An unexpected silver triflate-catalyzed reaction of 2-alkynylbenzaldoxime in the presence of benzoyl chloride

Article abstract of DOI:10.1039/c3ra40615f

An unexpected silver triflate-catalyzed reaction of 2-alkynylbenzaldoxime in the presence of benzoyl chloride under mild conditions gives rise to 2-(isoquinolin-1-yl)isoquinolin-1(2H)-ones in good yields. The Royal Society of Chemistry 2013.

Full text of DOI:10.1039/c3ra40615f

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An unexpected silver triflate-catalyzed reaction of
2-alkynylbenzaldoxime in the presence of benzoyl
chloride3
Cite this: RSC Advances, 2013, 3, 10666
Received 4th February 2013,
Accepted 15th May 2013
Gang Liu,*ab Hongliang Liu,a Shouzhi Pua and Jie Wu*bc
DOI: 10.1039/c3ra40615f
www.rsc.org/advances
An unexpected silver triflate-catalyzed reaction of 2-alkynylben-
zaldoxime in the presence of benzoyl chloride under mild
conditions gives rise to 2-(isoquinolin-1-yl)isoquinolin-1(2H)-ones
in good yields.
Tandem reactions have emerged as a powerful method for the
construction of heterocycles.1,2 Notable achievements have made
this strategy more attractive. Continuing with our efforts in the
synthesis of diversely functionalized natural product-like com-
pounds for the studies of chemical genetics,3 we recently disclosed
an efficient transformation for the formation of 1-aminoisoqui-
nolines via a silver triflate-catalyzed tandem reaction of 2-alky-
nylbenzaldoxime with amine.4 The presence of silver triflate was
demonstrated to promote the 6-endo cyclization of 2-alkynylben-
zaldoxime to afford isoquinoline-N-oxide.5–7 A phosphonium salt
(bromo-tris-pyrrolidino-phosphonium hexafluorophosphate) was
involved in the activation of N-oxide during the reaction process.8
With an expectation for the combinatorial synthesis of the
1-aminoisoquinoline library, we envisioned that benzoyl chloride
would be a good choice for the replacement of phosphonium salt
considering the atom economy, since the disadvantages of
phosphonium salt would hamper its further applications.
Scheme 1 Initial studies for the reaction of 2-alkynylbenzaldoxime with p-tolui-
dine promoted by benzoyl chloride.
Table 1 Initial studies for the silver triflate-catalyzed reaction of 2-alkynylben-
zaldoxime 1a in the presence of benzoyl chloride
The initial studies were performed for the reaction of
2-alkynylbenzaldoxime 1a with p-toluidine catalyzed by 10 mol%
of silver triflate in the presence of 1.0 equivalent of benzoyl
chloride in dichloethane (Scheme 1). To our surprise, an unknown
compound was generated in 10% yield instead of the desired
1-aminoisoquinoline. The structural illustration identified that
Entry
Base
PhCOCl
Solvent
Yield (%)a
1
2
3
4
5
6
7
8
Et3N
Et3N
Et3N
—
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
DCE
EtOH
1,4-dioxane
DCM
toluene
MeCN
0
38
50
92
0.5 equiv.
1.0 equiv.
1.5 equiv.
1.5 equiv.
1.5 equiv.
1.5 equiv.
1.5 equiv.
1.5 equiv.
1.5 equiv.
1.5 equiv.
1.5 equiv.
1.5 equiv.
1.5 equiv.
1.5 equiv.
1.5 equiv.
Et3N
iPr2NEt
DBU
50
trace
trace
trace
trace
trace
17
trace
56
39
aJiangxi Key Laboratory of Organic Chemistry, Jiangxi Science & Technology Normal
University, Nanchang 330013, China. E-mail: liugang0926@163.com
bDepartment of Chemistry, Fudan University, 220 Handan Road, Shanghai 200433,
China. E-mail: jie_wu@fudan.edu.cn; Fax: 86 21 6564 1740; Tel: 86 21 6510 2412
cKey Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry,
Chemical Engineering and Materials Science, Soochow University, Suzhou, 215123,
China
t-BuOK
KHCO3
K2CO3
Cs2CO3
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
9
10
11
12
13
14
15
16
Electronic supplementary information (ESI) available: Experimental procedure,
3
10
65
characterization data, 1H and 13C NMR spectra of compounds 2, and a CIF file of
compound 2g, CCDC 921037. For ESI and crystallographic data in CIF or other
electronic format see DOI: 10.1039/c3ra40615f
