Rhodium(III)-Catalyzed Alkynylation of 4-Arylphthalazin-1(2H)-one Scaffolds via C-H Bond Activation

Article abstract of DOI:10.1002/ejoc.201901731

Selective C–H bond alkynylation toward modular access to material and pharmaceutical molecules is of great desire in modern organic synthesis. Disclosed herein is rhodium(III)-catalyzed selective C–H bond mono-/bialkynylation of 4-aryl phthalazin-1(2H)-one was developed. The silver salt AgSbF₆ are demonstrated to play a vital role in promoting the bialkynylation reactions. The present alkynylation strategy is simple, efficient, and features high functional group tolerance and broad substrate scope under an air atmosphere. Additionally, 6-aryl pyridazin-3(2H)-one scaffold is amenable to the selective monoalkynylation and sequential bialkynylation, respectively.

Full text of DOI:10.1002/ejoc.201901731

A Journal of
Accepted Article
Title: Rhodium (III)-Catalyzed Alkynylation of 4-Arylphthalazin-1(2H)-
one Scaffolds via C-H Bond Activation
Authors: xuxin du, hongcen hou, yongli zhao, Junmin Chen, and shouri
sheng
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201901731
Link to VoR: http://dx.doi.org/10.1002/ejoc.201901731
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European Journal of Organic Chemistry
10.1002/ejoc.201901731
FULL PAPER
Rhodium (III)-Catalyzed Alkynylation of 4-Arylphthalazin-1(2H)-one Scaffolds via C-H Bond
Activation
[a]
[a]
[a]
[a]
[a]
Xuxin Du, Hongcen Hou, Yongli Zhao, shouri sheng, and Junmin Chen*
Dedication ((optional))
[a]
X.-X. Du, H.-C. Hou, Y.-L. Zhao, S.-R. Sheng, Dr. J.-M. Chen
Key Laboratory of Functional Small Organic Molecules, Ministry of Education and College of Chemistry & Chemical
Engineering, Jiangxi Normal University, Nanchang 330022 (P. R. China) http://www.jxnu.edu.cn/
E-mail: jxnuchenjm@163.com
http://www.jxnu.edu.cn
Supporting information for this article is given via a link at the end of the document.((Please delete this text if not appropriate))
Abstract: Selective C-H bond alkynylation toward modular
access to material and pharmaceutical molecules is of great
desire in modern organic synthesis. Disclosed herein is
rhodium (III)-catalyzed selective C-H bond mono-
O
O
O
N
N
NH
N
NH
N
MeO
/bialkynylation of 4-aryl phthalazin-1(2H)-one was
N
2
F HCO
OMe
OMe
developed. The silver salt AgSbF are demonstrated to play
6
COOEt
OMe
anti-hypentensive A
a vital role in promoting the bialkynylation reactions. The
present alkynylation strategy is simple, efficient, and
features high functional group tolerance and broad substrate
scope under an air atmosphere. Additionally, 6-aryl
pyridazin-3(2H)-one scaffold is amenable to the selective
PDE-4 inhibitor B
antiplatelet C
N
3
F C
O
N
N
Cl
N
N
N
NH
anticancer
D
kinase inhibitor E
monoalkynylation
respectively.
and
sequential
bialkynylation,
Figure
1
Representative examples of bioactive
phthalazinones/phathalazine and their derivatives
Introduction
Furthermore, phthalazin-1(2H)-one and pyridazin-3(2H)-
one are versatile building blocks in natural product
[8]
Phthalazin-1(2H)-one has emerged as a privileged synthesis and useful intermediates to construct other
[
9a]
[9b]
heterocyclic motif and gained immense attention of heterocycles such as pyridazine D
and phthalazine E.
synthetic as well as medicinal chemists because of its The former is a novel class of SMO inhibitors capable of
[9a]
ubiquitous fascinating structural architecture and wide range suppressing PXR transactivation, whereas the latter is a
[1]
[2]
[10]
of biological properties, such as antiulcer, antiasthmatic,
potential c-Met tyrosine kinase inhibitors. Owing to their
[3]
[4]
[5]
antimicrobial,
anti-inflammatory,
anti-hypertensive,
interesting structural features and broad spectrum of
[
6]
and antinociceptive agents (Figure 1). On the other hand, biological activities, literature examples for the synthesis of
pyridazin-3(2H)-ones are another important class of 4-phenyl phthalazin-1(2H)-ones and 6-phenyl pyridazin-
heterocyclic compounds that have been used as 3(2H)-ones typically begin from 2-benzoylbenzoic acid and
[7]
[11]
pharmacophores with a broad spectrum of bioactivities .
3-benzoylpropionic acid with hydrazine, respectively.
1
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European Journal of Organic Chemistry
10.1002/ejoc.201901731
FULL PAPER
Prevous work
R
R
However, their substitution diversity was restricted due to
their limited commercial source.
O
O
O
NH
N
N
NH
N
R
R
R
R
N
R
R
(1)
Ru
Ru
O2
H
N
2
Transition-metal catalyzed direct functionalization of the
inert C-H bond has emerged over the past decade as a
modern and environmentally friendly tool for organic
R = aryl
O
R
2
Present work
O
H(b)
O
NH
N
NH
N
Br
R
2
Br
R
2
NH
N
[12]
R
2
Rh
Rh
(2)
R
2
synthesis. In particular, multisiteselective C-H activation
of diverse heterocycles has received considerable attention
because this approach provides significantly expanded
chemical space for the rapid derivatization of important
H
(c)H
R1
H(a)
H
R
1
R
1
Scheme
1
Transition-metal-catalyzed
late-stage
functionalization of 4-phenyl phthalazin-1(2H)-one and its
analogues
[13]
privileged scaffolds. In this regard, development of a late
stage multiple and divergent C-H
activation/functionalization of 4-aryl phthalazin-1(2H)-one Results and Discussion
or its analogues would be valuable for their application in
We commenced our studies by choosing the reaction of
-phenylphthalazin-1(2H)-one (1a) with
bromoethynyl)triisopropylsilane (2a) as a model for
medicinal chemistry. Recently, Xu et al. demonstrated a
ruthenium-catalyzed switchable N-H/C-H alkenylation
reaction of 6-aryl pyridazin-3(2H)-ones with alkynes under
4
(
[
14]
optimizing catalytic conditions (Table 1). [Cp*RhCl2]2
catalyst was first choice because Echavarren et al.
demonstrated that Rh(III) species displayed high activity
and broad scope in the alkynylation of a variety of electron-
different reaction conditions (Scheme 1, eq 1).
Despite
the success reported thus far, the site selective direct C-H
alkynylation of the 4-aryl phthalazin-1(2H)-one motif
remains unsolved. Based on recent success in the field of
[17]
deficient arenes.
We were pleased to find that with
[15,16]
directing group-assisted
C-H
alkynylation,
we
[
RhCp*Cl ] as the catalyst, AgOAc as an silver salt, and
2
2
envisioned that the six-membered pyridazinone ring bearing
two intrinsic directing groups such as nitrogen atom and
carbonyl group could selectively promote direct C-H bond
activation at C-H (a) or C-H (b) position under different
reaction conditions (Scheme 1, eq 2). This strategy could not
only provide an additional example of DG-directed C–H
activation, but also offer a late-stage structural modification
on the biologically interesting privileged scaffolds. Herein,
we would like to report our recent achievement in the
rhodium-catalyzed swithable position C-H alkynylation of
dichloroethane (DCE) as the solvent, the reaction worked
o
smoothly at 100 C for 12 h and gave monoalkylnation as a
single product 3a with complete selectivity in 53% yields
(
Table 1, entry 1). It was worth mentioning that the
corresponding dialkylnation at C-H(c) position was not
detected, maybe it is attributed to the distorted coplanar
geometry arising from the steric repulsion which weakens
the interaction between the rhodium catalyst and proximate
aromatic C-H bond. Initially, various silver salts were
tested; we found that AgTFA and Ag SO can also afford
2
4
4
-aryl phthalazin-1(2H)-one and its analogues.
