Iodine-catalyzed three-component oxysulfenylation of alkenes with sulfonyl hydrazides and alcohols

Article abstract of DOI:10.1039/c3cc48961b

An unprecedented three-component oxysulfenylation reaction of alkenes with sulfonyl hydrazides and alcohols has been developed in the presence of 20 mol% iodine to give a range of structurally diverse β-alkoxy sulfides in good to excellent yields. The Royal Society of Chemistry.

Full text of DOI:10.1039/c3cc48961b

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Iodine-catalyzed three-component
oxysulfenylation of alkenes with sulfonyl
hydrazides and alcohols†
Fu-Lai Yang,a Fu-Xiang Wang,a Ting-Ting Wang,a Yi-Jie Wanga and Shi-Kai Tian*ab
Cite this: Chem. Commun., 2014,
50, 2111
Received 24th November 2013,
Accepted 23rd December 2013
DOI: 10.1039/c3cc48961b
www.rsc.org/chemcomm
An unprecedented three-component oxysulfenylation reaction of organic halides with sulfonyl hydrazides.10 In contrast to many
alkenes with sulfonyl hydrazides and alcohols has been developed other sulfenylating agents, sulfonyl hydrazides are readily acces-
in the presence of 20 mol% iodine to give a range of structurally sible solids and compatible with moisture. Prompted by this
diverse b-alkoxy sulfides in good to excellent yields.
background together with our interest in developing new multi-
component reactions,11 we envisioned that simple sulfonyl
Among many of the synthetic transformations of alkenes, hydrazides could act as sulfenylating agents to attack alkenes
1,2-difunctionalization of carbon–carbon double bonds consti- to form thiiranium ion (episulfonium ion) intermediates, which
tutes one of the most powerful methods for the introduction of would be opened up by external alcohols to yield b-alkoxy
functional groups into target compounds. In this regard, the sulfides (eqn (1)).1 Importantly, the proposed three-component
oxysulfenylation of alkenes has emerged as an ideal strategy for oxysulfenylation reaction of alkenes with sulfonyl hydrazides
the synthesis of b-alkoxy sulfides, which serve as versatile and alcohols was expected to generate water and molecular
building blocks in chemical synthesis.1 While several types of nitrogen as environmentally benign byproducts.9b
sulfenylating agents, such as sulfenyl halides,2 sulfenamides,3
sulfenate esters,4 disulfides,5 dimethyl(methylthio)sulfonium
(1)
salts,6 and methyl(bismethylthio)sulfonium salts,7 have been
identified for the two- and three-component oxysulfenylation of
alkenes, many of them are not amenable to preparation and
To test our hypothesis, sulfonyl hydrazide 1a, styrene (2a),
handling. Moreover, previously reported oxysulfenylation reactions and ethanol (3a) were subjected to our previously reported
of alkenes frequently require excess sulfenylating agents, suffer conditions for the sulfenylation of indoles, that is, with iodine
from a narrow substrate scope, and/or yield byproducts unfriendly as the catalyst in ethanol at 70 1C.9b While the desired three-
to the environment. Thus, it would be highly desirable to explore component reaction proceeded to give b-alkoxy sulfide 4a as a
new sulfenylating agents for the oxysulfenylation of alkenes, parti- single regioisomer, the yield was only 34% (Table 1, entry 1). To
cularly in a three-component manner, which would exhibit higher improve the yield, we screened a range of common organic
efficiency relative to the sequential synthesis of the same targets by solvents and found that the use of 1,2-dichloroethane led to the
conventional bimolecular reactions.8
formation of b-alkoxy sulfide 4a as a single regioisomer in 88%
As part of our efforts in exploring new chemistry of hydrazine yield (Table 1, entry 7). Nevertheless, the yield decreased
derivatives,9 we recently reported the use of sulfonyl hydrazides dramatically when replacing iodine with N-iodosuccinimide
as sulfenylating agents in a sulfenylation reaction of indoles.9b (NIS)12 or Bu4NI, reducing the catalyst loading, or decreasing
A few months later Singh and co-workers reported a hydrothiola- the temperature (Table 1, entries 9–12).
