An efficient Cu-catalyzed microwave-assisted synthesis of diaryl sulfones

Article abstract of DOI:10.1080/00397911.2016.1263337

An efficient and microwave-assisted simple protocol for the synthesis of symmetrical/asymmetrical diaryl sulfones through the Cu(II)-catalyzed reaction of sodium salt of sulfinic acid with aryl boronic acid has been described. Various diaryl sulfones have been synthesized in very short reaction times with moderate to very good yields. Additionally, the method is also useful for the synthesis of aryl vinyl sulfones.

Full text of DOI:10.1080/00397911.2016.1263337

Synthetic Communications
An International Journal for Rapid Communication of Synthetic Organic
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ISSN: 0039-7911 (Print) 1532-2432 (Online) Journal homepage: http://www.tandfonline.com/loi/lsyc20
An efficient Cu-catalyzed microwave-assisted
synthesis of diaryl sulfones
Ganesh C. Nandi
To cite this article: Ganesh C. Nandi (2017) An efficient Cu-catalyzed microwave-
assisted synthesis of diaryl sulfones, Synthetic Communications, 47:4, 319-323, DOI:
10.1080/00397911.2016.1263337
To link to this article: http://dx.doi.org/10.1080/00397911.2016.1263337
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Date: 04 February 2017, At: 04:40

SYNTHETIC COMMUNICATIONS®
2017, VOL. 47, NO. 4, 319–323
http://dx.doi.org/10.1080/00397911.2016.1263337
An efficient Cu-catalyzed microwave-assisted synthesis
of diaryl sulfones
Ganesh C. Nandi
Organic Chemistry Section, Chemical Science and Technology Division, CSIR – National Institute for
Interdisciplinary Science and Technology, Trivandrum, India
ABSTRACT
ARTICLE HISTORY
Received 28 September
2016
An efficient and microwave-assisted simple protocol for the synthesis
of symmetrical/asymmetrical diaryl sulfones through the Cu(II)-
catalyzed reaction of sodium salt of sulfinic acid with aryl boronic
acid has been described. Various diaryl sulfones have been
synthesized in very short reaction times with moderate to very good
yields. Additionally, the method is also useful for the synthesis of aryl
vinyl sulfones.
KEYWORDS
Aryl sulfinic acid; boronic
acid; Cu(OTf)2; microwave-
assisted synthesis; sulfones
GRAPHICAL ABSTRACT
Introduction
Sulfones are considered to be an important class of functional group owing to their
presence in broad range of biologically active molecules showing antifungal, antitumor,
antimicrobial, and antibacterial activities.[1] The diaryl sulfones are also acting as inhibitors
of COX-2 and HIV-1 reverse transcriptase.[2] In addition, these are used as synthetic
intermediates in organic synthesis.[3] As a result, plentiful methodologies have been
developed to construct the diaryl sulfones. Among them, the oxidation of sulfides,[4]
treatment of sulfonate esters with Grignard or organolithium reagents,[5] sulfinate–sulfone
rearrangement,[6] and reaction of arene with arene sulfonyl acids/sulfonyl halides are
common.[7] But the limitations of the above methods such as harsh/anhydrous reaction
conditions, lower yields, and restricted functional group compatibility leads to the
development of new improved protocols using the metal catalyzed coupling of aryl sulfonyl
hydrazide/chloride or sodium salt of aryl sulfinic acid with aryl halides.[8a–f] Additionally,
the reactions of sodium salt of aryl sulfinic acid with boronic acids are also described in
very few reports.[8g–m] Despite the fact that these metal-catalyzed protocols provided very
good yields, the main disadvantages of most of these methods are very longer reaction
CONTACT Ganesh C. Nandi
ganeshnandi@gmail.com
Organic Chemistry Section, Chemical Science and Technology
Division, CSIR – National Institute for Interdisciplinary Science and Technology, Trivandrum 695019, India.
Color versions of one or more of the figures in this article can be found online at www.tandfonline.com/lsyc.
1
Supplemental data (the spectral characterization data and copy of H and 13C NMR spectra) can be accessed on the
publisher’s website.
© 2017 Taylor & Francis

