ 148.17, 144.00, 138.57, 133.82, 130.67,
129.26, 128.10, 124.41, 58.66, 32.83, 30.82, 22.20, 13.82; IR (neat)
3330, 1634, 1022 cm-1; MS m/z 265 (M+ + 1, 100). HRMS calcd for
C15H20OS (M+ + 1 - OH): 248.1230. Found: 248.1268.
Method B: The reaction of (S)-1d (69 mg, 0.25 mmol), CuBr2 (223
mg, 1 mmol), and water/acetone (1:2, 2 mL) afforded 90 mg (97%) of
(S)-E-3bd, ee% ) 96%, dr ) 51:49.
(d) 2-Iodo-4,4-dimethyl-1-(phenylsulfinyl)-1(E)-penten-3(S)-ol ((S)-
E-3ae): The reaction of (S)-1e (110 mg, 0.50 mmol), I2 (153 mg, 0.60
9
J. AM. CHEM. SOC. VOL. 125, NO. 16, 2003 4827

A R T I C L E S
Ma et al.
(c) Z-3-Benzenesulfinyl-2-phenylprop-2-en-1-ol (Z-4a):28 E-3aa
(154 mg, 0.5 mmol), phenylboronic acid (91.5 mg, 0.75 mmol), Pd-
(PPh3)4 (29 mg, 5% mmol), n-Bu4NBr (15.7 mg, 10%), K2CO3 (2 M
in water, 0.75 mL, 1.5 mmol), and THF (4 mL) gave E-4a (116.1 mg,
90%), E/Z ) 3:97.
1.76-1.79 (m, 1H), 1.55-1.65 (m, 2H), 1.25-1.34 (m, 3H), 0.84 (t,
J ) 6.90 Hz, 3H). The following signal is discernible for the minor
isomer: 6.24 (s, 1H), 5.10-5.16 (m, 1H); ee% ) 99.1% (HPLC
conditions: Chiralpak AS column (0.46 cm φ × 25 cm); λ 254 nm;
rate, 0.7 mL/min; eluent, hexane/i-PrOH ) 80:20).
(d) Z-3-Benzenesulfinyl-2-phenylprop-2-en-1-ol (Z-4a):28 To a
solution of anhydrous ZnBr2 (1.35 g, 2.0 mmol) in dry THF (10 mL)
was added PhMgBr (1.1084 M, 5.4 mL, 2.0 mmol) at 0 °C. The reaction
mixture was stirred for 1 h at room temperature. After removing THF
by vacuum, a solution of E-3aa (616 mg, 2.0 mmol) in anhydrous DMF
(10 mL) and Pd(PPh3)4 (115 mg, 5 mol %) were added to the reaction
mixture. After the mixture was stirred for 1 h under N2 at ambient
temperature, saturated of NH4Cl (5 mL) was added. The mixture was
extracted with ether (3 × 30 mL), washed with brine (3 × 30 mL),
and dried over MgSO4. Filtration, evaporation, and flash chromatog-
raphy on silica gel (ethyl acetate/n-hexane ) 1:2) afforded Z-4a (484
mg, 94%) as solid, mp 95.5-96 °C (CH2Cl2/n-hexane). 1H NMR (300
MHz, CDCl3) δ 7.70-7.73 (m, 2H), 7.41-7.54 (m, 5H), 7.25-7.39
(m, 3H), 6.47 (s, 1H), 4.04 (d, J ) 13.80 Hz, 1H), 4.86 (d, J ) 13.50
Hz, 1H), 3.67 (bs, 1H); 13C NMR (75.4 MHz, CDCl3) δ 150.92, 144.09,
137.48, 134.81, 131.18, 129.71, 129.68, 128.99, 127.15, 124.79, 61.18;
MS m/z 259 (M+ + 1, 3.99), 103 (100); IR (KBr) 3380, 2915, 1598,
(h) Z-1-(Benzenesulfinyl)-2-phenylundec-1-en-3-ol (Z-4d): The
reaction of anhydrous ZnBr2 (5.06 g, 22.5 mmol), 0.79 M PhMgBr
(28.5 mL, 22.5 mmol), E-3ad (3.15 g, 7.5 mmol), and Pd(PPh3)4 (433
mg, 5 mol %) afforded 2.0959 g (76%) of Z-4d. The two isomers can
be separated by repeated chromatography on silica gel. Less polar
isomer: solid, mp 85-85.5 °C (CH2Cl2/n-hexane); 1H NMR (300 MHz,
CDCl3) δ 7.71-7.75 (m, 2H), 7.45-7.54 (m, 3H), 7.23-7.40 (m, 5H),
6.26 (s, 1H), 5.17-5.21 (m, 1H), 3.99 (bs, 1H), 1.72-1.82 (m, 1H),
1.41-1.60 (m, 2H), 1.20-1.25 (m, 11H), 0.85 (t, J ) 6.90 Hz, 3H);
13C NMR (75.4 MHz, CDCl3) δ 154.84, 144.20, 137.48, 134.89, 130.76,
129.26, 128.69, 128.21, 127.63, 124.54, 72.03, 35.92, 31.69, 29.29,
29.18, 29.03, 25.81, 22.52, 14.00; MS m/z 353 (M+ - H2O, 100); IR
(KBr) 3276, 2928, 1597, 1579, 1442, 1079, 1037 cm-1; Anal. Calcd
for C23H30O2S: C, 74.55; H, 8.16. Found: C, 74.81; H, 8.00. More
polar isomer: oil; 1H NMR (300 MHz, CDCl3) δ 7.69-7.72 (m, 2H),
7.37-7.45 (m, 3H), 7.19-7.28 (m, 5H), 6.16 (s, 1H), 5.04 (bs, 1H),
4.33 (bs, 1H), 1.47-1.52 (m, 2H), 1.12-1.19 (m, 12H), 0.78 (t, J )
6.9 Hz, 3H); 13C NMR (75.4 MHz, CDCl3) δ 155.52, 144.69, 138.12,
134.72, 130.74, 129.28, 128.72, 128.35, 127.54, 124.77, 72.79, 36.40,
1442, 1037, 737 cm-1
.
