Palladium-catalyzed desulfitative hydroarylation of alkynes with sodium sulfinates

Article abstract of DOI:10.1039/c3cc43723j

A palladium-catalyzed desulfitative hydroarylation of alkynes with aryl sulfinic acid sodium salts is described. The reaction showed good regio- and stereoselectivity, and afforded the hydroarylation products in good yields. Various functional groups were well tolerated under the optimized reaction conditions.

Full text of DOI:10.1039/c3cc43723j

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Palladium-catalyzed desulfitative hydroarylation of
alkynes with sodium sulfinates†
Saiwen Liu,a Yang Bai,a Xiangxiang Cao,a Fuhong Xiaoa and Guo-Jun Deng*ab
Cite this: Chem. Commun., 2013,
49, 7501
Received 17th May 2013,
Accepted 25th June 2013
DOI: 10.1039/c3cc43723j
www.rsc.org/chemcomm
A palladium-catalyzed desulfitative hydroarylation of alkynes with
aryl sulfinic acid sodium salts is described. The reaction showed
good regio- and stereoselectivity, and afforded the hydroarylation
products in good yields. Various functional groups were well
tolerated under the optimized reaction conditions.
Alkenes are ubiquitous in biologically active compounds and
natural products and serve as versatile starting materials for a
large number of chemical transformations.1 The stereoselective
synthesis of substituted alkenes has been one of the major
topics in the arena of organic synthesis for many decades.
Various methods have been developed to prepare substituted
alkenes,2 such as the classic elimination reactions, the Aldol-type
Scheme 1 Various approaches for hydroarylation of alkynes.
condensation,3 the Wittig–Horner reaction and its variants,4 metal-waste generation. Aryl halides,13 aromatic aldehydes (via
olefin metathesis5 and cross-coupling reactions (including decarbonylation)14 and aromatic carboxylic acids (via decarboxyl-
Heck reaction).6 In the past few decades, great attention has ation)15 were successfully used as aryl sources for alkyne hydro-
been paid to the metal-catalyzed hydroarylation of alkynes due arylations (Scheme 1, eqn (2)). In these processes, an aryl–metal
to its fast accessibility to highly functionalized arylalkenes.7 intermediate was formed in situ which can be subsequently
Organometallic compounds such as arylmagnesiums,8 aryltins,9 added to the alkyne triple bond. Meanwhile, the transition-
arylsilanes10 and arylborons were used as arylation reagents metal-catalyzed C–H activation affords a very promising approach
for multisubstituted arylalkene synthesis (Scheme 1, eqn (1)). for construction of C–C bonds with reduced operation steps. This
Among them, the arylboron reagents have drawn considerable strategy was also successfully employed for hydroarylation of
attention due to their advantages, such as good functional alkynes using symmetrical arenes as aryl sources.16 However,
group tolerance, easy availability, and good reactivity. In 2001, this method is mainly suitable for electron-rich arenes. Also, the
Hayashi and co-workers first reported rhodium-catalyzed hydro- control of the regioselectivity on arenes, in particular mono-
arylation of alkynes with arylboronic acids.11 Subsequently, substituted benzenes, is very difficult.17 Since multi-substituted
various transition-metal-catalyzed hydroarylation reaction systems arylalkenes play an important role in synthetic organic chemistry,
using arylboron reagents were developed. Rhodium, nickel, the development of an efficient synthetic approach with good
palladium, cobalt and copper were proved to be efficient catalysts regio- and stereo-selectivity is highly desirable. Sodium sulfinates
for this kind of transformation.12
are stable and easy to handle. These compounds have the
The replacement of a stoichiometric amount of organo- potential to serve as ideal aryl sources for C–C bond-forming
metallics for hydroarylation of alkynes has gained consider- reactions via extrusion of SO2.18 Recently, we and others developed
able interest since this strategy can significantly minimize various palladium-catalyzed desulfitative Heck-type reactions,19
addition reactions,20 homocoupling reactions,21 and cross-
a Key Laboratory of Environmentally Friendly Chemistry and Application of Ministry
coupling reactions22 under relatively mild conditions. In these
desulfitative reactions, various aromatic sulfinic acids (or salts)
were used as aryl sources. Herein, we describe a palladium-
catalyzed desulfitative hydroarylation of alkynes with good
of Education, College of Chemistry, Xiangtan University, Xiangtan 411105, China.
