Tetrabutylammonium iodide catalyzed allylic sulfonylation of α-methyl styrene derivatives with sulfonylhydrazides

Article abstract of DOI:10.1039/c2cc36960e

Sulfonyl radicals generated from sulfonylhydrazides by the Bu ₄NI-tert-butyl hydroperoxide (TBHP) catalysis system underwent addition to a variety of α-methyl styrene derivatives to give the corresponding allylic sulfones. This selective allylic sulfonylation is metal-free, operationally simple, and environmentally friendly. The Royal Society of Chemistry 2012..

Full text of DOI:10.1039/c2cc36960e

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COMMUNICATION
Tetrabutylammonium iodide catalyzed allylic sulfonylation of a-methyl
styrene derivatives with sulfonylhydrazidesw
Xiaoqing Li,* Xiangsheng Xu and Can Zhou
Received 25th September 2012, Accepted 2nd November 2012
DOI: 10.1039/c2cc36960e
Sulfonyl radicals generated from sulfonylhydrazides by the Bu4NI–
tert-butyl hydroperoxide (TBHP) catalysis system underwent
addition to a variety of a-methyl styrene derivatives to give the
corresponding allylic sulfones. This selective allylic sulfonylation
is metal-free, operationally simple, and environmentally friendly.
Table 1 Optimization of reaction conditionsa
Entry 1a/2a
TBHP (eq.) Solvent Temp (1C) Yieldb (%)
The construction of highly valuable functionalized allylic
compounds represents a highly desirable goal and long-term
challenge. The well-known Tsuji–Trost reaction,1 a palladium-
catalysed allylic substitution reaction, is one versatile and reliable
methodology which has been widely applied in the synthesis of
natural products and biologically active compounds.2 A drawback
of this reaction is the necessity to use prefunctionalized allylic
compounds, such as allyl acetates and allyl bromides, thus adding
steps towards the formation of desired products. Hence, the direct
introduction of a new functionality via direct allylic C–H bond
activation has drawn much attention in recent years.3 Although
several transition metal catalysts have proven to be highly effective
in such direct functionalization processes,4,5 the development of
new, cost-effective, and environmentally benign metal-free catalysis
processes remains a significant challenge.6
1
2
3
4
1 : 1.5
1 : 1.5
1 : 1.5
1 : 1.2
3
3
3
2
MeCN
EtOAc
MeCN
MeCN
80
75
70
80
74
51
57
74
a
Reaction conditions: 0.5 mmol of a-methylstyrene (1a), TsNHNH2
(2a), 20 mol% TBAI, TBHP (70% aqueous solution) in 2.0 mL of
b
solvent for 20 h. Isolated yield.
thermolysis or photolysis of sulfonyl chlorides and iodides in the
presence or absence of copper catalysts to alkenes followed by
dehydrohalogenation was also reported.11 Recently, Taniguchi
et al. have developed an environmentally friendly method for the
formation of radicals from hydrazine compounds with iron
catalysts and air.12 The only byproduct in this process is
molecular nitrogen. Herein, we wish to report a new metal-free
allylic sulfonylation based on radical addition employing TBAI
and TBHP.
Tetrabutylammonium-iodide (TBAI) has recently emerged as a
promising alternative as a catalyst for functionalization of C–H
bonds due to its low cost, low toxicity, and the mild reaction
conditions.7 The postulated tert-butoxyl and tert-butylperoxy
radical intermediates generated from TBAI catalyzed TBHP
(tert-butyl hydroperoxide) decomposition7b–e enabled numerous
important organic transformations such as C–O7c,d and C–N7b,e
bond formation. In particular, Wan et al. elegantly utilized the
TBAI–TBHP system for the synthesis of allylic esters via allylic
C–H oxidation and selective coupling of acyloxy and allylic
radicals.8
We initiated this work with the anticipation that the
generation of sulfonyl radicals from sulfonylhydrazides can
also be achieved with the TBAI–TBHP oxidative system. For
our initial experiments, 1.5 equivalents of p-toluenesulfonyl-
hydrazide (TsNHNH2) 2a were chosen as a radical precursor
and treated with one equivalent of a-methyl styrene 1a using
20 mol% of TBAI as a catalyst and 3 equivalents of TBHP
(70 wt% in water) as an external oxidant in MeCN at 80 1C.