(e) Z-3-(Benzenesulfinyl)-2-phenylhept-2-en-1-ol (Z-4b): The reac-
tion of anhydrous ZnBr2 (203 mg, 0.9 mmol), PhMgBr (0.7656 M, 1.2
mL, 0.9 mmol), E-3ah (109.2 mg, 0.3 mmol), and Pd(PPh3)4 (17 mg,
5 mol %) afforded E-4b (77.2 mg, 82%) as white needle solid, mp
94-95 °C (CH2Cl2/n-hexane). 1H NMR (300 MHz, CDCl3) δ 7.71 (d,
J ) 8.4 Hz, 2H), 7.39-7.49 (m, 3H), 7.26-7.30 (m, 3H), 7.16 (d, J )
8.1 Hz, 2H), 4.79 (m, 2H), 3.78 (bs, 1H), 2.09-2.19 (m, 1H), 1.89-
1.99 (m, 1H), 0.98-1.05 (m, 1H), 0.78-0.87 (m, 2H), 0.55-0.62 (m,
1H), 0.44 (t, J ) 7.5 Hz, 3H); 13C NMR (75.4 MHz, CDCl3) δ 147.84,
145.06, 142.44, 138.32, 129.95, 128.71, 128.16, 127.54, 127.46, 124.37,
62.34, 31.52, 23.95, 22.24, 12.95; MS m/z 314 (M+, 1.05), 91 (100);
IR (KBr) 3442, 2955, 1600, 1443, 1041, 749 cm-1; Anal. Calcd for
C19H22O2S: C, 72.57; H, 7.05; Found: C, 72.61; H, 7.05.
31.79, 29.38, 29.32, 29.16, 25.74, 22.61, 14.10; MS m/z 369 (M+
-
H, 1.59); IR (neat) 3300, 2922, 1444, 1004, 989, 747, 690 cm-1. HRMS
calcd for C23H29OS (M+ - OH): 353.1939. Found: 353.1905.
(i) (R)-Z-1-(Benzenesulfinyl)-2-phenylundec-1-en-3-ol ((R)-Z-4d):
The reaction of anhydrous ZnBr2 (193 mg, 0.86 mmol), 0.98 M PhMgBr
(0.87 mL, 0.86 mmol), (R)-E-3ad (120 mg, 0.29 mmol), and Pd(PPh3)4
1
(17 mg, 5 mol %) afforded 105.7 mg (78%) of (R)-Z-4d. H NMR
(300 MHz, CDCl3) δ 7.47-7.55 (m, 2H), 7.21-7.30 (m, 3H), 6.97-
7.14 (m, 5H), 6.00 (s, 1H), 4.95-4.99 (m, 1H), 1.50-1.54 (m, 1H),
1.19-1.36 (m, 2H), 0.96 (m, 11H), 0.62 (t, J ) 6.90 Hz, 3H); ee% )
98.1% (HPLC conditions: Chiralcel OD column (0.46 cm φ × 25 cm);
λ 254 nm; rate, 0.7 mL/min; eluent, hexane/i-PrOH ) 92:8).
(j) (S)-Z-1-(Benzenesulfinyl)-2-phenyl-undec-1-en-3-ol ((S)-Z-4d):
The reaction of anhydrous ZnBr2 (0.97 g, 4.30 mmol), 1.00 M PhMgBr
(4.30 mL, 4.30 mmol), (R)-E-3ad (600 mg, 1.43 mmol), and Pd(PPh3)4
(f) Z-1-(Benzenesulfinyl)-2-phenylhept-1-en-3-ol (Z-4c): The reac-
tion of anhydrous ZnCl2 (2.04 g, 15.0 mmol), PhMgBr (0.8275 M,
18.0 mL, 15.0 mmol), E-3ac (1.82 g, 5.0 mmol), and Pd(PPh3)4 (145
mg, 2.5 mol %) afforded 1.1073 g (71%) of Z-4c. The two isomers
can be separated by repeated chromatography on silica gel. Less polar
isomer: solid, mp 124-125 °C (CH2Cl2/n-hexane); 1H NMR (300 MHz,
CDCl3) δ 7.69-7.73 (m, 2H), 7.44-7.53 (m, 3H), 7.35-7.38 (m, 2H),
7.20-7.30 (m, 3H), 6.25 (s, 1H), 5.18-5.24 (m, 1H), 4.62 (d, J ) 4.8
Hz, 1H), 1.72-1.78 (m, 1H), 1.41-1.58 (m, 2H), 1.20-1.29 (m, 3H),
0.81 (t, J ) 7.05 Hz, 3H); 13C NMR (75.4 MHz, CDCl3) δ 155.22,
144.52, 137.79, 135.08, 131.10, 129.63, 129.02, 128.52, 128.05, 124.90,
72.06, 35.79, 28.34, 22.68, 14.21; MS m/z 314 (M+, 0.61), 241 (100);
IR (KBr) 3271, 2938, 1580, 1442, 1078, 1036 cm-1. Anal. Calcd for
C19H22O2S: C, 72.57; H, 7.05. Found: C, 72.54; H, 7.02. More polar
isomer:1H NMR (300 MHz, CDCl3) δ 7.67-7.70 (m, 2H), 7.41-7.49
(m, 3H), 7.24-7.33 (m, 5H), 6.18 (s, 1H), 5.05-5.08 (m, 1H), 3.04
(m, 1H), 1.59-1.63 (m, 1H), 1.39-1.43 (m, 1H), 1.18-1.29 (m, 4H),
0.79 (t, J ) 7.20 Hz, 3H); 13C NMR (75.4 MHz, CDCl3) δ 154.91,
144.31, 137.98, 134.81, 130.88, 129.35, 128.77, 128.39, 127.58, 124.65,
72.85, 36.12, 27.89, 22.35, 13.88; MS m/z 314 (M+, 1.02), 298 (100).
