Ionic liquid-mediated benzoyl transfer-coupling in the Suzuki and Sonogashira reactions and aryl transfer-coupling by decarbonylative Heck reaction, using N-Benzoyl-saccharin (NBSac) as reagent

Article abstract of DOI:10.1016/j.tetlet.2020.151987

The efficacy of N-benzoyl-saccharin (NBSac) as reagent for selective benzoyl transfer-coupling in the Suzuki reaction in BMIM-IL/[PAIM][NTf₂] as solvent/base, and in the Sonogashira reaction employing guanidinium-IL (GIL) as solvent, are demonstrated. Decarbonylative aryl transfer-coupling occurs in the Heck reaction employing GIL as solvent. The reactions are catalyzed by Pd(OAc)₂ or NiCl₂(dppp), are performed under mild conditions in good yields, and have the potential for recycling/reuse of the IL solvent. Collectively, these methods provide facile access to diverse libraries of diarylketones, keto-ethynes and diaryl-ethenes.

Full text of DOI:10.1016/j.tetlet.2020.151987

Tetrahedron Letters 61 (2020) 151987
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Ionic liquid-mediated benzoyl transfer-coupling in the Suzuki and
Sonogashira reactions and aryl transfer-coupling by decarbonylative
Heck reaction, using N-Benzoyl-saccharin (NBSac) as reagent
Shruti S. Malunavar a, Suraj M. Sutar a, Pavankumar Prabhala a, Rajesh G. Kalkhambkar a, ,1
,
⇑
Kenneth K. Laali b,
⇑
,2
a Department of Chemistry, Karnatak University’s Karnatak Science College, Dharwad, Karnatak 580001, India
b Department of Chemistry, University of North Florida, 1, UNF Drive, Jacksonville, FL 32224, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
The efficacy of N-benzoyl-saccharin (NBSac) as reagent for selective benzoyl transfer-coupling in the
Suzuki reaction in BMIM-IL/[PAIM][NTf2] as solvent/base, and in the Sonogashira reaction employing
guanidinium-IL (GIL) as solvent, are demonstrated. Decarbonylative aryl transfer-coupling occurs in
the Heck reaction employing GIL as solvent. The reactions are catalyzed by Pd(OAc)2 or NiCl2(dppp),
are performed under mild conditions in good yields, and have the potential for recycling/reuse of the
IL solvent. Collectively, these methods provide facile access to diverse libraries of diarylketones, keto-
ethynes and diaryl-ethenes.
Received 19 March 2020
Revised 14 April 2020
Accepted 27 April 2020
Available online 30 April 2020
Keywords:
Benzoylsaccharin
Benzoyl-transfer Suzuki and Sonogashira
coupling
Ó 2020 Elsevier Ltd. All rights reserved.
Decarbonylative Heck arylation
Guanidinium-IL (GIL)
BMIM-IL and PAIM-NTf2
Whereas N-halo-saccharins have been known as halogen
transfer reagents for over two decades [1], more recent discoveries
of N-functionalized saccharins bearing trifluoromethylthio (SCF3)
[2], formyl (CHO) [3,4], and acyl (RCO) [5,6] as functional group
transfer reagents have opened up new dimensions for their deploy-
ment in metal-mediated chemistry.
Focusing on N-benzoyl-saccharins as transfer benzoylation
reagents, two notable previous studies, namely the Suzuki cou-
pling via Pd-catalyzed N-acyl bond cleavage [5], and Heck arylation
via decarbonylation/arylation have been reported [6]. The Suzuki
coupling employed Pd along with PCy3HBF4, K2CO3 and H3BO3
for optimal performance with THF as solvent [5], while optimal
yields for the Heck coupling were reported with PdCl2 in NMP as
solvent at 160 °C.
benzoyl-transfer coupling in both the Suzuki and Sonogashira
reactions, and in the Heck reaction by decarbonylative aryl-
coupling. The Suzuki reaction employed [PAIM][NTf2] as the
basic-IL, [7f,7g] and [BMIM][PF6] or [BMIM][BF4] as solvent
(Fig. 1), whereas the Sonogashira reactions were performed in
ethylguanidinium ethylsulfate (GIL), [8] without the need for base
or any additive (Fig. 2).
Similarly, the Heck decarbonylative arylations were conve-
niently carried out in GIL as solvent (Fig. 3) without the need for
external base, CuX, or other additives.
All three types of transfer cross-coupling reactions were cat-
alyzed by either Pd or Ni in comparable yields, thus expanding
the catalytic scope of these transformations. The mild reaction con-
ditions employed, and recycling and reuse of the IL solvents pro-
vided additional benefits.
Table 1 summarizes the scope of the Suzuki coupling with
NBSac in IL employing various aromatic and alicyclic boronic acids,
[PAIM][NTf2] as basic-IL and [BMIM][X] as solvent, employing Pd
(OAc)2 or NiCl2(dppp) as catalyst, with isolated yields ranging from
88% to 82%, when using fresh IL, but with lower isolated yields
(81–63%) with the use of recycled ILs.
In continuation of our studies on synthetic and catalytic chem-
istry in ILs [7], and with our more recent emphasis on metal-medi-
ated cross-coupling reactions in imidazolium-ILs [7d]; [7f–7i], we
report here on the utility of N-benzoyl-saccharin (NBSac) for
⇑
Corresponding authors.
E-mail addresses: rgkalkhambkar@gmail.com (R.G. Kalkhambkar), Kenneth.
The scope of benzoyl-transfer coupling in the Sonogashira reac-
tion was examined by employing a diverse set of alkynes and the
results are summarized in Table 2. The reactions were performed
Laali@UNF.edu (K.K. Laali).
1
Tel.: +91 836 2215403; fax: +91836 2744334.
Tel.: +1 904 620 1503; fax: +1 904 620 3535.
2
https://doi.org/10.1016/j.tetlet.2020.151987
0040-4039/Ó 2020 Elsevier Ltd. All rights reserved.

