One-pot two-step reaction of selenosulfonate with isocyanides and allyl alcohol under aqueous conditions: Atom-economic synthesis of selenocarbamates and allyl sulfones

Article abstract of DOI:10.1016/j.cclet.2020.07.007

In many reactions involving selenosulfonate or thiosulfonate, the sulfone group often leaves in form of benzenesulfinic acid or sodium benzenesulfinate. A one-pot two-step reaction of selenosulfonate with isocyanides and allyl alcohol under aqueous conditions to afford selenocarbamates and allyl sulfone compounds is reported. The sulfinic acid as the first-step side product is converted to the allyl sulfone compound by water promoted reaction with allyl alcohol. Water acts as both an oxygen source of selenocarbamates and as a promoter to drive the second step reaction. The reactions have the advantages of mild conditions, green, environment-friendly, and high atomic economy.

Full text of DOI:10.1016/j.cclet.2020.07.007

Journal Pre-proof
One-pot two-step reaction of selenosulfonate with isocyanides and allyl
alcohol under aqueous conditions: Atom-economic synthesis of
selenocarbamates and allyl sulfones
Jing-Jing Ai, Jian Li, Shun-Jun Ji, Shun-Yi Wang
PII:
S1001-8417(20)30398-3
https://doi.org/10.1016/j.cclet.2020.07.007
CCLET 5732
DOI:
Reference:
To appear in:
Chinese Chemical Letters
Received Date:
Revised Date:
Accepted Date:
3 June 2020
17 June 2020
4 July 2020
Please cite this article as: Ai J-Jing, Li J, Ji S-Jun, Wang S-Yi, One-pot two-step reaction of
selenosulfonate with isocyanides and allyl alcohol under aqueous conditions: Atom-economic
synthesis of selenocarbamates and allyl sulfones, Chinese Chemical Letters (2020),
doi: https://doi.org/10.1016/j.cclet.2020.07.007
This is a PDF file of an article that has undergone enhancements after acceptance, such as
the addition of a cover page and metadata, and formatting for readability, but it is not yet the
definitive version of record. This version will undergo additional copyediting, typesetting and
review before it is published in its final form, but we are providing this version to give early
visibility of the article. Please note that, during the production process, errors may be
discovered which could affect the content, and all legal disclaimers that apply to the journal
pertain.
© 2020 Published by Elsevier.

Communication
One-pot two-step reaction of selenosulfonate with isocyanides and allyl alcohol under
aqueous conditions: Atom-economic synthesis of selenocarbamates and allyl sulfones
Jing-Jing Ai, Jian Li, Shun-Jun Ji, Shun-Yi Wang*
Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry, Chemical Engineering and Materials Science & Collaborative
Innovation Center of Suzhou Nano Science and Technology, Soochow University, Suzhou 215123, China
 Corresponding authors.
E-mail addresses: shunyi@suda.edu.cn (S.Y. Wang);
Graphical Abstract
A one-pot two-step reaction of selenosulfonate with isocyanides and allyl alcohol under aqueous conditions to afford selenocarbamates and allyl sulfone
compounds is reported. The sulfinic acid as the first-step side product is converted to the allyl sulfone compound by water promoted reaction with allyl
alcohol. Water acts as both an oxygen source of selenocarbamates and a promoter to drive the second step reaction. The reactions have the advantages
of mild conditions, green, environment-friendly, and high atomic economy.
ARTICLE INFO
Article history:
Received 3 June 2020
Received in revised form 17 June 2020
Accepted 28 June 2020
Available online
ABSTRACT
In many reactions involving selenosulfonate or thiosulfonate, the sulfone group often leaves in form of benzenesulfinic acid or sodium
benzenesulfinate. A one-pot two-step reaction of selenosulfonate with isocyanides and allyl alcohol under aqueous conditions to afford
selenocarbamates and allyl sulfone compounds is reported. The sulfinic acid as the first-step side product is converted to the allyl sulfone
compound by water promoted reaction with allyl alcohol. Water acts as both an oxygen source of selenocarbamates and as a promoter to
drive the second step reaction. The reactions have the advantages of mild conditions, green, environment-friendly, and high atomic
economy.