HRMS calcd for C19H22O2S: 314.1341. Found: 314.3332.
1
(80 mg, 5 mol %) afforded 408.1 mg (77%) of (S)-Z-4d. H NMR
(300 MHz,CDCl3) δ 7.72-7.77 (m, 2H), 7.49-7.55 (m, 3H), 7.26-
7.40 (m, 5H), 6.24 (s, 1H), 5.14-5.17 (m, 1H), 3.22 (br, 1H), 1.61-
1.65 (m, 1H), 1.43-1.48 (m, 2H), 1.18-1.27 (m, 11H), 0.86 (t, J )
6.90 Hz, 3H), dr ) 37:63, ee% ) 94.7% (HPLC conditions: Chiralcel
OD column (0.46 cm φ × 25 cm); λ 254 nm; rate, 0.7 mL/min; eluent,
hexane/i-PrOH ) 92:8).
(k) Z-3-(Benzenesulfinyl)-2-ethylprop-2-en-1-ol (Z-4e):28 The reac-
tion of anhydrous ZnBr2 (225 mg, 0.4 mmol), EtMgBr (0.7721 M in
THF, 1.3 mL, 1.0 mmol), E-3aa (123.2 mg in 4 mL of DMF, 0.4 mmol),
and Pd(PPh3)4 (23 mg, 5 mol %) afforded Z-4e (72.3 mg, 86%) as a
colorless oil. 1H NMR (300 MHz, CDCl3) δ 7.61-7.65 (m, 2H), 7.43-
7.54 (m, 3H), 6.02 (s, 1H), 4.65 (d, J ) 13.5 Hz, 1H), 4.42 (d, J )
13.8 Hz, 1H), 3.83 (bs, 1H), 2.30 (q, J ) 7.80 Hz, 2H), 1.04 (t, J )
7.35 Hz, 3H); 13C NMR (75.4 MHz, CDCl3) δ 156.73, 144.36, 131.15,
130.89, 129.52, 124.60, 61.51, 27.72, 11.77; MS m/z 193 (M+ + 1 -
H2O, 62.04), 51 (100); IR (neat) 3341, 2935, 1610, 1443, 1016, 746
cm-1
.
(l) Z-3-(Benzenesulfinyl)-2-(phenylacetylenyl)-2-en-1-ol (Z-4f):
After the flask was purged with nitrogen, a mixture of phenylacetylene
(122.4 mg, 1.2 mmol) and 3 mL of THF was treated with a solution of
n-BuLi (1.52 M in n-hexane, 0.8 mL, 1.2 mmol), which was added
over 10 min at -70 °C, and stirred for 15 min. Subsequently, a solution
of anhydrous ZnBr2 (270 mg, 1.2 mmol) in 2 mL of THF was added
over a few minutes with vigorous stirring at room temperature for
another 30 min followed by the subsequent addition of 1 mL of HMPA,
E-3aa (123 mg, 0.4 mmol), and Pd(PPh3)4 (23 mg, 5 mol %). After
(g) (R)-Z-1-(benzenesulfinyl)-2-phenyl-hept-1-en-3-ol ((R)-Z-4c):
The reaction of anhydrous ZnCl2 (1.54 g, 11.3 mmol), PhMgBr (0.8275
M, 13.7 mL, 11.3 mmol), E-(R)-3ac (1.37 g, 3.76 mmol), and Pd-
(PPh3)4 (108 mg, 2.5 mol %) afforded 869 mg (74%) of (R)-Z-4c. H
NMR (300 MHz, CDCl3) δ 7.71-7.78 (m, 2H), 7.48-7.55 (m, 3H),
7.26-7.40 (m, 5H), 6.26 (s, 1H), 5.14-5.20 (m, 1H), 2.60 (bs, 1H),
1
(28) Dubouclin, J. G.; Jousseaume, B.; Thoumazeau, E. Bull. Soc. Chim. Fr. II
1983, 105.
9
4828 J. AM. CHEM. SOC. VOL. 125, NO. 16, 2003

Halohydroxylation of 1,2-Allenyl Phenyl Sulfoxides
A R T I C L E S
1.5 h at ambient temperature with stirring, the mixture was quenched
with 2 mL of saturated aqueous solution of ammonium chloride. The
aqueous layer was extracted with ether, and the combined organic layer
was washed 4 times with brine and subsequently dried over MgSO4.
