Fluoroalkanosulfonyl fluorides-mediated cyclodehydration of β-hydroxy sulfonamides and β-hydroxy thioamides to the corresponding aziridines and thiazolines

Article abstract of DOI:10.1016/j.tetlet.2013.08.045

An efficient method for the fluoroalkanosulfonyl fluoride-induced cyclodehydration of β-hydroxy sulfonamides and β-hydroxy thioamides to the corresponding aziridines and thiazolines is reported. Mild reaction conditions, operational simplicity, and high y

Full text of DOI:10.1016/j.tetlet.2013.08.045

Tetrahedron Letters 54 (2013) 5788–5790
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Tetrahedron Letters
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Fluoroalkanosulfonyl fluorides-mediated cyclodehydration of
b-hydroxy sulfonamides and b-hydroxy thioamides to the
corresponding aziridines and thiazolines
a
a
b,
Zhaohua Yan a, , Chengbo Guan , Zhangxin Yu , Weisheng Tian
⇑
⇑
a Department of Chemistry, Nanchang University, Nanchang, Jiangxi Province, PR China
b Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
An efficient method for the fluoroalkanosulfonyl fluoride-induced cyclodehydration of b-hydroxy sulfon-
amides and b-hydroxy thioamides to the corresponding aziridines and thiazolines is reported. Mild reac-
tion conditions, operational simplicity, and high yields are the major advantages of this method.
Ó 2013 Elsevier Ltd. All rights reserved.
Received 7 June 2013
Revised 22 July 2013
Accepted 15 August 2013
Available online 22 August 2013
Keywords:
Fluoroalkanosulfonyl fluorides
Cyclodehydration
b-Hydroxy sulfonamides
b-Hydroxy thioamides
Aziridines
Thiazolines
Cyclodehydration reagent plays a very important role in organic
synthesis as a variety of organic heterocyclic compounds, such as
epoxides, aziridines, oxazolines, and thiazolines, etc., can be ac-
cessed via cyclodehydration of 1,2-diols, 1,2-amino alcohols as
well as their derivatives such as b-hydroxy sulfonamides and
b-hydroxy thioamides, etc. To date, lots of reagents have been
developed for this kind of transformation, including triphenylphos-
phine/diethyl azodicarboxylate (Mitsunobu system),1 N,N-dieth-
ylaminosulfur trifluoride (DAST reagent),2 bis(2-methoxyethyl)
catalysts in asymmetric synthesis.7 Besides aziridines, thiazolines
are also useful structural motifs in organic synthesis. Since the first
report of employing chiral thiazoline ligands in asymmetric catal-
ysis by Helmchen in 1991, a series of thiazoline-containing ligands
have been synthesized. Additionally, thiazoline moieties are also
found in some biologically active natural products, such as Mir-
abazoles, Lissoclinamides, Grassypeptolide A, etc.8 Moreover,
thiazolines are versatile precursors to the preparation of various
compounds such as aldehydes, ketones, thiazoles, b-amino thiols,
and thiazolinium salts.9 Therefore, new approaches to make aziri-
dines and thiazolines are highly desirable.
aminosulfur
trifluoride
(Deoxo-Fluor),3
methyl
N-(tri-
ethylammoniumsulfonyl)carbamate (Burgess reagent),4 Lawes-
son’s reagent,5 and classical thionyl chloride, methanesulfonyl
chloride, and p-toluenesulfonyl chloride. However, many of cyc-
lodehydration reagents are moisture sensitive and expensive;
some of them can give rise to considerable amounts of side
products.
Fluoroalkanosulfonyl fluorides including perfluoroalkanosulfo-
nyl fluorides and polyfluoroalkanosulfonyl fluorides (RfSO2F, such
as n-C8F17SO2F, n-C4F9SO2F, HCF2CF2OCF2CF2SO2F, etc.) are com-
mercially available and inexpensive fluorinated reagents. This class
of reagent is non-toxic and moisture-insensitive. Reactions
employing RfSO2F generally afford water-soluble fluoroalkanosulf-
onic salts as by-products, enabling easy work-up and purification.
Aziridine is an important class of organic compound, not only
due to the existence of aziridino moiety in many biologically active
molecules, but also due to the fact that it can engage in numerous
transformations, such as nucleophilic ring-opening, rearrange-
ment, reduction and elimination, etc., providing access to a great
number of useful synthetic intermediates.6 Very recently, aziridine
ring-containing chiral ligands were reported to be highly efficient
Furthermore, fluoroalkanosulfonic acid salts Rf SOꢀMþ are highly
3
valued surfactants. RfSO2F has been used to activate the hydroxyl
group in the synthesis of fluorinated compounds from the
corresponding alcohols.10 Similar transformations have been ap-
plied in the preparation of cis-epoxides from chiral vicinal diols
en route to the total synthesis of (ꢀ)-dehydroclausenamide.11
Moreover, this reactivity of RfSO2F has also been explored in the
synthesis of ( )-Spiniferin whereby a RfSO2F mediated homoallylic
⇑
Corresponding authors.
E-mail address: yanzh888@gmail.com (Z. Yan).
0040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2013.08.045

