Organic Letters
Letter
a
During the past few years, our group has established many
radical-triggered 1,n-enyne transformations for the synthesis of
a series of valuable cyclic structures with bioactive
Table 1. Condition Optimization for Product 3a
1
2
importance. To continue our efforts in radical trans-
formations and by means of sustainable characteristics of
4
electrosynthesis, we approach an electrochemical strategy to
install both a sulfonyl and an iodo moiety into the
spirocyclohexadienone-containing indene skeleton because of
the behaviors of sulfonyl and iodo groups in the wide
application of numerous chemical transformations, such as
b
entry
variation from the established conditions
3a/4, yield (%)
1
2
3
4
5
6
7
8
none
64/0
trace/42
43/0
40/0
52/0
36/0
trace/0
21/0
47/0
41/0
1
3
14
desulfonylation, cross-coupling reactions, and nucleophilic
10 mA instead of 20 mA, 4 h
30 mA instead of 20 mA, 4 h
NaI instead of KI
1
5
substitutions. The synthesis of (E)-spiroindenes incorporat-
ing both sulfonyl and iodo moieties, to the best of our
knowledge, remains unreported. For this reason, an electro-
catalytic annulation−iodosulfonylation of 1,5-enyne-containing
p-QMs 1 with arylsulfonyl hydrazides 2 in the presence of
potassium iodide (KI) was conducted, enabling a sulfonyl-
LiI instead of KI
NH I instead of KI
4
TBAI instead of KI
2.0 equiv of 2a
2.0 equiv of KI
GR(+)|Pt(−) instead of Pt(+)|Pt(−)
GR(+)|GR(−) instead of Pt(+)|Pt(−)
+
radical-triggered 1,6-addition and an I -mediated ipso-cycliza-
9
tion cascade to access spirocyclohexadienone-containing (E)-
indenes 3 with high efficiency (Scheme 1). Herein we
c
10
11
12
13
14
15
16
37/0
d
1,4-dioxane/H O (1:1) as solvent
trace/0
ND/0
66/0
77/0
42/0
2
Scheme 1. Profile for the Synthesis of (E)-Spiroindenes
DMF/H O (1:1) as solvent
2
DCE/CH OH (3:1) as solvent
3
e
e
DCE/CH OH/H O (3:1:0.25) as solvent
3
2
DCE/CH OH/H O (1:3:0.25) as solvent
3
2
a
Reaction conditions: Pt anode, Pt cathode, undivided cell, constant
current = 20 mA, 1a (0.1 mmol), 2a (0.3 mmol), and KI (0.3 mmol),
THF (2.0 mL), and H O (2.0 mL) under room temperature for 4 h.
2
b
c
Isolated yield based on substrate 1a. Graphite rod (GR) electrode.
Volume ratio. Total solvent (4.25 mL).
d
e
elaborate this attractive approach toward (E)-spiroindene
synthesis via the electrolysis of easily available substrates
along with nitrogen and hydrogen as major byproducts. This
electrochemical three-component reaction could be performed
at room temperature under air conditions without any
oxidative reagent or catalyst. Remarkably, the low-cost
potassium iodide behaved as an electrolyte, a redox catalyst,
and an iodination reagent.
electrolytes, the former three could drive the transformation
into 3a, but all demonstrated poor efficiency as compared with
KI (entries 4−6 vs entry 1), whereas the last one completely
suppressed the reaction process (entry 7). Moreover, lowering
the amount of 2a or KI was not beneficial for the yield of
product 3a, and its obvious loss was observed (entries 8 and
9). To probe the electrode effect, a graphite rod (GR)/
platinum plate and a GR/GR were used in this transformation
and delivered product 3a in 41 and 37% yield, respectively
(entries 10 and 11). Next, the effect of the solvents was
investigated (entries 12−16). A range of mixed solvents,
including DMF/H O, DCE/CH OH, and DCE/CH OH/
We initiated our studies by using 1,5-enyne-containing p-
QM 1a and TsNHNH (2a) as model substrates and two
2
platinum plates as the working electrodes to identify the
optimal reaction conditions (Table 1). The reaction of 1a with
2
3
3
2
a worked well in the presence of potassium iodide in a mixed
H O were screened, and of these three mixed solvents, the
2
solvent of THF and water (v/v 1/1) under a 20 mA constant
current mode at room temperature, and the expected (E)-
product 3a was obtained in 64% yield in a completely
stereoselective manner without the observation of 4 (entry 1).
The stereostructure of 3a was identified by single-crystal X-ray
diffraction (CCDC 1991999). The reaction efficiency was
found to have a profound dependence on the operating
current. Adjusting the operating current to 10 mA gave the 1,6-
addition product 4 in 42% yield, which was a key intermediate
for the formation of product 3 (entry 2; see the control
experiments). In contrast, increasing the operating current to
mixed DCE/CH OH/H O solvent (v/v/v 3/1/0.25) proved
3
2
to be the best choice for this domino process, as a higher yield
of 3a was provided (77%, entry 15).
With the optimized conditions in hand, a series of 1,5-
enyne-containing p-QMs 1 and arylsulfonyl hydrazides 2 were
prepared and exploited to systematically examine the general-
ization and limitation of this electrochemical annulation-
iodosulfonylation reaction. The results are presented in
Scheme 2. First, p-tolyl sulfonhydrazide (2a) was reacted
with p-QMs 1 with different electronic properties and positions
of substituents in the arylalkynyl moiety, and all of them could
be successfully engaged in this electrocatalytic cyclization with
good efficiency and complete (E)-selectivity. Different
substituents such as methyl (1b−d), ethyl (1e), tert-butyl
(1f), phenyl (1g), methoxy (1h and 1i), fluoro (1j), chloro
(1k−m), ester (1n), and cyano (1o) groups were compatible
with these electrocatalytic conditions, furnishing the corre-
sponding products 3b−o in 42−93% yield. Of these functional
groups, a strong electron-withdrawing ester group seemed
3
0 mA resulted in a lower conversion, and a remarkably
reduced yield of 3a was observed (entry 3). The results
revealed that potassium iodide acted as both a supporting
electrolyte and an iodine source. Therefore, some other
iodides, such as sodium iodide (NaI), lithium iodide (LiI),
ammonium iodide (NH I), and tetra-n-butylammonium iodide
4
(
TBAI), often employed as supporting electrolytes in the
electrocatalysis, were then evaluated. Among these supporting
B
Org. Lett. XXXX, XXX, XXX−XXX