the desired monoalkynylated product in moderate to good
yields (Table 1, entries 2 and 3). It was found that
Ag CO was a best choice for this reaction, giving 3a in 87%
2
3
isolated yield (Table 1, entry 4). Other silver salts such as
AgNTf , AgSbF6 and AgOTf completely inhibited the
2
alkynylation (Table 1, entries 5, 6, and 7). Interestingly,
Ag O gave the corresponding monoalkynylated product 3a
2
in 35% yield, along with the dialkynylated product 4a in
2
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European Journal of Organic Chemistry
10.1002/ejoc.201901731
FULL PAPER
1
7% yield (Table 1, entry 8). In order to check the
+ K
AgSbF
+Cs CO
3 4
PO
1
3
Ag
2
CO
3
6
DCE
78
1
3
possibility of carrying out the dialkynylation exclusively,
the reactions were conducted using 2.2 equiv of
2
3
1
4
Ag
2
CO
3
AgSbF
AgSbF
AgSbF
AgSbF
AgSbF
AgSbF
AgSbF
AgSbF
AgSbF
AgSbF
6
DCE
DCE
DCE
trace
trace
45
25
36
38
21
32
36
82
83
58
c
1
5
Ag
2
Ag
2
Ag
2
Ag
2
Ag
2
Ag
2
Ag
2
Ag
2
Ag
2
CO
CO
CO
CO
CO
CO
CO
CO
CO
3
3
3
3
3
3
3
3
3
6
d
1
6
6
(
bromoethynyl)triisopropylsilane (with respect to 1a), and
1
7
6
toluene
61
1
1
2
2
8
9
0
1
6
3
CH CN
trace
trace
trace
59
67
46
different additives (silver salts and bases) were screened
under similar conditions. Interestingly, the desired product
6
dioxane
THF
EtOH
DCE
6
6
e
2
2
6
4
a was obtained in 83% yield, along with only trace amount
of the monoalkynylated product 3a in the presence of
AgNTf (20 mol%), and LiOAc (20 mol%) as additives
f
2
3
6
DCE
32
a
Unless otherwise stated, reaction conditions: for entries 1-8,
1a (0.2 mmol), [Cp*RhCl ] (0.006 mmol), silver salt (0.2
2
2
2
(
Table 1, entry 9). Secondly, various additives were
mmol), 2a (0.22 mmol), and DCE (1mL) heated at 100 °C
b
investigated; the mayor dialkynylated product was afforded
in stable yields and the minor monoalkynylated product was
obtained in varying yields (Table 1, entries 10-13). Based on
the aboved results, we postulate that the base might be not
necessary to promote the present alkynylation reaction.
Control experiments showed that a comparable yield of 4a
was detected in the absence of LiOAc (Table 1, entry 14). In
for 12 h under air. Isolated yields; for entries 9-23, 1a (0.2
mmol), [Cp*RhCl ] (0.006 mmol), silver salt (0.2 mmol),
2
2
2
a (0.44 mmol), additive (silver salt 0.04 mmol; base 0.04
mmol), and DCE (1mL) heated at 100 °C for 12 h under air.
c
d
e
AgSbF6 (0.06 mmol).
AgSbF6 (0.02 mmol).
2%
f
o
[
Cp*RhCl ] . 80 C
2 2
Having establishing the optimal conditions for the
addtion, the amount of the AgNTf were also investigated,
2
selective mono- or dialkynylation in hand, we proceeded to
explore the scope of the current transformations, and the
results are summarized in Table 2. Initially, we set out to
probe its versatility in the nomoalkynylation of diverse 4-
arylphthalazin-1(2H)-one (1) scaffolds. To our delight, the
selective monoalkynylation of these substrates containing a
substituent on the para-position (Me, OMe, OEt, F, Cl;
respectively 1b-f) proceeded smoothly with 2a under
optimized conditions and afforded the corresponding
monoalkynylated products 3b-f (71-89%) in good to
excellent yields. When substrate (F, 1g) holding meta
substituent was employed, the reaction tended to occur at
the less hindered C-H bond, and afforded the expected
alkynated product 3g with excellent monoselectivity in 78%
yield. Among them, many synthetically valuable groups
such as halide (F, Cl) could be reserved under mild reactions,
which gave chances for further modification of the products
(3e, 3f). When the ortho-methoxy-containing substrate 1l
was employed, the desired product 3l was isolated in 62%
yield; it is also attributed to the distorted coplanar geometry,
which weakens the interaction between the rhodium catalyst
and proximate aromatic C-H bond. Furthermore, substrates
containing two methyl groups (1i, 1j, 1k) also worked nicely
the 20 mol% AgNTf2 is essential to promote the
dialkynylation (Table 1, entries 15 and 16). Screening of
solvents revealed that DCE was optimal (Table 1, entries
1
7-21). Temperature and the amount of catalyst loading
have a great impact on the reaction activity and selectivity; a
mixture of mon- and dialkynylated products was observed in
varying yields (Table 1, entries 22 and 23).
Table 1. Optimization studies
TIPS
O
O
O
[
Cp*RhCl
sliver salt (1 equiv)
2 2
] (3 mol%)
NH
N
TIPS
NH
N
NH
N
additive (0-20 mol%)
solvent
TIPS
TIPS
Br
00 oC, air, 12h
1
1a
2a
3a
4a
a
Entry
Sliver
Salt
Additive
3a
4a
Yield
(%)
Solvent
Yield(
b
b
%
)
1
2
3
4
5
6
7
8
9
AgOAc
AgTFA
/
/
/
/
/
/
/
/
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
53
68
42
0
0
0
0
0
0
0
17
83
AgNTf
2
Ag CO
2
3
87
AgSbF6
AgOTf
trace
trace
trace
35
Ag
2
SO
4
2
Ag O
Ag
2
Ag
2
Ag
2
Ag
2
CO
CO
CO
CO
3
3
3
3
AgSbF
LiOAc
AgSbF
NaOAc
AgSbF
Na CO
AgSbF
6
trace
+
1
0
1
2
6
DCE
DCE
DCE
79
80
79
1
1
6
4
+
1
1
6
+
2
3
6
9
3
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European Journal of Organic Chemistry
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FULL PAPER
and afford the desired products (3i, 3j, 3k) in good yield. mmol), Ag CO (0.2 mmol), AgSbF (0.004 mmol), 2 (0.44
2
3
6
Notably, triethyl (TES) protected bromoacetylenes 2b was mmol), DCE (1mL) heated at 100 °C for 12 h under air.
also a good coupling partner. For example, the substrates
(
1a, 1d, and 1e) could afford the desired products in good
Encouraged by these results, we turned our interest to
yield (3l, 3m, 3n).
alkynylation of 6-aryl pyridazin-3(2H)-one substrates (5)
Next, we examined the scope of substituents on the aryl which were common motifs in medicinal chemistry (Tabel
ring of 4-arylphthalazin-1(2H)-one (1) in the dialkynylation 3). We reasoned that the 6-aryl pyridazin-3(2H)-one
reactions. In all cases, the same substrates containing a substrate (5a), similar to biphenyl structural feature with less
substituent on the para-position (1b-f) and the meta-position steric repulsion, might proceed selective monoalkynylation
(
1g) with 2a proceeded smoothly and provided the desired and sequential bis-alkynylation. Indeed, the alkynation of
dialkynylated products 4b-g (67-85%) in good to high yields, pyridazin-3(2H)-one 5a with
along with only trace amount of the monoalkynylated (bromoethynyl)triisopropylsilane (2a) proceeded smoothly
products. Gratifyingly, the corresponding dialkynylated under conditions A and B, and afforded 6a and 7a in 93%
products (4h) were provided when triethyl (TES) protected and 84% yields, respectively. We then examined the scope
bromoacetylenes (2b) was employed as a coupling partner.
of substituents on the para-position (F, Cl, Me, OMe, OEt;
respectively 1b-f). The selective mono-/dialkynylation of
these substrates 1b-f proceeded smoothly with 2a and
provided the corresponding monoalkynylated products 6b-f
Table 2. Rh(III)-Catalyzed C−H Mono-/Dialkynylation of 4-
a,b
Aryl Phthalazin-1(2H)-one Scaffolds
R
2
(
76-88%) and dialkynylated products 7b-f (72-89%) in good
O
H
O
Br
R2
O
Br
Cp*RhCl
R
2
2
2
to excellent yields. In addition, by employing triethyl (TES)
protected bromoacetylenes 2b as a coupling partner under
the same condition, the corresponding mono-alkynated
products 6g and dialkynylated products 7g were obtained in
76% and 71% yields, respectively.
