Organic Letters
Letter
a b
,
The key to this approach is the high-energy UV-light, which
can directly cleave the C−S bond to form thianthrene radical
cations and aryl radicals.
Scheme 2. Substrate Scope for Arenes 1
At the initial stage of the investigation, 2-fluoroanisole was
chosen as a substrate to form aryl thianthrenium salt 2a, which
was utilized to explore the optimal conditions of a site-selective
C−H/C−H cross-coupling of simple arenes (Table 1). The
a
Table 1. Screening of Reaction Conditions
a
b
entry
1
variations from the optimal conditions
yield (%) of 4a
c
none
no light
62 (58)
d
2
0
0
d
3
390 nm instead of 254 nm
72 W instead of 144 W
K2CO3 as additive (72 W)
Al2O3 as additive (72 W)
SiO2 as additive (72 W)
phenothiazine as additive (72 W)
air instead of N2
d
4
55
34
53
47
32
35
<30
d
5
d
6
d
7
d
8
d
9
de
,
10
other solvent instead of DMSO
a
Reaction conditions: 2a (0.2 mmol), 3 (2 mL), DMSO (3 mL), UV-
b
light (254 nm, 144 W), quartz vial, rt, N2, 12 h. The yields were
determined by 19F NMR spectroscopy, with 4-fluorotoluene as an
c
d
internal standard. Yield of isolated product. The reaction time is 48
h. Other solvents: CH3COOH, acetone, DMF, CH3NO2, CH3CN,
a
e
Reaction conditions for the first step (see SI); Reaction conditions
for the second step: 2 (0.2 mmol), 3 (2 mL), DMSO (3 mL), UV-
CCl4, DCE, THF.
b
light (254 nm, 144 W), quartz vial, rt, N2, 12 h. Yield of isolated
c
product; yield in parentheses for the first step. 59% 19F NMR yield
was obtained by increasing the reaction scale to 2 mmol, reaction time
is 24h, DMSO (5 mL), furan (3 mL). 47% Yield of isolated product
for 2 mmol scale.
type of light, power, additive, reaction time, and solvent were
notably evaluated. Typically, a 50 mL flat-bottom cylindrical
quartz vial equipped with a magnetic stir bar is charged with
aryl thianthrenium salts 2a (0.2 mmol, 1.0 equiv), furan (2
mL), and DMSO (3 mL). The tube is sealed, and the mixture
is then stirred at room temperature under UV-light (254 nm,
144 W) for 12 h. 4a was obtained in 62% yield, as determined
by 19F NMR spectroscopy (Table 1, entry 1). In the absence of
light or when we used 390 nm UV-light instead of 254 nm UV-
light, 4a was not detected (Table 1, entries 2 and 3). When the
power of the light was reduced by half (72 W), the yield of 4a
dropped to 55%; moreover, it was associated with a longer
reaction time of 48 h (Table 1, entry 4). None of the additives
tested improved the yield (Table 1, entries 5−7). Interestingly,
when the reaction was carried out under air, the yield dropped
to 35%. Finally, among all other tested solvents, none afforded
more than 30% of the desired product (Table 1, entry 10).
With the optimized reaction conditions in hand, we first set
out to explore the scope of arenes 1. Initially, a range of anisole
derivatives was studied, affording promising yields. Various
functional groups were well tolerated under standard
conditions (4a−4m, Scheme 2), with the notable exception
of halides, such as Br-substituents, presumably because of their
incompatibility with the strong UV light. The high chemo-
selectivity observed in the first step is particularly noteworthy.
Furthermore, performing the reaction on a 2 mmol scale
afforded the target effectively (product 4a, 47% isolated yield,
Scheme 2). Subsequently, the substrate scope of intercepting
(hetero)arenes was studied under the standard reaction
d
conditions (Scheme 3). Various substituted nitrogen-contain-
ing heterocycles (5a, 6a), furans (7a, 8a), thiophene (9a, 10a),
and benzenes (11a, 12a) can successfully provide the
corresponding coupling products with encouraging yields.
Moreover, high chemoselectivity (5a, 7a, 8a, 9a, 10a) and
complete regiocontrol were observed.
In order to gain some insight into the reaction mechanism, a
range of control experiments were then carried out. The
reaction gave the desired product in low yields in the presence
of a radical scavenger, such as TEMPO (2,2,6,6-tetramethylpi-
peridin-1-oxyl) or 1,4-dinitrobenzene, suggesting that a radical
pathway is likely involved (Scheme 4, eq 1). This is consistent
with the aerobic condition experiment (Table 1, entry 9, 4a in
35% yield). Next, the radical trapped adducts were identified
and characterized (Scheme 4, eq 2). We could not extract the
TEMPO trapped adduct 13a. However, its reduction product
13b was obtained in 44% isolated yield. Thus, 13a might not
survive the strong UV-light conditions of the reaction.
Thereafter, several hydrogenation experiments were attempted
(Scheme 5). In the presence of cyclohexa-1,4-diene, both 4a
and 1a were obtained in 26% and 27% yield, respectively
(Scheme 5, eq 3). In the absence of furan, 1a was obtained in
69% yield (Scheme 5, eq 4). When 2c was utilized in the
otherwise same hydrogenation experiment, hydrogenation
product 1c was obtained in 58% isolated yield. Next, a UV
B
Org. Lett. XXXX, XXX, XXX−XXX