Dual roles of sulfonyl hydrazides in the catalyst-free sulfonylation of unsaturated benzylic alcohols in water

Article abstract of DOI:10.1039/c7gc01847a

An atom-economical sulfonylation of unsaturated benzylic alcohols in water is described. In this transformation, dual roles of sulfonyl hydrazides serving as both a sulfonyl source and a reductant have been demonstrated, which enabled a facile and green method to synthesize alkyl sulfones from unsaturated benzylic alcohols. Moreover, this approach provides a practical access to deuterated alkanes from the corresponding alkenes by employing the combination of sulfonyl hydrazides and the solvent D₂O.

Full text of DOI:10.1039/c7gc01847a

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Dual roles of sulfonyl hydrazides in the catalyst-free sulfonylation
of unsaturated benzylic alcohols in water
Received 00th January 20xx,
Accepted 00th January 20xx
Kun Xu, Lijun Li, Wen Yan, Yuanyuan Wu, Zhiqiang Wang and Sheng Zhang*
DOI: 10.1039/x0xx00000x
www.rsc.org/
An atom-economic sulfonylation of unsaturated benzylic alcohols
in water is described. In this transformation, dual roles of sulfonyl
hydrazides serving as both sulfonyl source and reductant have
been demonstrated, which enabled a facile and green method to
synthesize alkyl sulfones from unsaturated benzylic alcohols.
Moreover, this approach provides a practical access to deuterated
alkanes from the corresponding alkenes by employing the
combination of sulfonyl hydrazides and the solvent D2O.
Scheme 1 The dual roles of sulfonyl hydrazides in the synthesis of substituted pyrazoles.
Sulfonylation of alcohols as a conventional approach to
construct sulfones typically needs preactivation of hydroxy
group into halide or mesylate.7 To avoid the tedious steps,
direct sulfonylation of alcohols catalyzed by Pd(II) or Fe(III) was
disclosed by Chandrasekhar8 and Sreedhar groups9,
respectively (Scheme 2a). Tian and coworkers also described a
byproduct-catalyzed sulfonylation of benzylic and allylic
alcohols using sulfinyl chlorides as the sulfonylating reagents
(Scheme 2b).10 Promoted by these backgrounds together with
the reported results that sulfonyl hydrazides could serve as
reductants,11 we envisioned that the dual roles of sulfonyl
hydrazides would be achieved for the reaction with
unsaturated alcohols (Scheme 2c). Herein, we report a catalyst
Atom economy is regarded as one of the most important
principles of green chemistry, which generally requires
maximal incorporation of all materials used in the process into
the final product.1 In other words, fully utilizing an organic
reagent in the transformations is the ultimate goal of organic
chemists. Given this requirement in modern organic chemistry,
recent efforts have focused on the exploitation of multiple
functions of a versatile reactant in a single reaction.2 Among
various synthetically useful reagents, sulfonyl hydrazides have
been extensively explored to construct sulfonyl- or sulfenyl-
containing compounds,3-5 which are prevalent in diverse
biologically valued molecules.6 However, in most of these
protocols, sulfonyl hydrazides were always treated as the
sulfonylating or sulfenylating reagents, the functions of
hydrazine moiety in sulfonyl hydrazides were not used
simultaneously. In 2014, the dual functions of sulfonyl
hydrazides was reported by Wan and coworkers in a cobalt-
catalyzed reaction to access fully substituted pyrazoles
(Scheme 1).2a Dispite this advance, the development of new
reactions exploiting the multifunctions of sulfonyl hydrazides
in a green manner is still highly desired.
College of Chemistry and Pharmaceutical Engineering, Nanyang Normal University,
Nanyang, 473061 P. R. China
E-mail: shengzhang@nynu.edu.cn
Electronic Supplementary Information (ESI) available: [details of any
supplementary information available should be included here]. See
DOI: 10.1039/x0xx00000x
Scheme 2 Direct sulfonylation of benzylic alcohols.
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free sulfonylation and simultaneous reduction of unsaturated substrate under the standard conditions, affording the
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benzylic alcohols with sulfonyl hydrazides to furnish a wide corresponding product 3aq in 63% yield. DOI: 10.1039/C7GC01847A
array of alkyl sulfones in water.12 Moreover, this protocol also
provides a practical route to access deuterated alkanes from
Table 2 The scope of sulfonyl hydrazides in the direct sulfonylation.a
the corresponding alkenes with the combination of sulfonyl
hydrazides and the solvent D2O.