NH
N
NH
N
NH
N
[
2
]
2
(3 mol%)
Ag2CO3 (1 equiv)
[Cp*RhCl
Ag CO
2
]
2
(3 mol%)
(1 equiv)
R
2
2
3
R2
DCE, 100 oC, air, 12h
H
AgSbF6 (20 mmol%)
DCE, 100 oC, air, 12h
R
1
R1
R1
3
a
1a
4a
O
O
O
NH
N
R = H
TIPS R = CH
R = OCH
3a,
87%
NH
N
NH
3
3b, 83%
3c, 89%
3d, 88%
3e, 79%
3f, 85%
N
TIPS
TIPS
3
R = OC
R = F
2
H
5
MeO
R = Cl
R
F
Tabel 3 Rh(III)-Catalyzed C−H Mono-/Dialkynylation of 6-
3
g, 78%
3h, 62%
a,b
O
O
R
Aryl Pyridazin-3(2H)-one Scaffolds
O
O
NH
NH
N
NH
N
NH
N
TIPS
N
TES
O
O
Br
R2
O
TIPS
TIPS
Br
R
2
2(1.2 equiv)
Cp*RhCl (3 mol%)
Ag CO (1 equiv)
2
(2.4 equiv)
NH
N
NH
N
NH
N
[
2
]
2
[Cp*RhCl
Ag CO
2
]
2
(3 mol%)
R
2
2
3
(1 equiv)
R
R
2
2
3
2
R = H
R = OC
R = F
3l, 74%
3m, 76%
3n, 71%
DCE, 100 oC, air, 12h
Reaction condtion A
H
H
DCE, 100 oC, air, 12h
3i, 77%
3j, 67%
3k, 66%
2
H
5
R1
R
1
R1
Reaction condtion B
TES
6
5
7
TIPS
TIPS
O
O
O
O
O
NH
N
R = H
R = CH
R = OCH
R = OC2H5
R = F
R = Cl
4a,
4b,
4c,
4d,
4e,
4f,
83%
72%
81%
85%
83%
67%
NH
N
NH
N
NH
N
NH
N
3
TES
R = H
TIPS R = CH3
R = OCH
6a, 93%
6b, 88% TIPS
R = H
TIPS R = CH
3
7a, 84%
7b, 81%
7c, 89%
3
TIPS
TIPS
3
6c,
6d,
6e,
7f,
81%
82%
80%
85%
R = OCH3
R = F
R = Cl
R = Br
R = F
R =Cl
R = Br
7d
7e, 72%
7f, 79%
71%
F
F
4
g, 78%
4h, 71%
R
R
R
O
O
NH
N
NH
N
Reaction conditions: for monoalkynation: 1 (0.2 mmol),
Cp*RhCl ] (0.006 mmol), Ag CO (0.2 mmol), 2 (0.22
TES
76%
SET
TES
[
2
2
2
3
6
g,
7g, 61%
b
mmol), DCE (1mL) at 100 °C, under air, 12 h. Isolated
Reaction conditions: Reaction condition A: 5 (0.2 mmol),
Cp*RhCl ] (0.006 mmol), Ag CO (0.2 mmol), 2 (0.22
yields; for dialkynation: 1 (0.2 mmol), [Cp*RhCl ] (0.006
2
2
[
2
2
2
3
b
mmol), DCE (1mL) at 100 °C, under air, 12 h. Isolated
4
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European Journal of Organic Chemistry
10.1002/ejoc.201901731
FULL PAPER
[11a]
[11b]
yields; Reaction condition B: 5 (0.2 mmol), [Cp*RhCl2]2 phthalazinones 1a-k
and phathalazine 5a-f
were
(
(
0.006 mmol), Ag CO (0.2 mmol), 2 (0.44 mmol), DCE prepared according to well-known literature procedures.
2 3
1mL) heated at 100 °C for 12 h under air.
General procedure for Rh(III)-Catalyzed C−H
monoalkynylation of 4-arylphthalazin-1(2H)-ones.
A mixture of 4-arylphthalazin-1(2H)-ones 1 (0.20 mmol),
Conclusion
In conclusion, we have realized Rh(III)-catalyzed (triisopropylsilyl)ethynyl bromide 2a (57 mg, 0.2.2 mmol),
controllable mono- and dialkynylation of
4- [Cp*RhCl (5.3 mg, 0.006 mmol, 3 mol %), Ag CO (55
]
2
2
2
3
phenylphthalazin-1(2H)-ones. The monoalkynylation has mg, 0.2 mmol, 1equiv), and DCE (1 mL) were charged into
been conducted with complete selectivity. On the other hand, a reaction tube. The reaction mixture was stirred at 100 °C
the dialkynylation could be observed by adding catalytic for 12 h. After the mixture cooled to room temperature, the
amount of AgSbF under similar reaction conditions. A solvent was removed under reduced pressure and the residue
6
wide-range of mono-/dialkynylated 4-aryl phthalazin-1(2H)- was purified by silica gel chromatography using petroleum
ones have been synthesized in good to excellent yields. In ether/EtOAc to afford the desired product 3.
addition, 6-aryl pyridazin-3(2H)-ones could precede General procedure for Rh(III)-Catalyzed C−H
selective monoalkynylation and sequential dialkynylation dialkynylation of 4-arylphthalazin-1(2H)-ones.
under optimal conditions, respectively. Future studies are
A mixture of 4-arylphthalazin-1(2H)-ones 1 (0.20 mmol),
(0.44 mmol),
(5.3 mg, 0.006 mmol, 3 mol %), Ag CO (55
devoted to regiodivergent functionalization of other (triisopropylsilyl)ethynyl bromide
2
heteroarenes via Rh(III)-catalyzed C-H activation.
[Cp*RhCl
]
2
2
2
3
mg, 0.2 mmol, 1equiv), AgSbF (13.8 mg, 0.004 mmol, 20
6
mol %), and DCE (1 mL) were charged into a reaction tube.
The reaction mixture was stirred at 100 °C for 12 h. After
the mixture cooled to room temperature, the solvent was
removed under reduced pressure and the residue was
purified by silica gel chromatography using petroleum
ether/EtOAc to afford the desired product 4.
Experimental Section
General Information: All reactions were carried out
under air atmosphere in oven-dried glassware with magnetic
stirring, unless otherwise specified. All other reagents and
solvents were purchased from Energy Chemical or J&K
Chemical Company and used without any further
purification. TLC information was recorded on GF-254
4
-{2-[(Triisopropylsilanyl)-ethynyl]-phenyl}-2H-
phthalazin-1-one (3a). The product was obtained as a white
solid: yield 70 mg (87%); Rf 0.4 (2:1 petroleum
(
Qingdao Haiyang Chemical Co., Ltd. P. R. China) plates.
o
1
ether/EtOAc); mp 193-194 C; H NMR (400 MHz, CDCl ) :
3
Purification of reaction products was carried out by flash
chromatography using Silica gel (200-300 mesh, Qingdao
Haiyang Chemical Co. Ltd. P. R. China). All products were
recorded using Bruker Avance-400 instruments, calibrated
δ 10.57 (s, 1 H), 8.48 (d, J = 7.6 Hz, 1 H), 7.78-7.70 (m, 2
H), 7.66-7.64(m, 1 H), 7.50- 7.40 (m, 4 H), 0.80-0.79 (m, 21
13
H); C NMR (100 MHz, CDCl ): δ 151.5, 148.0, 137.6,
3
1
1
33.3, 132.8, 131.4, 130.3, 129.7, 129.1, 128.7, 128.0 ,
1
13
to TMS ( H NMR spectra) and CDCl ( C NMR spectra) as
3
27.4, 126.5, 124.0, 104.5, 96.3, 18.3, 10.9; HRMS (ESI)
the internal reference (0.00 ppm for 1H NMR spectra and
+
m/z Calcd for C H N OSi [M+H] 403.2200, found
25
31
2
13
1
00.00 ppm for C NMR spectra). High-resolution mass
4
4
2
03.2208.
spectra (HRMS) were recorded on a Bruker Apex IV FTMS
mass spectrometer using ESI (electrospray ionization).
Melting points were measured uncorrected. All starting
-{4-Methyl-2-[(triisopropylsilanyl)-ethynyl]-phenyl}-
H-phthalazin-1-one (3b). The product was obtained as a
white solid: yield 69 mg (83%); R 0.4 (2:1 petroleum
f
5
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European Journal of Organic Chemistry
10.1002/ejoc.201901731
FULL PAPER
o
1
1
ether/EtOAc); mp 164-165 C; H NMR (400 MHz, CDCl ): NMR (100 MHz, CDCl ) δ 162.7(d, J = 248 Hz) , 160.5,
3
3
CF
3
δ 11.52 (s, 1H), 8.52-8.46 (m, 1H), 7.76-7.68 (m, 2H), 7.48- 147.1, 133.9, 133.4, 131.7 (d, J = 9 Hz), 131.5, 130.2,
CF
3
2
7
1
.42 (m, 2H), 7.34 (d, J = 7.8 Hz, 1H), 7.28 (d, J = 7.7 Hz, 128.0, 127.2, 126.6, 125.9 (d, J = 10 Hz) , 119.5(d, J
=
CF
CF
1
3
2
H), 2.43 (s, 3H), 0.79 (d, J = 4.9 Hz, 21H); C NMR (100 23 Hz) , , 116.2(d, J = 21 Hz), 97.78, 18.25, 10.86;
CF
+
MHz, CDCl ): δ 160.9, 148.1, 139.0, 134. 9,133.2, 133.2, HRMS (ESI) m/z Calcd for C H FN OSi [M+H]
3
25 30
2
1
1
31.3, 130.4, 129.7, 129.6 , 127.9, 127.5, 126.5, 123.7, 421.2106, found 421.2116.