Filtration, evaporation, and flash chromatography on silica gel afforded
Z-4f (105.9 mg, 94%) as white solids: mp 104.5-105 °C (CH2Cl2/n-
mg, 0.4 mmol), and Ni(acac)2 (5 mg, 5 mol %) afforded the pure
product Z-5b (70.4 mg, 73%) as white solids, mp 99-100 °C (CH2-
Cl2/n-hexane). 1H NMR (300 MHz, CDCl3) δ 7.56-7.60 (m, 2H),
7.31-7.43 (m, 5H), 6.92-6.95 (m, 3H), 4.72 (s, 2H), 3.84 (s, 3H),
1.58 (bs, 1H); 13C NMR (75.4 MHz, CDCl3) δ 159.18, 141.15, 138.74,
131.38, 130.57, 129.71, 128.91, 127.74, 126.71, 114.07, 60.68, 55.54;
MS m/z 240 (M+, 55.16), 121 (100); IR (KBr) 3530, 1601, 1507, 1243,
1
hexane); H NMR (300 MHz, CDCl3) δ 7.70-7.73 (m, 2H), 7.51-
7.53 (m, 3H), 7.26-7.43 (m, 5H), 6.58 (s, 1H), 4.70 (d, J ) 14.10 Hz,
1H), 4.58 (d, J ) 13.80 Hz, 1H), 3.82 (bs, 1H); 13C NMR (75.4 MHz,
CDCl3) δ 143.30, 140.69, 134.42, 131.94, 131.19, 129.54, 129.32,
128.42, 124.67, 121.74, 96.16, 86.07, 62.19; MS m/z 282 (M+, 2.71),
105 (100); IR (KBr) 3204, 2206, 2178, 1570, 1440, 1010, 748; Anal.
Calcd for C17H14O2S: C, 72.31; H, 5.00. Found: C, 72.25; H, 5.16.
Z-1-(Benzenesulfonyl)-2-phenylundec-1-en-3-ol (Z-6e): A solution
of m-CPBA (85%, 91.4 mg, 0.45 mmol) in CH2Cl2 (3 mL) was added
to a solution of Z-4d (111 mg, 0.3 mmol) in CH2Cl2 (3 mL). The
mixture was stirred vigorously at 25 °C. After 30 min, saturated Na2-
SO3 (2 mL) and saturated NaHCO3 (2 mL) were added. The organic
layer was separated, and the aqueous layer was extracted with CH2-
Cl2. The combined organic layer was dried (MgSO4) followed by
evaporation of the solvent. The residue was purified by flash chroma-
tography (n-hexane/ethyl acetate ) 5:1) to give Z-6e (100.4 mg, 87%)
as white solids: mp 44-45 °C (CH2Cl2/n-hexane); 1H NMR (300 MHz,
CDCl3) δ 7.99-8.02 (m, 2H), 7.54-7.67 (m, 3H), 7.31-7.43 (m, 5H),
6.36 (s, 1H), 5.25-5.29 (m, 1H), 3.46-3.48 (m, 1H), 1.67-1.72 (m,
1H), 1.36-1.53 (m, 2H), 1.18-1.29 (m, 11H), 0.86 (t, J ) 6.9 Hz,
3H); 13C NMR (75.4 MHz, CDCl3) δ 160.51, 141.73, 137.92, 133.82,
129.62, 129.58, 129.56, 128.66, 128.09, 127.59, 70.94, 36.10, 32.04,
29.59, 29.46, 29.36, 25.97, 22.87, 14.35; MS m/z 386 (M+, 0.31), 103
(100); IR (KBr) 3864, 2920, 1612, 1282, 1294, 1145. Anal. Calcd for
C23H30O3S: C, 71.46; H, 7.82. Found: C, 71.64; H, 7.73.
1178 cm-1
.
General Procedure for the Synthesis of Z-5c-j: A solution of
dry zinc bromide in dry THF was added to a Grignard reagent at
ambient temperature. The thick white mixture was then stirred for 0.5-1
h at ambient temperature. The reaction mixture was cooled to 0 °C,
and a solution of benzenesulfinyl alcohol (Z-4a, Z-4c, and Z-4d) or
benzenesulfonyl alcohol (Z-6e) in DMF was added via a syringe
followed by the addition of Ni(acac)2. The mixture was stirred at 40
°C for 12-24 h. When the benzenesulfinyl alcohol disappeared, the
mixture was worked up with a saturated aqueous NH4Cl solution and
extracted with diethyl ether. The combined organic layer was dried
over anhydrous MgSO4. The resulting crude product was purified by
chromatography on silica gel to afford the pure product.
(c) Z-2,3-Diphenyl-2-propen-1-ol (Z-5c):30 The reaction of anhy-
drous ZnBr2 (450 mg, 2.0 mmol), PhMgBr (0.7905 M, 2.53 mL, 2.0
mmol), Z-4a (103.2 mg, 0.4 mmol, in 4 mL of DMF), and Ni(acac)2
(5 mg, 5 mol %) afforded Z-5c (70.5 mg, 84%) as solids, mp 78-79
°C (n-hexane). 1H NMR (300 MHz, CDCl3) δ 7.51-7.53 (d, J ) 6.72
Hz, 2H), 7.18-7.36 (m, 8H), 6.91 (s, 1H), 4.65 (s, 2H), 1.52 (bs, 1H);
13C NMR (75.4 MHz, CDCl3) δ 140.85, 140.38, 137.17, 131.56, 129.21,
128.95, 128.67, 128.00, 127.65, 126.87, 60.57; MS m/z 210 (M+, 48.8),
105 (100); IR (KBr) 3265, 1600, 1490, 1450, 1080, 1035, 774 cm-1
.