Gratifyingly, the desired allylic sulfone 3aa was obtained in
74% yield (Table 1, entry 1). In contrast, only 51% of the
desired product is achieved in EtOAc (Table 1, entry 2).
A lower reaction temperature led to a significantly lower yield
of 3aa (Table 1, entry 3), whereas no effect on yield was
observed with lower amounts of TsNHNH2 and TBHP
(Table 1, entry 4). No formation of other oxidation side-products
was observed under the standard reaction conditions.
Allylic sulfones are exceptionally versatile building blocks in
organic synthesis.9 Generally, they are synthesized by Tsuji–Trost
reaction of a sulfinate anion with allyl acetates and allyl
bromides.10 The addition of sulfonyl radicals produced by the
College of Chemical Engineering and Materials Science, Zhejiang
University of Technology, Hangzhou 310014, P. R. China.
E-mail: xqli@zjut.edu.cn; Fax: +86 571 88320799;
Tel: +86 571 88320799
w Electronic supplementary information (ESI) available: Detailed
experimental procedures and characterization data for compounds 3.
See DOI: 10.1039/c2cc36960e
The allylic sulfonylations of a variety of substituted
a-methyl styrenes with TsNHNH2 were then examined under
the standard reaction conditions, and representative results are
summarized in Table 2. The results indicated that a wide range
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Table 3 Scope of the reaction with styrene derivativesa
Table 2 Scope of the reaction with a-methyl styrenea
Entry
Ar
Product 3
Yieldb (%)
Entry
Alkene 1
Product 3
Yieldb (%)
1
2
3
4
5
6
7
8
C6H5, 1a
3aa
3ba
3ca
3da
3ea
3fa
3ga
3ha
3ia
74
62
50
60
70
75
64
68
57
21
73
70
61
p-MeC6H4, 1b
o-MeC6H4, 1c
p-MeOC6H4, 1d
m-MeOC6H4, 1e
p-FC6H4, 1f
p-ClC6H4, 1g
p-BrC6H4, 1h
m-BrC6H4, 1i
p-CF3C6H4, 1j
3,4-DiMeOC6H3, 1k
1-Naphthyl, 1l
2-Thiophenyl, 1n
1
2
n = 2, 1n
n = 1, 1o
3na
3oa
90
78
9
10
11
12
13
3ja
3ka
3la
3
71 (Z : E = 3 : 1c)
3ma
a
Reaction conditions: 0.5 mmol of a-methylstyrene (1a), 0.6 mmol of
TsNHNH2 (2a), 20 mol% TBAI, 2 equiv. of TBHP (70% aqueous
4
37
b
solution) in 2.0 mL of MeCN at 80 1C for 20 h. Isolated yield.
a
Reaction conditions: 0.5 mmol of alkenes (1), 0.6 mmol of
TsNHNH2 (2a), 20 mol% TBAI, 2 equiv. of TBHP (70% aqueous
of substituted groups, such as methyl, methoxyl, fluoro,
chloro, bromo, trifluoromethyl and naphthyl, were well tolerated
and the desired sulfones were produced in moderate to
good yields (Table 2, entries 1–12). Heteroaryl species such as
thiophenyl also underwent the desired reaction to give the
corresponding product in 61% yield (Table 2, entry 13).
b
c
solution) in 2.0 mL of MeCN at 80 1C for 20 h. Isolated yield. The
ratio of isomers was determined by 1H NMR spectroscopy of the
isolated product.
system reported by Wan et al.,8 the migration of the carbon–
carbon double bond also happened. However, different
mechanisms were proposed for these selective allylic C–H
bond functionalization processes. An iodo(III)cyclopropane
mechanism was involved in the former reaction, while the
radical coupling pathway was postulated in the latter one.