04.9, 95.6b, 21.1, 18.3, 10.9; HRMS (ESI) m/z Calcd for 4-{4-Chloro-2-[(triisopropylsilanyl)-ethynyl]-phenyl}-
+
C H N OSi [M+H] 417.2357, found 417.2358.
2H-phthalazin-1-one (3f). The product was obtained as a
2
6
33
2
4
2
-{4-Methoxy-2-[(triisopropylsilanyl)-ethynyl]-phenyl}-
white solid: yield 74 mg (85%); R 0.4 (2:1 petroleum
f
1
H-phthalazin-1-one (3c). The product was obtained as a ether/EtOAc); mp 184-185 °C; H NMR (400 MHz, CDCl ) :
3
white solid: yield 77 mg (89%); R 0.4 (2:1 petroleum δ 11.80 (s, 1H), 8.42 (dd, J = 7.0, 2.1 Hz, 1H), 7.70-7.63 (m,
f
1
ether/EtOAc); mp 185-186 °C; H NMR (400 MHz, CDCl ): 2H), 7.53 (d, J = 2.1 Hz, 1H), 7.37 (dd, J = 8.2, 2.1 Hz, 1H),
3
1
3
δ 11.25 (s, 1H), 8.49- 8.47 (m, 1H), 7.76-7.69 (m, 2H), 7.45 7.34-7.28 (m, 2H), 0.70 (d, J = 4.5 Hz, 21H); C NMR (100
dd, J = 6.8, 2.2 Hz, 1H), 7.36 (d, J = 8.5 Hz, 1H), 7.14 (d, J MHz, CDCl ): δ 161.0, 147.0, 136.1, 135.0, 133.3, 132.5,
(
3
=
2.6 Hz, 1H), 7.02 (dd, J = 8.5, 2.6 Hz, 1H), 3.89 (s, 3H), 131.5, 131.2, 130.1, 129.0, 127. 9, 127.1, 126.6, 125.6,
1
3
0
1
1
1
.79 (d, J = 5.0 Hz, 21H); C NMR (100 MHz, CDCl ): δ 103.2, 98.0, 18.3, 10.9; HRMS (ESI) m/z Calcd for
3
+
60.69, 159.88, 147.87, 133.20, 131.28, 131.06, 130.59, C H ClN NaOSi [M+Na] 459.1635, found 459.1613.
25
29
2
30.25, 127.93, 127.53, 126.45, 125.00, 117.46, 115.15, 4-{5-Fluoro-2-[(triisopropylsilanyl)-ethynyl]-phenyl}-2H-
04.58, 96.0, 55.55, 18.28, 10.92; HRMS (ESI) m/z Calcd phthalazin-1-one (3g). The product was obtained as a white
+
for C H N O Si [M+H] 433.2306, found 433.2296.
solid: yield 66 mg (78%); Rf 0.4 (2:1 petroleum
2
6
33
2
2
1
4
2
-{4-Ethoxy-2-[(triisopropylsilanyl)-ethynyl]-phenyl}-
ether/EtOAc); mp 200-201 °C; H NMR (400 MHz, CDCl
):
3
H-phthalazin-1-one (3d). The product was obtained as a δ 10.93 (s, 1H), 8.41 (d, J = 6.9 Hz, 1H), 7.72 – 7.64 (m,
white solid: yield 78 mg (88%); R 0.4 (2:1 petroleum 2H), 7.36 (t, J = 6.9 Hz, 2H), 7.18 (d, J = 7.8 Hz, 2H), 0.73
f
1
13
ether/EtOAc); mp 178-179 °C; H NMR (400 MHz, CDCl ) (d, J = 3.0 Hz, 21H); C NMR (100 MHz, CDCl ) δ 162.2(d,
3
3
1
δ 11.17 (s, 1H), 8.54-8.41 (m, 1H), 7.74-7.71 (m, 2H), 7.49-
JCF = 252 Hz) ,159.4, 145.7, 138.6, 132.4, 130.5,
3
7
1
1
.42 (m, 1H), 7.34 (d, J = 8.5 Hz, 1H), 7.14 (d, J = 2.6 Hz, 129.0 ,128.8 (d, J = 9 Hz), 126.9, 126.1, 125.6, 124.4,
CF
2
H), 7.00 (dd, J = 8.5, 2.7 Hz, 1H), 4.12 (q, J = 7.0 Hz, 2H), 115.2 (d, J = 21 Hz), 112.0, 101.6, 96.3, 17.2, 9.8; HRMS
CF
13
+
.46 (t, J = 7.0 Hz, 3H), 0.79-0.76 (d, J = 4.8 Hz, 21H);
C
(ESI) m/z Calcd for C H FN OSi [M+H] 421.2106, found
25 30 2
NMR (100 MHz, CDCl ) δ 160.7, 159.3, 147.9, 133.2, 421.2115.
3
1
1
31.3, 131.0, 130.6, 130.1, 127.9, 127.6, 126.4, 125.0, 118.2, 4-{2-Methoxy-6-[(triisopropylsilanyl)-ethynyl]-phenyl}-
15.5, 104.7, 95.8, 63.8, 18.3, 14.7, 10.9; HRMS (ESI) m/z 2H-phthalazin-1-one (3h). The product was obtained as a
+
Calcd for C H N NaOSi [M+Na] 469.2282, found white solid: yield 54 mg (62%); R 0.4 (2:1 petroleum
27
34
2
f
1
4
69.2293.
ether/EtOAc); mp 145-146 °C; H NMR (400 MHz, CDCl ):
3
4
-{4-Fluoro-2-[(triisopropylsilanyl)-ethynyl]-phenyl}-2H- δ 10.20 (s, 1H), 8.38 (t, J = 7.3 Hz, 1H), 7.68-7.59 (m, 2H),
phthalazin-1-one (3e). The product was obtained as a white 7.36-7.30 (m, 1H), 7.21-7.14 (m, 2H), 6.94 (t, J = 7.6 Hz,
1
3
solid: yield 67 mg (79%); Rf 0.4 (2:1 petroleum 1H), 3.64 (d, J = 7.3 Hz, 3H), 0.71 (d, J = 7.3 Hz, 21H); C
1
ether/EtOAc); mp 193-194 °C; H NMR (400 MHz, CDCl ) NMR (100 MHz, CDCl ): δ 160.3, 158.2, 145.2, 134.6,
3
3
δ 11.08 (s, 1H), 8.49 (dd, J = 6.8, 2.3 Hz, 1H), 7.79-7.71 (m, 133.3, 131.2, 130.3, 126.5, 126.4, 126.1, 125.6, 125.0, 123.9,
2
H), 7.45-7.38 (m, 2H), 7.34 (dd, J = 9.0, 2.6 Hz, 1H), 7.19 119.3, 111.5, 98.4, 55.9, 18.3, 10.9; HRMS (ESI) m/z Calcd
13
+
(
td, J = 8.3, 2.6 Hz, 1H), 0.79 (d, J = 4.2 Hz, 21H);
C
for C H N O Si [M+H] 433.2306, found 433.2305.
26 33 2 2
6
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European Journal of Organic Chemistry
10.1002/ejoc.201901731
FULL PAPER
4
-{4,5-Dimethyl-2-[(triisopropylsilanyl)-ethynyl]-
1H), 7.48 (t, J = 3.5 Hz, 2H), 7.47-7.43 (m, 2H), 0.69 (t, J =
1
3
phenyl}-2H-phthalazin-1-one (3i). The product was 7.9 Hz, 9H), 0.38-0.19 (m, 6H); C NMR (100 MHz,
obtained as a white solid: yield 58 mg (67%); R 0.4 (2:1 CDCl ): δ 160.3, 148.0, 137.8, 133.2, 132.6, 131.4, 130.2,
f
3
1
petroleum ether/EtOAc); mp 168-170 °C; H NMR (400 129.8, 129.1, 128.8, 127.9, 127.6, 126.5, 123.8, 104.0, 97.6,
+
MHz, CDCl ): δ 10.88 (s, 1H), 8.40 (dd, J = 7.0, 2.0 Hz, 7.1, 4.0; HRMS (ESI) m/z Calcd for C H N OSi [M+H]
3
23 28
2
1
H), 7.64-7.64 (m, 2H), 7.38 (dd, J = 7.1, 1.9 Hz, 1H), 7.34 376.1972, found 376.1976.
