Gold-catalyzed addition of sulfonic acids to alkynes to form vinyl sulfonates

Article abstract of DOI:10.1039/b818863g

In the presence of a catalytic amount of (Ph₃P)AuNO₃ and phthalimide, the addition of toluenesulfonic acid or methanesulfonic acid to alkynes has been shown to proceed and gives vinyl tosylates and vinyl mesylates in good yields and

Full text of DOI:10.1039/b818863g

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Gold-catalyzed addition of sulfonic acids to alkynes to form vinyl
sulfonatesw
Dong-Mei Cui,*a Qian Meng,a Jin-Zhou Zhenga and Chen Zhang*b
Received (in Cambridge, UK) 24th October 2008, Accepted 8th January 2009
First published as an Advance Article on the web 3rd February 2009
DOI: 10.1039/b818863g
In the presence of a catalytic amount of (Ph3P)AuNO3 and
phthalimide, the addition of toluenesulfonic acid or methanesulfonic
acid to alkynes has been shown to proceed and gives vinyl tosylates
and vinyl mesylates in good yields and regioselectivity.
74% isolated yield with perfect regioselectivity (Table 1, entry 3).
Other possible isomers could be hardly detected. Decreasing
the amount or the absence of PhthNH resulted in lower yield,
and the addition of a large amount of PhthNH did not affect
the reaction (Table 1, entries 1, 2, 4 and 5).
Different solvents were screened, and dichloroethane was
found to be the most suitable one (Table 1, entries 6–8). The
superior efficiency of the weakly coordinating anion nitrate
was demonstrated through a comparison with other weakly or
non-coordinating anions trifluoromethanesulfonate, tetra-
fluoroborate, and hexafluoroantimonate under the same con-
ditions. While treatment of 1a and 2a with (Ph3P)AuCl and
AgBF4 resulted in only trace formation of 3a, use of
(Ph3P)AuCl and AgSbF6 produced 3a in lower yields,
(Ph3P)AuCl and AgOTf provided no catalytic activity
(Table 1, entries 11–14). The reaction did not proceed in the
absence of the Au catalyst (Table 1, entries 9 and 10). In all
case, 1-(4-butylphenyl)ethanone as the hydration product
could be detected due to water that was present in small
amounts in the reaction solution. In addition, the reaction of
1-(4-butylphenyl)ethanone, instead of 1a, with 2a did not
proceed at all under the same conditions.
During the past ten years, several research groups have
developed gold-catalyzed homogeneous catalytic reactions.1
A variety of organic transformations have been shown to be
mediated by gold(I) or gold(III) complexes in solution.2 In
addition to its ability to activate alkynes and related
substrates, the catalysis of nucleophilic addition by gold
complexes for the formation of carbon–carbon and carbon–
heteroatom bonds has been one of the most investigated
reactions in modern organometallic catalysis.3 Various
nucleophilic reagents, such as water,4 alcohols,1g amines,5
acetic acid4e etc., have been used in the intermolecular addition
to alkynes. As part of our ongoing studies on metal-catalyzed
