A Parallel Approach to 7-(Hetero)arylpyrazolo[1,5- a]pyrimidin-5-ones

Article abstract of DOI:10.1021/acscombsci.8b00032

A modular, two-pot assembly of 7-arylpyrazolo[1,5-a]pyrimidones from aryl/heteroaryl halides and aminopyrazoles in library format was developed. Sonogashira coupling of aryl bromides with triethyl orthopropiolate, followed by in situ orthoester hydrolysis

Full text of DOI:10.1021/acscombsci.8b00032

Subscriber access provided by UNIV OF DURHAM
A Parallel Approach to 7-(Hetero)arylpyrazolo[1,5-a]pyrimidin-5-ones
Daniel C. Schmitt, Nootaree Niljianskul, Neal W Sach, and John I Trujillo
ACS Comb. Sci., Just Accepted Manuscript • DOI: 10.1021/acscombsci.8b00032 • Publication Date (Web): 04 Apr 2018
Downloaded from http://pubs.acs.org on April 5, 2018
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a service to the research community to expedite the dissemination
of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in
full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully
peer reviewed, but should not be considered the official version of record. They are citable by the
Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore,
the “Just Accepted” Web site may not include all articles that will be published in the journal. After
a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web
site and published as an ASAP article. Note that technical editing may introduce minor changes
to the manuscript text and/or graphics which could affect content, and all legal disclaimers and
ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or
consequences arising from the use of information contained in these “Just Accepted” manuscripts.
is published by the American Chemical Society. 1155 Sixteenth Street N.W.,
Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the course
of their duties.

Page 1 of 12
ACS Combinatorial Science
1
2
3
4
5
6
7
8
9
A Parallel Approach to
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
7ꢀ(Hetero)arylpyrazolo[1,5ꢀa]pyrimidinꢀ5ꢀones
Daniel C. Schmitt,* Nootaree Niljianskul, Neal W. Sach, and John I. Trujillo
Pfizer Worldwide Research and Development, Eastern Point Road, Groton, Connecticut 06340,
United States
Department of Chemistry, La Jolla Laboratories, Pfizer Inc., 10770 Science Center Drive, San
Diego, California 92121, United States
KEYWORDS: ynoates, parallel synthesis, 7ꢀarylpyrazolo[1,5ꢀa]pyrimidinꢀ5(4H)ꢀones,
regioselective, orthoester, Sonogashira
ABSTRACT: A modular, twoꢀpot assembly of 7ꢀarylpyrazolo[1,5ꢀa]pyrimidones from
aryl/heteroaryl halides and aminopyrazoles in library format was developed. Sonogashira
coupling of aryl bromides with triethyl orthopropiolate followed by in situ orthoester hydrolysis
provides access to βꢀaryl ynoates, which undergo regioselective cyclocondensation with
aminopyrazoles. The ability to vary the C7 vector of 7ꢀarylpyrazolo[1,5ꢀa]pyrimidones in two
steps using readily available (hetero)aryl halides significantly enhances synthetic access to this
challenging vector.
R
aza-Michael
N
Sonogashira
N
R'
O
N
H
cyclocondensation
ACS Paragon Plus Environment
1

ACS Combinatorial Science
Page 2 of 12
1
2
3
4
5
6
7
8
9
The ability to introduce structural diversity from abundant building blocks with minimal
synthetic operations is critical to the rapid generation of structureꢀactivity relationship (SAR) and
progression of drug discovery projects.1 Among potential sources of Csp2 diversity, heteroaryl
halides are widely commercially available and provide access to broad chemical space. Ideally,
heteroaryl halides may be introduced in the final step of analog production via crossꢀcoupling
with an organometallic partner. However, in cases where an organometallic coupling partner is
unstable or inaccessible, the enablement of heteroaryl halides as a diversity source requires an
alternative solution.2ꢀ3 Recently, we sought to rapidly produce diverse 7ꢀheteroaryl pyrazolo[1,5ꢀ
a]pyrimidones, preferably utilizing heteroaryl halides for exploration of the C7ꢀvector. Despite
the prevalence of pyrazolo[1,5ꢀa]pyrimidꢀ5ꢀone derivatives in drug discovery (Scheme 1a)4ꢀ6,
C7ꢀheteroaryls are exceedingly scarce, likely due to the challenges associated with their
preparation. To our knowledge, only one route has been disclosed for the synthesis of a 7ꢀ
heteroaryl triazolo[1,5ꢀa]pyramidꢀ5ꢀone;7 this route requires a nine step synthesis from
heteroaryl halide starting materials, rendering it unsuitable for parallel synthesis (Scheme 1b).
Herein, we describe an operationally simple, twoꢀpot parallel synthesis of pyrazolo[1.5ꢀ
a]pyrimidꢀ5ꢀones permitting C7 variation with heteroaryl halide building blocks.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
ACS Paragon Plus Environment
2

