Copper-Catalyzed Aerobic Oxidative Reaction of Sulfonyl Hydrazides with Alcohols: An Easy Access to Sulfinates

Article abstract of DOI:10.1002/asia.201501262

A Cu-catalyzed aerobic oxidative reaction between sulfonyl hydrazides and alcohols has been developed. In this reaction, sulfonyl hydrazides act as the sulfinic acid precursors to react with alcohols, resulting in sulfinic esters with up to 72 % yield. This catalytic system tolerates a wide range of sulfonyl hydrazide substrates, and represents a new strategy for the transformation of readily available sulfonyl hydrazides.

Full text of DOI:10.1002/asia.201501262

DOI: 10.1002/asia.201501262
Communication
Oxidation
Copper-Catalyzed Aerobic Oxidative Reaction of Sulfonyl
Hydrazides with Alcohols: An Easy Access to Sulfinates
Bingnan Du,[a] Zan Li,[a] Ping Qian,[a] Jianlin Han,*[a, b] and Yi Pan*[a, b]
Abstract: A Cu-catalyzed aerobic oxidative reaction be-
tween sulfonyl hydrazides and alcohols has been devel-
oped. In this reaction, sulfonyl hydrazides act as the sulfin-
ic acid precursors to react with alcohols, resulting in sulfin-
ic esters with up to 72% yield. This catalytic system toler-
ates a wide range of sulfonyl hydrazide substrates, and
represents a new strategy for the transformation of readily
available sulfonyl hydrazides.
Development of novel transition-metal-catalyzed reactions for
construction of organic molecules has gained great attention
in organic chemistry during the past decades.[1] Several transi-
tion metals have been explored as catalysts for such reactions,
among which, the copper-catalyzed reaction has become one
of the most active areas, because copper is cheap, has low tox-
icity, and high natural abundance transition metal compared
to palladium or other noble metals.[2,3] Oxygen as the simplest
and cleanest oxidant can be used to oxidize the low oxidation
states of copper in a number of catalytic reactions. Actually,
compatible with molecular oxygen, the reactions with copper
Scheme 1. The transformation of sulfonyl hydrazides.
catalysts have been used as powerful tools in current organic
synthesis.[4]
Sulfonyl hydrazides belong to an important class of organic
intermediates. In the past decades, the reducibility[5] and nucle-
ophilicity of sulfonyl hydrazides through release of hydrazide[6]
have been well explored. Very recently, sulfonyl hydrazides
were developed as a versatile coupling agent for CÀC and CÀS
bonds formation. One of the transformations is used as an aryl
source for the palladium-catalyzed coupling reactions with va-
rieties of C(sp2)ÀH bonds, and these elegant works have been
reported by the research groups of Tian, Kwong, Jiang, You
and others (Scheme 1a).[7] The second is the catalytic sulfura-
tion reaction for the preparation of thioethers, which was inde-
pendently reported by the research groups of Tian, Singh,
Jiang, Kumaraswamy, Xiang and others (Scheme 1b).[8] Finally,
sulfonyl hydrazides can be converted into a sulfonyl radical,
which undergoes a radical addition[9] or coupling reactions[10]
to unsaturated CÀC bonds (Scheme 1c)
Despite the elegant studies that have been developed on
sulfonyl hydrazides, to the best of our knowledge, there is no
report on the conversion of sulfonyl hydrazides into sulfinic
acid that is followed by esterification with alcohols to prepare
sulfinic esters. It should be mentioned that there are few suc-
cessful examples on the esterification of sulfinic acids because
of the instability of sulfinic acids (Scheme 1d).[11] Herein, we
report a copper-catalyzed oxidative reaction of sulfonyl hydra-
zides with alcohols to afford sulfinic esters as products
(Scheme 1e). This oxidative reaction could be carried out
under mild conditions with stable sulfonyl hydrazides as sulfin-
ic acid precursors, affording sulfinates in moderate-to-good
yields; this provides a new and easy way for the preparation of
sulfinic esters.
[a] B. Du, Z. Li, P. Qian, Dr. J. Han, Prof. Dr. Y. Pan
School of Chemistry and Chemical Engineering
State Key laboratory of Coordination Chemistry
Nanjing University
Nanjing, 210093 (P. R. China)
E-mail: hanjl@nju.edu.cn
yipan@nju.edu.cn
[b] Dr. J. Han, Prof. Dr. Y. Pan
MaAnShan High-Tech Research Institute of Nanjing University
MaAnShan, 238200 (P. R. China)
Our initial studies on this copper-catalyzed process focused
on the reaction between benzenesulfonyl hydrazine (1a) and
methanol (2a) in the presence of Cu(OAc)2 at 708C with O2 as
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/asia.201501262.