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G. C. NANDI
times (12–72 h) with the requirement of high temperature and anhydrous reaction
conditions. Hence, there is a scope of further perfection toward lower reaction time with
very good yields.
Microwave (MW) heating in organic synthesis is well known for its efficiency to reduce
the reaction times and increase the product yields. In this regard, this report describes the
microwave-assisted simple protocol for the synthesis of symmetrical/asymmetrical diaryl
sulfones through the Cu(II)-catalyzed reaction of sodium salt of sulfinic acid with aryl
boronic acids for the first time. Moreover, the new method takes much shorter time than
previously reported methods with boronic acids.
Results and discussion
The optimization process begins with the reaction of sodium benzene sulfinate 1a
(1.5 equiv.) and 4-methylboronic acid 2a (1.0 equiv.) in the presence of the catalyst Cu
(OTf)2 (10 mol%) and ligand 1,10-phenanthroline (20 mol%) in acetonitrile (MeCN) at
120 °C under MW heating. The reaction completed smoothly with 57% of diaryl sulfones
3a in 30 min. To improve the reaction yield, other catalysts such as Cu(OAc)2 and CuBr2
were investigated retaining the same reaction condition (Table 1, entries 2 and 3).
Although Cu(OAc)2 yielded 53% of 3a, CuBr2 furnished only 20% of diaryl sulfone 3a.
The replacement of ligand 1,10-phenanthroline with 2,2′-bipyridyl enhanced the yield to
63% in 30 min (Table 1, entry 4). Consequently, the effects of other solvents such dichlor-
oethane (DCE), H2O, and N,N-dimethylformamide (DMF) were also studied for this
transformation in the presence of catalyst Cu(OTf)2 and ligand 2,2′-bipyridyl. Delightfully,
DCE afforded maximum 73% of diaryl sulfone 3a in 25 min (Table 1, entry 5) and H2O pro-
vided only 32% of 3a (Table 1, entry 6). A complex reaction mixture was obtained in DMF
with trace amount of 3a (Table 1, entry 7). The effort to optimize the catalyst loading revealed
that 20 mol% of Cu(OTf)2 afforded 78% of 3a in 20 min (Table 1, entry 8) and a higher
amount of catalyst (25 mol%) is ineffective in improving the yield (Table 1, entry 9). An
Table 1. Optimization for the formation of sulfonesa.
Entry
Conditions (catalyst: mol%)
Yieldb
1
Cu(OTf)2 (10), 1,10-phenanthroline, MeCN, 120 °C, MW, 30 min
Cu(OAc)2 (10), 1,10-phenanthroline, MeCN, 120 °C, MW, 30 min
CuBr2 (10), 1,10-phenanthroline, MeCN, 120 °C, MW, 30 min
Cu(OTf)2 (10), 2,2′-bipyridyl, MeCN, 120 °C, MW, 30 min
Cu(OTf)2 (10), 2,2′-bipyridyl, DCE, 120 °C, MW, 25 min
Cu(OTf)2 (10), 2,2′-bipyridyl, H2O, 120 °C, MW, 45 min
Cu(OTf)2 (10), 2,2′-bipyridyl, DMF, 120 °C, MW, 30 min
Cu(OTf)2 (20), 2,2′-bipyridyl, DCE, 120 °C, MW, 20 min
Cu(OTf)2 (25), 2,2′-bipyridyl, DCE, 120 °C, MW, 20 min
Cu(OTf)2 (20), 2,2′-bipyridyl, DCE, 140 °C, MW, 20 min
Cu(OTf)2 (20), 2,2′-bipyridyl, DCE, 100 °C, MW, 20 min
Cu(OTf)2 (20), DCE, 120 °C, MW, 45 min
57%
53%
20%
63%
73%
32%
Trace
78%
78%
76%
52%
Trace
2
3
4
5
6
7
8
9
10
11
12
aIn all cases, 1.5 equiv. of sodium benzene sulfinate 1a, 1.0 equiv. of 4-methylboronic acid 2a, and 20 mol% of ligands were
used and the reactions were performed under air.
bIsolated yield.

