Facile Access to Diverse Libraries of Internal Alkynes via Sequential Iododediazoniation/Decarboxylative Sonogashira Reaction in Imidazolium ILs without Ligand or Additive

Article abstract of DOI:10.1002/ejoc.201900093

Convenient access to diverse libraries of internal alkynes via decarboxylative Sonogashira reaction of alkynyl-carboxylic acids with iodoarenes, employing imidazolium-ILs as solvent, along with piperidine-appended imidazolium [PAIM][NTf₂] as task-specific basic IL is demonstrated, without the need for any ligand or additive. The feasibility to perform these reactions by sequential one-pot iododediazoniation/decarboxylative Sonogashira reaction is also shown, and the scope of the methods is underscored by providing 29 examples. The potential for recycling and reuse of the IL solvent is also examined.

Full text of DOI:10.1002/ejoc.201900093

A Journal of
Accepted Article
Title: Facile Access to Diverse Libraries of Internal Alkynes via
Sequential Iododediazoniation/Decarboxylative Sonogashira
Reaction in Imidazolium ILs without Ligand or Additive
Authors: Pavankumar Prabhala, Hemantkumar Savanur, Rajesh
Kalkhambkar, and Kenneth K. Laali
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201900093
Link to VoR: http://dx.doi.org/10.1002/ejoc.201900093
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10.1002/ejoc.201900093
European Journal of Organic Chemistry
1
Facile Access to Diverse Libraries of Internal Alkynes via Sequential
Iododediazoniation/ Decarboxylative Sonogashira Reaction in Imidazolium ILs
without Ligand or Additive.
Pavankumar Prabhala,a Hemantkumar M. Savanur,a Dr. Rajesh G. Kalkhambkar,a*
Prof. Kenneth K. Laalib*
a Department of Chemistry, Karnatak University’s Karnatak Science College, Dharwad,
Karnatak 580001, India (corresponding author e-mail: rgkalkhambkar@gmail.com)
b Department of Chemistry, University of North Florida, 1 UNF Drive, Jacksonville, FL, 32224,
USA
Corresponding author e-mail: Kenneth.laali@UNF.edu
URL: https://www.unf.edu/coas/chemistry/faculty/Kenneth_Laali.aspx
Keywords: decarboxylative Sonogashira; alkynyl-carboxylic acids; iododediazoniation;
[PAIM][NTf2] as basic-IL; [BMIM][X] as solvent
Abstract: Convenient access to diverse libraries of internal alkynes via decarboxylative
Sonogashira reaction of alkynyl-carboxylic acids with iodoarenes, employing imidazolium-ILs as
solvent along with piperidine-appended imidazolium [PAIM][NTf2] as task-specific basic IL is
demonstrated, without the need for any ligand or additive. The feasibility to perform these
reactions by sequential one-pot iododediazoniation/decarboxylative Sonogashira reaction is also
shown, and the scope of the methods is underscored by providing 29 examples. The potential for
recycling and reuse of the IL solvent is also examined.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201900093
European Journal of Organic Chemistry
2
Graphical Abstract
TOC Text:
A facile one-pot method comprising sequential iododediazoniation/Sonogashira reaction is used
to prepare diverse libraries of internal alkynes. The method uses imidazolium-ILs as base and
solvent and does not require ligand or additive.
Key topic: sequential reactions
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10.1002/ejoc.201900093
European Journal of Organic Chemistry
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Introduction
In their seminal studied, Baran et al.[1] examined the decarboxylative cross coupling
reactions via alkyl-aryl(heteroaryl) bond formation, by employing the Negishi, Suzuki, and
Kumada protocols utilizing nickel or iron catalysts and carboxylic acid activators. They also
studied decarboxylative alkynylation reactions by using redox-active esters and alkynyl-zinc
compounds.[2] Examples of alkynylation of arene carboxylates with terminal alkynes was also
reported by Itami, Yamaguchi, and associates.[3] These transformation required Pd, along with
ligand, CuI, base, and additive, and were performed in 1,4-dioxane at high temperature. The Pd-
catalyzed coupling of alkynyl-carboxylic acids with aryl- and benzyl halides, employing XPhos
and base in THF solvent,[4] and sp-sp bond formation via decarboxylative cross coupling of
terminal alkynes with propyolic acids using copper catalyst, ligand, and base in DMF or DMSO
as solvent to form conjugated diynes have also been reported.[5]
Limited studies of the Sonogashira decarboxylative coupling reaction reported to date
have involved the use of [Pd] and [Cu] catalysts, along with ligand, and base, and were typically
performed in DMF or THF as solvent.[6-8] To our knowledge there is only one report of
decarboxylative Sonogashira using arenediazonium salts.[9] This study utilized Pd-MnFe2O4 as
catalyst, along with an iodine source and base, and employed solvents such as DMSO, DMF, and
NMP.