Page 3 of 12
ACS Combinatorial Science
1
2
3
4
Scheme 1. Literature examples of azolo[1.5-a]pyrimidines and new route
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Our synthetic approach was inspired by Reimlinger’s regioselective cyclocondensation of
aminopyrazole with ethyl phenylpropiolate to afford the 7ꢀphenyl pyrazolo[1.5ꢀa]pyrimidone.8
Presumably, this reaction proceeds through azaꢀMichael addition of the pyrazole ring nitrogen to
the ynoate, followed by cyclization of the exocyclic amine onto the ester to provide the 7ꢀphenyl
regioisomer.9 In contrast, cyclocondensation of aminopyrazole with ethyl benzoylacetate is
known to provide the 5ꢀphenyl regioisomer (Scheme 2).10
ACS Paragon Plus Environment
3

ACS Combinatorial Science
Page 4 of 12
1
2
3
4
Scheme 2. Regioselectivity of Amino-Azole Cyclocondensation
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Noting that ynoates would likely be required to achieve the desired regioselectivity
(rather than βꢀketoesters, vinylogous carbamates,11 or other 1,3ꢀdielectrophiles), we aimed to
devise a high throughput sequence for the conversion of aryl halides to βꢀaryl ynoates. βꢀAryl
ynoates are common key intermediates in the synthesis of bioactive molecules12ꢀ13 so a parallel
approach to their synthesis would be beneficial. However, the direct Sonogashira coupling of
propiolate esters to aryl halides is a notoriously difficult transformation, which has been
attributed to slow generation of the Cuꢀacetylide intermediate and product decomposition via
conjugate addition.14ꢀ15
While the Sonogashira coupling of propiolic acid with aryl bromides is established,16ꢀ17
this approach was not pursued as the resulting βꢀarylꢀpropiolic acid would likely not participate
in the subsequent cyclocondensation, necessitating an additional esterification step. Despite
wellꢀdocumented challenges associated with ynoate Sonogashira coupling, our initial
experiments sought to identify general conditions for the direct coupling of methyl propiolate
with readily available and diversely substituted heteroaryl bromides. Preliminary attempts to
couple various heteroaryl bromides with methyl propiolate under standard Sonogashira
conditions provided no trace of desired βꢀaryl ynoate (Table 1, entries 1ꢀ4). We next turned our
attention to Sarkar’s conditions (entry 5), which have been shown to permit Sonogashira
coupling of methyl propiolate with substituted bromobenzenes;18 however, the conditions were
ACS Paragon Plus Environment
4