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Chart 1. Substrate scope for the synthesis of diaryl sulfones.
elevated temperature (140 °C) is delivering the same result as 120 °C, but the yield diminishes
at 100 °C (Table 1, entries 10 and 11). A control experiment without ligand provided only
traces of product with unreacted reactants after 45 min (Table 1, entries 12). So, the best
result was obtained with 20 mol% of Cu(OTf)2, 2,2′-bipyridyl (20 mol%), in DCE at 120 °C
under MW irradiation (Table 1, entries 8). It must be noted that all the reactions stated above
were performed under air.
The generality of the reaction was investigated using the optimized reaction conditions
(Table 1, entry 8) and the result has been described in Chart 1. The simple cross coupling
reaction has been applied to various arylboronic acids. The electron-withdrawing or
electron-donating substituents on the arylboronic acids are equally effective for this
transformation. The presence of -methyl, -bromo, and -fluoro group at various points of
aryl boronic acid does not affect the product formation (Chart 1, 3a, c, f, j, k). The benzoyl
group-substituted aryl boronic acids are also well tolerated for this sulfonylation process
and provided the corresponding sulfone in very good yields (Chart 1, 3d, e). The
benzofused boronic acid, i.e., 2-naphthyl boronic acid/1-naphthyl boronic acids reacts
smoothly affording the corresponding sulfones (Chart 1, 3 h, i, l, m) in very good yield.
Sulfones synthesized from the formyl group-substituted boronic acids were obtained in
good yield (Chart 1, 3g, n). In addition to the monosubstituted aryl boronic acid, also
the bulky trisubstituted boronic acid works well for the transformation (Chart 1, 3j).
Furthermore, effectiveness of this protocol was also successfully examined with the vinyl
boronic acid (Chart 1, 3o).
Conclusion
In conclusion, an efficient, MW-assisted Cu(II)-catalyzed cross coupling technique has
been developed for the synthesis of diaryl sulfones through the reaction of boronic acids
and sodium salt of sulfinic acids. In addition, the method is also applicable for the synthesis
of aryl vinyl sulfones. The main advantage of this method is that it takes very short time for

322
G. C. NANDI
completion with very good yields. The substituents’ compatibility, moderate to very good
yields, clean reactions are also the attractive factors for this protocol.
Experimental section
General
All the starting material and catalysts were purchased from various suppliers and used as
1
received. The H NMR spectra were recorded on Bruker AMX-500 spectrophotometer
operating at 500 MHz. HRMS were recorded on Thermo Scientific Exactive Mass
Spectrometer. Anton Paar Synthos 3000 Microwave reaction system was used to perform
these reactions. Melting points were recorded on a Stuart apparatus and were uncorrected.
General procedure for the synthesis of diaryl sulfones
Aryl boronic acid (0.3 mmol), sodium salt of aryl sulfinic acid (1.5 equiv.), 2,2′-bipyridyl (20
mol%), and Cu(OTf)2 were placed in a microwave vial containing 4 mL of dichloroethane.
The reaction mixture was then irradiated in MW (power 600 W, 120 °C) for 20–30 min.
After completion, water was added to reaction mixture and extracted with dichloromethane
(2 � 10 mL). The organic layer was then dried (Na2SO4), evaporated, and purified with
column chromatography using 7–10% of EtOAc in hexane as eluent.
Acknowledgments
Ganesh C. Nandi is grateful to the DST-INSPIRE for INSPIRE Faculty Fellowship and Research
Grant (GAP-135739). The author is also thankful to Dr. K. V. Radhakrishnan and Dr. V. Nair of
CSIR-NIIST and their team members for allowing to use their laboratory facilities and chemicals
for this research. The author also acknowledges the effort given by Ms. Nayana, UG student, for this
work.
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