(d) Z-3-(2-Methoxyphenyl)-2-phenylprop-2-en-1-ol (Z-5d): The
reaction of anhydrous ZnBr2 (450 mg, 2.0 mmol, in 2.2 mL THF),
o-CH3OC6H4MgBr (0.53 M, 3.8 mL, 2.5 mmol), Z-4a (129 mg, 0.5
mmol, in 6 mL of DMF), and Ni(acac)2 (12.8 mg, 10 mol %) afforded
(S)-Z-1-(Benzenesulfonyl)-2-phenylundec-1-en-3-ol ((S)-Z-6e): The
reaction of m-CPBA (85%, 244 mg, 1.2 mmol) and (S)-Z-4d (420 mg,
1.0 mmol) gave (S)-Z-6e (348.9 mg, 80%) as oil. 1H NMR (300 MHz,
CDCl3) δ 7.99-8.01 (m, 2H), 7.55-7.65 (m, 3H), 7.33-7.41 (m, 5H),
6.35 (s, 1H), 5.22 (m, 1H), 3.30 (d, J ) 7.5 Hz, 1H), 1.67-1.72 (m,
1H), 1.36-1.54 (m, 2H), 1.18-1.25 (m, 11H), 0.86 (t, J ) 6.9 Hz,
3H); ee% ) 96.0% (HPLC conditions: Chiralcel AD column (0.46
cm φ × 25 cm); λ 254 nm; rate, 0.7 mL/min; eluent, hexane/i-PrOH
) 95:5).
1
Z-5d (81.5 mg, 68%) as an oil. H NMR (300 MHz, CDCl3) δ 7.62-
7.66 (m, 2H), 7.26-7.43 (m, 5H), 6.92-7.03 (m, 3H), 4.63 (s, 2H),
3.85 (s, 3H), 1.79 (bs, 1H); 13C NMR (75.4 MHz, CDCl3) δ 157.05,
140.29, 139.88, 130.14, 128.82, 128.45, 127.46, 126.53, 126.50, 125.85,
120.39, 110.43, 60.47, 55.40; MS m/z 240 (M+, 38.96), 108 (100); IR
(neat) 3396, 2940, 1597, 1577, 1245, 1111 cm-1. HRMS calcd for
C16H16O2: 240.1150. Found: 240.1192.
(e) Z-1,2-(Diphenyl)undec-1-en-3-ol (Z-5e): The reaction of an-
hydrous ZnBr2 (450 mg, 2.0 mmol), PhMgBr (1.0 M, 2.0 mL, 2.0
mmol), Z-4d (148 mg, 0.4 mmol, in 4 mL of DMF), and Ni(acac)2 (10
Coupling Reaction of C-S Bond. A. Coupling Reaction of
Carbon-Sulfinyl Bond. (a) Z-3-(4′-Chlorophenyl)-2-phenylprop-
2-en-1-ol (Z-5a): A three necked flask equipped with a thermometer,
a gas inlet, and an addition funnel was charged under N2 with 1-chloro-
4-iodobenzene (477 mg, 2.0 mmol) in 2 mL of THF and cooled to
-78 °C followed by the addition of n-BuLi (2.5 M in n-hexane, 0.8
mL, 2.0 mmol) over 5 min. The resulting solution was stirred for another
5 min followed by the addition of a THF (2 mL) solution of ZnBr2
(450 mg, 2.0 mmol). After an additional 30 min, a DMF (4 mL) solution
of Z-4a (103.2 mg, 0.4 mmol) and Ni(acac)2 (5 mg, 5mol %) was added,
and then the reaction mixture was stirred for 1.5 h at 80 °C. The mixture
was quenched by pouring it into a saturated aqueous NH4Cl solution
(2 mL) and was extracted with diethyl ether. The combined organic
layer was dried over anhydrous MgSO4. The resulting crude product
was purified by chromatography on silica gel to afford the pure product
1
mg, 10 mol %) afforded Z-5e (88.3 mg, 68.6%) as an oil. H NMR
(300 MHz, CDCl3) δ 7.56-7.59 (m, 2H), 7.26-7.42 (m, 8H), 6.73 (s,
1H), 4.90 (t, J ) 7.03 Hz, 1H), 1.70 (bs, 1H), 1.52-1.63 (m, 2H),
1.18-1.33 (m, 12H), 0.87 (t, J ) 7.03 Hz, 3H); 13C NMR (75.4 MHz,
CDCl3) δ 144.75, 140.85, 137.15, 132.18, 129.14, 128.88, 128.54,
128.24, 127.47, 127.30, 70.50, 36.00, 32.04, 29.66, 29.61, 29.40, 26.03,
22.89, 14.37; MS m/z 322 (M+, 2.12), 209 (100); IR (neat) 3389, 2925,
1600, 1493, 772 cm-1. HRMS calcd for C23H30O: 322.2297. Found:
322.2292.