Keywords: Aqueous conditions; One-pot two-step process; Benzenesulfinic acid; Selenocarbamate; Allyl sulfone compound

Sulfur and selenium play a prominent role in organic synthesis [1], and widely exist in natural products, bioactive molecules and
organic materials [2]. In 2005, Takahashi’s group reported the selenocarbamates could be used as effective superoxide anion radical
scavengers in vitro [3]. Govindasamy and his colleagues synthesized spirodiazaselenurane by spirocyclization of corresponding aryl
selenides for the first time, and found that the anti-inflammatory compound ebselen has antioxidant activity [4]. Masahiro and co-workers
found benzo[b]benzo[4,5]thieno[2,3-d]thiophene (BTBT) is the basic structural unit of organic semiconductor materials [5]. Therefore,
the construction of C−S and C-Se bonds is of strategic importance in current synthetic chemistry. In most of the explorations, selenium
powder and diselenide were employed as starting material to construct the C-Se bond [6], and thioalcohol, inorganic sulfur and disulphide,
to construct the C-S bond, respectively [7]. For example, Sonda’s group reported a multicomponent reaction of alkyl halides, amide,
carbon monoxide and selenium powder to construct selenocarbamates [8]. However, the selenium powder used in the reaction is sensitive
to air and moisture, and has certain toxicity. Buchwald's team used thioalcohol to react with aryl halogenated hydrocarbons to construct
aryl thioether compounds, but the thioalcohol used was irritating and toxic [9]. In recent years, as a new type of selenium and sulfur
reagent, thiosulfonate and selenosulfonate are more stable and less toxic than the traditional selenium and sulfur reagents, Promoting
them to be applied in a variety of organic transformations as pivotal synthetic building blocks. Traditionally, sulfonyl groups are often
removed in the form of sulfinic acid or sodium sulfite, when thiosulfonates and selenosulfonates react with nucleophilic reagents (Scheme
1a) [10]. In 2016, Xu and his co-workers reported the construction of o‑ alkynyl arylsulfides from aryne, alkyne, and
benzenesulfonothioate [11]. Unfortunately, the sulfonyl group was deserted as a by-product. Our group reported the synthesis of
selenocarbamates through metal-free multicomponent reactions of isocyanides, selenosulfonates, in the present of water [12].
Unavoidably, in this reaction, sulfonyl group merely left in the form of sulfinic acid.
Scheme 1. One-pot two-step reaction.
Sulfones exist widely in many bioactive natural products as well as some of the best-selling drugs [13]. The most common drugs are
Eletriptan ([2H]-SB-3CT) for the treatment of migraine headache and MMP-2, MMP-9 inhibitor for the treatment of prostate cancer
[14]. On one hand, sulfuryl exhibits good nucleophilicity. Consequently, in some reactions involving thiosulfonates and selenosulfonates,
the separated sulfonyl groups can react with other electrophilic reagents in the system (Scheme 1b) [15]. For instance, In 2005, Shi’s
group reported the DABCO-catalyzed addition of selenosulfonates to α,β-unsaturated ketones to generate α-selenylated ketones [16]. In
this case, the sulfonyl group leaves at first, but eventually participates in the β-difunctionalization process. Similarly, in 2018, Xu and
his co-workers realized oxidative trifunctionalization of olefins by thiosulfonates with the copper catalyst, ensuring the full utilization of
thiosulfonates [17]. On the other hand, sulfinic acid and sodium sulfite can also be used in the synthesis of sulfonyl compounds directly.
In 2005, Lu’s group synthesized β-fluorosulfonyl compounds by the reaction of styrene with aryl sulfite under the catalysis of palladium
[18]. Three years later, Loh et al. successfully constructed the allyl sulfone compounds, through the water-catalyzed reaction of sulfonic
acid and allyl alcohol [19].