2
S.S. Malunavar et al. / Tetrahedron Letters 61 (2020) 151987
Fig. 1. Trans-benzoylation Suzuki cross-coupling using NBSac.
Fig. 2. Trans-benzoylation Sonogashira cross-coupling in GIL using NBSac.
Fig. 3. Decarbonylative Heck coupling in GIL using NBSac.
Table 1
Benzoyl-transfer Suzuki coupling with NBSac employing Pd(OAc)2 or NiCl2(dppp) as catalyst.
Entry
1
Boronic acid
Producta
IL
Timeb (h)
4
Yieldf (%)
86c,y
[BMIM][BF4]
2
3
[BMIM][BF4]
[BMIM][BF4]
5
4
88c,y
74d,x
4
5
6
[BMIM][PF6]
[BMIM][PF6]
[BMIM][BF4]
5.5
5.5
4.5
70d,y
84c,y
74c,x
7
8
[BMIM][BF4]
[BMIM][BF4]
4
4
81d,x
63e,y

S.S. Malunavar et al. / Tetrahedron Letters 61 (2020) 151987
3
Table 1 (continued)
Entry
9
Boronic acid
Producta
IL
Timeb (h)
5
Yieldf (%)
68e,x
[BMIM][BF4]
10
11
[BMIM][PF6]
[BMIM][PF6]
5
71d,y
4.5
87c,x
12
[BMIM][PF6]
5.5
82c,y
a
Reaction conditions: NBSac (1 mmol), Boronic acid 2 (2 mmol), [PAIM][NTf2], [BMIM][X] (5–7 mL) and Pd(OAc)2 or NiCl2(dppp) (5 mol %).
b
c
d
e
f
Oil bath temperature 70–80 °C.
Yield employing fresh IL.
Yield using recycled IL (2nd cycle).
Yield using recycled IL (3rd cycle).
Isolated yield of pure compound.
Using Pd(OAc)2.
x
y
Using NiCl2(dppp).
Table 2
Benzoyl-transfer Sonogashira coupling employing Pd(OAc)2 or NiCl2(dppp) as catalyst.
Entry
13
Alkyne
Producta
IL
Timeb (h)
1.5
Yieldf (%)
91c,y
GIL
14
15
GIL
GIL
2
2
61d,y
66d,x
16
17
GIL
GIL
2
2
64c,x
68c,y
18
GIL
1.5
80d,y
19
20
GIL
GIL
2
56e,x
2.5
57e,x
(continued on next page)