(f) (S)-Z-1,2-(Diphenyl)undec-1-en-3-ol ((S)-Z-5e): The reaction
of anhydrous ZnBr2 (450 mg, 2.0 mmol), PhMgBr (0.7905 M, 2.5 mL,
2.0 mmol), (S)-Z-4d (148 mg, 0.4 mmol, in 4 mL of DMF), and Ni-
(acac)2 (10 mg, 10 mol %) afforded (S)-Z-5e (82.2 mg, 64%) as oil.
1H NMR (300 MHz, CDCl3) δ 7.56-7.59 (m, 2H), 7.26-7.44 (m,
8H), 6.72 (s, 1H), 4.86-4.92 (m, 1H), 1.69 (bs, 1H), 1.47-1.64 (m,
2H), 1.17-1.37 (m, 12H), 0.87 (t, J ) 6.9 Hz, 3H); ee% ) 95.6%
(HPLC conditions: Chiralcel OD column (0.46 cm φ × 25 cm); λ 254
nm; rate, 0.7 mL/min; eluent, hexane/i-PrOH ) 85:15).
1
Z-5a (66.9 mg, 68%) as solid: mp 70-71 °C (CH2Cl2/n-hexane); H
NMR (300 MHz, CDCl3) δ 7.56-7.59 (m, 2H), 7.34-7.44 (m, 7H),
6.90 (s, 1H), 4.67 (s, 2H), 1.57 (bs, 1H); 13C NMR (75.4 MHz, CDCl3)
δ 140.85, 140.59, 135.55, 133.49, 130.53, 130.38, 128.99, 128.82,
128.17, 126.81, 60.48; MS m/z 246 (M+(37Cl), 14.87), 244 (M+(35Cl),
48.19), 105 (100); IR (KBr) 3262, 1595, 1489, 1464, 1094, 1037, 697
cm-1. Anal. Calcd for C15H13ClO: C, 73.62; H, 5.35. Found: C, 73.75;
H, 5.51.
(g) Z-1-(4′-Methoxyphenyl)-2-phenylundec-1-en-3-ol (Z-5f): The
(b) Z-3-(4-Methoxyphenyl)-2-phenylprop-2-en-1-ol (Z-5b):29 The
reaction of 4-iodoanisole (468 mg, 2.0 mmol), n-BuLi (2.5 M in
n-hexane, 0.8 mL, 2.0 mmol), ZnBr2 (450 mg, 2.0 mmol), Z-4a (103.2
(29) Brenna, E.; Fuganti, C.; Serra, S. J. Chem. Soc., Perkin. Trans. 1, 1998,
901.
(30) Nalesnik, T. E.; Fish, J. G.; Horgan, S. W.; Orchin, M. J. Org Chem. 1981,
46, 1987.
9
J. AM. CHEM. SOC. VOL. 125, NO. 16, 2003 4829

A R T I C L E S
Ma et al.
reaction of anhydrous ZnBr2 (450 mg, 2.0 mmol), p-MeOC6H4MgBr
(0.55 M, 3.6 mL, 2.0 mmol), Z-4d (148 mg, 0.4 mmol, in 5 mL of
DMF), and Ni(acac)2 (10 mg, 10 mol %) afforded Z-5f (84.6 mg, 60%)
(l) Z-2-Phenyl-1-(m-methylphenyl)undec-1-en-3-ol ((S)-Z-5h): The
reaction of anhydrous ZnBr2 (315 mg, 1.4 mmol), m-MeC6H4MgBr
(0.8675 M, 1.6 mL, 1.4 mmol), (S)-Z-6e (135 mg, 0.35 mmol, in 3.5
mL of DMF), and Ni(acac)2 (9.0 mg, 10 mol %) afforded (S)-Z-5h
1
as an oil. H NMR (300 MHz, CDCl3) δ 7.47-7.50 (m, 2H), 7.19-
1
7.32 (m, 5H), 6.85 (d, J ) 8.7 Hz, 2H), 6.59 (s, 1H), 4.85 (t, J ) 6.30
Hz, 1H), 3.77 (s, 3H), 1.71 (bs, 1H), 1.47-1.54 (m, 2H), 1.11-1.25
(m, 12H), 0.80 (t, J ) 6.9 Hz, 3H); 13C NMR (75.4 MHz, CDCl3) δ
158.90, 143.62, 141.13, 131.87, 130.43, 129.58, 128.85, 128.20, 127.30,
113.95, 70.54, 55.48, 36.00, 32.06, 29.67, 29.64, 29.41, 26.09, 22.89,
14.35; MS m/z 352 (M+, 13.92), 121 (100); IR (neat) 3408, 2926, 1607,
1510, 1249, 1178 cm-1. HRMS calcd for C24H32O2: 352.2402.
Found: 352.2359.
(66.4 mg, 57%) as an oil. H NMR (300 MHz, CDCl3) δ 7.53-7.56
(m, 2H), 7.22-7.38 (m, 4H), 7.08-7.14 (m, 3H), 6.67 (s, 1H), 4.89 (t,
J ) 6.00 Hz, 1H), 2.37 (s, 3H), 1.70 (bs, 1H), 1.53-1.58 (m, 2H),
1.17-1.28 (m, 12H), 0.85 (t, J ) 6.60 Hz, 3H); ee% ) 94.5% (HPLC
conditions: Chiralcel OD column (0.46 cm φ × 25 cm); λ 254 nm,
rate, 0.7 mL/min; eluent, hexane/i-PrOH ) 90:10).
