Organic Letters
Letter
because of their good chemical and photostability, high
oxidation and reduction potentials, and relatively long
excited-state lifetimes. Among them, photopromoted radical
Heck-type reactions utilizing alkyl radical species generated
from alkyl halides,8a,c phthalimides,8b and alkylpyridinium
salts8d,e have been reported for the synthesis of alkylated
alkenes (Scheme 1c). However, transition-metal-based photo-
redox catalysts have several disadvantages, such as high cost
and toxicity. Recently, the development of metal-free methods
using organo-photoredox catalysts has also garnered much
attention because these catalysts are inexpensive, less toxic, and
easy to modify.7 Despite the recent progress in the area of
photoredox catalysis, ATRS couplings promoted by organo-
photoredox catalysts remain underdeveloped, with only a few
reports.9
formation of γ-lactone 5a as the major product (entry 7). In
order to increase the yield of 3a, the reaction was carried out
using various additives. Although the use of inorganic bases
such as K2CO3 and Cs2CO3 afforded high yields of 3a, t-BuOK
and Et3N were found to be ineffective for this reaction (entries
8−11). Using 2 equiv of (TMS)2NH was particularly effective
in promoting ATRS, giving a better yield of 3a than the other
bases (entry 12). The yield of 3a did not significantly change
when the reaction was carried out using a lower amount of
(TMS)2NH (1.2 equiv; entry 13). Surprisingly, when the base
and solvent were changed, carboesterification proceeded
selectively to produce 5a in 89% yield (entry 14).
Having identified the optimal reaction conditions, the scope
and limitations of the visible-light-promoted ATRS were
examined. As shown in Table 2, the reaction of various alkyl
On the basis of the chemistry of the ATRS reactions, we
herein report an organo-photoredox-catalyst-mediated inter-
molecular ATRS reaction of alkenes 2 with alkyl halides 1
(Scheme 1, this work). Moreover, we also show that ATRS can
be switched to the corresponding carboesterification reaction
by changing the base.
Table 2. Substrate Scope of the ATRS Reaction with Alkyl
Halides
a
Initially, we screened various organo-photoredox catalysts
for ATRS between the test substrates, ethyl 2-bromoisobuty-
rate (1a) and 1,1-diphenylethylene (2a) (Table 1). Upon the
a
Table 1. Optimization of the Reaction Conditions
b
entry
catalyst
solvent
additive
3a/5a (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
PDI
MeCN
MeCN
MeCN
MeCN
toluene
CH2Cl2
DMSO
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
DMSO
trace
n.r.
eosin Y
BDN
PTH
PTH
PTH
PTH
PTH
PTH
PTH
PTH
PTH
PTH
PTH
55/28
68/22
26/39
59/7
15/60
81/5
76/12
33/13
n.r.
K2CO3
Cs2CO3
tBuOK
a
A mixture of 1a (1.0 mmol), 2 (0.5 mmol), (TMS)2NH (1.0 mmol),
1.0 mol % of PTH, and CH2Cl2 (1 mL) was stirred at room
temperature upon LED (365 nm) irradiation for 24 h under N2.
Et3N
(TMS)2NH
(TMS)2NH
Cs2CO3
88/0
86 (83 )/0
0/89 (88 )
c
d
c
d
halides 1a−e with 2a afforded the corresponding ATRS
products 3a−e in yields of 60−85%. The reaction was not
significantly affected by the substituent on the α-carbon of the
carbonyl group, including the presence of a long-chain alkyl
group or a cyclic alkyl group such as cyclobutyl or cyclohexyl.
Secondary and primary α-bromo esters also gave excellent
yields of ATRS products 3f−h. The reaction of α-bromo
lactones produced good yields of the corresponding ATRS
products 3i and 3j. α-Bromomalonate was converted to 3k in
79% yield. Therefore, this reaction is compatible with various
functional groups, including ketones, nitriles, and nitro groups,
and generates ATRS products in good to excellent yields.
Furthermore, perfluoroiodides could also be employed to form
the coupling products 3o and 3p in moderate yields.
a
A mixture of 1a (1.0 mmol), 2a (0.5 mmol), additive (1.0 mmol),
1.0 mol % PTH, and the solvent (1 mL) was stirred at room
temperature with LED irradiation for 24 h under N2. NMR yields
b
determined using 1,1,2,2-tetrabromoethane as an internal standard.
c
d
1.2 equiv of (TMS)2NH was used. The yield of the isolated product
is given in parentheses.
LED irradiation at 420 nm, PDI and eosin Y were found to be
ineffective for ATRS. However, the addition of BDN and PTH
under LED irradiation at 365 nm afforded the ATRS product
3a in 55% and 68% yield, respectively, and the carboester-
ification byproduct 5a was also obtained in 28% and 22% yield,
respectively (entries 1−4). With PTH as the optimal catalyst, a
series of solvents were screened for the reaction. Lower yield
and selectivity for 3a were observed in toluene, while in
CH2Cl2 the desired product 3a was formed with high
selectivity (entries 5 and 6). The use of DMSO led to the
As shown in Table 3, a variety of substituted vinylarenes
were reacted with 1a under the optimal conditions, and good
to high yields of the desired products 4 were obtained. Styrene
was converted to 4a in 67% yield with an E/Z ratio of 45/55. It
B
Org. Lett. XXXX, XXX, XXX−XXX