(
s, 1H), 7.14 (s, 1H), 2.25 (d, J = 4.2 Hz, 6H), 0.71 (d, J = 4-(4-Ethoxy-2-triethylsilanylethynyl-phenyl)-2H-
1
3
5
1
1
.3 Hz, 21H); C NMR (100 MHz, CDCl ): δ 159.5, 147.2, phthalazin-1-one (3m). The product was obtained as a
3
1
36.8, 136.7, 134.1, 132.7, 132.1, 130.2, 129.9, 129.4 , white solid: yield 61 mg (76%); H NMR (400 MHz,
26.9, 126.6, 125.4, 120.1, 103.9, 93.8, 18.7, 18.4, 17.3, 9.9; CDCl ): δ 10.42 (s, 1H), 8.41 (d, J = 7.3 Hz, 1H), 7.71-7.64
3
+
HRMS (ESI) m/z Calcd for C H N NaOSi [M+Na]
(m, 2H), 7.41 (d, J = 8.8 Hz, 1H), 7.28 (d, J = 8.5 Hz, 1H),
7.06 (d, J = 2.6 Hz, 1H), 6.94 (dd, J = 8.5, 2.6 Hz, 1H), 4.04
(q, J = 7.0 Hz, 2H), 1.39 (t, J = 7.0 Hz, 3H), 0.61 (t, J = 7.9
27
34
2
4
53.2333, found 453.2321.
-{3,5-Dimethyl-2-[(triisopropylsilanyl)-ethynyl]-
4
1
3
phenyl}-2H-phthalazin-1-one (3j).The product was Hz, 9H), 0.20 (q, J = 8.2 Hz, 6H); C NMR (100 MHz,
obtained as a white solid: yield 57 mg (66%); R 0.8 (2:1 CDCl ): δ 160.3, 159.3, 147.9, 133.1, 131.3, 131.0, 130.5,
f
3
1
petroleum ether/EtOAc); mp 176-177 °C; H NMR (400 130.1, 127.7, 126.4, 124.7, 117.8, 115.9, 114.6, 104.1, 97.2,
MHz, CDCl ): δ 10.22 (s, 1H), 7.88 (d, J = 7.6 Hz, 1H), 63.8, 14.8, 7.1, 4.0; HRMS (ESI) m/z Calcd for
3
+
7
.58 (t, J = 7.8 Hz, 1H), 7.20 (d, J = 8.0 Hz, 1H), 7.15 (d, J C H N O Si [M+H] 420.2234, found 420.2231.
25
32
2
2
=
8.0 Hz, 2H), 7.11 (d, J = 8.1 Hz, 1H), 2.40 (s, 3H), 2.07 (s, 4-(4-Fluoro-2-triethylsilanylethynyl-phenyl)-2H-
1
3
3
H), 1.20 (d, J = 2.6 Hz, 21H); C NMR (100 MHz, CDCl ): phthalazin-1-one (3n). The product was obtained as a white
3
1
δ 158.8, 147.8, 139.1, 138.4, 136.9, 132.3, 131.5, 131.4, solid: yield 54 mg (71%); H NMR (400 MHz, CDCl ): δ
3
1
1
31.2, 129.7, 128.3, 126.8, 126.7, 123.7, 104.7, 100.2, 21.3, 10.63 (s, 1H), 8.53-8.45 (m, 1H), 7.80-7.73 (m, 2H), 7.44
9.6, 18.7, 11.5; HRMS (ESI) m/z Calcd for (dd, J = 8.3, 5.4 Hz, 2H), 7.33 (d, J = 8.9 Hz, 1H), 7.20 (t, J
+
C H N NaOSi [M+Na] 453.2333, found 453.2323.
= 9.5 Hz, 1H), 0.68 (t, J = 7.9 Hz, 9H), 0.28 (q, J = 7.4, 6.9
2
7
34
2
13
4
-{3,6-Dimethyl-2-[(triisopropylsilanyl)-ethynyl]-
Hz, 6H); C NMR (100 MHz, CDCl ): δ 147.2, 133.9,
3
phenyl}-2H-phthalazin-1-one (3k). The product was 133.3, 131.7, 131.6, 131.6, 130.1, 129.2, 127.8, 127.4, 126.6,
obtained as a white solid: yield 66 mg (77%); R 0.8 (2:1 119.4, 116.4, 116.2, 102.7, 99.1, 7.1, 3.9; HRMS (ESI) m/z
f
1
+
petroleum ether/EtOAc); mp 117-118 °C; H NMR (400 Calcd for C H FN OSi [M+H] 394.1877, found 394.1875.
23
27
2
MHz, CDCl ): δ 11.11 (s, 1H), 7.78 (d, J = 7.6 Hz, 1H), 8-[(Triisopropylsilanyl)-ethynyl]-4-{2-
3
7
.48 (t, J = 7.8 Hz, 1H), 7.11 (s, 1H), 7.08 (s, 2H), 6.99 (s, [(triisopropylsilanyl)-ethynyl]-phenyl}-2H-phthalazin-1-
H), 2.25 (s, 3H), 1.95 (s, 3H), 1.09 (d, J = 3.5 Hz, 21H); one (4a). The product was obtained as a white solid: yield
C NMR (100 MHz, CDCl ): δ 159.4, 147.7, 138.3, 135.4, 97 mg (83%); R 0.4 (5:1 petroleum ether/EtOAc); mp 134-
1
1
3
3
f
1
1
1
34.3, 133.9, 132.3, 131.4, 130.3, 130.3 , 129.9, 128.2, 135 °C; H NMR (400 MHz, CDCl ): δ 10.23 (s, 1H), 7.84
3
26.7, 123.6, 104.8, 100.1, 20.8, 19.1, 18.7, 11.5; HRMS (d, J = 7.6 Hz, 1H), 7.64-7.60 (m, 1H), 7.57 (t, J = 7.8 Hz,
+
(
ESI) m/z Calcd for C H N OSi [M+H] 431.2513, found 1H), 7.49-7.44 (m, 2H), 7.44-7.41 (m, 1H), 7.28-7.25 (m,
27
35
2
1
3
4
4
31.2496.
-(2-Triethylsilanylethynyl-phenyl)-2H-phthalazin-1-one
1H), 1.19 (d, J = 2.7 Hz, 21H), 0.84-0.78 (m, 21H);
C
NMR (100 MHz, CDCl ): δ 158.7, 147.2, 138.1, 137.8,
3
(
3l). The product was obtained as a white solid: yield 53 mg 132.8, 132.1, 131.2, 129.7, 129.0, 128.7, 128.1, 127.1, 124.1,
1
(
74%); H NMR (400 MHz, CDCl ): δ 10.54 (s, 1H), 8.49 (d, 123.6, 104.8, 104.4, 99.8, 96.5, 18.7, 18.3, 11.4, 11.0;
3
J = 7.7 Hz, 1H), 7.82-7.69 (m, 2H), 7.63 (dd, J = 4.9, 2.8 Hz,
7
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European Journal of Organic Chemistry
10.1002/ejoc.201901731
FULL PAPER
+
+
HRMS (ESI) m/z Calcd for C H N OSi [M+H] 583.3534, m/z Calcd for C H N O Si [M+H] 627.3797, found
36
51
2
2
38 55
2
2
2
found 583.3519.
-{4-Methyl-2-[(triisopropylsilanyl)-ethynyl]-phenyl}-8-
(triisopropylsilanyl)-ethynyl]-2H-phthalazin-1-one (4b). [(triisopropylsilanyl)-ethynyl]-2H-phthalazin-1-one
The product was obtained as a white solid: yield 86 mg (4e).The product was obtained as a white solid: yield 100
627.3804.
4
4-{4-Fluoro-2-[(triisopropylsilanyl)-ethynyl]-phenyl}-8-
[
(
72%); R 0.4 (5:1 petroleum ether/EtOAc); mp 170-171 °C; mg (83%); R 0.4 (5:1 petroleum ether/EtOAc); mp
f f
1
1
H NMR (400 MHz, CDCl ) δ 10.11 (s, 1H), 7.84 (d, J = 7.2 121−122 °C; H NMR (400 MHz, CDCl ) δ 7.77 (d, J = 7.5
3
3
Hz, 1H), 7.56 (t, J = 7.8 Hz, 1H), 7.44 (s, 1H), 7.29 (d, J = Hz, 1H), 7.51 (d, J = 7.7 Hz, 1H), 7.49-7.39 (m, 1H), 7.32
8
.0 Hz, 3H), 2.42 (s, 3H), 1.20 (s, 21H), 0.83-0.81 (m, 21H); (dd, J = 8.4, 5.7 Hz, 1H), 7.23 (dd, J = 8.9, 2.2 Hz, 1H),
1
3
C NMR (100 MHz, CDCl ): δ 158.7, 147.3, 139.1, 138.1, 7.17-7.07 (m, 2H), 1.11-1.10 (m, 21H), 0.75-0.73 (m, 21H);
3
1
3
1
1
1
34.9, 133.3, 132.1, 131.4, 129.6, 128.1, 127.3, 123.8, 123.5,
C NMR (100 MHz, CDCl ): δ 162.6 (d, J = 248 Hz) ,
3 CF
3
04.8, 104.7, 99.7, 95.9, 21.1, 18.7, 18.3, 11.5, 11.0; HRMS 159.0 , 146.3 , 138.1 , 134.0 , 132.2 , 131.6(d, J = 9 Hz),
CF
+
3
3
(
ESI) m/z Calcd for C H N NaOSi [M+Na] 619.3510, 131.3, 131.2 (d, J = 5 Hz), 128.1, 126.8, 126.0 (d, J
=
CF
3
7
52
2
2
CF
2
2
found 619.3519.
