Carbomagnesiation of acetylenic sulfones catalyzed by CuCN and its application in the stereoselective synthesis of polysubstituted vinyl sulfones

Article abstract of DOI:10.1055/s-2003-37524

Polysubstituted vinyl sulfones were prepared stereoselectively by the carbomagnesiation of acetylenic sulfones in the presence of Cu(I). Bisubstituted vinyl sulfones were obtained by the carbomagnesiation of acetylenic sulfones followed by hydrolysis. Tri

Full text of DOI:10.1055/s-2003-37524

LETTER
477
Carbomagnesiation of Acetylenic Sulfones Catalyzed by CuCN and its
Application in the Stereoselective Synthesis of Polysubstituted Vinyl Sulfones
Carbomagnesiation of
e
A
cetylenic
i
S
ulfon
h
e
s
Catalyzed
u
by
C
uC
N
a Xie,a,b Xian Huang*a
a
Department of Chemistr, Zhejiang University (Xixi Campus), Hangzhou, 310028, P. R. China
Fax +86(571)88807077; E-mail: huangx@mail.hz.zj.cn
b
Department of Chemistry, Anhui Normal University, Wuhu, 241000 P. R. China
Received 20 November 2002
Dedicated to Professor Wei-Shan Zhou on the occasion of his 80th birthday.
siation of acetylenic sulfones in the presence of Cu(I)
Abstract: Polysubstituted vinyl sulfones were prepared stereose-
lectively by the carbomagnesiation of acetylenic sulfones in the
presence of Cu(I). Bisubstituted vinyl sulfones were obtained by the
carbomagnesiation of acetylenic sulfones followed by hydrolysis.
underwent smoothly to give the addition product
(Scheme 1). The results are summarized in Table 1. At
–20 °C, 1-phenyl-2-(p-tolylsulfonyl)ethyne was added to
Trisubstituted vinyl sulfones were obtained by the carbomagnesia- the solution of PhMgBr in THF in the presence of 10
tion of acetylenic sulfones followed by reacting with other electro-
philes.
mol% CuI, after stirring for 30 minutes followed by hy-
drolysis, the desired adduct 1,1-diphenyl-2-(p-tolylsulf-
Key words: carbomagnesiation, acetylenic sulfone, vinyl sulfone,
1,4-dienes, conjugated enynes
onyl)ethene (3a) was obtained in 42% yield (entry 1,
Table 1). A better yield was obtained when 10 mol%
CuCN was used (entry 2, Table 1). When CH2Cl2 was
added as cosolvent (THF–CH2Cl2, 1:4), the yield of the
Carbon-carbon bond formation is the fundamental opera- desired adduct improved (Table 1, entries 3, 4,). The best
tion in the construction of organic molecules and the car- reaction conditions were found to carry out the reaction in
bometallation of acetylene is one of the most important THF–CH2Cl2 in the presence of 10 mol% CuCN.
carbon-carbon bond forming reactions.1 Since the first
carbometallation discovered by Ziegler and Bähr in 1927,
tion analysis12 (Figure 1).
The structure of adduct 3a was verified by X-ray diffrac-
a number of additions of organometallics to carbon-
carbon multiple bond have been reported.2 Vinyl sulfones
are versatile intermediates in organic chemistry and have
been extensively studied.3 The available methodology
for vinyl sulfone synthesis mainly consists of Horner–
Emmons reactions of carbonyl compounds and sulfonyl
phosphoranes,4 Peterson reactions,5 β-elimination of
selenosulphones6 or selenosulfonation of acetylene.7 In
view of the importance of vinyl sulfones, it was of interest
to find new method to synthesize vinyl sulfones regio- and
stereoselectively. Recently, we have reported the stereo-
selective synthesis of functionalized vinyl sulfones by the
hydrometallation8 or selenomagnesiation9 of acetylenic
sulfones. As an extension of our study in the stereoselec-
tive synthesis of vinyl sulfones, we wish to report herein
the regio- and stereoselective synthesis of vinyl sulfones
by the carbomagnesiation of acetylenic sulfones and its
further reaction with electrophiles in the presence of
CuCN.