tion reaction of terminal alkynes and a sulfenylation reaction of
Under the optimized reaction conditions, a range of aryl-
and alkylsulfonyl hydrazides smoothly reacted with arylethenes
and alcohols to give structurally diverse b-alkoxy sulfides in
good to excellent yields with extremely high regioselectivity
(Table 2). It is noteworthy that both electron-withdrawing and
electron-donating groups were successfully introduced into the
aromatic rings of the products by employing the sulfonyl
hydrazides or the arylethenes bearing such groups. While
primary and secondary alcohols could serve as suitable oxygen
a Department of Chemistry, University of Science and Technology of China, Hefei,
Anhui 230026, China. E-mail: tiansk@ustc.edu.cn; Fax: +86-551-6360-1592;
Tel: +86-551-6360-0871
b Key Laboratory of Synthetic Chemistry of Natural Substances, Shanghai Institute
of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China
† Electronic supplementary information (ESI) available: Experimental proce-
dures, characterization data, and copies of 1H NMR and 13C NMR spectra. See
DOI: 10.1039/c3cc48961b
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Table 1 Optimization of reaction conditionsa,b
1a and ethanol (3a) gave a 64 : 36 mixture of b-alkoxy sulfides 4q
and 4q0 (eqn (2)).
Entry
Catalyst (mol%)
Solvent
Temp. (1C)
Yieldc (%)
(2)
1
2
3
4
5
6
7
8
I2 (20)
I2 (20)
I2 (20)
I2 (20)
I2 (20)
I2 (20)
I2 (20)
I2 (20)
NIS (40)
Bu4NI (40)
I2 (10)
I2 (20)
EtOH
DMSO
DMF
MeCN
EtOAc
Dioxane
DCE
Toluene
DCE
DCE
70
70
70
70
70
70
70
70
70
70
70
50
34
0
0
Trace
Trace
79
88
82
While the three-component reaction failed to proceed with
acyclic 1,2-disubstituted and more highly substituted alkenes,
such as (E)-stilbene and 2-methyl-1-phenyl-1-propene, cyclohex-
ene (2g) was demonstrated to serve as a suitable substrate
(eqn (3)). Moreover, the desired product, b-alkoxy sulfide 4r,
was obtained in 74% yield as a single stereoisomer with trans
9
67
Trace
51
10
11
12
DCE
DCE
47
a
Reaction conditions: sulfonyl hydrazide 1a (0.20 mmol), alkene 2a configuration. This result lends substantial support to the
(0.24 mmol), alcohol 3a (50 mL), catalyst (20 or 40 mol%), solvent
generation of a thiiranium ion intermediate during the reaction
(see below). In contrast, the reaction with 1,1-diphenylethene
b
(0.50 mL), 70 or 50 1C (oil bath), 16 h. In all cases compound 4a
was obtained as a single regioisomer. Isolated yield.
c
(2h) did not give the corresponding b-alkoxy sulfide at all under
the same conditions. Instead, another reaction pathway was
established to give vinyl thioether 5a in 86% yield (eqn (4)).
Table 2 Three-component oxysulfenylation of arylethenes with sulfonyl
hydrazides and alcoholsa,b
(3)
Entry 1, R1
2a–e, R2
3, R
4a–p Yieldc (%)
1
2
3
4
5
6
7
8
1a, 4-MeC6H4
1b, Ph
1c, 4-MeOC6H4 2a, Ph
1d, 4-FC6H4
1e, 4-BrC6H4
1f, 4-IC6H4
2a, Ph
2a, Ph
3a, Et
3a, Et
3a, Et
3a, Et
3a, Et
3a, Et
3a, Et
3a, Et
3a, Et
3a, Et
3a, Et
3a, Et
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
88
85
71
82
74
76
61
75
72
91
90
63
81
85
94
77
(4)
2a, Ph
2a, Ph
2a, Ph
2a, Ph
When the alkene was tethered with a hydroxy group,
the corresponding oxysulfenylation proved to be useful
for the formation of a functionalized heterocycle. For example,
2-allylphenol (2i) was treated with sulfonyl hydrazide 1a and
20 mol% iodine to give 2,3-dihydrobenzofuran 4s in 87%
yield (eqn (5)).
1g, 3-O2NC6H4
1h, 2,5-Cl2C6H3 2a, Ph
9
1i, 2-naphthyl
1j, (CH2)7Me
1a, 4-MeC6H4
1a, 4-MeC6H4
1a, 4-MeC6H4
1a, 4-MeC6H4
1a, 4-MeC6H4
1a, 4-MeC6H4
2a, Ph
2a, Ph
2b, 4-ClC6H4
2c, 4-NCC6H4
2d, 2-naphthyl 3a, Et
2e, 1-naphthyl 3a, Et
10
11
12
13
14
15
16
2a, Ph
2a, Ph
3b, nBu 4o
i
(5)
3c, Pr
4p
a
Reaction conditions: sulfonyl hydrazide 1 (0.20 mmol), alkene 2
(0.24 mmol), alcohol 3 (50 mL), iodine (20 mol%), DCE (0.50 mL),
b
70 1C (oil bath), 16 h. No regioisomer was detected by 1H NMR
In sharp contrast, treatment of TsNHNHCOPh (6a), an
N0-substituted sulfonyl hydrazide, with styrene (2a), ethanol
(3a), and 20 mol% iodine did not give b-alkoxy sulfide 4a at all.