Over the years, practices of synthesis have generally relied on assembling several synthesis operation processes in a stop-and-go
process. But we should notice the stop-and-go practice not only compromises the overall efficiency of the synthesis process, but also
results significant amounts of waste, particularly organic solvents. As a continuation of our interests in green chemistry, we focus on
developing effective ways to transform sulfinic acid, a by-product in the reaction of traditional selenosulfonates or thiosulfonates, into
other useful substances without stop-and-go process. Therefore, we design a one-pot two-step reaction of selenosulfonates, isocyanides
and allyl alcohols under aqueous conditions to afford selenocarbamates and allyl sulfone compounds. Through this novel design, we not
only achieved the goal of killing two birds with one stone, but also greatly improved the atomic economy of the reaction.
The study was commenced by investigating the reaction of commercially available 2-isocyano-2-methylpropane 1a, Se-(2-
phenoxyethyl)benzenesulfonoselenoate 2a with 1,3-diphenyl-2-enol 3a. The reaction was carried out in one-pot two-step way. The
system after the reaction of 2-isocyano-2-methylpropane (1a) with Se-(2-phenoxyethyl)benzenesulfonoselenoate (2a) in the presence of
water, and added 1,3-diphenyl-2-enol (3a) and 2 mL water directly to it without separated. To our delight, we could obtain 4a and 5a in
87% and 44% yield, respectively. Then, we hope to increase the yield of the product 5a mainly by changing the conditions. Firstly, we
investigated a series of solvents added in the second step (Table 1, entries 1-6). It was found that the desired products 4a could be obtained
in moderate to good yields, but the yield of 5a has no obvious change, except that the addition of 0.5 mL water resulted in lower yields

of 4a and 5a products. Subsequently, we gradually increased the amount of 3a to observe the reaction efficiency (Table 1, entries 7-9).
It shows us that when 3a was 0.4 mmol, the reaction effect was the best, and the desired products 4a and 5a could be obtained in 90%
and 65% yield, respectively. Then, we extended the reaction time of the second step to 48 h, but the reaction efficiency did not change
significantly (Table 1, entry 10). Finally, we adjusted the reaction temperature of the second step (Table 1, entries 11-13). We found that
increasing the temperature would decompose the product 4a, and the yield of 5a was not improved. However, reducing the temperature
o
could not consume the selenosulfonate completely and reduce the reaction effect. Therefore, 30 C was the most suitable reaction
temperature.
Table 1
Optimization of the reaction conditions.a
Yield (%)b
Entry
Solvent (mL)
3a (mmol)
4a
87
80
94
70
92
85
87
90
90
90
84
86
trace
5a
44
45
30
25
56
42
49
65
65
67
65
66
-
1
2
3
4
5
6
7
8
9
10c
11d
12e
13f
H2O (2.0)
H2O (1.5)
H2O (1.0)
0.2
0.2
0.2
0.2
0.2
0.2
0.3
0.4
0.6
0.4
0.4
0.4
0.4
H2O (0.5)
H2O/EtOH (1.5/0.5)
H2O/EtOH (1.0/1.0)
H2O (2.0)
H2O (2.0)
H2O (2.0)
H2O (2.0)
H2O (2.0)
H2O (2.0)
H2O (2.0)
a Reaction conditions: 1a (0.60 mmol), 2a (0.40 mmol), H2O (4.00 mmol) in DMF (2 mL) were stirred at 40 oC for 12 h, and added 3a (0.2
mmol), H2O (2 mL) stirred at 30 oC for 24 h.
b Isolated yield.
c t2 = 48 h.
d T2 = 25 oC.
e T2 = 40 oC.
f T2 = 50 oC.