In continuation of our work on developing synthetic methods in ILs as catalysts and
solvents,[10] and in relation to our recent studies on sequential metal-mediated coupling reactions
in ILs employing task-specific ILs as base,[11,12] we report here a convenient method to access
diverse libraries of internal alkynes via decarboxylative Sonogashira reaction of alkynyl-
carboxylic acids with iodoarenes via iododediazoniation with TMSI, employing imidazolium-ILs,
without the need for any additive or ligand. These transformations can also be achieved by
sequential one-pot iododediazoniation/decarboxylative Sonogashira reaction starting with the
diazonium salts. The scope of the methods is underscored by providing 29 examples, and the
prospects for recycling and reuse of the IL solvent is also addressed.
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10.1002/ejoc.201900093
European Journal of Organic Chemistry
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Results and Discussion
In an initial feasibility study, when phenyl propiolic acid was allowed to react with Ph-I in
[BMIM][BF4] as solvent, with Pd(OAc)2 as catalysts and piperidine-appended imidazolium IL
[PAIM][NTf2] as base, diphenyl acetylene was isolated in 89% yield upon mild heating (60-70
oC), and the yield was further improved to 95% by repeating the reaction in fresh [BMIM][PF6]
(Table 1, entries 1-2). To identify an optimal catalyst and for comparison, the reaction was
repeated by employing several other Pd catalysts (Table 1), showing that Pd(OAc)2 was in fact
the best choice under these conditions.
INSERT Table 1 and its header
Encouraged by these findings, a library of iodoarenes were prepared via
iododediazoniation from the corresponding aryldiazonium salts with TMSI,[13] and were
subsequently allowed to react with various alkynyl-carboxylic acids (with R = Ph, alkyl, and
cyclopropyl), and the corresponding diaryl-acetylenes were isolated in respectable isolated yields
(Table 2a, entries 1-16). It is noteworthy that higher isolated yields could be reached by using
fresh IL solvents.
INSERT Table 2a and its header
Turing our attention to the heterocyclic analogs, decarboxylative Sonogashira reactions of
alkynyl-COOH with 7-iodo-chromones and 3-iodopyridine, prepared via iododediazoniation from
the corresponding diazonium salts with TMSI, were carried out and the corresponding diaryl-
acetylenes were similarly obtained in acceptable yields (Table 2b; entries 19-22).
INSERT Table 2b and its header
In the next phase of the study, the iododediazoniation and the Sonogashira reaction were
performed in sequence in one-pot reactions without isolation of the iodoarene. Employing both
benzenediazonium and chromone-diazonium salts in overall yields ranging from 68 to 85%
(Table 3).
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10.1002/ejoc.201900093
European Journal of Organic Chemistry
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INSERT Table 3 and its header
To get a sense for the limits of recovery and reuse of the IL solvent, reaction in entry 1
Table 1 was repeated in [BMIM][BF4] and [BMIM][PF6] up to five times to compare isolated
yields. The results are presented in graphical form in the supporting information file. The data
illustrate a relatively consistent trend of decreasing yields after each cycle, with [BMIM][PF6]
appearing more resilient to reuse and hence the preferred IL solvent.
In summary, we have demonstrated a facile method for the synthesis of diverse internal
alkynes via decarboxylative Sonogashira reaction of alkynyl-carboxylic acids with iodoarenes,
employing imidazolium-ILs as solvent along with [PAIM][NTf2] as task-specific basic IL. The
iodoarenes were easily prepared by iododediazoniation starting from readily available diazonium
salts by reaction with TMSI. We have also shown that iododediazoniation and the Sonogashira
reaction can be performed in sequence in one-pot reactions starting from the diazonium salts. The
method uses available imidazolium ILs along with [PAIM][NTf2] without ligand and additive and
under mild heating. We also demonstrated the possibility to recycle and reuse the IL solvent for a
limited number of cycles.
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10.1002/ejoc.201900093
European Journal of Organic Chemistry
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Table 1. Catalyst optimization in [BMIM][X]
Basic IL, Pd-Catalyst
COOH
Ph
Ph
I
Ph
+
[BMIM][X], 5-9 h, Heat
1: X = BF4
2: X = PF6
Entry
Catalyst
IL
Time (h)
Yield
(%)
1
2
Pd(OAc)2
Pd(OAc)2
Pd(PPh3)4
Pd(PPh3)4
1
2
2
1
2
1
2
1
2
1
2
1
7
6
5
7
5
4
5
4
8
9
6
8
89
95
43
28
59
62
43
36
NR
NR
NI
NI
3
4
5
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(dppf)
PdCl2(dppf)
PdI2
6
7
8
9
10
11
12
PdI2
Pd(acac)2
Pd(acac)2
a) Reactions were carried out using phenyl propiolic acid (1 mmol); Ph-I (1 mmol);
[Pd] (10 mol%); [PAIM][NTf2] (4-5 mmol); [BMIM][X] (7 mL); Oil-bath
o
temperature was kept at 60-70 C; Yields refer to isolated yields of pure product;
NI = not isolated; NR = no reaction
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10.1002/ejoc.201900093
European Journal of Organic Chemistry
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Table 2a. Two-step decarboxylative Sonogashira reaction
Entry
No.