This result suggests that the NHNH2 group is essential for the
c
spectroscopic analysis of the crude product. Isolated yield.
nucleophiles, the reaction was not applicable to bulky alcohols sulfonyl hydrazide to serve as an effective sulfenylating agent in
such as tert-butyl alcohol probably because of steric hindrance. the three-component oxysulfenylation reaction.
As demonstrated by the results summarized in Table 2, the
reaction tolerated a variety of functional groups such as alkoxy, to decompose in ethanol to give disulfide 7a, sulfonothioate 8a,
fluoro, chloro, bromo, iodo, nitro, and nitrile groups.
sulfinic acid 9a, and sulfinate ester 10a (eqn (6)).9b Each of
Sulfonyl hydrazide 1a was demonstrated by previous studies
A few other types of alkenes were examined in their three- these decomposition products of sulfonyl hydrazide 1a was
component oxysulfenylation with sulfonyl hydrazides and treated with styrene (2a), ethanol (3a), and 20 mol% iodine, and
alcohols under the standard reaction conditions. In sharp b-alkoxy sulfide 4a was obtained in a yield ranging from 0 to
contrast to arylethenes, poor regioselectivity was observed in 40%, which is much lower than that for the corresponding
the reaction with alkylethenes. For example, the iodine- reaction with sulfonyl hydrazide 1a (88%, Table 2, entry 1).
catalyzed oxysulfenylation of alkene 2f with sulfonyl hydrazide These results indicate that it is unlikely for such decomposition
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According to the above experimental results and previous
relevant studies,1,5h,9b we propose the major reaction pathway
depicted in Scheme 1 for the iodine-catalyzed three-component
oxysulfenylation of alkenes with sulfonyl hydrazides and
alcohols. Sulfonyl hydrazide 1 reacts with iodine to yield
sulfenyl iodide 12,9b electrophilic addition of which to alkene
2 gives thiiranium ion 11.5h,13 Subsequently, ring-opening of
thiiranium ion 11 (R4 = H) with alcohol 3 results in the
formation of b-alkoxy sulfide 4, and the regioselectivity is
determined by the steric and electronic properties of the R2
and R3 groups.1,5h When a 1,1-disubstituted alkene serves as
the substrate, thiiranium ion 11 (R3 = H) is bulky and prefers to
eliminate HI to give vinyl thioether 5. In these steps, iodine has
been converted to HOI and HI, the two of which react to give
water and regenerate iodine to continue the catalytic cycle.
In summary, we have developed, for the first time, an
efficient three-component oxysulfenylation reaction of alkenes
with sulfonyl hydrazides and alcohols. In the presence of 20 mol%
iodine, a range of aryl- and alkylsulfonyl hydrazides smoothly
reacted with alkenes and alcohols to give structurally diverse
b-alkoxy sulfides in good to excellent yields. It is noteworthy that
the reaction tolerated a variety of functional groups such as
alkoxy, fluoro, chloro, bromo, iodo, nitro, and nitrile groups and
that water and molecular nitrogen were generated as environmen-
tally benign byproducts. Moreover, a plausible major reaction
pathway involving thiiranium ion intermediates has been
proposed for the three-component oxysulfenylation reaction.
We are grateful for the financial support from the National
Natural Science Foundation of China (21232007 and 21172206)
and the National Key Basic Research Program of China
(2014CB931800).
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12 The reaction mixture turned purple, and it suggested that iodine
was generated from NIS.
13 Electrospray ionization (ESI) mass spectrometric analysis of
the iodine-catalyzed reaction mixture of sulfonyl hydrazide 1a,
styrene (2a), and ethanol (3a) permitted us to assign thiiranium
ion 11a (R1 = 4-MeC6H4, R2 = R3 = H, R4 = Ph) according to the high
resolution mass data [HRMS (ESI) calcd for C15H15S+ 227.0889,
found 227.0890].
Notes and references
1 C. M. Rayner, in Organosulfur Chemistry: Synthetic Aspects, ed. P. Page,
Academic Press, London, 1995, p. 89.
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