Initially, the solvent effect on the direct sulfonylation of
unsaturated alcohol 1a with p-toluene sulfonhydrazide 2a was
investigated. As shown in the Table 1, the protonic solvent
ethanol and water proved to be superior to other solvents
(
3aa). To conduct the reaction in a greener version, the
environmentally benign water was chose as the optimal
solvent. With these optimized conditions identified, the scope
of benzylic alcohols was examined in the direct sulfonylation
reaction (Table 1). Firstly, a range of readily accessible ortho-
hydroxyl substituted homoallylic alcohols were tested. It was
found that the reaction performance is largely independent
from the arene substitution pattern in the substrates. For
instance, electron-rich substituents as well as bromide group
at the aryl group are well tolerated delivering the products
3aa-3fa with moderate to excellent yields. Ortho-amino
substituted substrate also tolerated well to furnish the product
3ga in 87% yield. Changing the hydroxyl group to para position
led to formation of product 3ha in 73% yield. Replacing of
hydroxyl group with dimethyl amino group gave the
corresponding product 3ia in 75% yield.
Table 1 The scope of unsaturated alcohols in the direct sulfonylation. a
a The reaction of 1a (0.5 mmol) with 2 (1 mmol) was performed in water at 120 ºC
for 12 h. The product was isolated by column chromatography.
In order to expand the utility of this methodology,
homopropargyl, allyl and non-allyl alcohols were also tested
under the standard conditions (Scheme 3). For homopropargyl
alcohol
sulfone 3aa in 63% yield; In the case of non-allylic alcohol
the corresponding sulfone was obtained in 71% yield. With
respect to the allyl alcohol , an unexpected reductive
dehydroxy alkane was obtained with 80% yield. This
4, the reaction underwent smoothly to give alkyl
5
,
6
a The reaction of 1 (0.5 mmol) with 2a (1 mmol) was performed in water at 120 ºC
for 12 h. The product was isolated by column chromatography.
7
8
exceptional result might be attributed to the conjugation
effect of the olefin moiety.
Subsequently, we probed the generality of sulfonyl
hydrazides in the reaction with the homoallylic alcohol 1a. As
shown in Table 2, the reaction was tolerant of electronically
and sterically diverse substituents on the phenyl ring, giving
sulfones 3ab-3am in 65-90% yields. The multiple substituted
sulfonyl hydrazides proved to be compatible in this reaction,
providing the desired products 3an and 3ao in 62% and 67%
yields, respectively. Additionally, the fused ring substituted
product 3ap was also readily afforded in 83% yield. It is
noteworthy that aliphatic hydrazide was also a suitable
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subsequent nucleophilic substitution reactiVoienw ArtaicnledOnline
a
2
DOI: 10.1039/C7GC01847A
simultaneous reduction reaction by d -diimide to give final
product d2-3aa
.
Scheme 3 Other types of substrates.
Scheme 5 Plausible reaction pathway for the formation of d2-3aa
To shed light on the reaction mechanism, control
experiments were performed as shown in Scheme 4. First, the
Conclusions
reactant sulfonyl hydrazide was replaced with sulfinic acid
9 to
investigate the possible intermediate in the reaction (Scheme
4a). A direct sulfonylation product 10 was detected without
reduction of the carbon-carbon double bond in the substrate,
even under the hydrogen atmosphere. These results illustrate
that the sulfinic acid is a key intermediate in the sulfonylation
process, while the hydrazine moiety in sulfonyl hydrazide
would play an important role in the reduction process. To
identify the reduction role of sulfonyl hydrazide, deuteration
reaction were subsequently perfomed. When unsaturated
alcohol 1a was reacted with deuterated sulfonyl hydrazide 11
in H2O, product 3aa was obtained in 82% yield (Scheme 4b);
when unsaturated alcohol 1a was reacted with sulfonyl
hydrazide 2a in D2O, deuterated product d2-3aa was obtained
in 81% yield (Scheme 4c). These results may attribute to the
H,D-exchange between the reactive intermediates with water.