Time
[h]d
Yield*
[%]
Substrate R Substrate R'
Product
IL
I
[BMIM][PF6]
4
6
5
5
89a
95a
70c
82d
01
I
[BMIM][PF6]
[BMIM][PF6]
[BMIM][BF4]
02
03
04
O
I
O
I
Cl
I
[BMIM][BF4]
[BMIM][BF4]
[BMIM][BF4]
[BMIM][BF4]
5
6
7
6
80b
76c
78c
87a
05
06
07
08
Cl
I
Me
I
Me
O
I
Me
O
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10.1002/ejoc.201900093
European Journal of Organic Chemistry
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I
[BMIM][BF4]
5
91a
Et
Et
Et
09
10
11
12
13
I
5
6
6
6
82c
89a
74c
78b
[BMIM][PF6]
[BMIM][PF6]
[BMIM][PF6]
[BMIM][PF6]
O
I
O
I
O
I
O
I
[BMIM][PF6]
6
87a
14
NC
NC
I
[BMIM][PF6]
[BMIM][PF6]
5
6
84b
78c
15
16
O2N
O2N
I
F
F
Reaction conditions: alkynyl-COOH (1 mmol), Ar/Het-I (1.1 mmol), basic-IL (4.5 mmol),
o
a
[BMIM][X] (7 mL), and Pd(OAc)2 (10 mol %); Oil-bath temperature: 60-65 C; Yield
b
c
employing fresh IL; Yield using recycled IL (2nd time); Yield using recycled IL (3rd time);
*Isolated yield of pure product.
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10.1002/ejoc.201900093
European Journal of Organic Chemistry
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Table 2b. Heterocyclic Analogs via two-step decarboxylative Sonogashira
Entry
No.
Time
[h]d
Yield*
[%]
R
Het-Aryl-I
Product
IL
O
O
O
[BMIM][BF4]
6
5
74b
79b
17
I
O
[BMIM][BF4]
[BMIM][BF4]
[BMIM][PF6]
[BMIM][PF6]
[BMIM][PF6]
18
O
O
I
I
O
O
O
O
5
6
6
82
78a
69b
Me
Me
19
20
21
O
O
O
O
O
O
I
I
N
N
7
61c
22
I
N
N
Reaction conditions: alkynyl-COOH (1 mmol), basic-IL (4.5 mmol), [BMIM][X] (7 mL), and
o
a
b
Pd(OAc)2 (10 mol %); Oil-bath temperature: 60-65 C; Yield employing fresh IL; Yield using
recycled IL (2nd time); Yield using recycled IL (3rd time); *Isolated yield of pure product.
c
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10.1002/ejoc.201900093
European Journal of Organic Chemistry
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Table 3. Sequential one-pot iododediazoniation/decarboxylative Sonogashira reaction
Entry
No.
Time
[h]
Yield*
[%]
R
[R'-I]
Product
IL
I
01
[BMIM][BF4]
10
85a
I
02
03
Et
Et
“
“
11
12
79a
81a
O
I
O
I
04
[BMIM][PF6]
10
78a
NC
NC
I
05
06
07
Me
Me
Me
“
“
“
9
78c
72
11
12
O
O
I
O
O
O
O
O
O
68a
I
Reaction conditions: alkynyl-COOH (1 mmol), basic-IL (4.5 mmol), [BMIM][X] (7 mL), and
o
a
b
Pd(OAc)2 (10 mol %); Oil-bath temperature: 60-65 C; Yield employing fresh IL; Yield using
recycled IL (2nd time); Yield using recycled IL (3rd time); *Isolated yield of pure product.
c
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10.1002/ejoc.201900093
European Journal of Organic Chemistry
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Acknowledgments
Authors at Karnatak University thank the University Scientific and Instrument Center, KUD for
1
13
IR, GC, GC–MS, H and C NMR, and the NMR Research Centre at Indian Institute of Science
1
Bangalore for H and 13C NMR Spectra. Financial assistance by Department of Science and
Technology, Science and Engineering Research Board New Delhi (DST-SERB) Project No.
SB/FT/CS-175/2013 is gratefully acknowledged. KKL thanks University of North Florida for the
outstanding faculty scholarship and presidential professorship awards, as well as faculty
scholarship and UNF Foundation Board grants.
Supporting information
Synthetic procedures, IL recycling feasibility studies, analytical data for isolated compounds, and
NMR spectral data
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10.1002/ejoc.201900093
European Journal of Organic Chemistry
12
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