It has been reported that the reaction of Grignard reagent
with acetylenic sulfone to afford the products of overall
substitution of the sulfone moiety.10 While organocupper
reagents can add to acetylenic sulfones to afford a mixture
of (Z)- and (E)-type vinyl sulfones.11 So we investigated
Figure 1 The molecular structure of 3a
the reaction of Grignard reagent with acetylenic sulfones
catalyzed by Cu(I). The results show that the carbomagne-
In the case of the reaction of phenylmagnesium bromide
with 1-(p-tolylsulfonyl)-1-heptyne, (E)-2-phenyl-1-(p-
Synlett 2003, No. 4, Print: 12 03 2003.
tolylsulfonyl)-1-heptene (3b) was obtained exclusively in
Art Id.1437-2096,E;2003,0,04,0477,0480,ftx,en;U11802ST.pdf.
82% yield (entry 5, Table 1). It suggests that a syn-addi-
© Georg Thieme Verlag Stuttgart · New York
ISSN 0936-5214

478
M. Xie, X. Huang
LETTER
tion happened when PhMgBr reacts with acetylenic sul- 1,4-Dienes13 and conjugated enynes14 are typical structur-
fone. The E-configuration of 3b was confirmed by the al fragments of many natural compounds and their synthe-
NOE spectrum, which shows the correlation between the sis has attracted much interest. In order to extend the
vinylic proton and the protons of the phenyl while there is application of the carbomagnesium of acetylenic sulfones,
no correlation between the vinylic proton and the protons we further investigated the reaction of intermediate 2 with
of n-C5H11 group.
allyl bromide or alkynylphenyliodonium tosylate other
than proton for the hope to synthesize sulfonyl-substituted
1,4-dienes or conjugated enynes (Scheme 2 and
Scheme 3). Acetylenic sulfone was added to the solution
of ArMgBr in THF–CH2Cl2 at –20 °C in the presence of
10 mol% CuCN. After the completion of the reaction
(about 30 min, monitored by TLC), allyl bromide or alky-
nylphenyliodonium tosylate was added. After stirring for
2–2.5 hours, the expected adducts 4 or 5 were formed in
good yields. The results are summarized in Table 2.
R
SO2Tol
MgBr
Cu(I)
R
SO2Tol
+
PhMgBr
–20 °C
Ph
1
2
H3O+
R
SO2Tol
H
Ph
3
Scheme 1
R1
Ar
SO2R2
MgBr
10 mol% CuCN
R1
SO2R2
+ ArMgBr
Table 1 Reaction of PhMgBr with Acetylenic Sulfonesa
THF/CH2Cl2, –20 °C
2
1
Entry
R
Cu(I) (10
mol%)
Solvent
Isolated yield
of 3 (%)b
R1
Br
SO2R2
1
2
3
4
5
Ph
CuI
THF
3a 42
3a 58
3a 65
3a 80
3b 82
Ar
Ph
CuCN
CuI
THF
4
Ph
THF–CH2Cl2
THF–CH2Cl2
THF–CH2Cl2
Scheme 2
Ph
CuCN
CuCN
R1
Ph
SO2Tol
MgBr
10 mol% CuCN
R1
SO2R2
+ PhMgBr
n-C5H11-
THF/CH2Cl2, –20 °C
a The reaction was carried out at –20 °C by adding Cu(I) (10 mol%)
and 1 (0.5 mmol) to the solution of PhMgBr (0.6 mmol).
b Isolated yield based on 1.
2
1
+
R1
Ph
SO2Tol
Ph
Ph
IPh–OTs
5
Scheme 3
Table 2 Reaction of Phenylmagnesium Bromide, Acetylenic Sulfones and Allyl Bromide or Alkynylphenyliodonium Tosylate in the
Presence of CuCN (10 mol%)a
Entry
1
R1
R2
Ar
E+
Yield of 4 or 5 (%)b
4a 70
Br
C6H5-
CH3C6H4-
C6H5-
2
3
4
5
6
7
8
9
C6H5-
C6H5-
C6H5-
4b 76
4c 73
4d 70
4e 76
4f 82
4g 78
5a 56
5b 59
Br
Br
Br
Br
Br
Br
n-C5H11-
n-C4H9-
C6H5-
CH3C6H4-
CH3C6H4-
CH3CH2-
CH3C6H4-
CH3C6H4-
CH3C6H4-
CH3C6H4-
C6H5-
C6H5-
C6H5-
C6H5-
CH3C6H4-
CH3C6H4-
C6H5-
n-C5H11-
C6H5-
+
–OTs
–OTs
Ph
Ph
IPh
n-C5H11-
C6H5-
+
IPh
a Allyl bromide or alkynyliodonium tosylate (0.8 mmol) was added to the reaction mixture of 1 (0.5 mmol) and ArMgBr (0.6 mmol) in THF–
CH2Cl2 (1:4) at –20 °C.
b Isolated yield of purified 4 or 5 based on 1.