Several control experiments were conducted to elucidate the
mechanism. Firstly, TEMPO, a radical-trapping reagent, was
introduced into the reaction mixture and the formation of the
desired sulfone was completely suppressed (Scheme 2, eqn (1)),
indicating that the reaction presumably underwent a radical
pathway. Then, a-methyl styrene alone was treated with
TEMPO under the standard conditions, and no adduct of
TEMPO and the allylic radical was isolated (Scheme 2,
eqn (2)). This result implied that the reaction pathway may
be not followed in catalysis involving allylic radicals.13 Thus,
selective coupling of sulfonyl and allylic radicals should be
excluded. At last, the coupling of styrene with TsNHNH2
Next, the reaction was examined with phenyl and p-bromo-
phenyl substituted sulfonylhydrazides 2b–c, which were
treated with a-methylstyrene 1a under the standard reaction
conditions (Scheme 1). The sulfonylation worked smoothly,
leading to the formation of the corresponding sulfones
3ab and 3ac in 61% and 60% yields, respectively.
Finally, a series of other terminal alkenes were investigated.
Both exocyclic and noncyclic styrene derivatives underwent
the allylic sulfonylation, leading to the formation of sulfones
in moderate to excellent yields (Table 3). Notably, the reaction
shows high regioselectivity. In all cases, the sulfonylations
took place at the terminal carbon of double bonds with the
migration of the double bonds. Thus, a-ethyl styrene resulted
in the formation of two isomeric double bonds of sulfone 3pa
in 71% yield (Z : E = 3/1) (Table 3, entry 3). a-Benzyl styrene
1q was also a compatible substrate for this transformation and
gave rise to a single Z isomer of stilbene 3qa in 37% yield
(Table 3, entry 4), perhaps as a result of steric hindrance. But
internal alkenes such as cyclohexene failed in the reaction to
give the desired allylic sulfone due to the steric effect.12b
Surprisingly, attempts to carry out the corresponding allylic
sulfonylation of vinylcyclohexane and allylbenzene were also
unsuccessful. It is worth mentioning that in allylic amination
employing a hypervalent iodine(III) reagent reported by Muniz
et al.6 and allylic esterification employing the TBAI–TBHP
Scheme 1 Reactions of various sulfonylhydrazides.
Scheme 2 Investigation into the reaction mechanism.
Chem. Commun., 2012, 48, 12240–12242 12241
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Scheme 3 Proposed preliminary mechanisms.
could also take place to form sulfone 4, albeit in lower yield
(Scheme 2, eqn (3)). Hence, the radical addition pathway is
most likely involved.11
On the basis of results described above and in previous
reports,8,12 a plausible mechanism is proposed (Scheme 3).
Initially, TBHP decomposes to generate the tert-butoxyl and
tert-butylperoxy radicals with the assistance of the iodide
anion. These radicals subsequently abstract hydrogen atoms from
sulfonylhydrazides to generate sulfonyl radicals with the release of
molecular nitrogen. The addition of resultant sulfonyl radicals to
alkenes and subsequent abstraction of the resultant radical inter-
mediate by tert-butoxyl or tert-butylperoxy radicals affords
sulfones 3. One should note that the highly selective H-abstraction
of the radical intermediate in this reaction is unexpected as it was
reported that the C-centered radicals generated by radical
addition can be trapped with tert-butylperoxyl radicals.14
In summary, we have developed a new metal-free direct
allylic sulfonylation reaction, in which the generation of
sulfonyl radicals from sulfonylhydrazides with the
TBAI–TBHP system was involved. The use of cheap and
nontoxic TBAI as a catalyst and the elimination of molecular
nitrogen as a byproduct during the sulfonyl radicals genera-
tion make this selective allylic sulfonylation environmentally
friendly. Investigation of a detailed mechanism and radical
reactions based on the TBAI–TBHP system catalyzed radical
species generation from other hydrazine compounds is under-
way in our laboratory.
8 E. Shi, Y. Shao, S. Chen, H. Hu, Z. Liu, J. Zhang and X. Wan,
Org. Lett., 2012, 14, 3384.
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13 It was reported that an adduct of TEMPO and the allylic radical
was isolated when allylbenzene was treated under the similar
reaction conditions, see ref. 8.
We thank the National Natural Science Foundation of
China (21102130) for financial support.
Notes and references
1 For selected reviews, see: (a) B. M. Trost and M. L. Crawley,
Chem. Rev., 2003, 103, 2921; (b) B. M. Trost and D. L. V. Vranken,
Chem. Rev., 1996, 96, 395.
14 W. Liu, Y. Li, K. Liu and Z. Li, J. Am. Chem. Soc., 2011,
133, 10756.
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This journal is The Royal Society of Chemistry 2012