With the optimized conditions in hand, we explored the substrate scope of various isocyanides 1 (Table 2). To our delight, we could
obtain 4a and 5a in 90% and 65% yields. Alkyl isocyanides, including (1R,3S,5R,7R)-2-isocyanoadamantane, could react smoothly under
standard conditions. The desired products (4b-4e) and 5a were obtained in moderate yields. When aromatic isocyanides were employed
in the reactions, we could obtain a small amount of the desired product.
Subsequently, the scope of the various simple allylic alcohols 3 was explored (Table 2). A fluorine at the ortho- and para-position of
2-phenyl respectively provided the desired products 4a in 84% and 88% yields, while product 5b and 5d in relatively low yields of 50%
and 41%. By comparison, when the substituent group is methyl, we could obtain the desired products in medium to excellent yields (4a
and 5c, 5e).
Table 2
Substrate scope of isocyanides and allylic alcohols.a
Yield (%)b
4
Entry R1
Ar
5

1
2
3
4
5
6
4a, 90
4b, 64
4c, 63
4d, 65
4e, 44
trace
5a, 65
5a, 30
5a, 45
5a, 41
5a, 11
trace
7
8
4a, 84
4a, 78
5b, 50
5c, 68
9
4a, 88
4a, 89
5d, 41
10
5e, 71
a Reaction conditions: 1 (0.60 mmol), 2a (0.40 mmol), H2O (4.00 mmol) in DMF (2 mL) were stirred at 40 oC for 12 h, and added 3 (0.2 mmol),
H2O (2 mL) stirred at 30 oC for 24 h.
b Isolated yield.
When we used (E)-1-phenyl-3-(p-tolyl)prop-2-en-1-ol (3f) as the substrate, We can obtain the target product 4a with a separation yield
of 89% and a mixture of target products 5j and 5j' was obtained with a separation yield of 87%. According to the nuclear magnetic
hydrogen spectrum, we analyzed that the ratio of 5j and 5j' in the mixture is about 1/1. Replacing 3f with 3g can also obtain the target
product 4a in 81% yield, and a mixture of 5j and 5j' in 87% separation yield. But the ratio of the mixture has changed a little, and it has
become 1.4 / 1 (Scheme 2).
Scheme 2. Scope of allylic alcohols. Reaction conditions: 1a (0.60 mmol), 2a (0.40 mmol), H2O (4.00 mmol) in DMF (2 mL) were stirred at 30
oC for 12 h, and added 3f or 3g (0.2 mmol), H2O (2 mL) stirred at 30 oC for 24 h.
We further studied the substrate scope using a series of selenosulfonates 2 with different R2 and R3 groups (Table 3). Different
substituted Se-benzyl benzenesulfonoselenoates were employed in the reactions. The desired products could be isolated in 47%-84%
yields (4f-4i and 5a). To our delight, Se-(3-phenylpropyl)benzenesulfonoselenoate was proven to be suitable candidates for the reaction.
The desired products 4j and 5a were isolated in 97% and 64% yields, respectively. Branched and cyclane-substituted selenosulfonates
were compatible with the mild reaction conditions as well, leading to the desired products in moderate yields. When we replace
selenosulfonate with S-benzyl benzenesulfonothioate, the reaction could proceed smoothly, and could obtain the desired product 5a and
4n in the yields of 76% and 62%.

Table 3.
Substrate scope of allylic alcohols.a
Yield (%)b
Entry
Substrate R2
Substrate R3
4
5
1
2
4f, 73
4g, 84
4h, 73
4i, 82
4j, 97
4k, 73
4l, 66
4m, 63
4a, 81
4a, 72
5a, 60
5a, 47
5a, 60
5a, 49
5a, 64
5a, 69
5a, 50
5a, 52
5f, 75
5g, 62
3
4
5
6
7
8
9
10
11
12
4a, 76
4a, 81
4n, 76
5h, 71
5i, 51
5a, 62
13c
o
aReaction conditions: 1a (0.60 mmol), 2a (0.40 mmol) are selenosulfonates, H2O (4.00 mmol) in DMF (2 mL) were stirred at 30 C for 12 h,
and added 3a (0.2 mmol), H2O (2 mL) stirred at 30 oC for 24 h.
b Isolated yield.
c Se-(2-phenoxyethyl) benzenesulfonoselenoate was replaced by S-benzyl benzenesulfonothioate.