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Communication
Table 1. Optimization of reaction condition.[a]
Entry
Catalyst [mol%]
Oxidant
T [8C]
Yield [%][b]
1
2
3
4
5
6
7
8
Cu(OAc)2 (10)
Cu(acac)2 (10)
Cu(OTf)2 (10)
CuBr (10)
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
70
70
70
70
70
70
70
70
70
60
40
25
40
40
40
40
40
40
40
32
14
43
13
27
0
0
0
0
47
56
38
71
trace
26
30
66
trace
0
Cu (10)
Ni(OTf)2 (10)
Ag(OTf)2 (10)
Mg(OTf)2 (10)
In(OTf)3 (10)
Cu(OTf)2 (10)
Cu(OTf)2 (10)
Cu(OTf)2 (10)
Cu(OTf)2 (20)
Cu(OTf)2 (20)
Cu(OTf)2 (20)
Cu(OTf)2 (20)
Cu(OTf)2 (20)
Cu(OTf)2 (20)
–
9
10
11
12
13
14
15
16
17
18
19
O2
PhI(OAc)2
H2O2
m-CPBA
BQ
–
O2
[a] Reaction conditions: 1a (0.25 mmol), 2a (2.0 mL), in the presence of
catalyst for 12 h. [b] NMR yield, CH2Br2 as an internal standard.
Scheme 2. Substrate scope for the copper-catalyzed reactions between
methanol and sulfonyl hydrazides. Reaction conditions: 1 (0.25 mmol), 2a
(2.0 mL), Cu(OTf)2 (20 mol%), 408C, O2 (balloon), 12 h; yields of isolated
products based on 1.
an oxidant. To our delight, the reaction proceeded and the ex-
pected sulfinate 3aa was obtained in 32% yield (Table 1,
entry 1). Inspired by this result, various copper salts such as
Cu(acac)2, Cu(OTf)2, CuBr, and Cu0 were tested for this transfor-
mation to improve the yield (Table 1, entries 2–5). Cu(OTf)2 was
found to be the best, and the target product 3aa was afforded
in 43% yield (Table 1, entry 3). To further optimize the reaction
conditions, other trifluoromethanesulfonate salts such as
Ni(OTf)2, Ag(OTf)2, Mg(OTf)2, and In(OTf)2 were investigated in
this reaction (Table 1, entries 6–9). However, they did not show
any catalytic activity, and no expected product was formed.
Then, the reaction time and the amount of catalyst were inves-
tigated, and we found that in the presence of 20% mol of
Cu(OTf)2 at 408C for 12 h, the desired product 3aa could be
obtained in the highest yield (71%; Table 1, entry 13). Finally,
other oxidants, such as meta-chloroperbenzoic acid (m-CPBA),
H2O2, or 1,4-benzoquinone (BQ), were used instead of O2, how-
ever, the reaction was not improved (Table 1, entries 15–17).
Almost no desired product was obtained when iodosobenzene
diacetate (PhI(OAc)2) was employed as the oxidant (Table 1,
entry 14). Further optimization of the conditions showed that
the reaction could not proceed without the use of O2 as oxi-
dant (Table 1, entry 18) or without using Cu(OTf)2 as a catalyst
(Table 1, entry 19).
tron-donating groups on the aromatic ring, such as para-Me
(1b), para-OMe (1c), and para-tBu (1d), worked well in these
reactions, resulting in good yields (68–72%, 3ba–3da). Sulfo-
nyl hydrazides substituted by electron-withdrawing groups (F,
Br, Cl and I) could also been tolerated in this reaction with
lower chemical yields (3ea–3ja). It should be mentioned that
halo substituents on the aromatic ring, in particular, the iodo
group, were difficult to be retained in many transition-metal
catalyzed coupling reactions. It is noteworthy that di- and tri-
substituted aryl sulfonyl hydrazides were also suitable sub-
strates to afford the corresponding products (3ka–3ma). How-
ever, only 11 % yield was achieved in the reaction of tri-isopro-
pyl-substituted sulfonyl hydrazide, mainly because of the high
steric hindrance (3na). Naphthalene-1-sulfonohydrazide and
naphthalene-2-sulfonohydrazide could also be employed as
substrates, thereby generating the corresponding products in
69% and 70% yield, respectively (3oa, 3pa).