9 Hz), 123.7, 119.4 (d, J = 23 Hz), 116.1(d, J = 22 Hz),
CF CF
2
4
8
-{4-Methoxy-2-[(triisopropylsilanyl)-ethynyl]-phenyl}-
-[(triisopropylsilanyl)-ethynyl]-2H-phthalazin-1-one
115.7(d, JCF = 22 Hz), 104.7, 100.1, 18.7, 18.2, 11.4, 11.0;
+
HRMS (ESI) m/z Calcd for C36
H
50FN
OSi
2
[M+H]
2
(
4c).The product was obtained as a white solid: yield 99 mg 601.3440, found 601.3432.
(
81%); R 0.4 (5:1 petroleum ether/EtOAc); mp 156-157 °C; 4-{4-Chloro-2-[(triisopropylsilanyl)-ethynyl]-phenyl}-8-
f
1
H NMR (400 MHz, CDCl ): δ 10.27 (s, 1H), 7.84 (dd, J = [(triisopropylsilanyl)-ethynyl]-2H-phthalazin-1-one (4f).
3
7
2
3
2
1
1
1
6
4
.6, 1.2 Hz, 1H), 7.57 (t, J = 7.8 Hz, 1H), 7.35 – 7.28 (m, The product was obtained as a white solid: yield 83 mg
H), 7.11 (d, J = 2.6 Hz, 1H), 7.01 (dd, J = 8.5, 2.7 Hz, 1H), (67%); R 0.4 (5:1 petroleum ether/EtOAc); mp 175-176 °C;
f
1
.88 (s, 3H), 1.19 (d, J = 2.9 Hz, 21H), 0.82 (d, J = 5.8 Hz,
H NMR (400 MHz, CDCl ): δ 10.66 (s, 1H), 7.85 (dd, J =
3
13
1H); C NMR (100 MHz, CDCl ): δ 159.9, 158.7, 147.1, 7.6, 1.2 Hz, 1H), 7.60 (d, J = 1.9 Hz, 1H), 7.57 (d, J = 7.8
3
38.1, 132.1, 131.5, 131.0, 130.4, 128.1, 127.3, 125.1, 123.5, Hz, 1H), 7.45 (dd, J = 8.3, 2.2 Hz, 1H), 7.37 (d, J = 8.2 Hz,
17.5, 115.1, 104.8, 104.4, 99.7, 96.2, 55.6, 18.7, 18.3, 11.5, 1H), 7.25 (dd, J = 8.1, 1.2 Hz, 1H), 1.20-1.86 (m, 21H),
+
13
1.0; HRMS (ESI) m/z Calcd for C H N O Si [M+H]
0.83- 0.78 (m, 21H); C NMR (100 MHz, CDCl ): δ 158.9,
3
7
52
2
2
2
3
13.3640, found 613.3640.
-{4-Ethoxy-2-[(triisopropylsilanyl)-ethynyl]-phenyl}-8-
146.1, 138.2, 136.3, 135.0, 132.5, 132.2, 131.1, 131.0, 129.0,
128.1, 126.7, 125.7, 123.7, 104.7, 103.1, 100.1, 98.3, 18.7,
[
(triisopropylsilanyl)-ethynyl]-2H-phthalazin-1-one (4d). 18.3, 11.4, 11.0; HRMS (ESI) m/z Calcd for
+
The product was obtained as a white solid: yield 106 mg C H ClN OSi [M+H] 617.3145, found 617,3161.
36
50
2
2
(
85%); R 0.4 (5:1 petroleum ether/EtOAc); mp 195-196 °C; 4-{5-Fluoro-2-[(triisopropylsilanyl)-ethynyl]-phenyl}-8-
f
1
H NMR (400 MHz, CDCl ): δ 9.93 (s, 1H), 7.84 (d, J = 7.6 [(triisopropylsilanyl)-ethynyl]-2H-phthalazin-1-one (4g).
3
Hz, 1H), 7.57 (t, J = 7.9 Hz, 1H), 7.31 (d, J = 8.3 Hz, 2H), The product was obtained as a white solid: yield 94 mg
7
.11 (d, J = 2.6 Hz, 1H), 6.99 (dd, J = 8.5, 2.6 Hz, 1H), 4.11 (78%); R 0.4 (5:1 petroleum ether/EtOAc); mp 143-144 °C;
f
1
(
q, J = 6.8 Hz, 2H), 1.46 (t, J = 7.0 Hz, 3H), 1.19 (d, J = 2.5
H NMR (400 MHz, CDCl ): δ 10.60 (s, 1H), 7.77 (d, J =
3
1
3
Hz, 21H), 0.82 (d, J = 5.7 Hz, 21H); C NMR (100 MHz, 7.6 Hz, 1H), 7.50 (t, J = 7.9 Hz, 1H), 7.39 – 7.30 (m, 1H),
CDCl ): δ 159.3, 158.6, 147.2, 138.1, 132.1, 131.6, 130.9, 7.19 (d, J = 7.8 Hz, 1H), 7.14 (t, J = 8.3 Hz, 2H), 1.11-1.10
3
1
3
1
9
30.1, 128.1, 127.3, 125.1, 123.5, 118.2, 115.5, 104.8, 104.5, (d, J = 3.5 Hz, 21H), 0.77-0.75 (m, 21H); C NMR (100
1
9.7, 96.1, 63.8, 18.7, 18.3, 14.7, 11.5, 11.0; HRMS (ESI) MHz, CDCl ): δ 163.16(d, J = 252 Hz), 158.89, 145.84,
3
CF
3
1
39.87, 138.13, 132.16, 130.95, 129.80 (d, J = 9 Hz),
CF
8
This article is protected by copyright. All rights reserved.

European Journal of Organic Chemistry
10.1002/ejoc.201901731
FULL PAPER
2
1
1
28.1, 126.72, 125.42, 123.73, 116.28, 116.07, 113.1(d, J
ether/EtOAc); mp 144−145 °C; H NMR (400 MHz, CDCl ):
3
CF
=
16 Hz), 100.08, 97.27, 18.68, 18.24, 11.45, 10.95; HRMS δ 12.59 (s, 1H), 7.95 (d, J = 9.8 Hz, 1H), 7.54-7.51 (m, 2H),
+
(
ESI) m/z Calcd for C H FN OSi [M+H] 601.3440, 7.34-7.30 (m, 2H), 6.90 (d, J = 9.8 Hz, 1H), 1.00 (s, 21H);
36
50
2
2
13
found 601.3431.
C NMR (100 MHz, CDCl ): δ 162.0, 146.8, 137.3, 135.2,
3
8
-Triethylsilanylethynyl-4-(2-triethylsilanylethynyl-
134.0, 129.1, 128.9, 128.3, 121.7, 105.0, 97.1, 18.6, 11.3;
+
phenyl)-2H-phthalazin-1-one (4h).The product was HRMS (ESI) m/z Calcd for C H N NaOSi [M+Na]
2
1
28
2
1
obtained as a white solid: yield 73 mg (71%); H NMR (400 375.1863, found 375.1871.