Z. Yan et al. / Tetrahedron Letters 54 (2013) 5788–5790
5789
Table 2
n-C4F9SO2F
RfSO2F-induced cyclodehydration of b-hydroxy thioamidesa
Et3N
Ph
OH
NHTs
Ph
NTs
CH2Cl2
rt, 1 h
93%
Entry Substrates
Products
Isolated yield (%)
H
N
Ph
N
2a
1a
Ph
OH
OH
1
87
85
S
4a
S
S
3a
3b
Scheme 1. RfSO2F-induced cyclodehydration of 1a.
N
H
N
Ph
Ph
2b
S
carbocation rearrangement of 19-hydroxymethyl steroid was
reported.12 Fluoroalkanosulfonyl fluorides have also been success-
fully employed to activate the hydroxyl group of carboxylic ester-
ification, amidation, and anhydride formation reactions.13 Very
recently, Chan reported cyclodehydration of N-acylamino alcohols
induced by fluoroalkanosulfonyl fluorides leading to an improved
formation of oxazoline derivatives.14 However, to the best of our
knowledge, the reactions of fluoroalkanosulfonyl fluorides with
b-hydroxy sulfonamides and b-hydroxy thioamides have not yet
been studied. In the present work, we disclose the results of fluor-
oalkanosulfonyl fluoride-induced cyclodehydration of b-hydroxy
sulfonamides and b-hydroxy thioamides to the corresponding azir-
idines and thiazolines.
We first examined the reaction of fluoroalkanosulfonyl fluorides
with b-hydroxy sulfonamides using 1a as the model substrate
(Scheme 1). Treatment of 1a (2.0 mmol) with n-C4F9SO2F
(4.0 mmol) and Et3N (6.0 mmol) in CH2Cl2 at room temperature, af-
fords quantitatively the corresponding aziridine product 2a with
no observable side products. After simple aqueous work-up proce-
dure, 2a was obtained in 93% isolated yield. Encouraged by this re-
sult, we went on to screen other fluoroalkanosulfonyl fluoride
reagents and found that both n-C8F17SO2F and HCF2CF2OCF2CF2-
SO2F possessed similar activity to that of n-C4F9SO2F; using 1,8-
diazabicyclo[5.4.0]undec-7-ene (DBU) to replace Et3N as base did
not alter the yield either. However, longer reaction time resulted
in formation of an unidentified by product which was postulated
to derive from the ring-opening of aziridine by fluoride anion.
With the formation of 2a in a satisfactory yield, a variety of b-
hydroxy sulfonamides were subjected to RfSO2F-induced cyclode-
4b
H
N
H3C
N
Ph
H3C
Ph
OH
Ph
3
4
83
85
S
4c
S
3c
H
N
Ph
Ph
N
OH
S
4d
S
S
3d
3e
H
N
N
Ph
Ph
OH
5
88
82
S
4e
OH
N
H
N
Ph
Ph
6b
S
4f
S
S
3f
H
N
N
OH
7
90
Ph
3g
S
4g
a
All the reactions were run at room temperature; 3:n-C4F9SO2F:Et3N = 1:2:3
(molar ratio); the reaction time is 1–2 h.
b
Both 3b and 3f are racemic substrates.
hydration to investigate the scope and utility of this method. The
condition was found to effect cyclodehydration smoothly on a vari-
ety of substrates, generating the corresponding aziridines in 61–
95% isolated yields15 (Table 1). In the cases of less sterically chal-
Table 1
RfSO2F-induced cyclodehydration of b-hydroxy sulfonamidesa
Entry
Substrates
Products
Isolated yield (%)
93
Ph
OH
NHTs
Ph
NTs
1
2a
1a
OH
NHTs
NTs
2
3
4
5
95
86
92
90
2b
1b
OH
NTs
2c
NHTs
1c
OH
NHTs
NTs
NTs
2d
2e
1d
NHTs
OH
1e
NHTs
OH
NTs
6b
87
61
2f
1f
OH
CH3SO2
COOEt
CO2Et
7c
NHTs
N
CH3SO2
1g
Ts
2g
a
b
c
All the reactions were run at room temperature; 1:n-C4F9SO2F:Et3N = 1:2:3 (molar ratio); the reaction time is 1 h.
Using racemic 1f as substrate.
Using DBU as base, and the reaction time is 10 h.