In summary, we have developed a one-pot two-step reaction of selenosulfonate with isocyanides and allyl alcohol under aqueous
conditions to afford selenocarbamates and allyl sulfone compounds. The sulfinic acid as the first step side product is converted to the
allyl sulfone compound by water promoteed reaction with allyl alcohol. Water acts as both an oxygen source of selenocarbamates and as
a promoter to drive the second step reaction. The reactions have the advantages of mild conditions, green, environment-friendly, and
high atomic economy.
Notes
The authors declare no completing financial interest.
Acknowledgments
We gratefully acknowledge the National Natural Science Foundation of China (Nos. 21971174, 21772137, 21672157), the Ph.D.
Programs Foundation of PAPD, the Project of Scientific and Technologic Infrastructure of Suzhou (No. SZS201708), the Major Basic
Research Project of the Natural Science Foundation of the Jiangsu Higher Education Institutions (No. 16KJA150002), Soochow
University, and State and Local Joint Engineering Laboratory for Novel Functional Polymeric Materials for financial support.
References

[1] (a) C.W. Nogueira, G. Zeni, J.B.T. Rocha, Chem. Rev. 104 (2004) 6255-6285;
(b) A.D. Giuseppe, R. Castarlenas, J.J. Pérez-Torrenté, et al., J. Am. Chem. Soc. 134 (2012) 8171-8183;
(c) A. Ferry, T. Billard, B. R. Langlois, E. Bacqu, Angew. Chem. Int. Ed. 48 (2009) 8551-8555;
(d) G. Danoun, B. Bayarmagnai, M.F. Gruenberg, L.J. Goossen, Chem. Sci. 5 (2014) 1312-1316;
(e) C.P. Zhang, D.A. Vicic, J. Am. Chem. Soc. 134 (2012) 183-185;
(f) D. Yang, K. Yan, W. Wei, et al., J. Org. Chem. 80 (2015) 6083-6092;
(g) G. Teverovskiy, D.S. Surry, S.L. Buchwald, Angew. Chem. Int. Ed. 50 (2011) 7312-7314.
[2] (a) P.C. Srivastava, R.K. Robins, J. Med. Chem. 26 (1983) 445-448;
(b) G. Mugesh, W.W. Mont, H. Sies, Chem. Rev. 101 (2001) 2125-2179;
(c) A. Heredia, A.B. Peñéñory, J. Org. Chem. 13 (2017) 910-918;
(d) Y. Li, M. Wang, X. Jiang, ACS Catal. 7 (2017) 7587-7592;
(e) E.A. Ilardi, E. Vitaku, J.T. Njardarson, J. Med. Chem. 57 (2014) 2832-2842;
(f) Y. Li, M. Wang, X. Jiang, ACS Catal. 7 (2017) 7587-7592.
[3] H. Takahashia, A. Nishinaa, R. Fukumotoa, et al., Eur. J. Pharm. Sci. 24(2005) 291-295.
[4] (a) B.K. Sarma, D. Manna, M. Minoura, G. Mugesh, J. Am. Chem. Soc. 132 (2010) 5364-5374;
(b) B.K. Sarma, G. Mugesh, Chem. Eur. J. 14 (2008) 10603-10614.
[5] K. Takimiya, I. Osaka, T. Mori, M. Nakano, Acc. Chem. Res. 47 (2014) 1493-1502.
