Visible light-mediated dehydrogenative β-arylsulfonylation of tertiary aliphatic amines with arylsulfonyl chlorides

Article abstract of DOI:10.1039/c4ob01713g

The novel synthesis of β-arylsulfonyl enamines has been achieved by visible light-mediated dehydrogenative arylsulfonylation of tertiary aliphatic amines with arylsulfonyl chlorides in moderate yield. This journal is

Full text of DOI:10.1039/c4ob01713g

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Visible light-mediated dehydrogenative
β-arylsulfonylation of tertiary aliphatic amines
with arylsulfonyl chlorides†
Cite this: DOI: 10.1039/c4ob01713g
Received 11th August 2014,
Accepted 29th September 2014
Min Chen, Zhi-Tang Huang and Qi-Yu Zheng*
DOI: 10.1039/c4ob01713g
www.rsc.org/obc
The novel synthesis of β-arylsulfonyl enamines has been achieved Nicewicz,7 it is crucial to match oxidants with reductants
by visible light-mediated dehydrogenative arylsulfonylation of ter- subject to the redox potential of the photocatalysts in the
tiary aliphatic amines with arylsulfonyl chlorides in moderate yield.
photocatalytic cycle. That inspired us to look for other reduc-
tive agents such as tertiary amines involved in photoredox
catalysis with arylsulfonyl chlorides. In addition, compared
to tertiary anilines, simple tertiary aliphatic amines that are
commercially available had drawn little attention.8
On the other hand, β-functionalization of unactivated
substrates is always a challenging target. With strong oxidants
or transition metal catalysts, some striking reactions could
be realized.9 Recently, MacMillan fulfilled the β-arylation of
ketones and aldehydes via merging photoredox catalysis with
organocatalysis under mild conditions.10 Herein we report the
first visible light-mediated dehydrogenative β-arylsulfonylation
of tertiary aliphatic amines11 with arylsulfonyl chlorides in the
air (Scheme 1b).
Our investigation started with the reaction of p-tolylsulfonyl
chloride with 2 equivalents of triethylamine in the presence of
2.5 mol% Ru(bpy)3(PF6)2 in an atmosphere of argon under
the irradiation of 23 W fluorescent light, which afforded the
partially deoxygenated product (E)-N,N-diethyl-1-(p-tolylthio)-
2-tosyl-ethenamine A (the structure was confirmed by X-ray
analysis of an analogous product starting from N,N-diisopropyl-
One of the major themes for organic chemists is to develop
green and efficient synthetic methods. In this context, in the
last few years visible light photoredox catalysis1 with Ru/Ir
complexes2 or organic dyes3 as photosensitizers seems to play
a more and more important role. Many photo-catalytic reac-
tions have been successfully developed to prepare various com-
pounds. For example, Stephenson4 and others1d,5 reported
that trapping iminium ions generated from tertiary
amines under visible light at room temperature with various
nucleophiles could give rise to α-functionalized products
(Scheme 1a). Our group also found that arylsulfonyl chlorides
could be reduced to arene hypochlorothioites by indoles
subsequently leading to 3-(arylthio)-1H-indoles in visible
light.6 As indicated in some elegant work reported by
ethylamine, Fig. 1a) and
a non-deoxygenated product
(E)-N,N-diethyl-2-tosylethenamine B (Fig. 1b) (Scheme 2a). So
additional oxidants were introduced to improve the yield of
the latter product B.
The same reaction was carried out using an O2 balloon,
and sulfonamide was formed exclusively perhaps as a result
of overoxidation or being sensitive to the concentration of
Scheme 1 Tertiary amines involved in photoredox reactions.
12
O2 (Scheme 2b). However, once this reaction was open to air
in 3 minutes, TsCl was consumed completely and the sole
product β-arylsulfonyl enamine B was formed (Scheme 2c).
Then we screened some factors such as the solvent, photo-
catalyst, temperature, and so on (for detailed information,
see ESI†), achieving the best conditions, under which 1 equiv.
of arylsulfonyl chloride and 4 equiv. of tertiary amine reacted
with 1 mol% Ru(bpy)3(PF6)2 as photocatalyst in the air
between −5 and 5 °C with gentle stirring in acetone.
Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Molecular
Recognition and Function, Chinese Academy of Sciences, Beijing 100190, China.
E-mail: zhengqy@iccas.ac.cn; Fax: +86 010 62554449; Tel: +86 010 62652811
†Electronic supplementary information (ESI) available: Detailed experimental
procedures, analytical data. X-ray crystal data. CCDC 997482 and 997483. For
ESI and crystallographic data in CIF or other electronic format see DOI:
10.1039/c4ob01713g
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Table 1 Scope of arylsulfonyl chlorides
Fig. 1 The crystal structures of (E)-N-isopropyl-N-(2-(p-tolylthio)-2-
tosylvinyl)propan-2-amine (a) and (E)-N,N-diethyl-2-tosylethenamine
(3a, b) (C: gray; H: white; N: blue; O: red; S: yellow).
a Unless otherwise specified, all reactions were carried out with 1
(1 mmol), 2a (4 mmol), photocatalyst (1 mol%) in acetone, under 23 W
fluorescent light between −5 and 5 °C open to air for 3–10 min, and