Synlett 2003, No. 4, 477–480 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
Carbomagnesiation of Acetylenic Sulfones Catalyzed by CuCN
479
From Table 2 we can see that the intermediate 2, which
formed from the addition of ArMgBr to acetylenic sulf-
one, coupled with allyl bromide or alkynyliodonium
tosylate readily to give the corresponding 1,4-dienes 4 or
conjugated enynes 5, respectively. The acetylenic sulf-
ones could be alkyl- or phenyl-substituted acetylenic sulf-
ones.
References
(1) Trost, B. M.; Fleming, I.; Semmelhack, M. F.
Comprehensive Organic Synthesis, Vol. 4; Pergamon Press:
New York, 1991.
(2) Fujiwara, N.; Yamamoto, Y. J. Org. Chem. 1997, 62, 2318.
(3) (a) Simpkins, N. S. Sulfones in Organic Synthesis;
Pergamon Press: Oxford, 1993. (b) Fuchs, P. L.; Braish, T.
F. Chem. Rev. 1986, 86, 903. (c) Simpkin, N. S.
Tetrahedron 1990, 46, 6951. (d) NáJera, C.; Yus, M.
Tetrahedron 1999, 55, 10547.
(4) Popoff, I. C.; Denver, J. L. J. Org. Chem. 1969, 34, 1128.
(5) Ley, S. V.; Simpkins, N. S. J. Chem. Soc., Chem. Commun.
1983, 1281.
(6) Gancarz, R. A.; Kice, J. L. Tetrahedron Lett. 1980, 21, 4155.
(7) Back, T. G.; Collins, S.; Kerr, R. G. J. Org. Chem. 1983, 48,
3077.
(8) (a) Huang, X.; Duan, D. H. Chem. Commun. 1999, 1741.
(b) Huang, X.; Liang, C. G.; Xu, Q.; He, Q. W. J. Org. Chem.
2001, 66, 74.
The stereochemistry of the addition reaction of Grignard
reagent with acetylenic sulfones and its further reaction
with electrophiles was affirmatively verified by the
NOESY spectra of compound 4g and the X-ray structure
of compound 4f 15 (Figure 2). The NOESY spectra of 4g
shows that there are strong correlation between the allylic
protons of the allyl group and the protons of the tolyl
while no correlation was found between the allylic proton
of the allyl group and the n-C5H11-group. From Figure 2
we can also see the allyl is cis oriented with tolyl. These
results demonstrated that the addition of Grignard reagent
with acetylenic sulfones is in the syn-fashion.
(9) (a) Huang, X.; Xie, M. H. Org. Lett. 2002, 4, 1331.
(b) Huang, X.; Xie, M. H. J. Org. Chem. 2002, 67, 8895.
(10) Smorada, R. L.; Truce, W. E. J. Org. Chem. 1979, 44, 3444.
(11) (a) Fiandanese, V.; Marchese, G.; Naso, F. Tetrahedron Lett.
1978, 51, 5131. (b) Russell, R. A.; Ngoviwatchai, P. J. Org.
Chem. 1989, 54, 1836.
(12) Crystal Data for 3a: C21H18O2S, MW = 334.41,
monoclinic, space group P21/n, a = 12.8256(6),
b = 5.8678(7), c = 23.871(3) Å; α = 90°, β = 105.360(3)°,
γ = 90°. V = 1732.3(4) Å3, T = 293 K, Z = 4, Dc = 1.282
gcm–1, µ = 0.196 mm–1, λ = 0.71073 Å; F(000) 704, 4060
independent reflections (Rint = 0.0848), 10150 reflections
collected; refinement method, Full – matrix least – squares
on F2; goodness of fit on F2 = 0.623; Final R indices
[I>2σ(I)] R1 = 0.0427, wR2 = 0.0461.
(13) Okamoto, S.; Takayama, Y.; Gao, Y.; Sato, F. Synthesis
2000, 975.
(14) Pirguliyev, N. S.; Brel, V. K. Tetrahedron 1999, 55, 12377.
(15) Crystal Data for 4f: C25H24O2S, MW = 388.50, monoclinic,
space group P21/n, a = 5.9754(5), b = 22.733(2),
c = 15.3647(3) Å; α = 90°, β = 92.512(2)°, γ = 90°.