[6] (a) Y. Fang, T. Rogge, L. Ackermann, S.Y. Wang, S.J. Ji, Nat. Comm. 9 (2018) 2240;
(b) H. Liu, Y. Fang, L. Yin, S.Y. Wang, S.J. Ji, J. Org. Chem. 82 (2017) 10866-10874;
(c) H. Liu, Y. Fang, S.Y. Wang, S.J. Ji, Org. Lett. 20 (2018) 930-933;
(d) C. Liu, Y. Fang, S.Y. Wang, S.J. Ji, Org. Lett. 20 (2018) 6112-6116.
[7] (a) J.H. Li, Q. Huang, W. Rao, S.Y. Wang, S.J. Ji, Chem. Commun. 55 (2019) 7808-7811;
(b) J.H. Li, Q. Huang, S.Y. Wang, S.J. Ji, Org. Lett. 20 (2018) 4704-4708;
(c) B.B. Liu, X.Q. Chu, H. Liu, et al., J. Org. Chem. 82 (2017) 10174-10180.
[8] S. Fujiwara, K. Okada, Y. Shikano, et al., J. Org. Chem. 72 (2007) 273-276.
[9] J. Xu, R.Y. Liu, C.S. Yeung, S.L. Buchwald, ACS Catal. 9 (2019) 6461-6466.
[10] (a) X. Ma, S.B. Herzon, Beilstein, J. Org. Chem. 14 (2018) 2259-2265;
(b) A.P. Schaffner, F. Montermini, D. Pozzi, et al., Adv. Synth. Catal. 350 (2008) 1163-1167;
(c) X. Ma, S.B. Herzon, Chem. Sci. 6 (2015) 6250- 6255;
(d) P. Mampuys, Y. Zhu, T. Vlaar, et al., Angew. Chem. Int. Ed. 53 (2014) 12849-12854;
(e) J. Li, D. Zhu, L. Lv, C.J. Li, Chem. Sci. 9 (2018) 5781-5786;
(f) W. Kong, C. Yu, H. An, Q. Song, Org. Lett. 20 (2018) 4975-4978;
(g) B. Xu, D. Li, L. Lu, et al., Org. Chem. Front. 5 (2018) 2163-2166.
[11] X. Peng, C. Ma, C.H. Tung, Z. Xu, Org. Lett. 18 (2016) 4154-4157.
[12] Y. Fang, C. Liu, F. Wang, et al., Org. Chem. Front. 6 (2019) 660-663.
[13] (a) S. Oida, Y. Tajima, T. Konosu, et al., Chem. Pharm. Bull. 48 (2000) 694-707;
(b) N.A. McGrath, M. Brichacek, J.T. Njardarson, J. Chem. Educ. 87 (2010) 1348-1349;
(c) A.B. Pritzius, B. Breit, Angew. Chem. Int. Ed. 54 (2015) 3121-3125.
[14] M. Lee, M. Ikejiri, D. Klimpel, et al., ACS Med. Chem. Lett. 3 (2012) 490-495.
[15] (a) T. Song, H. Li, F. Wei, C.H. Tung, Z. Xu, Tetrahedron Lett. 60 (2019) 916-919;
(b) H. Qian, K. Sulfones, X. Huang, Synthesis 12 (2006) 1934-1936;
(c) S. Huang, Z. Chen, H. Mao, et al., Org. Biomol. Chem. 17 (2019) 1121-1129;
(d) R.A. Gancarz, J.L. Kice, J. Org. Chem. 46 (1981) 4899-4906.
(e) C. Rao, S. Maia, Q. Song, Chem. Commun. 54 (2018) 5964-5967.
[16] Y.L. Shi, M. Shi, Org. Biomol. Chem. 3 (2005) 1620-1621.
[17] S. Huang, N. Thirupathi, C.H. Tung, Z. Xu, J. Org. Chem. 83 (2018) 9449-9455.
[18] Z. Yuan, H.Y. Wang, X. Mu, et al., J. Am. Chem. Soc. 137 (2015) 2468-2471.
[19] P. Xie, J. Wang, Y. Liu, et al., Nat. Commun. 9 (2018) 1321.