4
S.S. Malunavar et al. / Tetrahedron Letters 61 (2020) 151987
Table 2 (continued)
Entry
21
Alkyne
Producta
IL
Timeb (h)
3
Yieldf (%)
72c,y
GIL
22
GIL
GIL
2.5
70d,y
23
2
66c,y
a
Reaction conditions: NBSac (1 mmol), Alkyne(1.25 mmol), GIL (3–5 mL) and Pd(OAc)2or NiCl2(dppp)(5 mol %).
b
c
d
e
f
Oil bath temperature 55–70 °C.
Yield employing fresh IL.
Yield using recycled IL (2nd cycle).
Yield using recycled IL (3rd cycle).
Isolated yield of pure compound.
UsingPd(OAc)2.
x
y
UsingNiCl2(dppp).
in GIL as solvent with Pd(OAc)2 or NiCl2(dppp) as catalyst, in iso-
lated yields ranging from 91% to 66% by using fresh GIL, and with
80–56% yields when using the recycled IL.
Table 3 summarizes the scope of decarbonylative Heck aryla-
tion with NBSac in GIL solvent employing Pd(OAc)2 or NiCl2(dppp)
as catalyst with isolated yields ranging from 88% to 74% using fresh
GIL.
Focusing on the recycling/reuse of the BMIM-IL solvents, reac-
tion 1 in Table 1 was repeated four consecutive times in [BMIM]
[PF6] and in [BMIM][BF4] solvents. The results presented in graph-
Table 3
Decarbonylative Heck coupling employing Pd(OAc)2 or NiCl2(dppp) as catalyst.
Entry
24
Arylethene
Producta
IL
Timeb (h)
2.5
Yieldf (%)
85c,y
GIL
25
26
GIL
GIL
3
3
72d,y
60e,x
27
28
GIL
GIL
2.5
2.5
78c,y
80c,x
29
30
GIL
GIL
3
3
73d,x
72d,y