(m) Z-2-Phenyl-1-(p-methylphenyl)undec-1-en-3-ol (Z-5i): The
reaction of anhydrous ZnBr2 (450 mg, 2.0 mmol), p-MeC6H4MgBr (0.85
M, 2.35 mL, 2.0 mmol), Z-6e (193 mg, 0.5 mmol, in 5 mL of DMF),
and Ni(acac)2 (12.85 mg, 10 mol %) afforded Z-5i (110 mg, 66%) as
an oil. 1H NMR (300 MHz, CDCl3) δ 7.57-7.60 (m, 2H), 7.19-7.41
(m, 7H), 6.71 (s, 1H), 4.93 (t, J ) 6.75 Hz, 1H), 2.40 (s, 3H), 1.78
(bs, 1H), 1.54-1.62 (m, 2H), 1.20-1.35 (m, 12H), 0.89 (t, J ) 7.20
Hz, 3H); 13C NMR (75.4 MHz, CDCl3) δ 144.25, 141.06, 137.06,
134.23, 132.20, 129.27, 129.10, 128.89, 128.23, 127.38, 70.55, 35.97,
32.09, 29.69, 29.65, 29.44, 26.07, 22.93, 21.47, 14.40; MS m/z 336
(h) (S)-Z-1-(4-Methoxyphenyl)-2-phenylundec-1-en-3-ol ((S)-Z-
5f): The reaction of anhydrous ZnBr2 (450 mg, 2.0 mmol), p-MeOC6H4-
MgBr (0.55 M, 3.6 mL, 2.0 mmol), (S)-Z-4d (148 mg, 0.4 mmol, in 5
mL of DMF), and Ni(acac)2 (10 mg, 10 mol %) afforded (S)-Z-5f (75
1
mg, 57%) as oil. H NMR (300 MHz, CDCl3) δ 7.55-7.70 (m, 2H),
7.27-7.40 (m, 5H), 6.95 (d, J ) 6.9 Hz, 2H), 6.67 (s, 1H), 4.92 (t, J
) 6.6 Hz, 1H), 3.85 (s, 3H), 1.74 (bs, 1H), 1.53-1.60 (m, 2H), 1.12-
1.32 (m, 12H), 0.87 (t, J ) 6.9 Hz, 3H); ee% ) 95.8% (HPLC
conditions: Chiralcel OD column (0.46 cm φ × 25 cm); λ 254 nm;
rate, 0.7 mL/min; eluent, hexane/i-PrOH ) 85:15).
(M+, 5.44), 223 (100); IR (neat) 3395, 2925, 1600, 1510, 1465 cm-1
HRMS calcd for C24H32O: 336.24 532. Found: 336.246 92.
;
(i) Z-1-(4′-Dimethylaminophenyl)-2-phenylhept-1-en-3-ol (Z-5 g):
The reaction of anhydrous ZnBr2 (360 mg, 1.6 mmol), p-N(CH3)2C6H4-
MgBr (0.85 M, 1.9 mL, 1.6 mmol), Z-4c (125.6 mg, 0.4 mmol, in 4
mL of DMF), and Ni(acac)2 (10.28 mg, 10 mol %) afforded Z-5 g
(n) Z-2-Phenyl-1-(p-methylphenyl)undec-1-en-3-ol ((S)-Z-5i): The
reaction of anhydrous ZnBr2 (450 mg, 2.0 mmol), p-MeC6H4MgBr (0.85
M, 2.35 mL, 2.0 mmol), (S)-Z-6e (193 mg, 0.5 mmol, in 5 mL of DMF),
and Ni(acac)2 (12.85 mg, 10 mol %) afforded Z-5i (108.5 mg, 65%) as
oil. 1H NMR (300 MHz, CDCl3) δ 7.45-7.49 (m, 2H), 7.21-7.29 (m,
3H), 7.07-7.21 (m, 4H), 6.59 (s, 1H), 4.81 (t, J ) 7.2 Hz, 1H), 2.28
(s, 3H), 1.67 (s,1H), 1.44-1.50 (m, 2H), 1.08-1.23 (m, 12H), 0.77 (t,
J ) 6.9 Hz, 3H); ee% ) 96.6% (HPLC conditions: Chiralcel OD
column (0.46 cmφ × 25 cm); λ 254 nm; rate, 0.7 mL/min; eluent,
hexane/i-PrOH ) 90:10).
(o) Z-1-(4′-Methoxyphenyl)-2-phenylundec-1-en-3-ol (Z-5f): The
reaction of anhydrous ZnBr2 (225 mg, 1.0 mmol), p-CH3OC6H4MgBr
(1.00 M, 1.00 mL, 1.0 mmol), Z-6e (96.5 mg, 0.25 mmol, in 2.5 mL
of DMF), and Ni(acac)2 (6.4 mg, 10 mol %) afforded Z-5f (52.8 mg,
60%) as oil.