To extend the utility of this reaction, different alcohol part-
ners (2b–2g) were investigated (Scheme 3). In the case of eth-
anol (2b) and isopropanol (2c), the reactions gave the desired
product with very poor yields (<10%). The other examined al-
cohols (2d–2g) could work in the current system, affording
the desired product with obvious lower yields compared to
the reactions with methanol. This result clearly discloses that
the steric hindrance has an obvious effect on the reaction.[11a]
To gain insight into this reaction mechanism, an ESI-MS
spectroscopic analysis experiment was carried out on the reac-
With the optimized reaction conditions in hand, we then ex-
amined the substrate scope of this Cu-catalyzed oxidative cou-
pling reaction of methanol with varieties of aryl sulfonyl hydra-
zides (Scheme 2). In general, most of the reactions could pro-
ceed smoothly and afforded the desired sulfinate products in
moderate-to-good yields. In addition, the substrates with elec-
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Scheme 3. Substrate scope for the copper-catalyzed reactions between alco-
hols and sulfonyl hydrazides. Reaction conditions: 1a (0.25 mmol), 2
(2.0 mL), Cu(OTf)2 (20 mol%), 408C, O2 (balloon), 12 h; yields of isolated
products based on 1a.[a] alcohol/toluene=1:9 (2 mL).
Scheme 5. Proposed mechanism.
tion mixture. Fortunately, the benzenesulfinic acid peak was
found in the negative ion mode (see the Supporting Informa-
tion). This positive result strongly suggested that catalytic
cycle might proceed via benzenesulfinic acid as the intermedi-
ate. Then, two key control experiments were performed to
study the reaction mechanism (Scheme 4). Sodium benzenesul-
with methanol to form intermediate E. Finally, the intermediate
E releases Cu(OTf)2 catalyst to give the final product 3aa. It
should be mentioned that sulfinic acid intermediate could also
be oxidized by O2 to give benzenesulfonic acid C at the same
time, which has also been detected by ESI-MS (see the Sup-
porting Information). This might be one of the reasons that ac-
counts for the moderate yields in most cases.
In conclusion, we have demonstrated an unprecedented Cu-
catalyzed oxidative reaction of alcohols with aryl sulfonyl hy-
drazides using oxygen as an oxidant. In this reaction, sulfonyl
hydrazides were used for the first time as sulfinic acid precur-
sors. The reaction tolerates a wide range of sulfonyl hydrazide
substrates that react with alcohols for the direct synthesis of
sulfinic esters with moderate-to-good yields. The mechanism
has been investigated, and discloses that the transformation
proceeds through sulfinic acid as an intermediate. This method
not only enriched the content of sulfonyl hydrazide related
conversions, but also provides a new access to sulfinic esters.
Further investigations of the mechanism and synthetic applica-
tions are currently underway in our group.
Scheme 4. Control experiments.
finate, instead of sulfonyl hydrazide 1a, was used to react with
methanol under the standard reaction conditions. However, no
desired sulfinic ester 3aa was obtained in this reaction
(Scheme 4a). The reaction of benzenesulfinic acid with metha-
nol (Scheme 4b), was performed under the same reaction con-
ditions, and afforded the desired product 3aa in 62% isolated
yield, which further implies that benzenesulfinic acid might be
the active specie in the copper-catalyzed coupling reaction.
Based on the above control experiment results and literature
reports,[6a,8g] a plausible catalytic cycle for the Cu-catalyzed oxi-
dative process has been proposed (Scheme 5). Initially, sulfonyl
hydrazide 1a reacts with copper(II) to give the intermediate A.
Then, the intermediate A undergoes b-hydride elimination af-
fording intermediate B[7a,12] and HCuOTf species, which is trans-
ferred to CuII for the next cycle through aerobic oxidation.
Then, release of N2 from intermediate B affords the key inter-
mediate sulfinic acid C,[8g] which has been detected by ESI-MS
(see the Supporting Information). Sulfinic acid intermediate C
reacts with Cu(OTf)2 resulting in intermediate D, which reacts
Experimental Section
Typical procedure for Cu-catalyzed oxidative coupling reaction:
Benzenesulfonylhydrazine 1a (43.1 mg, 0.25 mmol) and Cu(OTf)2
(18.1 mg, 0.05 mmol) were added to a 25 mL Schlenk tube under
O2, followed by addition of methanol 2a (2.0 mL). The mixture was
stirred at 408C under O2 (1 atm, balloon) for 12 h, then the result-
ing mixture was concentrated by rotary evaporator. The crude
product was purified over a column of silica gel (eluant: petroleum
ether/ethyl acetate 15:1) to afford the desired product 3aa.
Acknowledgements
We gratefully acknowledge the financial support from the Na-
tional Natural Science Foundation of China (Nos. 21102071 and
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Manuscript received: November 17, 2015
Accepted Article published: November 25, 2015
Final Article published: December 3, 2015
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