S.S. Malunavar et al. / Tetrahedron Letters 61 (2020) 151987
5
Table 3 (continued)
Entry
31
Arylethene
Producta
IL
Timeb (h)
3
Yieldf (%)
63e,y
GIL
32
33
GIL
3
3
70c,x
GIL
61e,y
a
Reaction conditions: NBSac (1 mmol), arylethene(1.5 mmol), GIL (3–4 mL), and Pd(OAc)2 or NiCl2(dppp)(5 mol %).
b
c
d
e
f
Oil bath temperature 55–70 °C.
Yield employing fresh IL.
Yield using recycled IL (2nd cycle).
Yield using recycled IL (3rd cycle).
Isolated yield of pure compound.
UsingPd(OAc)2.
x
y
UsingNiCl2(dppp).
ical format (SI file, chart 1), indicate a fairly consistent trend of
decreasing yields after each cycle, in line with our findings from
previous studies, [7] with [BMIM][PF6] exhibiting a slightly better
recovery/reuse profile as compared to [BMIM][BF4]. Recycling
and reuse of the GIL solvent was explored by selecting entry 13
in Table 2 and entry 24 in Table 3, and each reaction was repeated
four consecutive times. The results presented in graphical format
(SI file, charts 2 and 3) show notable drop in conversions after
the second cycle.
In summary, we have demonstrated the efficacy of NBSac for
transfer-benzoylation coupling in the Suzuki and Sonogashira reac-
tions in BMIM and GIL solvents respectively, with Pd or Ni as cat-
alysts, and for decarbonylation arylation in Heck coupling in GIL
solvent.
Appendix A. Supplementary data
Supplementary data to this article can be found online at
https://doi.org/10.1016/j.tetlet.2020.151987.
References
[1] a) Mozek, I.; Sket, B. Synth. Commun. 1992, 22, 2513-2520; b) Sharma, K.; Jain,
I.; Sharma, V. K. Oxid.Commun. 2015, 38, 631-645; c) Dolenc, D. Synlett. 2000, 4,
544-546;d) Urankar, D.; Rutar, I.; Modec, B.; Dolenc, D. Eur. J. Org. Chem. 2005,
11, 2349-2353
[2] C. Xu, B. Ma, Q. Shen, Angew. Chem. Int. Ed. 53 (2014) 9316–9320.
[3] T. Ueda, H. Konishi, K. Manabe, Angew. Chem. Int. Ed. 52 (2013) 8611–8615.
[4] P.H. Gehrtz, V. Hirschbeck, I. Fleischer, Chem. Comm. (2015) 12574–12577.
[5] C. Liu, G. Meng, Y. Liu, R. Liu, R. Lalancette, R. Szostak, M. Szostak, Org. Lett. 18
(2016) 4194–4197.
[6] C. Liu, G. Meng, Szostak, M, J. Org. Chem. 81 (2016) 12023–12030.
[7] a) R.G. Kalkhambkar, S.N. Waters, K.K. Laali, Tetrahedron Lett. 52 (2011)
867–871;
Collectively, these methods provide facile and efficient access to
diverse libraries of diarylketones, keto-ethynes and diaryl-ethenes
in IL media using NBSac as reagent.
b) G.C. Nandi, K.K. Laali, Tetrahedron Lett. 54 (2013) 2177–2179;
c) A.S. Reddy, K.K. Laali, Tetrahedron Lett. 56 (2015) 5494–5499;
d) A. Srinivas Reddy, K. Laali, K, Tetrahedron Lett. 56 (2015) 4807–4810;
e) H.M. Savanur, R.G. Kalkhambkar, K.K. Laali, Tetrahedron Lett 57 (2016)
3029–3035;
Declaration of Competing Interest
f) H.M. Savanur, R.G. Kalkhambkar, K.K. Laali, Appl. Catal. A. Gen. 543 (2017)
150–161;
g) H.M. Savanur, R.G. Kalkhambkar, K.K. Laali, Eur. J. Org. Chem. (2018)
5285–5288;
h) P. Prabhala, H.M. Savanur, R.G. Kalkhambkar, K.K. Laali, Eur. J. Org. Chem.
(2019) 2061–2064;
i) S.M. Sutar, H.M. Savanur, S.S. Malunavar, P. Prabhala, R.G. Kalkhambkar, K.K.
Laali, Eur. J. Org. Chem. (2019) 6088–6093;
The authors declare that they have no known competing finan-
cial interests or personal relationships that could have appeared
to influence the work reported in this paper.
Acknowledgments
j) S.S. Malunavar, S.M. Sutar, H.M. Savanur, R.G. Kalkhambkar, K.K. Laali,
Tetrahedron Lett. 61 (2020) 151509–151513.
[8] a) L. Lin, Y. Li, S. Li, Synlett. (2011) 1779–1783;
Authors at Karnatak University thank the University Scientific
and Instrument Center, KUD for IR, 1H and 13C NMR, and the
NMR Research Centre at Indian Institute of Science Bangalore for
1H and 13C NMR & HRMS Spectra. Financial assistance by VGST-
RGS/F/GRD742/2017-18 is gratefully acknowledged. KKL thanks
University of North Florida for the outstanding faculty scholarship
and presidential professorship awards, as well as Dean’s Research
Council and UNF Foundation Board grants.
b) S. Li, Y. Lin, H. Xie, S. Zhang, J. Xu, Organic Lett. 8 (2006) 391–394;
c) L.C. Branco, A. Serbanvic, M.N. da Ponte, C.A.M. Afonso, ACS Catal 1 (2011)
1408–1413;
d) S.S. Chavan, M.S. Degani, Catal Lett. 141 (2011) 1693–1697;
e) A. Zhu, T. Jiang, D. Wang, B. Han, L. Liu, J. Huang, J. Zhang, D. Sun, Green
Chem. 7 (2005) 514–517.