Page 5 of 12
ACS Combinatorial Science
1
2
3
4
5
6
7
8
9
not compatible with 5ꢀBrꢀpyrimidine. The alkynylzinc species was also found to be unsuitable
for propiolate coupling with heteroaryl bromides despite precedence with iodobenzene (entry
6).19 We next performed an extensive conditions screen, varying ligand, solvent, and base for
the coupling of methyl propiolate with 5ꢀbromopyrimidine (192 total conditions on 1 ꢀmol scale,
see supporting information for experimental details). Notably one set of conditions stood out and
was repeated on 0.2 mmol scale, (entry 7) providing 59% isolated yield of the desired aryl
ynoate. We next tested the generality of this protocol, but found it unsuitable for other aryl
halides (entries 8 and 9).
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Without a suitable general condition for propiolate Sonogashira, we next aimed to
mitigate the electronꢀwithdrawing nature of the ester by masking it as an orthoester, a strategy
pioneered by Sakamoto.14, 20 While the ethyl orthopropiolate has limited commercial vendors, it
may be rapidly accessed by addition of trimethylsilylꢀacetylene to tetraethyl orthocarbonate.21
The propiolate orthoester successfully underwent Sonogashira coupling with both 5ꢀBrꢀ
pyrimidine and 2ꢀBrꢀpyridine in 41% yield (entries 10ꢀ11). Buchwald’s Cuꢀfree conditions22
provided a slight increase in yield even after deprotection of the ester with HCl (entry 12). With
suitable conditions in hand for the synthesis of (hetero)aryl ynoates, we next attempted
cyclocondensation with 3ꢀaminopyrazole. A survey of amine and alkoxide bases revealed that
lithium and sodium methoxide promote cyclocondensation in nꢀbutanol at 120 °C to afford the
desired 7ꢀ(hetero)arylpyrazolo[1,5ꢀa]pyrimidinꢀ5ꢀone. Furthermore, the crude product of the
oneꢀpot Sonogashira / deprotection sequence could be concentrated and then subjected directly to
cyclocondensation conditions without any aqueous extraction or purification. Lithium
methoxide was selected for all subsequent cyclocondensations as it provided increased solubility
and improved mixing relative to sodium methoxide. A recent study of aminopyrazole
ACS Paragon Plus Environment
5

ACS Combinatorial Science
Page 6 of 12
1
2
3
4
5
6
cyclocondensation with ynoates also identified alkoxide bases to be optimal, likely due to their
ability to induce E/Z isomerization of the intermediate enamine.23
7
8
9
Table 1. Propiolate Sonogashira Optimization
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
To determine the general applicability of our method, we examined a range of electronꢀ
deficient and electronꢀrich aryl halides in the Sonogashira / cyclocondensation sequence in
parallel. Aryl bromides bearing metaꢀ and paraꢀalkylphenyl substitutions were compatible (1-2),
but stericallyꢀhindered 2ꢀiꢀPrꢀbromobenzene only provided a trace amount of product (3) by LCꢀ
MS analysis. Monoꢀ and diꢀmethoxyphenyl bromides were suitable substrates (4ꢀ5). 5ꢀ
Membered heteroaryl bromides were also competent in the sequence, albeit in diminished yields
(6 and 7). Notably, aryl ynoates bearing electronꢀrich aromatic groups (4, 5, and 6) provided
detectable amounts of the minor 5ꢀarylpyrazolo[1,5ꢀa]pyrimidinꢀ7ꢀone regioisomer in the
cyclocondensation step, but the 7ꢀaryl regioisomer was the major isomer in all cases. Electronꢀ
ACS Paragon Plus Environment
6

Page 7 of 12
ACS Combinatorial Science
1
2
3
4
deficient phenyl and heteroaryl halides were compatible with the sequence (8ꢀ13) providing
5
6
complete regioselectivity for the depicted 7ꢀ(hetero)aryl isomer.
7
8
9
In all cases the yields were poor but suitable for high throughput analog production in
medicinal chemistry. The only byproducts identified were transesterified butyl ynoate 14 and
carboxylic acid 15, likely resulting from azaꢀMichael addition of the lessꢀhindered ring nitrogen
followed by saponification (Figure 1). Options for future yield optimization could include
thorough screening of cyclocondensation bases and solvents or application of Abarbri’s recently
disclosed twoꢀstep cyclocondensation conditions (heat without base for azaꢀMichael addition,
then stir with sodium methoxide at room temperature to induce ring closure), which were shown
to provide higher yields for similar substrates.23 Additionally, the low solubility of several of the
pyrazolopyrimidone products likely impedes product recovery from chromatography;
purification via recrystallization could provide improved yields and would represent an
operationally preferred approach on larger scale.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
ACS Paragon Plus Environment
7

ACS Combinatorial Science
Page 8 of 12
1
2
3
4
Table 2. Two-pot Sonogashira / cyclocondensation sequence: aryl bromide scope
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Figure 1. Byproducts
ACS Paragon Plus Environment
8