In conclusion, dual roles of sulfonyl hydrazide as sulfonyl
source and reductant have been achieved in the reaction with
unsaturated benzylic alcohols in water. The environmental-
benign medium, catalyst-free reaction conditions, and high
atom-economy make this reaction a green and practical
approach to sulfones synthesis. Moreover, this protocol also
provides a straightforward route to access deuterated alkanes
from the corresponding alkenes by using the combination of
sulfonyl hydrazides and the solvent D2O.
Acknowledgements
We are grateful to the Natural Science Foundation of China
(21602119, U1504208), and acknowledged the financial support
from Nanyang Normal University (ZX2017016, QN2017037).
Notes and references
1
(a) B. M. Trost, Science, 1991, 254, 1471; (b) B. M. Trost,
Angew. Chem. Int. Ed., 1995, 34, 259; (c) P. T. Anastas and J.
C. Warner, in Green Chemistry: Theory and Practice, Oxford
University Press, New York, 1998; (d) B. M. Trost, Acc. Chem.
Res., 2002, 35, 695; (e) C.-J. Li and B. M. Trost, Proc. Natl.
Acad. Sci. U. S. A., 2008, 105, 13197. (f) P. T. Anastas and N.
Eghbali, Chem. Soc. Rev., 2010, 39, 301. (g) C.-J. Li and P. T.
Anastas, Chem. Soc. Rev., 2012, 41, 1413.
2
3
4
(a) J. Zhang, Y. Shao, H.-X. Wang, Q. Luo, J.-J. Chen, D.-M. Xu
and X.-B. Wan, Org. Lett., 2014, 16, 3312 (b) H. Bounar, Z.-H.
Liu, L. Zhang, X.-X. Guan, Z.-L. Yang, P.-Q Liao, X.-H. Bi and X.-
Q. Li, Org. Biomol. Chem., 2015, 13, 8723; (c) J.-J. Zhang, Q.-H.
Gao, X. Wu, X. Geng, Y.-D. Wu and A.-X. Wu, Org. Lett., 2016,
18, 1686.
Forming hydrazones and heterocycles, see: (a) Z. Shao and H.
Zhang, Chem. Soc. Rev., 2012, 41, 560; (b) J. Barluenga and C.
Valdés, Angew. Chem. Int. Ed., 2011, 50, 7486; (c) R. O.
Hutchins and M. K. Hutchins, in Comprehensive Organic
Synthesis, Vol. 8 (Eds.: B. M. Trost and I. Fleming), Pergamon,
Oxford, 1991, p. 327.
Scheme 4 Control experiments.
On the basis of the control experiments and the related
report,4a,5a a plausible reaction pathway for the formation of
d2-3aa was proposed (Scheme 5). Initially, the tosylhydrazide is
decomposed into active species sulfinic acid (TsH) and diimide
via an elimination process under high temperature. The in-situ
generated TsH and diimide could readily undergo H,D-
exchange with D2O to give TsD and d2-diimide. Protonation of
Using sulfonyl hydrazides as sulfonyl reagents, see: (a) A.
Deavin and C. W. Rees, J. Chem. Soc., 1961, 4970; (b) T.
Taniguchi, A. Idota and H. Ishibashi, Org. Biomol. Chem.,
2011,
9, 3151; (c) X.-Q. Li, X.-S. Xu and C. Zhou, Chem.
Commun., 2012, 48, 12240; (d) S. Tang, Y. Wu, W.-Q. Liao, R.-
P. Bai, C. Liu and A.-W. Lei, Chem. Commun., 2014, 50, 4496;
alcohol 1a gives intermediate 12
, which undergoes a
This journal is © The Royal Society of Chemistry 20xx
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Page 4 of 5
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Journal Name
(e) K. Xu, V. Khakyzadeh, T. Bury, and B. Breit, J. Am. Chem.
Soc., 2014, 136, 16124; (f) Y.Yang, L. Tang, S. Zhang, X.-F. Guo,
Z.-G. Zha and Z.-Y. Wang, Green Chem., 2014, 16, 4106; (g)
Z.-Z. Chen, S. Liu, W.-J. Hao, G. Xu, S. Wu, J.-N. Miao, B. Jiang,
View Article Online
DOI: 10.1039/C7GC01847A
S.-L. Wang, S.-J. Tu and G.-G. Li, Chem. Sci., 2015, 6, 6654; (h)
G. C. Senadi, B.-C. Guo, W.-P. Hu and J.-J. Wang, Chem.
Commun., 2016, 52, 11410. (i) L. Tang, Y. Yang, L.-X. Wen, X.-
K. Yang and Z.-Y. Wang, Green Chem., 2016, 18, 1224. (j) F.-L.
Yang and S.-K. Tian, Tetrahedron Lett., 2017, 58, 487.