E-mail: gjdeng@xtu.edu.cn; Fax: +86 0731-5829-2251; Tel: +86 0731-5829-8601
b Key Laboratory of Molecular Recognition and Function, Institute of Chemistry,
Chinese Academy of Sciences, Beijing 100080, China
† Electronic supplementary information (ESI) available. See DOI: 10.1039/c3cc43723j regio- and stereo-selectivity (Scheme 1, eqn 3).
c
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Table 2 Hydroarylation of various alkynesa
We began our investigation by examining the reaction of
sodium benzenesulfinate (1a) with diphenylethyne (2a) in
1,4-dioxane–water (3 : 1) using trifluoroacetic acid. When 1a
reacted with 1.5 equiv. of 2a in the presence of PdCl2 (5 mol%)
and 1,8-naphthalenediamine (1,8-naph, 10 mol%) under argon,
the desired product was observed in 90% yield as detected by
the GC method. Subsequently, various palladium(II) salts were
tested for this desulfitative hydroarylation reaction and good
yields were observed. Among them, Pd(OAc)2 showed the best
efficiency, and the desired product 3a was obtained in 96%
yield. The use of the palladium catalyst is necessary for this
kind of transformation, and only 8% yield was obtained when
the reaction was carried out in its absence. Other nitrogen-
containing ligands were investigated for this reaction under
similar conditions. Among them, DABCO (triethylenediamine)
was also effective and gave the product in 82% yield. The
solvent had a significant impact on the reaction yield. Much
Entry Substrate 1 Alkyne (2)
Product Yieldb [%]
1
2
3
4
5
6
7
8
1a
1a
1a
1a
1a
1b
1b
1b
R1 = R2 = 4-Me-C6H4 (2b)
3o
85
R1 = R2 = 4-MeO-C6H4 (2c) 3p/4p
R1 = Ract2 = 4-F-C6H4 (2d) 3q
80 (2.5 : 1)
95
90
55
81
80
78
R1 = R2 = 4-ClC6H4 (2e)
3r
3s
3t
3u
3v
R1 = Ph, R2 = Me (2f)
2b
2d
2e
a
Conditions: 1 (0.3 mmol), 2 (0.2 mmol), Pd(OAc)2 (7.5 mol%),
1,8-naphthalenediamine (15 mol%), TFA (0.3 mmol), 1,4-dioxane
(0.3 mL), H2O (0.1 mL), 120 1C, 24 h under argon unless otherwise
b
noted. Isolated yield based on 2, ratios were determined by GC.
lower yield was observed when the reaction was carried out in a sodium salt (1f) reacted with 2a, the desired products were
mixture of toluene, anisole, diglyme and DMF with water. obtained in 82% and 80% yields with a good trans/cis ratio
Notably, the desired addition product 3a could be obtained in (95/5). A series of functional groups including fluoro, chloro,
45% yield in water. Trifluoroacetic acid played an important bromo, trifluoromethyl and trifluoromethoxy survived under
role in this reaction, and replacement of trifluoroacetic acid the optimal reaction conditions, and the desired products were
with acetic acid significantly decreased the reaction yield to obtained in good yields (entries 7–11). The position of sub-
30%. Only 10% yield was achieved in the absence of any acid stituents on sulfinic acid sodium salts dramatically affected the
additives (see ESI,† Table S1).
yield of hydroarylation. For example, when sodium 2-methyl
With the optimized reaction conditions in hand, we then benzenesulfinate (1l) and 2-naphthylsulfinic acid sodium salt
explored the scope and generality of this transformation in the (1m) reacted with 2a, the desired products 3l and 3m were
presence of a variety of functional groups of the arylsulfinic obtained in 48% and 70% yields, respectively (entries 12 and 13).
acid sodium salts, as shown in Table 1. Electron-rich substi- Unfortunately, aliphatic sodium sulfinates such as 1n are not
tuents at the para position of sulfinic acid did not affect the suitable substrates for this kind of transformation under the
reaction yield significantly (entries 2–6). In general, the trans optimal conditions (entry 14).