Page 9 of 12
ACS Combinatorial Science
1
2
3
4
5
6
7
8
9
The scope of aminoꢀazole was next examined in the cyclocondensation with ethyl
phenylpropiolate. Aminotriazole was effective to provide triazolopyrimidone 16 as the major
isomer of the four possible regioisomers. C3ꢀ and C4ꢀsubstituted pyrazolo[1,5ꢀa]pyrimidinꢀ7ꢀ
ones were also accessed by this approach (17ꢀ23). Notably, valuable functional group handles
such as bromide (21) and NꢀBocꢀpiperidine (23) were wellꢀtolerated providing additional vectors
for subsequent SAR generation. Yields for the cyclocondensation step using the commercially
available ynoate (Table 3) are comparable to the yields over two steps (Table 2), indicating that
the cyclocondensation is the lowerꢀyielding step.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Table 3. Cyclocondensation: amino-azole scope
Ph
Ph
N
HN
LiOMe
N
R2
N
R2
BuOH
120 °C
A
H2N
O
N
R1
A = C or N
R1
CO2Et
H
7-phenylazolo[1,5-a]
ethyl
pyrimidin-5-one
phenylpropiolate amino-azole
Ph
Ph
Ph
N
N
N
N
N
N
N
O
O
N
H
O
N
H
O
N
H
18, 25% yield
17, 24% yield
16
, 18% yield
Ph
Ph
Ph
N
N
N
N
N
N
F
O
O
N
N
H
O
N
H
H
Br
19, 17% yield
20, 18% yield
21
, 20% yield
Ph
N
Ph
N
CF3
N
N
O
N
H
O
N
H
NBoc
23, 7% yield
22, 11% yield
In conclusion, we have developed a novel parallel synthesis of pyrazolo[1,5ꢀa]pyrimidinꢀ
5ꢀones via Sonogashira coupling and regioselective ynoate cyclocondensation. The value of this
ACS Paragon Plus Environment
9

ACS Combinatorial Science
Page 10 of 12
1
2
3
4
5
6
method lies in the ability to access diverse 7ꢀ(hetero)aryl substituents in two steps from abundant
(hetero)aryl halide building blocks, significantly accelerating SAR generation relative to prior
7
8
approaches.
Furthermore, the method is compatible with substituted aminopyrazole
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
cyclocondensation partners enabling the combinatorial assembly of 7ꢀarylpyrazolo[1,5ꢀ
a]pyrimidinꢀ5ꢀones. The ability to convert (hetero)aryl halides to (hetero)aryl ynoates in parallel
will have impact beyond pyrazolopyrimidone synthesis as ynoates are pervasive intermediates in
organic synthesis.
ASSOCIATED CONTENT
Supporting Information.
The Supporting Information is available free of charge on the ACS Publications website.
Complete description of reactions, characterization data (1H and 13C NMR, LCMS) of all new
compounds, and copies of 1H and 13C NMR spectra.
AUTHOR INFORMATION
Corresponding Author
*Eꢀmail: daniel.schmitt@pfizer.com
Author Contributions
The manuscript was written through contributions of all authors. All authors have given approval
to the final version of the manuscript.
Funding Sources
ACS Paragon Plus Environment
10