5
Using sulfonyl hydrazides as as sulfenylating reagents, see: (a)
F.-L. Yang and S.-K. Tian, Angew. Chem. Int. Ed., 2013, 52
,
4929; (b) R. Singh, D. S. Raghuvanshi and K. N. Singh, Org.
Lett., 2013, 15, 4202; (c) F.-L. Yang, F.-X. Wang, T.-T. Wang,
Y.-J. Wang and S.-K. Tian, Chem. Commun., 2014, 50, 2111; (d)
X. Zhao, L.-P. Zhang, T.-J. Li, G.-Y. Liu, H.-M. Wang and K. Lu,
Chem. Commun., 2014, 50, 13121; (e) A. K. Bagdi, S. Mitra, M.
Ghosh and A. Hajra, Org. Biomol. Chem., 2015, 13, 3314; (f) X.
Zhao, Z.-J. Deng, A.-Q. Wei, B.-Y. Li and K. Lu, Org. Biomol.
Chem., 2016, 14, 7304; (g) Y. Yang, S. Zhang, L. Tang, Y.-B. Hu,
Z.-G. Zha and Z.-G. Wang, Green Chem., 2016, 18, 2609.
For sulfur containing drugs, see: (a) E. A. Ilardi, E. Vitaku and
J. T. Njardarson, J. Med. Chem., 2014, 57, 2832; (b) M.-H.
Feng, B.-Q.Tang, S.-H. Liang and X.-F. Jiang, Curr Top Med
Chem., 2016, 16, 1200.
6
7
(a) J. K. Crandall and C. Pradat, J. Org. Chem., 1985, 50, 1327;
(b) T. Murakami and K. Furusawa, Synthesis, 2002, 4, 479; (c)
Y.-H Ju, D. Kumar and R. S. Varma, J. Org. Chem., 2006, 71
,
6697; (d) F. Zhao, Q. Tan, F.-H. Xiao, S.-F. Zhang and Guo-Jun
Deng, Org. Lett., 2013, 15, 1520;
S. Chandrasekhar, V. Jagadeshwar, B. Saritha and C.
Narsihmulu, J. Org. Chem., 2005, 70, 6506.
M. A. Reddy, P. S. Reddy and B. Sreedhar, Adv. Synth. Catal.,
2010, 352, 1861.
8
9
10 H.-H. Li, D.-J. Dong, Y.-H. Jin and S.-K. Tian, J. Org. Chem.,
2009, 74, 9501.
11 Using sulfonyl hydrazides as reductants, see: (a) N. J. Cusack,
C. B. Reese, A. C. Risius and B. Roozpeikar, Tetrahedron, 1976,
32, 2157; (b) D. J. Pasto and R. T. Taylor, Org. React., 1991,
40, 91; (c) K. R. Buszek and N. Brown, J. Org. Chem., 2007, 72
,
3125; (d) B. J. Marsh and D. R. Carbery, J. Org. Chem., 2009,
74, 3186.
12 Other method for alkyl sulfones synthesis, see: (a) X.-W.
Feng, J. Wang, J. Zhang, J. Yang, N. Wang and X.-Q. Yu, Org.
Lett., 2010, 12, 4408; (b) C. S. Richards-Taylor, D. C.
Blakemoreb and M. C. Willis, Chem. Sci., 2014, 5, 222; (c) W.-
C. Yang, P. Dai, K. Luo and L. Wu, Adv. Synth. Catal., 2016,
358, 3184; (d) P. K. Shyam and H.-Y. Jang, J. Org. Chem., 2017,
82, 1761; (e) M. W. Johnson, S. W. Bagley, N. P. Mankad, R. G.
Bergman, V. Mascitti and F. D. Toste, Angew. Chem. Int. Ed.,
2014, 53, 4404; (f) A. Shavnya, K. D. Hesp, V. Mascitti and A.
C. Smith, Angew. Chem. Int. Ed., 2015, 54, 13571; (g) J.-J.
Chen, W. Guo, Z.-R. Wang, L. Hu, F. Chen and Y.-Z. Xia, J. Org.
Chem., 2016, 81, 5504.
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