a
Isolated yield based on 2-alkynylbenzaldoxime 1a.
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Table 2 Synthesis of 2-(isoquinolin-1-yl)isoquinolin-1(2H)-ones via a silver triflate-catalyzed reaction of 2-alkynylbenzaldoxime in the presence of benzoyl chloridea
a
Isolated yield based on 2-alkynylbenzaldoxime 1.
this product was 2-(isoquinolin-1-yl)isoquinolin-1(2H)-one 2a,
which indicated that p-toluidine was not involved in the
transformation. This interesting result promoted us for its further
investigation. No reaction occurred in the absence of benzoyl
chloride (Table 1, entry 1). Compound 2a could be isolated in 50%
yield when the reaction took place in THF in the presence of 1.0
equivalent of benzoyl chloride and triethylamine (Table 1, entry 3).
To our delight, the yield was increased to 92% when 1.5 equivalent
of benzoyl chloride was employed in the reaction (Table 1, entry 4).
We next explored other bases, including organic and inorganic
bases (Table 1, entries 5–10). The expected product 2a was
detected when other bases were examined. Further screening of
solvents revealed that THF was the best choice (Table 1, entries
11–16).
The scope and generality of this unexpected silver triflate-
catalyzed tandem reaction of 2-alkynylbenzaldoxime in the
presence of benzoyl chloride were then explored. The results are
presented in Table 2. All reactions proceeded smoothly to afford
the corresponding 2-(isoquinolin-1-yl)isoquinolin-1(2H)-one 2 in
good yields. The structure of compound 2g was confirmed by X-ray
diffraction analysis as well (see the ESI ). Different substitutions
3
attached on the aromatic ring or triple bond were all compatible
under the standard conditions. The scaffold of the product was
i
furnished in 50% yield when Pr2NEt was used in the reaction
(Table 1, entry 5). However, only a trace amount of product was
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formation of multi-bonds in a one-pot procedure. Exploration of
benzoyl chloride for the activation of N-oxide is ongoing in our
laboratory.
Acknowledgements
Financial support from the National Natural Science
Foundation of China (No. 21262015) and China Postdoctoral
Science Foundation (No. 2012M520817) is gratefully acknowl-
edged.
Fig. 1 X-ray ORTEP illustration of 2-(isoquinolin-1-yl)isoquinolin-1(2H)-one 2g (30%
Notes and references
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interesting, which incorporated both isoquinoline and isoquino-
lin-1(2H)-one skeletons (Fig. 1).
A possible mechanism for the formation of this unexpected 2-
(isoquinolin-1-yl)isoquinolin-1(2H)-ones
2
was proposed in
Scheme 2. As mentioned above, the presence of silver triflate
would promote the 6-endo cyclization of 2-alkynylbenzaldoxime 1,
leading to isoquinoline-N-oxide A.5,6 Then intermediate B would
be produced when benzoyl chloride and triethylamine were
involved. An intramolecular attack of oxygen of the carbonyl
group would generate intermediate C, which would undergo
deprotonation to furnish isoquinoline D. The release of carbonyl
group with the formation of isoquinolin-1(2H)-one in situ would
promote its further nucleophilic addition to intermediate B, which
would go through deprotonation with the release of a benzoic
group to furnish the unexpected product 2.
In conclusion, we have reported an unexpected silver triflate-
catalyzed reaction of 2-alkynylbenzaldoxime in the presence of
benzoyl chloride under mild conditions, giving rise to 2-
(isoquinolin-1-yl)isoquinolin-1(2H)-ones in good yields. Molecular
complexity is generated during the reaction process with the
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Scheme 2 A proposed mechanism for the silver triflate-catalyzed reaction of
2-alkynylbenzaldoxime in the presence of benzoyl chloride.
10668 | RSC Adv., 2013, 3, 10666–10668
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