Page 11 of 12
ACS Combinatorial Science
1
2
3
4
The work was supported by Pfizer Inc.
5
6
7
Notes
8
9
The authors declare no competing financial interest.
ACKNOWLEDGMENT
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
The authors thank Louise Bernier for set up of the Sonogashira conditions screen and Ivan
Samardjiev for Xꢀray crystallographic assistance. Dr. David Blakemore and Dr. Yvette Fobian
are thanked for manuscript review.
REFERENCES
1.
Society of Chemistry: 2016; Vol. 2.
2. Campeau, L.ꢀC.; Rousseaux, S.; Fagnou, K., A Solution to the 2ꢀPyridyl Organometallic
Blakemore, D. C. D., P. M.; Fobian, Y. M., Synthetic Methods in Drug Discovery. Royal
CrossꢀCoupling Problem:ꢁ Regioselective Catalytic Direct Arylation of Pyridine NꢀOxides. J.
Am. Chem. Soc. 2005, 127 (51), 18020ꢀ18021.
3.
Markovic, T.; Rocke, B. N.; Blakemore, D. C.; Mascitti, V.; Willis, M. C., Pyridine
sulfinates as general nucleophilic coupling partners in palladiumꢀcatalyzed crossꢀcoupling
reactions with aryl halides. Chem. Sci. 2017, 8 (6), 4437ꢀ4442.
4.
Cox, J. M.; Chu, H. D.; Kuethe, J. T.; Gao, Y.ꢀD.; Scapin, G.; Eiermann, G.; He, H.; Li,
X.; Lyons, K. A.; Metzger, J.; Petrov, A.; Wu, J. K.; Xu, S.; SinhaꢀRoy, R.; Weber, A. E.; Biftu,
T., The discovery of novel 5,6,5ꢀ and 5,5,6ꢀtricyclic pyrrolidines as potent and selective DPPꢀ4
inhibitors. Bioorg. Med. Chem. Lett. 2016, 26 (11), 2622ꢀ2626.
5.
Babaoglu, K.; Boojamra, C. G.; Eisenberg, E. J.; Hui, H. C.; Mackman, R. L.; Parrish, J.
P.; Sangi, M.; Saunders, O. L.; Siegel, D.; Sperandio, D., Pyrazolo [1,5ꢀa] pyrimidines as
antiviral agents. PCT Int. Appl. 2011163518, December 29, 2011.
6.
Ellermann, M.; Valot, G.; Cancho Grande, Y.; Hassfeld, J.; Kinzel, T.; Koebberling, J.;
Beyer, K.; Roehrig, S.; Sperzel, M.; Stampfuss, J.; Meyer, I.; Koellnberger, M.; Burkhardt, N.;
Schlemmer, K.ꢀH.; Stegmann, C.; Schuhmacher, J.; Werner, M.; Heiermann, J.; Hengeveld, W.
J. Piperidinylpyrazolopyrimidinones as plasminogen inhibitors and their preparation. PCT Int.
Appl. 2016071216, May 12, 2016.
7.
Haga, T.; Kimura, H.; Morita, M.; Ueda, T.; Ueki, T.; Kiriyama, K.; Yoshida, K.;
Hamamoto, T.; Kodama, T. Preparation of pyridylꢀtriazolopyrimidine derivatives as pesticides.
PCT Int. Appl. 2010018853, February 18, 2010.
8.
Reimlinger, H.; Peiren, M. A.; Merényi, R., Synthesen mit heterocyclischen Aminen, I.
Reaktionen des 3(5)ꢀAminoꢀpyrazols mit α,βꢀungesättigten Estern. Darstellung und
Charakterisierung isomerer Oxoꢀdihydroꢀpyrazoloꢀpyrimidine. Chem. Ber. 1970, 103 (10),
3252ꢀ3265.
9.
Waechtler, J. F., D. P.; Quincoces Saurez, J. A.; Michalik, D.; Villinger, A.; Kragl, U.;
Vogel, C., Arkivoc 2012, 110ꢀ133.
ACS Paragon Plus Environment
11