5790
Z. Yan et al. / Tetrahedron Letters 54 (2013) 5788–5790
lenging substrates such as 1a to 1f, the corresponding aziridines
could be obtained in excellent yields of 80–95% after 1 h, and only
trace amounts of unidentified impurities can be found. However,
upon subjecting these substrates to the reaction conditions for a
longer period of time, more impurities were isolated. In the case
of substrate 1g, both stronger base DBU and longer reaction time
were required to drive the cyclodehydration to completion due
to higher steric hindrance, which accordingly led to more side
products. Meanwhile in the case of 1g, less than 3% of epimeriza-
tion at C(2) center was detected by NMR spectroscopy.
References and notes
1. (a) Mitsunobu, O.; Yamada, M. Bull. Chem. Soc. Jpn. 1967, 40, 2380; (b) Bisai, A.;
Singh, V. K. Tetrahedron Lett. 2007, 48, 1967.
2. Hudlicky, M. Org. React. 1988, 35, 513.
3. Lal, G. S.; Pez, G. P.; Pesarezi, R. J.; Prozonic, F. M.; Cheng, H. J. Org. Chem. 1999,
64, 7048.
4. Burgess, E. M.; Penton, H. R., Jr.; Taylor, E. A.; Williams, W. M. Org. Synth. 1977,
56, 40.
5. Takehito, N.; Sekiguchi, H. Heterocycles 2002, 58, 203.
6. (a) Tanner, D. Angew. Chem., Int. Ed. 1994, 33, 599; (b) Ghorai, M. K.; Nanaji, Y. J.
Org. Chem. 2013, 78, 3867; (c) Takahashi, M.; Suzuki, N.; Ishikawa, T. J. Org.
Chem. 2013, 78, 3250.
To broaden the scope of this RfSO2F-mediated cyclodehydration
reaction, various b-hydroxy thioamides were treated under the
same reaction conditions as developed above. RfSO2F was found
to be effective cyclodehydration reagent, resulting in the clean con-
version of b-hydroxy thioamides into thiazolines in high yields of
82–90%15 (Table 2). Et3N and DBU gave similar yields for all the
substrates in Table 2.
In summary, RfSO2F can efficiently induce cyclodehydration of
b-hydroxy sulfonamides and b-hydroxy thioamides to the corre-
sponding aziridines and thiazolines. This operationally simple
method allows the transformation to be achieved in high yields un-
der mild conditions. Further studies of RfSO2F-mediated cyclode-
hydration in the synthesis of chiral thiazoline ligands and
thiazoline-containing natural products are currently underway.
7. Rachwalski, M.; Jarzynski, S.; Lesniak, S. Tetrahedron: Asymmetry 2013, 24, 421.
8. (a) Liu, H.; Liu, Y.; Wang, Z.; Xing, X.; Maguire, A. R.; Luesch, H.; Zhang, H.; Xu,
Z.; Ye, T. Chem. -Eur. J. 2013, 19, 6774; (b) Zhou, X.; Huang, H.; Chen, Y.; Tan, J.;
Song, Y.; Zou, J.; Tian, X.; Hua, Y.; Ju, J. J. Nat. Prod. 2012, 75, 2251.
9. Gaumont, A. C.; Gulea, M.; Levillain, J. Chem. Rev. 2009, 109, 1371.
10. Bennua-Skalmowski, B.; Vorbruggen, H. Tetrahedron Lett. 1995, 36, 2611.
11. Yan, Z.; Wang, J.; Tian, W. Tetrahedron Lett. 2003, 44, 9383.
12. Sun, Y.-S.; Ding, K.; Tian, W.-S. Chem. Commun. 2011, 47, 10437.
13. Yan, Z.; Tian, W.; Zeng, F.; Dai, Y. Tetrahedron Lett. 2009, 50, 2727.
14. Chan, A. S. C.; Ding, K.; Yu, W. Y. Patent WO2010/015211, 2010.
15. The general procedure for the RfSO2F-induced cyclodehydration of b-hydroxy
sulfonamide to the corresponding aziridine: At room temperature, n-C4F9SO2F
(4.0 mmol, 2.0 M equiv) was slowly added via syringe to a solution of b-
hydroxy sulfonamide (2.0 mmol) and Et3N (6.0 mmol, 3.0 M equiv) in CH2Cl2,
and the resulting mixture was stirred at room temperature for 1–2 h. After
evaporation of the reaction mixture to remove volatile components, the
residue obtained was purified through silica gel column chromatography
(petroleum:ethyl acetate = 10:1, v/v), providing the corresponding aziridine in
the yields of 61–95%.
The general procedure for the RfSO2F-induced cyclodehydration of b-hydroxy
thioamide to the corresponding thiazoline: At room temperature, n-C4F9SO2F
(4.0 mmol, 2.0 M equiv) was slowly added via syringe to a solution of b-
hydroxy thioamide (2.0 mmol) and Et3N (6.0 mmol, 3.0 M equiv) in CH2Cl2, the
resulting mixture was stirred at room temperature for 1–2 h. After evaporation
of the reaction mixture to remove volatile components, the residue obtained
was purified through silica gel column chromatography (petroleum/ethyl
acetate = 20:1, v/v), providing the corresponding aziridine in the yields of 82–
90%.
Acknowledgments
We thank Key Laboratory of Synthetic Chemistry of Natural
Substances, Shanghai Institute of Organic Chemistry, Chinese
Academy of Sciences and Jiangxi Provincial Natural Science Foun-
dation for financial supports.
Supplementary data
Supplementary data associated with this article can be found,
in the online version, at http://dx.doi.org/10.1016/j.tetlet.
2013.08.045.