atom-economical reactions, we have been interested in the use
of gold for simple and highly efficient transformations.6 On the
other hand, vinyl sulfonates are important building blocks in
organic synthesis, especially as electrophiles for cross-coupling
chemistry.7 Further, vinyl tosylates and vinyl mesylates are
more convenient to use because they are more stable to water
than triflates. Surprisingly few vinyl tosylates and vinyl
mesylates have been documented in the literature, and the
majority of methods for their synthesis are the sulfonylation of
the ketone with sulfonic anhydride by base.7d,8 In contrast to
the sometimes-difficult synthesis and protection of carbonyls,
alkynes are known to be synthetically robust, and the synthesis
of substituted alkynes can be quite simple. Hirsch and
co-workers reported the addition of methanesulfonic acid to
tert-butylacetylene catalyzed by HgO, but only with one
example.9 In this paper, we wish to develop a gold(I) complex
catalyzed addition of sulfonic acids to alkynes to synthesize
vinyl tosylates and vinyl mesylates.
In order to assess the scope of this process, we have
examined the addition to several alkynes with aliphatic and
aromatic sulfonic acids under the optimized conditions
Table 1 Au-catalyzed addition of toluenesulfonic acid (2a) to
p-butylphenylacetylene (1a) to form 3aa
Entry 2 mol% [Au] Additive (mol%) Solvent
Yield (%)b
1
2
3
4
5
6
7
8
9
10
11
12
13
14
(Ph3P)AuNO3 PhthNH (100)
(Ph3P)AuNO3 PhthNH (50)
(Ph3P)AuNO3 PhthNH (4)
(Ph3P)AuNO3 PhthNH (2)
Cl(CH2)2Cl
Cl(CH2)2Cl
Cl(CH2)2Cl
Cl(CH2)2Cl
Cl(CH2)2Cl
Toluene
Dioxane
Chlorobenzene
Toluene
Cl(CH2)2Cl
Toluene
Toluene
Cl(CH2)2Cl
Toluene
72
74
74
59
58
57
16
0
The reaction of 4-butylphenylacetylene (1a) (1.0 mmol) with
toluenesulfonic acid (2a) (0.5 mmol) in the presence of a
catalytic amount of (Ph3P)AuNO3 (2 mol%) and phthalimide
(PhthNH) (4 mol%) in dichloroethane (2 mL) at 100 1C
proceeded efficiently to form the Markovnikov adduct 3a in
(Ph3P)AuNO3 —
(Ph3P)AuNO3 PhthNH (4)
(Ph3P)AuNO3 PhthNH (4)
(Ph3P)AuNO3 PhthNH (4)
a College of Pharmaceutical Science, Zhejiang University of
Technology, Hangzhou 310014, PR China.
—
—
PhthNH (4)
—
0
0
(Ph3P)AuCl
(Ph3P)AuCl
(Ph3P)AuCl
(Ph3P)AuCl
AgBF4 (4)
AgSbF6 (4)
AgSbF6 (4)
AgOTf (4)
Trace
24
40
0
E-mail: cuidongmei@zjut.edu.cn; Fax: 86(0)571 88208459;
Tel: 86(0)571 88208459
b School of Pharmaceutical Sciences, Zhejiang University,
Hangzhou 310058, PR China
a
w Electronic supplementary information (ESI) available: General
procedure and characterization of adducts; X-ray data for product
3p. CCDC 702536. For ESI and crystallographic data in CIF or other
electronic format, see DOI: 10.1039/b818863g
The reactions were performed with 0.5 mmol of toluenesulfonic acid,
1.0 mmol of 4-butylphenylacetylene, [Au], and additive in 2 mL of
b
solvent at 100 1C for 4 h. Isolated yield.
ꢀc
This journal is The Royal Society of Chemistry 2009
Chem. Commun., 2009, 1577–1579 | 1577