ACS Combinatorial Science
Page 12 of 12
1
2
3
4
5
6
10.
C
Kodimuthali, A.; Nishad, T. C.; Prasunamba P. L.; Pal, M. Reactivity of the –C(Cl) C–
N– moiety towards AlCl3ꢀinduced C–C bond forming reactions: a new synthesis of 7ꢀ
(hetero)arylꢀsubstituted pyrazolo[1,5ꢀa]pyrimidines. Tetrahedron Lett. 2009 50 (3), 354ꢀ358.
11. Drev, M.; Grošelj, U.; Mevec, Š.; Pušavec, E.; Štrekelj, J.; Golobič, A.; Dahmann, G.;
7
Stanovnik, B.; Svete, J., Regioselective synthesis of 1ꢀ and 4ꢀsubstituted 7ꢀoxopyrazolo[1,5ꢀ
a]pyrimidineꢀ3ꢀcarboxamides. Tetrahedron 2014, 70 (44), 8267ꢀ8279.
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
12.
Archana, S.; Geesala, R.; Rao, N. B.; Satpati, S.; Puroshottam, G.; Panasa, A.; Dixit, A.;
Das, A.; Srivastava, A. K., Development of constrained tamoxifen mimics and their
antiproliferative properties against breast cancer cells. Bioorg. Med. Chem. Lett. 2015, 25 (3),
680ꢀ684.
13.
Vitale, P.; Tacconelli, S.; Perrone, M. G.; Malerba, P.; Simone, L.; Scilimati, A.;
Lavecchia, A.; Dovizio, M.; Marcantoni, E.; Bruno, A.; Patrignani, P., Synthesis,
Pharmacological Characterization, and Docking Analysis of a Novel Family of Diarylisoxazoles
as Highly Selective Cyclooxygenaseꢀ1 (COXꢀ1) Inhibitors. J. Med. Chem. 2013, 56 (11), 4277ꢀ
4299.
14.
Sakamoto, T.; Shiga, F.; Yasuhara, A.; Uchiyama, D.; Kondo, Y.; Yamanaka, H.,
Preparation of Ethyl Arylpropiolates from Aryl Iodides by PalladiumꢀCatalyzed CrossꢀCoupling
Reaction. Synthesis 1992, 1992 (08), 746ꢀ748.
15.
Deficient Alkynes Using Diaryliodonium Salts. Org. Lett. 2001, 3 (6), 859ꢀ860.
16. Anderson, K. W.; Buchwald, S. L., General Catalysts for the Suzuki–Miyaura and
Sonogashira Coupling Reactions of Aryl Chlorides and for the Coupling of Challenging
Substrate Combinations in Water. Angew. Chem. Int. Ed. 2005, 44 (38), 6173ꢀ6177.
17.
Synthesis of Arylalkynecarboxylic Acids from Aryl Bromides at Low Temperature. Eur. J. Org.
Chem. 2013, 2013 (10), 1973ꢀ1978.
18.
Aryl and Heteroaryl Halides. Synthesis 2013, 45 (06), 817ꢀ829.
19. Anastasia, L.; Negishi, E.ꢀi., Highly Satisfactory Procedures for the PdꢀCatalyzed Cross
Coupling of Aryl Electrophiles with in Situ Generated Alkynylzinc Derivatives. Org. Lett. 2001,
3 (20), 3111ꢀ3113.
20.
heteroaromatic ring systems. XXIV. Palladiumꢀcatalyzed cyclization of 2ꢀsubstituted
phenylacetylenes in the presence of carbon monoxide. Tetrahedron 1994, 50 (41), 11803ꢀ11812.
21.
Direct, Catalytic Synthesis of Carbapenams via Cycloaddition/Rearrangement Cascade Reaction:
Unexpected Acetylenes’ Structure Effect. J. Org. Chem. 2010, 75 (22), 7580ꢀ7587.
22.
and Tosylates with Terminal Alkynes: Use of a Copper Cocatalyst Inhibits the Reaction. Angew.
Chem. Int. Ed. 2003, 42 (48), 5993ꢀ5996.
23.
Access to 5,7‐Disubstituted Pyrazolo[1,5‐a]pyrimidines by Pd‐Catalyzed Sequential Arylation,
Alkynylation and SNAr Reaction. Eur. J. Org. Chem. 2017, 2017 (41), 6168ꢀ6178.
Radhakrishnan, U.; Stang, P. J., PalladiumꢀCatalyzed Arylation of Enynes and Electronꢀ
Park, K.; You, J. M.; Jeon, S.; Lee, S., Palladium‐Catalyzed Sonogashira Reaction for the
Panda, B.; Sarkar, T. K., Gold and Palladium Combined for the Sonogashira Coupling of
Kondo, Y.; Shiga, F.; Murata, N.; Sakamoto, T.; Yamanaka, H., Condensed
Mames, A.; Stecko, S.; Mikołajczyk, P.; Soluch, M.; Furman, B.; Chmielewski, M.,
Gelman, D.; Buchwald, S. L., Efficient PalladiumꢀCatalyzed Coupling of Aryl Chlorides
Jismy, B.; Guillaumet, G.; Allouchi, H.; Akssira, M.; Abarbri, M., Concise and Efficient
ACS Paragon Plus Environment
12