V = 2085.1(3) Å3, T = 293 K, Z = 4, Dc = 1.238 gcm–1,
µ = 0.173 mm–1, λ = 0.71073 Å; F(000) 824, 4772
independent reflections (Rint = 0.1229), 12695 reflections
collected; refinement method, Full – matrix least – squares
on F2; goodness – of – fit on F2 = 0.879; Final R indices [
I>2σ(I)] R1 = 0.0545, wR2 = 0.1176.
(16) General Procedure for the Reaction of Acetylenic
Sulfone and PhMgBr, Synthesis of 1-Diphenyl-2-(p-
tolylsulfonyl)ethene (3a). To the solution of PhMgBr (0.6
mmol) in THF–CH2Cl2 (1:4, 5 mL) was added CuCN (10
mol%) and 1-phenyl-2-(p-tolylsulfonyl)ethyne (0.5 mmol)
at –20 °C with stirring. The reaction mixture was stirred at
–20 °C for 30 min. Then the reaction was quenched with sat.
NH4Cl and extracted with CH2Cl2. The organic phase was
washed with sat. brine and dried over MgSO4. After
filtration and removal of the solvent in vacuo, the crude
product was purified with flash chromatography (silica/
hexanes–EtOAc, 10:1) and the desired adduct 1, 1-diphenyl-
2-(p-tolylsulfonyl)ethene (3a) was obtained as colorless
crystal. Mp 101 °C (from hexanes–EtOAc) (Lit.18 102–
103 °C). 1H NMR (400 MHz, CDCl3): δ = 7.47 (d, J = 8.24
Hz, 2 H), 7.37–7.35 (m, 7 H), 7.31–7.27 (m, 2 H), 7.14 (d,
J = 7.96 Hz, 1 H), 7.10–7.08 (m, 2 H), 6.99 (s, 1 H), 2.37 (s,
3 H). IR (KBr): 1326, 1142 cm–1. MS (EI): m/z (%) = 335
(46) [M+ + 1], 178 (100).
Figure 2 The molecular structure of 4f
In conclusion, the carbomagnesiation of acetylenic sul-
fone and further reaction with electrophiles in the pres-
ence of 10 mol% CuCN provides an efficient synthesis of
polysubstituted vinyl sulfones regio- and stereoselective-
ly. Efforts are made in our laboratory to investigate the re-
action of intermediate 2 with other electrophiles to
synthesize various substituted vinyl sulfones.
Acknowledgment
Project 20272050 was supported by the National Natural Science
Foundation of China.
Synlett 2003, No. 4, 477–480 ISSN 0936-5214 © Thieme Stuttgart · New York

480
M. Xie, X. Huang
LETTER
(17) General Procedure for the Reaction of Acetylenic
Sulfone and PhMgBr and further Reaction with Allyl
Bromide or Alkynyphenylliodonium Tosylate. To the
solution of PhMgBr (0.6 mmol) in THF–CH2Cl2 (1:4, 5 mL)
was added CuCN (10 mol%) and acetylenic sulfone (0.5
mmol) at –20 °C with stirring. After the addition completed
(monitored by TLC), allyl bromide or alkynylphenyl
iodonium tosylate (0.8 mmol) was added. The reaction
mixture was stirred at –20 °C for 2–2.5 h. Then the reaction
was quenched with sat. NH4Cl and extracted with CH2Cl2.
After usual workup, the desired adduct 4 or 5 was obtained.
Product 1,1-diphenyl-2-(p-tolylsulfonyl)-1,4-pentadiene
(4a): Mp 136 °C (from hexanes/ethyl acetate). 1H NMR (400
MHz, CDCl3): δ = 7.30–7.24 (m, 5 H), 7.17–7.15 (m, 1 H),
7.12–7.10 (m, 4 H), 7.08–7.04 (m, 2 H), 6.97–6.95 (m, 2 H),
6.04–5.91 (m, 1 H), 5.11–5.00 (m, 2 H), 3.35 (d, J = 6.32 Hz,
2 H), 2.35 (s, 3 H). IR (KBr): 3078, 1302, 1145 cm–1. MS
(EI): m/z (%) = 375 (10) [M+ + 1], 218 (100). Anal. Calcd for
C24H22O2S: C, 76.97; H, 5.92. Found: C, 76.86; H, 5.88.
(18) Gancarz, R. A.; Kice, J. L. J. Org. Chem. 1981, 46, 4899.
Synlett 2003, No. 4, 477–480 ISSN 0936-5214 © Thieme Stuttgart · New York