alkene products were formed dominantly and only trace
The reaction results of various alkynes with sodium benzene-
amounts of cis products were observed as determined by GC sulfinate (1a) or sodium 4-methyl benzenesulfinate (1b) are
and 1H NMR methods. When the (4-tert-butylphenyl)sulfinic presented in Table 2. The reactions with alkynes bearing electron-
acid sodium salt (1e) and the (4-methoxyphenyl)sulfinic acid donating groups (entries 1, 2 and 6) and electron-withdrawing
substituents (entries 3, 4, 7 and 8) at the aromatic ring proceeded
smoothly to give the desired products in moderate to good
Table 1 Desulfitative hydroarylation of 2a with various sodium sulfinates 1a
yields. However, the use of 1,2-bis(4-methoxyphenyl)ethyne (2c)
showed much lower selectivity, and gave the hydroarylation
products 3p and 4p in 80% combination yield (3p/4p = 2.5/1,
entry 2).23 Notably, the hydroarylation reaction of non-symmetrical
Product
Entry
Sodium sulfinate
Yieldb [%]
1-phenylpropyne (2f) with 1a also afforded the desired product 3s
1
2
3
4
Ar = Ph
1a
1b
1c
1d
1e
1f
1g
1h
1i
1j
1k
1l
1m
1n
3a
3b
3c
3d
3e/4e
3f/4f
3g
3h
3i
3j
3k
3l
3m/4m
3n
90
88
84
80
82 (95 : 5)
80 (95 : 5)
86
88
75
68
78
48
70 (93 : 7)
0
Ar = 4-Me-C6H4
Ar = 4-ethyl-C6H4
Ar = 4-isopropyl-C6H4
Ar = 4-tBu-C6H4
Ar = 4-MeO-C6H4
Ar = 4-F-C6H4
Ar = 4-Cl-C6H4
Ar = 4-Br-C6H4
Ar = 4-CF3-C6H4
Ar = 4-CF3O-C6H4
Ar = 2-Me-C6H4
Ar = 2-naphthalene
CH3SO2Na
5
6c
7d
8
9d
10
11
12
13
14
a
Conditions: 1 (0.3 mmol), 2a (0.2 mmol), Pd(OAc)2 (5 mol%), 1,8-
naphthalenediamine (10 mol%), TFA (0.3 mmol), 1,4-dioxane (0.3 mL),
H2O (0.1 mL), 120 1C, 24 h under argon unless otherwise noted.
b
Isolated yield based on 2a, the ratio of 3/4 was determined by GC.
10 mol% Pd(OAc)2was used. 5 mol% Pd(OAc)2 was used.
c
d
Scheme 2 Proposed mechanism.
c
7502 Chem. Commun., 2013, 49, 7501--7503
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A plausible mechanism to rationalize this transformation is
outlined in Scheme 2. The catalytic cycle may contain four
steps: (1) coordination of the aromatic sulfinic acid sodium salt to
palladium(II) to give complex I; (2) extrusion of SO2 to generate an
aryl–palladium intermediate II; (3) insertion of intermediate II
into the alkyne triple bond to afford intermediate III; (4) proto-
nation of intermediate III by the acid to give the final addition
product and regenerate the palladium(II) catalyst.
In conclusion, we have developed a palladium-catalyzed
desulfitative hydroarylation of aryl sulfinic acid sodium salts to
alkynes. The reaction showed good regio- and stereo-selectivity
as well as functional group tolerance. This method affords
an efficient alternative route for multi-substituted arylalkene
formation using sodium sulfinates as aryl sources. The scope,
mechanism, and synthetic applications of this reaction are
under investigation.
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This work was supported by the National Natural Science
Foundation of China (21172185), the Hunan Provincial Natural
Science Foundation of China (11JJ1003, 12JJ7002), the New Century
Excellent Talents in University from Ministry of Education of
China (NCET-11-0974), and the Hunan Provincial Innovative
Foundation for Postgraduate (CX2012B250).
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c
This journal is The Royal Society of Chemistry 2013
Chem. Commun., 2013, 49, 7501--7503 7503