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indicated in entry 3 of Table 1. The results are summarized in
Table 2. Regarding the sulfonic acids, methanesulfonic acid
was also converted into the expected addition products, the
regioselectivity was higher under the same conditions (Table 2,
entries 1–10). To further look at possible electronic effects and
to expand the scope of this method, acetylenes bearing
aromatic groups of various electron densities were also
studied. Alkynes with an electron-donating alkyl group on
the benzene ring with either methanesulfonic acid or toluene-
sulfonic acid all gave good isolated yields of the corresponding
vinyl sulfonates with high regioselectivity (Table 2, entries 2–3,
12–13). With a more electron-donating alkoxy group, the
expected adducts were obtained in excellent yields and regio-
selectivity (Table 2, entries 5 and 6). In sharp contrast, as an
electron-withdrawing group, the meta-fluoro-substituted
alkyne yielded the anti-Markovnikov adduct 4h as the main
product (Table 2, entry 7). Under the same reaction con-
ditions, the addition to an alkyl alkyne with sulfonic acids also
took place smoothly and showed similar reactivity and selec-
tivity to the aryl alkynes (Table 2, entries 8 and 12). Further-
more, internal alkynes also worked well. Diphenylacetylene
reacted with sulfonic acids to afford cis-adducts 3j and 3p
with high selectivity (Table 2, entries 9 and 15). For the
unsymmetrical internal alkyne, two adducts 3k1 and 3k2 were
obtained in 82% yield with high regioselectivity (Table 2, entry 10).
Single crystals of the compound 3p suitable for X-ray
crystallographic analysis were also obtained (Fig. 1). It shows
that 3p is the E isomer, the ester oxy link being trans to one of
the phenyl groups (Fig. 1).
Fig. 1 X-Ray structure of 3p (30% thermal ellipsoid).
The proposed catalytic cycle, which involves the anti-addition
of gold and the sulfonic acid to mono- and disubstituted
alkynes, is shown in Scheme 1. The gold cation coordinates
to the alkyne to form an Au–p-alkyne complex A. The sulfonic
acid as the nucleophile attacks the gold cation-coordinated
CRC bond to form a vinylgold species B or C. Then, the
organogold intermediate B or C liberates the adduct 3 or 4 and
the gold catalyst by protodemetallation. Regioselectivity is
determined by electronic factors; attack of the sulfonic acid
takes place at the electro-deficient alkynyl moiety, though
almost all nucleophilic additions follow Markovnikov’s rule.10
Isomerization from the Z-isomer of 3 to the E-isomer of 3 can
be envisaged through the protonation–deprotonation of inter-
mediate C via the cationic gold carbene D. In comparison to
forming 3k as a mixture of E and Z isomers, for R2 = Ph, 3j
and 3p were produced with an exclusive E selectivity; perhaps
due to steric hindrance, complete equilibration to the more
favored intermediate E leads to the formation of a single
isomer. On the other hand, although the source of the catalytic
activity of PhthNH as an additive is unclear, a possible role
for PhthNH is to stabilize the gold fragment forming
Table 2 Au-catalyzed addition of sulfonic acids to alkynesa
(Ph3P)AuNPhth. Furthermore, using
2
mol% of
(Ph3P)AuNPhth synthesized11 as the catalyst, addition of 2a
Entry
R1
R2
R3
Yield of product (%)b
to 1a could proceed to give 3a in 52% yield under the same
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
C6H5
H
H
H
H
H
H
H
H
C6H5
CH3
H
H
H
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
4-Tol
4-Tol
4-Tol
4-Tol
4-Tol
60 (3b : 4b = 93 : 7)
82 (3c : 4c = 100 : 0)
80 (3d : 4d = 94 : 6)
78 (3e : 4e = 499 : 1)
95 (3f : 4f = 100 : 0)
94 (3g : 4g = 100 : 0)
60 (3h : 4h = 7 : 93)
74 (3i : 4i = 90 : 10)
73 (3j : 4j = 100 : 0)
82 (3k : 4k = 100 : 0)c
60 (3l : 4l = 84 : 16)
62 (3m : 4m = 100 : 0)
76 (3n : 4n = 100 : 0)
75 (3o : 4o = 100 : 0)
50 (3p : 4p = 100 : 0)
4-C2H5C6H4
4-nC4H9C6H4
4-nC5H11C6H4
4-CH3OC6H4
4-C2H5OC6H4
3-FC6H4
nC8H17
C6H5
4-CH3OC6H4
C6H5
nC8H17
4-C2H5C6H4
4-nC5H11C6H4
C6H5
H
C6H5
a
Reaction conditions: alkyne (1.0 mmol), sulfonic acid (0.5 mmol),
(Ph3P)AuNO3 (2 mol% based on sulfonic acid), phthalimide (4 mol%
based on sulfonic acid) in Cl(CH2)2Cl (2 mL) at 100 1C for
b
1
4 h. Isolated yield; ratio was determined by H NMR spectroscopy.
c
Ratio of 3k (3k1 and 3k2) was 53 : 47.
Scheme 1 Proposed mechanism for the addition of sulfonic acids to
alkynes.
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In summary, we have developed a new process of ionic
gold-catalyzed addition of sulfonic acids to alkynes to provide
vinyl sulfonates. This reaction takes place under mild con-
ditions with effective and high regio- and stereoselectivity;
the adducts are synthetically important as substrates for
metal-catalyzed cross-coupling reactions. Detailed mechanistic
studies and scope expansion work are currently underway in
our laboratory.
This work was partially supported by the Natural Science
Foundation of China (No. 20672099, 20572094).
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