O.M. Mulina, A.I. Ilovaisky, T. Opatz et al.
Tetrahedron Letters 64 (2021) 152737
without eosin Y or without light irradiation (Entries 13 and 14).
Hence, according to the obtained experimental data, the reaction
proceeded optimally under an inert atmosphere with 1 mol% of
eosin Y as the photocatalyst, 1.5 equivalents of sulfinate 2a and
EtOH as the solvent (Table 1, Entry 9).
With the optimized reaction conditions in hand (Table 1, Entry
9
), we investigated the scope of photoredox-catalyzed synthesis of
N-unsubstituted enaminosulfones (Table 2). A range of aromatic
sodium sulfinates 2 containing both electron-donating and elec-
tron-withdrawing groups were compatible with the developed
process resulting in enaminosulfones 3a-3f in moderate to high
yields. Sodium methanesulfinate also provided the desired product
3g in 52% yield. Various aromatic vinyl azides gave the desired
enaminosulfones 3h-3j in 38–68% yield.
Scheme 1. Formation of N-unsubstituted enamine derivatives through radical
addition to vinyl azides.
Initial reaction conditions (catalyst loading and solvent, Entry 1)
were chosen according to optimal conditions for the photoredox-
catalyzed sulfonylation of alkenes reported by Kӧnig and co-work-
ers [22]. Firstly, the amount of eosin Y necessary for the effective
synthesis of enaminosulfone 3a was studied (Entries 1–3). It was
shown that even 1 mol% led to the formation of 3a in a 56% yield
In order to gain insight into the reaction mechanism we carried
out additional fluorescence quenching experiments with eosin Y
(Scheme 2). Nitrobenzene and sodium benzenesulfinate 2a were
tested as potential quenchers. When nitrobenzene was added,
the fluorescence of eosin Y decreased roughly proportionally to
the added amount (Scheme 2a). Addition of sodium benzenesulfi-
nate 2a to eosin Y caused a slight increase of eosin Y fluorescence
(Scheme 2b). Presumably, this is due to a salt effect and/or inhibi-
tion of self-quenching of eosin Y. Further increase of 2a concentra-
tion did not result in any significant changes of fluorescence.
Based on these results and the reported literature [10,22], we
have proposed a plausible pathway for the formation of N-unsub-
stituted enaminosulfones 3 from vinyl azides 1 and sodium sulfi-
nates 2 (Scheme 3). Initially, the process presumably involves an
oxidative quenching cycle and begins with the generation of a
nitrobenzene radical anion under the action of photoexcited eosin
Y. The formed eosin Y radical cation oxidizes the starting sodium
sulfinate 2a to the corresponding sulfonyl radical A [10]. Subse-
quently, radical A adds to the double bond of vinyl azide 1a with
(
Entry 3). Then, screening of solvents was performed (Entries 4–
). Use of DMF-H O and EtOH-H O mixtures gave slightly inferior
results with yields of 48% and 47%, respectively (Entries 4–5).
Application of DMF-H O resulted in 3a only in a 38% yield (Entry
). Entry 7 showed that application of an inert atmosphere led to
6
2
2
2
6
a slight increase in the yield of enaminosulfone 3a, while repro-
ducibility of the results was much better in this case. Therefore,
all further experiments were performed under an inert atmo-
sphere. The correlation between the molar ratio of starting
reagents and the yield of 3a was then investigated (Entries 8–
1
0). Use of a 1.5-fold molar amount of vinyl azide 1a did not result
in noticeable changes of enaminosulfone 3a yield (Entry 8), while
increasing the amount of sulfinate 2a to 1.5 equivalents increased
the yield of 3a up to 67% (Entry 9). Application of a twofold excess
of 2a did not lead to a further rise in the yield of 3a (Entry 10).
Some control experiments were also carried out. When the amount
of nitrobenzene was decreased or it was excluded from the reac-
tion, the yield of 3a dropped (Entries 11 and 12). Product 3a was
obtained only in trace amounts when reactions were performed
the release of N resulting in iminyl radical B [23–25]. The formed
2
radical B is reduced by the nitrobenzene radical anion. Finally, the
resulting anion C is protonated to give the corresponding imine D,
which tautomerizes into the desired product 3a.
Table 1
a
Reaction optimization for the visible light photoredox-catalyzed synthesis of N-unsubstituted enaminosulfone 3a.
Entry
Molar ratio 1a:2a
Eosin Y (mol%)
Solvent
Atmosphere
Yield 3a (%)b
1
2
3
4
5
6
7
8
9
1:1
1:1
1:1
1:1
1:1
1:1
1:1
1.5:1
1:1.5
1:2
1:2
1:2
1:2
1:2
10
3
1
1
1
1
1
1
1
1
1
1
0
1
EtOH
EtOH
EtOH
DMF-H
DMF-EtOH (1:1)
EtOH- H
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
air
air
air
air
air
air
argon
argon
argon
argon
argon
argon
argon
argon
27
55
56
48
38
47
59
57
67 (62)
68
57
47
traces
traces
2
O (1:1)
2
O (1:1)
10
11
12
13
14
c
d
e
a
General procedure: a solution of vinyl azide 1a (145–218 mg, 1–1.5 mmol), sodium benzenesulfinate 2a (164–328 mg, 1–2 mmol), nitrobenzene (123 mg, 1 mmol), and
eosin Y (7–70 mg, 1–10 mol%) in solvent (4 mL) was irradiated with green LEDs for 14 h at room temperature under magnetic stirring.
b
c
1
The yields were determined by H NMR spectroscopy using 1,4-dinitrobenzene as an internal standard; the isolated yield is reported in parentheses.
The reaction was carried out with 50 mol% of nitrobenzene.
The reaction was carried out without nitrobenzene.
The reaction was carried out without green LEDs irradiation.
d
e
2