(p) Z-1-(4′-Dimethylaminophenyl)-2-phenylundec-1-en-3-ol (Z-
5j): The reaction of anhydrous ZnBr2 (225 mg, 1.0 mmol), p-N(CH3)2-
C6H4MgBr (0.80 M, 1.25 mL, 1.0 mmol), Z-6e (96.5 mg, 0.25 mmol,
in 2.5 mL of DMF), and Ni(acac)2 (6.4 mg, 10 mol %) afforded Z-5j
(64 mg, 70%) as an oil. 1H NMR (300 MHz, CDCl3) δ 7.53-7.60 (m,
2H), 7.24-7.37 (m, 5H), 6.72-6.76 (m, 2H), 6.63 (s, 1H), 4.99 (t, J
) 6.90 Hz, 1H), 2.98 (s, 6H), 1.55-1.67 (m, 3H), 1.18-1.25 (m, 12H),
0.85 (t, J ) 6.9 Hz, 3H); 13C NMR (75.4 MHz, CDCl3) δ 149.48,
141.71, 141.32, 132.26, 130.01, 128.58, 127.88, 126.78, 124.84, 112.05,
70.42, 40.45, 35.70, 31.81, 29.45, 29.43, 29.17, 25.92, 22.65, 14.12;
MS m/z 365 (M+, 4.87), 248 (100); IR (neat) 3410, 2855, 1610, 1521,
1355, 1166, 815, 701 cm-1. HRMS calcd for C25H35NO: 365.2719.
Found: 365.2687.
1
(93.6 mg, 76%) as an oil. H NMR (300 MHz, CDCl3) δ 7.60-7.62
(m, 2H), 7.28-7.41 (m, 5H), 6.75 (d, J ) 8.40 Hz, 2H), 6.67 (s, 1H),
5.04 (t, J ) 7.2 Hz, 1H), 3.01 (s, 6H), 1.97 (bs, 1H), 1.57-1.68 (m,
2H), 1.19-1.31 (m, 4H), 0.85 (t, J ) 6.90 Hz, 3H); 13C NMR (75.4
MHz, CDCl3) δ 149.77, 141.97, 141.66, 132.59, 130.34, 128.90, 128.18,
127.09, 125.16, 112.39, 70.65, 40.78, 35.69, 28.46, 22.90, 14.37; MS
m/z 309 (M+, 61.81), 252 (100); IR (neat) 3419, 2953, 1609, 1520,
1355 cm-1. HRMS calcd for C21H27NO: 309.2093. Found: 309.2125.
(j) (R)-Z-1-(4-Dimethylamino-phenyl)-2-phenylhept-1-en-3-ol ((R)-
Z-5g): The reaction of anhydrous ZnBr2 (360 mg, 1.6 mmol),
p-N(CH3)2C6H4MgBr (0.85 M, 1.9 mL, 1.6 mmol), (R)-Z-4c (125.6
mg, 0.4 mmol, in 4 mL of DMF), and Ni(acac)2 (10.28 mg, 10 mol %)
afforded (R)-Z-5 g (89.7 mg, 73%) as oil. 1H NMR (300 MHz, CDCl3)
δ 7.57-7.60 (m, 2H), 7.26-7.40 (m, 5H), 6.75 (d, J ) 9 Hz, 2H),
6.66 (s, 1H), 5.03 (t, J ) 7.2 Hz, 1H), 3.00 (s, 6H), 1.87 (bs, 1H),
1.56-1.68 (m, 2H), 1.18-1.41 (m, 4H), 0.85 (t, J ) 6.90 Hz, 3H);
ee% ) 94.0% (HPLC conditions: Chiralpak AD column (0.46 cm φ
× 25 cm); λ 254 nm; rate, 0.7 mL/min; eluent, hexane/i-PrOH ) 90:
10).
B. Coupling Reaction of Carbon-Sulfonyl Bond. (k) Z-2-Phenyl-
1-(m-methylphenyl)undec-1-en-3-ol (Z-5h): The reaction of anhydrous
ZnBr2 (450 mg, 2.0 mmol), m-MeC6H4MgBr (0.8675 M, 2.30 mL, 2.0
mmol), Z-6e (193 mg, 0.5 mmol, in 5 mL of DMF), and Ni(acac)2
1
(12.85 mg, 10 mol %) afforded Z-5h (106.2 mg, 63.2%) as an oil. H
NMR (300 MHz, CDCl3) δ 7.53-7.57 (m, 2H), 7.26-7.38 (m, 4H),
7.08-7.14 (m, 3H), 6.68 (s, 1H), 4.89 (t, J ) 6.00 Hz, 1H), 2.37 (s,
3H), 1.70 (bs, 1H), 1.51-1.63 (m, 2H), 1.17-1.29 (m, 12H), 0.85 (t,
J ) 6.75 Hz, 3H); 13C NMR (75.4 MHz, CDCl3) δ 144.65, 140.95,
138.10, 137.11, 132.26, 129.87, 128.90, 128.43, 128.23, 128.06, 127.43,
126.19, 70.50, 35.97, 32.07, 29.69, 29.63, 29.42, 26.03, 22.91, 21.73,
14.37; MS m/z 336 (M+, 5.71), 224 (100); IR (neat) 3393, 2925, 1601,
1492, 1464 cm-1. HRMS calcd for C24H32O: 336.24532. Found:
336.24254.
Acknowledgment. We are grateful to the Major State Basic
Research Development Program (Grant No. G2000077500) and
the National Natural Science Foundation of China. S.M. is the
recipient of the 1999 Qiu Shi Award for Young Scientific
Workers issued by the Hong Kong Qiu Shi Foundation of
Science and Technology (1999-2003).
JA034039Q
9
4830 J. AM. CHEM. SOC. VOL. 125, NO. 16, 2003