Nickel-Catalyzed Intramolecular Coupling of Sulfones via the Extrusion of Sulfur Dioxide

Article abstract of DOI:10.1002/adsc.201801733

We describe a method for intramolecular desulfonylative coupling using bis(cyclooctadiene)nickel as a catalyst. A broad range of aromatic, heteroaromatic and aliphatic sulfones can be utilized as substrates in this process. This method provides an atom-economical route to the synthesis of various biaryls and an efficient tool for the catalytic conversion of sulfonyl groups, representing a significant advancement in organic synthesis. (Figure presented.).

Full text of DOI:10.1002/adsc.201801733

Title: Nickel-Catalyzed Intramolecular Coupling of Sulfones via the
Extrusion of Sulfur Dioxide
Authors: Tian-Yang Yu, Zhaojing Zheng, Jing-Hua Bai, Hong Fang,
and Hao Wei
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To be cited as: Adv. Synth. Catal. 10.1002/adsc.201801733
Link to VoR: http://dx.doi.org/10.1002/adsc.201801733

10.1002/adsc.201801733
Advanced Synthesis & Catalysis
COMMUNICATION
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Nickel-Catalyzed Intramolecular Coupling of Sulfones via the
Extrusion of Sulfur Dioxide
Tian-Yang Yu,+a Zhao-Jing Zheng,+b Jing-Hua Bai,a Hong Fang,a Hao Weia*
a
Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of Ministry of Education, Department of
Chemistry & Materials Science, Northwest University, Xi’an 710127, P. R. China.
E-mail: haow@nwu.edu.cn
State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, P. R. China.
These authors contributed equally to this work.
b
+
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.(
Abstract. We describe a method for intramolecular
desulfonylative coupling using bis(cyclooctadiene)nickel as
a catalyst. A broad range of aromatic, heteroaromatic and
aliphatic sulfones can be utilized as substrates in this
process. This method provides an atom-economical route to
the synthesis of various biaryls and an efficient tool for the
catalytic conversion of sulfonyl groups, representing a
significant advancement in organic synthesis
Keywords: Desulfonylative coupling; Nickel-catalysis;
Biaryl; Sulfone; C–S activation
The development of new methods for carbon-carbon
(C–C) bond formation is currently an important goal
in organic chemistry. Transition metal-catalyzed C–C
bond-forming reactions have emerged as a powerful
synthetic tool in this regard.[1] Among these new
methods, the extrusion of CO from ketones has
attracted much attention in recent decades, and has
been investigated in pioneering works by Murai,[2]
Chatani,[3] Shi,[4] Dong,[5] and own our group.[6] The
extension of this strategy to other functional groups is
highly desirable,[7] because this would represent a
new aproach to the formation of C–C bonds.
Sulfonyl compounds are a versatile class of
organic compounds [8] and the sulfonyl moiety can be
employed as a directing group to allow the
functionalization of adjacent positions on an aromatic
ring structure.[9] Therefore, the development of new
methods for the conversion of sulfonyl groups would
provide significant opportunities for the facile
construction of complex molecules. To date, various
intermolecular cross-coupling reactions involving
sulfone moieties have been reported.[10] However, in
these cases, only one part of the sulfonyl molecule is
involved, which is undesirable with regard to atom
economy (Scheme 1).
Scheme 1. Two types of desulfonylative coupling and this
work
Based on our previous work,[6] it is apparent that
the application of the extrusion strategy to sulfones
could be highly useful. Employing this strategy
allows both parts of the sulfone to be fully used in
one transformation, such that a single, common
sulfonyl group becomes the site for C–C bond
formation. However, compared with intermolecular
desulfonylative couplings, intramolecular reactions
face additional challenges. These difficulties are
associated with the activation of both C−S bonds,
which may be at different positions, under the same
conditions. To date, only few methods have been
reported for this type of reaction,[11] and so the
intramolecular desulfonylative coupling of sulfones is
still a relatively unexplored research area. The
present research demonstrates a nickel-catalyzed