the yield is the isolated yield.
Scheme 2
With the standard conditions in hand, we investigated
a range of commercially available arylsulfonyl chlorides.
The products are E-form exclusively.13 Besides p-tolylsulfonyl
chloride, o- and m-methyl substituted benzene sulfonyl
chlorides gave almost the same yield of products regardless of
hindrance of the o-methyl group (Table 1, 3a–3c). Benzene sul-
fonyl chloride without any substituents produced the corres-
ponding products in a little lower yield (Table 1, 3d), which
was the same as that of the electron-donating derivative
(Table 1, 3e). The yields varied with the electron-withdrawing
properties, and the reactions involving p-Br and p-Cl benzene
sulfonyl chloride were in higher yield than that of p-F benzene
sulfonyl chloride (Table 1, 3f–3h). The hetero-arylsulfonyl
chloride proceeded well too (Table 1, 3i).
albeit in lower yield (Table 2, 4f). Tertiary amine with hin-
drance, N-cyclohexyl-N-propyl-cyclohexanamine, reacting with
sulfonyl chloride afforded the corresponding β-arylsulfonyl
enamines in acceptable yield (Table 2, 4g).
To probe the intermediary radical species, we added a
radical trapping agent TEMPO to the model reaction of 1a and
2a. The reaction was quenched, and 5 could be detected by
LC-MS (eqn (1)). Thus, the sulfonyl radical may be an inter-
mediate radical. It is worth mentioning that when most of the
above reactions were conducted under vigorous stirring in the
air, a small amount of sulfonamides was generated concomi-
tant with the corresponding β-arylsulfonyl enamines. The side
product sulfonamides were
Next, the scope of tertiary amines was investigated. We
were delighted to find that the sulfonyl chloride reacted with
N,N-diisopropylethylamine (DIPEA) at the terminal of ethyl
rather than isopropyl exclusively (Table 2, 4a). When tri-n-
propylamine and tri-n-butylamine were applied, E- without any
Z-products were obtained (Table 2, 4b–c, for NOESY exper-
iments see ESI†). Cycloamines were examined (Table 2, 4d–e)
from which both regio-isomeric products were obtained. Inter-
estingly, the isomers with endo-double bond were obtained in
higher yield than those with the exo-double bond. Moreover,
the selectivity was excellent when the acycloamines were used
ð1Þ
presumably formed by the reactions of arylsulfonyl chlorides
with secondary amines which may be produced from tertiary
amines. Actually, in 2010, Loh14 reported the process of
copper-catalyzed tertiary amine oxidative conversion to second-
ary amine or enamine via an intermediate iminium ion. And
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Table 2 Scope of tertiary amines
Scheme 4 Proposed mechanism.
10 or 11, respectively. On the other hand, after the hydrogen
atom being abstracted by 11, 7 gives an iminium ion 8,
which lead to two distinct destinies. One is that 8 hydrolyses
to propionaldehyde and diethylamine being converted
into sulfonamide 13, the other is forming enamine 9. Sub-
sequently, 9 may be attacked by 10, followed by being oxidized
and losing a proton, providing the final product 3a.20 However,
the path of 12 reacting with TsCl giving 13 and subsequent E2
elimination of HCl could not be excluded now, although 13
was not detected even by MS.21
a Unless otherwise specified, all reactions were carried out with 1a
(1 mmol), 2 (4 mmol), photocatalyst (1 mol%) in acetone, under 23 W
fluorescent light between −5 and 5 °C open to air for 3–10 min, and
the yield is the isolated yield. b 40 min. c Room temperature, 40 min.
Conclusions
In conclusion, we herein report a novel synthesis method of
β-arylsulfonyl enamines by photoredox catalysis. This reaction
was carried out in non-pretreated acetone open to air, and
most of them completed within 10 minutes without any addi-
tives. Importantly, all of the products are in E-form.
Scheme 3 Enamine involved in reactions.
Acknowledgements
Stephenson15 also verified the feasibility of the iminium ion to
enamine with the photocatalyst. We deduced that the pivotal
intermediate enamine was generated in our system. Therefore,
additional experiments were conducted. When enamine 616
was treated with TsCl under our optimised conditions, 4b was
obtained. While without a photocatalyst within 30 minutes, 4b
was undetectable in the mixture of the reaction (Scheme 3).
Based on the above results and the matched reductive
potential1d of tertiary amines with that of Ru(bpy)32+*/
This work was supported by Major State Basic Research
Development Program of China (2011CB808602).
Notes and references
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Ru(bpy)3 , a possible mechanism is postulated in Scheme 4.
2+
The photosensitizer Ru(bpy)3 is excited by visible light
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+
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2+
cation 7. The highly reducing Ru(I) can regenerate Ru(bpy)3
by transferring one electron to TsCl or O2,19 affording radical
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