MHz, CDCl ): δ 8.43 (d, J = 7.9 Hz, 1H), 7.67 (dd, J = 13.9, 6-{4-Methyl-2-[(triisopropylsilanyl)-ethynyl]-phenyl}-
3
7
.7 Hz, 2H), 7.34 (dd, J = 16.8, 8.2 Hz, 2H), 7.25 (d, J = 9.0 2H-pyridazin-3-one (6b). The product was obtained as a
Hz, 1H), 7.13 (td, J = 8.3, 2.4 Hz, 1H), 0.91 (d, J = 7.8 Hz, white solid: yield 64 mg (88%); R 0.3 (2:1 petroleum
f
13
1
1
8H), 0.56 (d, J = 7.9 Hz, 12H); C NMR (100 MHz, ether/EtOAc); mp 153-154 °C; H NMR (400 MHz, CDCl ):
3
CDCl ): δ 161.4, 159.4, 146.4, 134.0, 132.9, 131.8, 131.6, δ 7.94 (d, J = 9.7 Hz, 1H), 7.43 (d, J = 8.0 Hz, 1H), 7.32 (s,
3
1
6
29.6, 127.6, 127.2, 126.9, 125.7, 119.2, 116.2, 99.0, 84.6, 1H), 7.13 (d, J = 7.9 Hz, 1H), 6.88 (d, J = 9.8 Hz, 1H), 2.29
1
3
1.6, 52.2, 7.3, 4.3; HRMS (ESI) m/z Calcd for (s, 3H), 1.00 (s, 21H); C NMR (100 MHz, CDCl ): δ 161.8,
3
+
C H FN OSi [M+H] 501.2738, found 501.2734.
146.7, 139.2, 135.2, 134.6, 134.4, 129.9, 128.8, 128.3, 121.4,
3
1
38
2
General procedure for Rh(III)-Catalyzed C−H 105.3, 96. 5, 21.0, 18.6, 11.3; HRMS (ESI) m/z Calcd for
+
Monoalkynylation of 6-aryl ylpyridazin-3(2H)-ones.
C H
22
N
31
2
OSi [M+H] 367.2200, found 367.2208.
A mixture of 6-aryl ylpyridazin-3(2H)-ones 5 (0.20 6-{4-Methoxy-2-[(triisopropylsilanyl)-ethynyl]-phenyl}-
mmol), (triisopropylsilyl)ethynyl bromide 2 (0.22 mmol), 2H-pyridazin-3-one (6c). The product was obtained as a
[
Cp*RhCl ] (5.3 mg, 0.006 mmol, 3 mol %), Ag CO (55 white solid: yield 62 mg (81%); R 0.4 (2:1 petroleum
2 2 2 3 f
1
mg, 0.2 mmol, 1equiv), and DCE (1 mL) were charged into ether/EtOAc); mp 251-252 °C; H NMR (400 MHz, CDCl ):
3
a reaction tube. The reaction mixture was stirred at 100 °C δ 12.02 (s, 1H), 7.93 (d, J = 9.8 Hz, 1H), 7.47 (d, J = 8.7 Hz,
for 12 h. After the mixture cooled to room temperature, the 1H), 7.00 (d, J = 2.6 Hz, 1H), 6.87 (t, J = 9.8 Hz, 2H), 3.78
1
3
solvent was removed under reduced pressure and the residue (s, 3H), 1.00 (s, 21H); C NMR (100 MHz, CDCl ): δ 160.0,
3
was purified by silica gel chromatography using petroleum 146.5, 135.3, 130.3, 130.1, 128.3, 122.7, 118.6, 115.4, 105.0,
ether/EtOAc to afford the desired product 6.
96.8, 55.5, 18.6, 11.3; HRMS (ESI) m/z Calcd for
+
General procedure for Rh(III)-Catalyzed C−H
dialkynylation of 6-aryl ylpyridazin-3(2H)-ones.
C H
22
N
31
2
O
2
Si [M+H] 383.2149, found 383.2136.
6-{4-Fluoro-2-[(triisopropylsilanyl)-ethynyl]-phenyl}-2H-
A mixture of 6-aryl ylpyridazin-3(2H)-ones 5 (0.20 pyridazin-3-one (6d). The product was obtained as a white
mmol), (triisopropylsilyl)ethynyl bromide 2 (0.44 mmol), solid: yield 61 mg (82%); Rf 0.3 (2:1 petroleum
o
1
[
Cp*RhCl ] (5.3 mg, 0.006 mmol, 3 mol %), Ag CO (55 ether/EtOAc); mp 143-144 C; H NMR (400 MHz, CDCl ):
2 2 2 3 3
mg, 0.2 mmol, 1equiv), and DCE (1 mL) were charged into δ 12.48 (s, 1H), 7.91 (d, J = 9.8 Hz, 1H), 7.52 (dd, J = 8.7,
a reaction tube. The reaction mixture was stirred at 100 °C 5.6 Hz, 1H), 7.20 (dd, J = 8.8, 2.8 Hz, 1H), 7.04 (td, J = 8.3,
for 12 h. After the mixture cooled to room temperature, the 2.7 Hz, 1H), 6.90 (d, J = 9.8 Hz, 1H), 1.00 (d, J = 3.6 Hz,
13
solvent was removed under reduced pressure and the residue 21H); C NMR (100 MHz, CDCl ): δ 163.90, 161.41,
3
4
3
was purified by silica gel chromatography using petroleum 145.93, 135.04, 133.6(d, J = 3 Hz), 131.0(d, J = 9 Hz),
CF
CF
3
2
ether/EtOAc to afford the desired product 7.
-{2-[(Triisopropylsilanyl)-ethynyl]-phenyl}-2H-
128.44, 123.5(d, J = 10 Hz), 120.4(d, J = 23 Hz),
CF CF
2
6
116.5(d, JCF = 22 Hz), 103.71, 98.51, 18.56, 11.22; HRMS
+
pyridazin-3-one(6a).The product was obtained as a white (ESI) m/z Calcd for C H FN OSi [M+H] 371.1949, found
2
1
28
2
solid: yield 66 mg (93%); Rf 0.3 (2:1 petroleum 371.1959.
9
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European Journal of Organic Chemistry
10.1002/ejoc.201901731
FULL PAPER
6
2
-{4-Chloro-2-[(triisopropylsilanyl)-ethynyl]-phenyl}-
6-{4-Methyl-2,6-bis-[(triisopropylsilanyl)-ethynyl]-
H-pyridazin-3-one (6e). The product was obtained as a phenyl}-2H-pyridazin-3-one (7b). The product was
white solid: yield 62 mg (80%); R 0.3 (2:1 petroleum obtained as a white solid: yield 89 mg (81%); R 0.4 (5:1
f
f
1
1
ether/EtOAc); mp 108-109 °C; H NMR (400 MHz, CDCl ): petroleum ether/EtOAc); mp 283-284 °C; H NMR (400
3
δ 7.93 (d, J = 9.7 Hz, 1H), 7.50-7.44 (m, 2H), 7.33-7.27 (m, MHz, CDCl ): δ 7.28 (s, 2H), 2.27 (s, 3H), 0.94 (s, 42H);
3
13
13
1
H), 6.90 (d, J = 9.7 Hz, 1H), 1.00 (d, J = 3.2 Hz, 21H); C
C NMR (100 MHz, CDCl ): δ 160.9, 145.8, 138.9, 135.8,
3
NMR (100 MHz, CDCl ): δ 145.8, 135.6, 135.2, 134. 9, 133.5, 137.5, 128.9, 123.4, 104.2, 95.9, 20.8, 18.5, 11.2;
3
+
1
33.6, 130.2, 129.2, 128.5, 123.1, 103.6, 98.8, 18.6, 11.2; HRMS (ESI) m/z Calcd for C H N NaOSi [M+Na]
33 50 2 2
+
HRMS (ESI) m/z Calcd for C H ClN NaOSi [M+Na]
569.3354, found 569.3345.
2
1
27
2
4
6
2
09.1473, found 409.1477.
-{4-Bromo-2-[(triisopropylsilanyl)-ethynyl]-phenyl}-
6-{4-Methoxy-2,6-bis-[(triisopropylsilanyl)-ethynyl]-
phenyl}-2H-pyridazin-3-one(7c).The product was obtained
H-pyridazin-3-one(6f).The product was obtained as a as a white solid: yield 100 mg (89%); R 0.4 (5:1 petroleum
f
1
white solid: yield 73 mg (85%); R 0.3 (2:1 petroleum ether/EtOAc); mp 270−271 °C; H NMR (400 MHz, CDCl ):
f
3
1
ether/EtOAc); mp 120-121 °C; H NMR (400 MHz, CDCl ): δ 7.33 (d, J = 9.7 Hz, 1H), 6.98 (s, 2H), 6.85 (d, J = 9.7 Hz,
3
1
3
δ 12.40 (s, 1H), 7.92 (d, J = 9.5 Hz, 1H), 7.65 (d, J = 1.8 Hz, 1H), 3.78 (s, 3H), 0.95 (s, 42H); C NMR (101 MHz,
1
H), 7.48-7.39 (m, 2H), 6.89 (d, J = 9.8 Hz, 1H), 1.00 (d, J CDCl ): δ 160.6, 159.3, 145.9, 136.2, 133.0, 128.9, 124.6,
3
13
=
3.6 Hz, 21H); C NMR (100MHz, CDCl ): δ 145.7, 136.4, 118.6, 104.0, 96.3, 55.7, 18.5, 11.1; HRMS (ESI) m/z Calcd
3
+
1
1
36.1, 134.8, 132.1, 130.3, 128.6, 123.4, 123.1, 103.5, 98.9, for C H N NaO Si [M+Na] 585.3303, found 585.3310.