intramolecular desulfonylative coupling with a broad
substrate scope and satisfactory yields, based on the
1
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10.1002/adsc.201801733
Advanced Synthesis & Catalysis
use of a directing group (Scheme 1). This reaction
offers an efficient catalytic system for desulfonylative
coupling and is expected to significantly mitigate the
limitations currently associated with this field.
control experiments showed that both Ni (cod)2 and
PCy3 were necessary for an efficient catalytic system
(Table 1, entries 9–10). Finally, the efficiencies of
various directing groups were investigated, and
substrate 1a with pyridine as the directing group gave
the best result (Table 1, entries 11–13). We also
attempted to capture SO2 released from the reaction
using DABCO,[12] but the results were not
satisfactory (Table 1, entry 14).
Table 1. Optimization of the reaction conditions.[a]
Table 2. Scope of intramolecular desulfonylative
coupling.[a,b]
Entry
Ligand
Solvent
T (oC) Yield (%)[b]
1
2
3
4
5
6
7
8
PCy3
PMe3
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
toluene
150
150
150
150
150
150
150
130
150
150
150
150
150
150
56
43
12
72
63
11
trace
34
n.d.
19
68
P(i-Pr)3
P(n-Bu)3
P(n-Bu)3
P(n-Bu)3
P(n-Bu)3
P(n-Bu)3
P(n-Bu)3
---
P(n-Bu)3
P(n-Bu)3
P(n-Bu)3
P(n-Bu)3
THF
CH3CN
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
9[c]
10
11[d]
12[e]
13[f]
14[g]
n.r.
n.r.
trace
[a] Unless otherwise noted, the reactions were carried out
with 1a (0.1 mmol), Ni(cod)2 (0.01 mmol) and ligand
(0.02 mmol) in the indicated solvent (0.5 mL) for 36 h.
[b] Isolated yield after flash chromatography.
[c] Without Ni(cod)2.
[a]
Unless otherwise noted, the reactions were carried out
[d] Using 1i as starting material.
with 1 (0.1 mmol), Ni(cod)2 (0.01 mmol) and P(n-Bu)3
(0.02 mmol) in 1,4-dioxane (0.5 mL) at 150 oC for 36 h.
[b] Isolated yields.
[e] Using 3a as starting material.
[f] Using 3b as starting material.
[c] 1.0 mmol scale.
[g] Using DABCO as additive.
Ni(cod)2 = bis(cyclooctadiene)nickel, n. r. = no reaction.
Having determined the optimized reaction
conditions, variations of the substituted phenyl
sulfone 1 were investigated to assess the versatility of
this catalytic system. Substrates having different
substituents at the para-position of the benzene ring
were initially examined. As shown in Table 2,
regardless of the electronic properties of the
substituents, moderate to good yields were obtained
with this desulfonylative reaction, although, the
yields of some substrates (2b, 2c, 2g) were relatively
low, due to lower degrees of conversions. The
reaction also exhibited excellent compatibility with a
In
initial
trials,
2-(2-
(phenylsulfonyl)phenyl)pyridine (1a) was used as a
model substrate to optimize the reaction conditions.
The reaction proceeded smoothly to provide the
desired product 2a in the presence of catalytic
amounts of Ni (cod)2 and PCy3 (Table 1, entry 1).
This result encouraged us to pursue further
optimization and a variety of phosphine ligands were
assessed (Table 1, entries 1–4), showing that P(n-
Bu)3 was more efficient than other ligands (Table 1,
entry 4). Several solvents were subsequently screened
and 1,4-dioxane was found to be optimal (Table 1,
entries 5–7). Attempts to lower the temperature (to
variety
of
functional
groups,
including
trifluoromethyl (2e), nitrile (2d) and fluoride (2f). A
substrate with a substituent at the meta-position also
o
130 C) led to a lower yield (Table 1, entry 8), while
2
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10.1002/adsc.201801733
Advanced Synthesis & Catalysis
worked to give the product (2g). Notably, a
heteroaromatic sulfone (2h) also showed satisfactory
reactivity and gave the desired product in good yield.
To the best of our knowledge, the direct
construction of C(sp3)−C(sp2) bonds via metal-
catalyzed intramolecular desulfonylative coupling has
not yet been reported. Thus, we attempted to apply
this method to alkyl sulfones (1j and 1k). The
reaction of alkyl sulfone 1j proceeded smoothly to
give the desired product in 74% yield using this
catalytic system. Unfortunately, alkyl sulfone 1k did
not work well, presumably due to steric hindrance
(Scheme 2).
Table 3. Scope of intramolecular desulfonylative coupling
with indolyl sulfones. [a,b]
