Organic Letters
Letter
a
irradiation of blue LED with excellent yields under mild
conditions without the involvement of any transition metal
reagents or organic dyes. Various functional groups and other
heterocyclic compounds are tolerated (Scheme 1, bottom).
Herein, we report our results on visible-light-induced
transition-metal-free dehalogenation of aryl fluorides, chlor-
ides, bromides, and iodides in detail.
Scheme 2. Reaction Scope of Aryl Chlorides
First, the reaction conditions were investigated using the
dechlorination of 4-chloro-1,1′-biphenyl 1a as a model reaction
(Table 1). When the reaction was performed in the presence of
a
Table 1. Reaction Conditions
b
b
entry
x
light source
blue LED
T (°C)
time (h)
2a (%)
1a (%)
1
2
3
4
5
6
3
3
3
3
4
5
5
35
35
90
35
35
35
10
10
10
24
24
24
24
43
̵
51
39
16
40
13
̵
c
̵
̵
c
19
60
87
96
̵
blue LED
blue LED
blue LED
blue LED
d
7
35
100
a
t
Conditions: 1a (0.5 mmol), BuOK (2.5 mmol), dry DMF (4 mL),
3
5 °C, under irradiation of blue LED (405 nm, 27 W) under the
b
1
atmosphere of argon. Yields were determined by H NMR analysis
of crude products using nitromethane as an internal standard. No
light. Tetrahydrofuran, benzonitrile, or octane was used as the
c
d
solvent.
t
3
equiv of BuOK in DMF under the irradiation of blue LED
(
405 nm, 27 W), 43% of dechlorinated product 2a was
obtained with 51% of 1a recovered (entry 1). When
dechlorination of 1a was performed in the absence of blue
LED irradiation, no 2a was generated (entry 2). Elevated
temperature without light gave only 19% of 2a (entry 3).
Prolonging the reaction time or increasing the amount of
a
t
Conditions: 1 (0.5 mmol), BuOK (2.5 mmol), dry DMF (4 mL), 35
C, under irradiation of blue LED (405 nm, 27 W) under the
°
t
BuOK resulted in the improvement in yield of 2a (entries 4−
b
c
atmosphere of argon, isolated yields. 10 mL of DMF. 1.5 mmol of
t
d
e
t
6
). Other solvent such as tetrahydrofuran, benzonitrile, or
BuOK, 6 mL of DMF. DMSO as a solvent. 1.0 mmol of BuOK, 6
octane was used as the solvent but gave no desired product
mL of DMF.
t
(
entry 7). Reaction in the presence of MeOK instead of BuOK
was also investigated, affording 2a in 11% yield with 89%
recovery of 1a. These indicate that both BuOK and DMF are
necessary for this reaction. The reaction conditions in Table 1
t
11
grows rapidly, light-induced hydrodefluorination of aryl
fluoride remains rare. Wu et al. reported UV light-induced
reduction of aryl halides with excess trimethylamine, and one
example of hydrodefluorination of aryl fluoride is reported with
(
entry 6) were then selected as the standard conditions.
With the optimized reaction conditions in hand, we first
10a
explored the scope of aryl chlorides (Scheme 2). Biphenyl
1a), naphthyl (1b,c), as well as anthracenyl (1d) chlorides
68% yield. Fagnoni and co-workers reported that electron-
rich aryl fluorides could be converted to the corresponding
electron-rich arenes by UV irradiation either in neat
isopropanol or in an acetonitrile solution of hypophosphorous
(
reacted smoothly under the standard conditions, providing the
corresponding reduction products in 70−97% yields. More-
over, aryl halides bearing either electron-withdrawing (1e−i)
or electron-donating (1j−k) groups proved to be competent
substrates affording the corresponding arenes in 51−100%
yields. Chlorinated heteroarenes such as chlorodibenzofuran
10e
acid.
When aryl fluorides 3a−e were subjected to the
standard conditions stated in Table 1 (entry 6), hydro-
defluorination proceeded smoothly to afford the corresponding
arenes in excellent yields (Scheme 3). This result indicates that
this method might be useful for both organic synthesis and
pharmacy. Hydrodehalogenation of aryl halides bearing two
halogens 3f−h was also investigated. To our delight, with
prolonged reaction time both halides on the aryl halides could
be reduced effectively, yielding the corresponding arenes 2 in
good yields. This demonstrated the utility of this method.
To further investigate the scope of this system, aryl halides
bearing bromides 4 and iodides 5 were also tested, and the
(
1l), chloroindole (1m−n), chlorocarbazole (1o), chloroqui-
noline (1p−s), chloroisoquinoline (1t−v), as well as
chloromethylquinoline (1w) were also tolerated.
Hydrodefluorination of organic fluorides is not only a useful
method for detoxification of environmentally hazardous
chemicals containing halogen atoms but also an important
strategy for functionalizing molecules especially in drug
discovery. Although the development of hydrodefluorination
B
Org. Lett. XXXX, XXX, XXX−XXX