33
50
2
2
2
8.6, 11.2; HRMS (ESI) m/z Calcd for C H BrN NaOSi 6-{4-Fluoro-2,6-bis-[(triisopropylsilanyl)-ethynyl]-
21
27
2
+
[
M+Na] 453.0968, found 453.0969.
phenyl}-2H-pyridazin-3-one(7d).The product was obtained
6
-(2-Triethylsilanylethynyl-phenyl)-2H-pyridazin-3-one
as a white solid: yield 78 mg (71%); R 0.4(5:1 petroleum
f
1
(
6g).The product was obtained as a white solid: yield 47 mg ether/EtOAc); mp 275−276 °C; H NMR (400 MHz, CDCl ):
3
1
(
76%); H NMR (400 MHz, CDCl ): δ 11.85 (s, 1H), 7.93 (d, δ 11.55 (s, 1H), 7.32 (d, J = 9.7 Hz, 1H), 7.16 (d, J = 8.6 Hz,
3
1
3
J = 9.8 Hz, 1H), 7.52 (t, J = 5.6 Hz, 2H), 7.33 (p, J = 7.5 Hz, 2H), 6.87 (d, J = 9.7 Hz, 1H), 0.94 (d, J = 1.8 Hz, 42H); C
2
H), 6.90 (d, J = 9.8 Hz, 1H), 0.92 (t, J = 7.9 Hz, 9H), 0.56 NMR (100 MHz, CDCl ): δ 163.0, 160.5, 145.04, 136.63,
3
13
3
2
(
q, J = 7.9 Hz, 6H); C NMR (100 MHz, CDCl ): δ 161.4, 135.56, 129.12, 125.5 (d, J = 11 Hz), 119.8 (d, J = 23
3 CF CF
1
1
46.7, 137.4, 135.1, 133.8, 129.1, 129.0, 128.8, 128.3, 121.5, Hz), 102.91, 97.99, 18.47, 11.08; HRMS (ESI) m/z Calcd
+
04.2, 98.1, 7.4, 4.2; HRMS (ESI) m/z Calcd for for C H FN OSi [M+H] 551.3284, found 551.3272.
32
48
2
2
+
C H N OSi [M+H] 311.1580, found 311.1577.
6-{4-Chloro-2,6-bis-[(triisopropylsilanyl)-ethynyl]-
1
8
23
2
6
-{2,6-Bis-[(triisopropylsilanyl)-ethynyl]-phenyl}-2H-
phenyl}-2H-pyridazin-3-one(7e).The product was obtained
pyridazin-3-one (7a). The product was obtained as a white as a white solid: yield 82 mg (72%); R 0.4 (5:1 petroleum
f
1
solid: yield 89 mg (84%); Rf 0.4 (5:1 petroleum ether/EtOAc); mp 260-261 °C; H NMR (400 MHz, CDCl ):
3
1
ether/EtOAc); mp 254-255 °C; H NMR (400 MHz, CDCl ): δ 7.43 (s, 2H), 7.32 (d, J = 9.7 Hz, 1H), 6.88 (d, J = 9.7 Hz,
3
13
δ 10.65 (s, 1H), 7.54 (d, J = 7.8 Hz, 2H), 7.42 (d, J = 9.7 Hz, 1H), 0.94 (d, J = 1.8 Hz, 42H); C NMR (100 MHz, CDCl ):
3
1
H), 7.33 (t, J = 7.8 Hz, 1H), 6.94 (d, J = 9.7 Hz, 1H), 1.02 δ 159.8, 143.9, 137.5, 134.4, 133.6, 131.5, 128.1, 124.1,
1
3
(
s, 42H); C NMR (100 MHz, CDCl ): δ 145.9, 139.9, 101.7, 97.2, 17.5, 10.1; HRMS (ESI) m/z Calcd for
3
+
1
1
5
35.7, 132.9 , 129.2, 128.8, 123.6, 103.9, 100.0, 96.6, 18.5, C H ClN OSi [M+H] 567.2988, found 567.3004.
32
48
2
2
+
1.1; HRMS (ESI) m/z Calcd for C H N NaOSi [M+Na]
6-{4-Bromo-2,6-bis-[(triisopropylsilanyl)-ethynyl]-
3
2
48
2
2
55.3197, found 555.3187.
phenyl}-2H-pyridazin-3-one(7f).The product was obtained
as a white solid: yield 96 mg (79%); R 0.4 (5:1 petroleum
f
1
0
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European Journal of Organic Chemistry
10.1002/ejoc.201901731
FULL PAPER
1
ether/EtOAc); mp 251-252 °C; H NMR (400 MHz, CDCl ): [7] a) W. H. Moos, C. C. Humblet, I. Sircar, C. Rithner, R.
3
δ 11.44 (s, 1H), 7.66 (s, 2H), 7.38 (d, J = 9.7 Hz, 1H), 6.94
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Coelho, E. Raviña, N. Fraiz, M. Yáñez, R. Laguna, E.
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5547-5556; e) Z. K. Sweeney, J. P. Dunn, Y. Li, G.
Heilek, P. Dunten, T. Elworthy, X. Han, S. H. Harris, D.
R. Hirschefeld, J. H. Hogg, W. Huber, A. C. Kaiser, D.
J. Kertesz, W. Kim, T. Mirzadegan, M. G. Roepel, Y. D.
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1
3
(
(
d, J = 9.7 Hz, 1H), 1.02 (d, J = 1.8 Hz, 42H); C NMR
100 MHz, CDCl ): δ 160.7, 144.9, 139.0, 135.4, 135.3,
3
1
29.2, 125.2, 122.3, 102.5, 98.4, 18.5, 11.1; HRMS (ESI)
+
m/z Calcd for C H BrN OSi [M+H] 611.2483, found
32
48
2
2
6
11.2481.
-(2,6-Bis-triethylsilanylethynyl-phenyl)-2H-pyridazin-3-
6
one (7g). The product was obtained as a white solid: yield
1
5
7
5 mg (61%); H NMR (400 MHz, CDCl ): δ 11.32 (s, 1H),
3
.45 (d, J = 7.8 Hz, 2H), 7.38 (d, J = 9.7 Hz, 1H), 7.25 (t, J
=
7.8 Hz, 1H), 6.90 (d, J = 9.7 Hz, 1H), 0.86 (t, J = 7.9 Hz,
13
1
8H), 0.49 (q, J = 7.9 Hz, 12H); C NMR (100 MHz,
CDCl ): δ 160.9, 145.7, 140.2, 135.6, 132.8, 128.8, 128.7,
3
1
23.4, 103.3, 97.6, 7.4, 4.2; HRMS (ESI) m/z Calcd for
+
C H N OSi [M+H] 449.2245, found 449.2241.
2
6
37
2
2
Acknowledgements
This work is supported by the National Natural Science
Foundation of China (21762022) and the Foundation of
Jiangxi Educational Committee (Grant No. GJJ160287).
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European Journal of Organic Chemistry
10.1002/ejoc.201901731
FULL PAPER
Entry for the Table of Contents
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O
NH
N
R2
R1
7
examples
Br
R2 [Cp*RhCl ] (3 mol%)
2 2
1
.1 equiv)
H
Ag CO (1 equiv)
2 3
R2
O
O
O
NH
[
Cp*RhCl2]2 (3 mol%)
Ag CO (1 equiv)
[Cp*RhCl ] (3 mol%)
2 2
Ag CO (1 equiv)
2 3
NH
N
N
2
3
NH
DCE, 100 oC, air, 12h
Br R2
N
R2
H
H
AgSbF (20 mmol%)
6
R2
DCE, 100 oC, air, 12h
R1
Br
R2
R1
[
Cp*RhCl ] (3 mol%)
1
4 examples
Br
R2
.2 equiv)
2 2
8 examples
Ag CO (1 equiv)
2
3
2
O
NH
N
R2
R2
R1
7 examples
Regoselective alkynylation! Rhodium (III)-catalyzed selective C-H bond mono-/bialkynylation of 4-aryl phthalazin-1(2H)-
one was developed. The silver salt AgSbF are demonstrated to play a vital role in promoting the bialkynylation reactions.
6
Additionally, 6-aryl pyridazin-3(2H)-one scaffold is amenable to the selective monoalkynylation and sequential
bialkynylation, respectively. The present alkynylation strategy is simple, efficient, and features high functional group
tolerance and broad substrate scope under an air atmosphere.
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