Scheme 2. Intramolecular desulfonylative coupling of 1j
and 1k.
This new method was also applied to substrates
with no directing groups. Under standard conditions,
the reaction did not work well, and only a trace
amount of product was observed (6a), although the
yield was improved to 80% when a stoichiometric
amount of Ni(cod)2 was employed. We also assessed
the performance of a benzothiophene sulfone (6b)
and the desired product was obtained in 53% yield
(Scheme 3).
[a]
Unless otherwise noted, the reactions were carried out
with 4 (0.1 mmol), Ni(cod)2 (0.01 mmol) and P(n-Bu)3
(0.02 mmol) in 1,4-dioxane (0.5 mL) at 150 oC for 40 h.
[b] Isolated yields.
To further explore the generality of this novel
method, we applied this technique to various
substituted indolyl sulfones. As shown in Table 3,
substrates with either electron withdrawing or
donating substituents all worked well to afford the
desired products in moderate to good yields, and a
variety of functional groups were also well tolerated.
Notably, fluoride and chloride substituents provided
good results (5e, 5j and 5k), demonstrating the
possibility of a wide range of functionalization. In
addition, ether (5d, 5n) and ester groups (5l) were
also compatible under these conditions. The data
show that the position of the substituent had little
effect on the yield (5f-5i). Finally, sulfone substrates
with other directing groups also worked well (5m,
5n). A crossover experiment was also conducted and
no intermolecular disulfenylation was observed,
please see supporting information for details.
Scheme 3. Application to substrates with no directing
group.
Based on these data and previous publications,[6,11b]
a possible mechanism is proposed. As shown in
Scheme 4, initially, with the assistance of the
directing group, the Ni(0) complex coordinates with
substrate 1a to form intermediate M1. Intermediate
M2 is then formed via the oxidative cleavage of one
C−S bond by the complex. Subsequently, a
desulfonylative reaction produces the corresponding
3
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10.1002/adsc.201801733
Advanced Synthesis & Catalysis
nickel complex M3. Finally, M3 undergoes reductive
elimination to afford product 2a, along with the
regeneration of the Ni(0) catalyst.
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Scheme 4. Proposed mechanism.
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[7] For C–P bond activation, see: a) R. Yu, X. Chen, S. F.
Martin, Z. Wang, Org. Lett. 2017, 19, 1808–1811; For
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Guo, M. Rueping, Chem. Eur. J. 2017, 23, 11771–
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N. Ichiishi, M. S. Sanford, Org. Lett. 2017, 19, 4142–
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In summary, we have demonstrated the efficient,
high atom-economy, nickel-catalyzed intramolecular
desulfonylative coupling of sulfonyl compounds.
This approach can also employ a broad range of
substrates. This methodology not only provides a
novel pathway for the catalytic conversion of sulfonyl
groups, but is also expected to facilitate the discovery
of important trends in nickel-catalyzed C−S bond
activation.
Experimental Section
In a glovebox, P(n-Bu)3 (0.02 mmol) was added to a
solution of Ni(cod)2 (0.01 mmol) and sulfone (0.1 mmol)
in 1,4-dioxane (0.5 mL). Then the vessel was sealed and
removed from glovebox. The mixture was stirred at 150 oC
for 36 or 40 h. After completion of reaction, the solvent
was removed and the residue was purified by flash column
chromatography to afford desired product.
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Acknowledgements
We are grateful to the financial support from the National
Natural Science Foundation of China (NSFC 21502149 and
21632003) and the Key Science and Technology Innovation Team
of Shaanxi Province (2017KCT-37).
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5
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10.1002/adsc.201801733
Advanced Synthesis & Catalysis
COMMUNICATION
Nickel-Catalyzed Intramolecular Coupling of
Sulfone via Extrusion of Sulfur Dioxide
Adv. Synth. Catal. Year, Volume, Page – Page
Tian-Yang Yu, Zhao-Jing Zheng, Jing-Hua Bai,
Hong Fang and Hao Wei*
6
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