ARTICLE IN PRESS
JID: CCLET
[m5G;June 8, 2021;14:4]
K. Yan, H. He, J. Li et al.
Chinese Chemical Letters xxx (xxxx) xxx
Table 1
Optimization of the reaction conditions.a
Entry
Base
Solvent
1a:2a (molar)
Yield (%)b
1
–
DCM
DCM
DCM
DCM
DCM
DCM
DCE
Tol
1:4
1:4
1:4
1:4
1:4
1:4
1:4
1:4
1:4
1:4
1:4
1:7
1:10
1:12
trace
33
32
30
38
55
54
54
43
0
2
KOH
t-BuOK
K2CO3
DBU
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
3
4
5
6
7
8
9
PhCl
HFIP
H2O
H2O
H2O
H2O
10
11
12
13
14
66
73
88
82
a
Reaction conditions: 1a (0.1 mmol), 2a (1.0 mmol), and Et3N (2.0 equiv.)
were dissolved in 1 mL of solvent indicated and were irradiated at room
temperature with blue LEDs (10 W, 470 nm) for 24 h.
b
Isolated yield.
high reactivity [43,44]. A particularly practical reaction to access
cyclopropylenes is the cyclopropenization reaction of alkynes, for
which a variety of expensive, precious metal catalysts, based on
AuII, RhII, IrI, and AgI have been reported [45–48]. Also, a metal-
free cyclopropenization reaction using tosylhydrazones has been
reported, despite the shortcomings of low yields and elevated tem-
perature [34,40,49–51]. In the context of the development of en-
vironmentally benign methods for the synthesis of cyclopropy-
lenes and our previous work, herein we developed a blue light-
induced cyclopropenization reaction of N-tosylhydrazones with
alkynes (Scheme 1c). Notably, this is the first report on light-
induced metal-free cyclopropenizations of N-tosylhydrazones in
water.
Scheme 2. Substrate scope of N-tosylhydrazones and alkynes. Reaction conditions:
1 (0.1 mmol), 2 (1.0 mmol) and Et3N (2.0 equiv.) were dissolved in 1.0 mL of H2O
and were irradiated at room temperature with blue LEDs (10 W, 470 nm) for 24 h.
Isolated yield by chromatography on silica gel.
3aa). Among them, the electronic effect of substituted functional
groups had a strong influence on the yields of target compounds,
which mainly manifested that the transformation efficiency of the
electron-withdrawing substituents was generally lower than that
of electron-donating substituents. Surprisingly, styrenes possessing
fluorine at the benzene ring were exceptions and afforded the cor-
responding cyclopropenes in 83% and 91% yields (3k, 3l), respec-
tively. It is worth mentioning that N-tosylhydrazone and alkyne
substituted by naphthalene had poor compatibility with optimal
conditions, and their corresponding cyclopropylenes were achieved
in yields of 52% and 52% (3r, 3ad). Besides, we explored other
substrates such as heterocyclic terminal alkynes, alkynes bearing
electron-withdrawing groups, and non-aromatic terminal alkynes.
Unfortunately, they were not suitable for this reaction condition,
and no expected cyclopropenes were obtained (2ae-2aj).
Furthermore, other carbene transfer reactions involving the
visible light photolysis of N-tosylhydrazones, such as X-H inser-
tions and cyclopropanations were proved to compatible with these
water-mediated conditions.
Initially, the blue-light-mediated cyclopropenization of N-
tosylhydrazone 1a (0.1 mmol) and phenylacetylene 2a (10 equiv.)
was examined in dichloromethane (DCM) at 25 °C without the
base. Unfortunately, no desired product was detected (Table 1, en-
try 1). Surprisingly, required methyl 1,2-diphenylcycloprop-2-ene-
1-carboxylate (3a) was obtained in yields ranging from 30% to 55%
when using KOH, t-BuOK, K2CO3, Et3N, and DBU as bases, and Et3N
gave the best result (entries 2–6). After that, we further screened
the solvent (entries 6–11), and the results showed that the reaction
proceeded smoothly in water delivering the desired product in 66%
isolated yield (entry 11). Besides, we investigated the equivalents
of phenylacetylene and found that adding 10 equiv. of phenylacety-
lene significantly increased the yield of the target product (entry
13). Finally, through a detailed investigation of the amount of base
and the reaction concentration, we have obtained the optimal re-
action conditions.
Based on the success of the light-mediated cyclopropeniza-
tions of N-tosylhydrazones in water, we further studied the ap-
plicability of this optimal condition to other carbene transfer re-
actions. First, we investigated the insertion reactions between N-
tosylhydrazones and X-H bonds (Scheme 3). Primarily, we focused
on testing N-tosylhydrazones and a variety of aromatic amines. The
results showed that under the optimal conditions, both monosub-
stituted and disubstituted aromatic amines reacted smoothly with
N-tosylhydrazones, and all the expected amino acid ester products
were obtained in good to excellent yields (5a-5n). However, naph-
thalamine reacted with N-tosylhydrazons and afforded the desired
product in 66% yield under these conditions (5o). Unfortunately,
other aliphatic thiols, alcohols, phenols and amines did not pro-
vide the expected products. (4r-4v). Besides, we investigated the
With the optimized conditions in hand (Table 1, entry 13),
we next explored the functional group tolerance of both the N-
tosylhydrazones 1 and alkynes 2 (Scheme 2). In general, sub-
strates with different substituents were compatible with the op-
timized reaction conditions, and the corresponding cyclopropy-
lenes were obtained with moderate to excellent yields (3a-
2