Organic Letters
Letter
mmol), 2a (0.4 mmol), and 2,4,5,6-tetra(9H-carbazol-9-
yl)isophthalonitrile (4CzIPN) (5 mol %) in dimethyl
carbonate (DMC, 2 mL) as a green solvent at room
temperature under the irradiation of a blue LED (5 W) and
an air atmosphere for 6 h.
With the optimal conditions in hand, we further explored
the scope of this reaction (Scheme 2). Initially, the suitability
in situ generated acyl radical was converted into the more
stable tert-butyl radical via decarbonylation. Moreover, to
evaluate the practicability of this acylation reaction, the gram-
scale synthesis of 3aa was carried out, and a 79% yield was
obtained, suggesting that the current protocol is practical and
promising for preparative synthesis. (For details, see the
To explore the applicability of this photocatalytic system, we
next investigated substrates other than 1. (For details, see the
arylpropiolamides 4a and 2a using benzoyl peroxide (BPO) as
an oxidant in CH3CN under a N2 atmosphere gave the
acylated azaspiro[4.5]trienone (5a) in 77% yield (Scheme 3).
Scheme 2. Synthesis of Benzimidazo/Indolo[2,1-
a]isoquinolin-6(5H)-ones
a
Scheme 3. Synthesis of Aroylazaspiro[4.5]trienones and
a
Acylated Thioflavones
a
Reaction conditions: 1 (0.2 mmol), 2 (0.4 mmol), and 4CzIPN (5
mol %) in DMC (2 mL) at room temperature for 6 h in an air
b
atmosphere under a blue LED. Isolated yields are given. On the gram
scale.
of a series of α-oxocarboxylic acids was investigated. As
anticipated, the aliphatic and aromatic α-keto acids with both
electron-donating and electron-withdrawing substituents such
as −Me, −Ph, −OMe, −F, and −CF3 could be converted into
the desired annulation products (3aa−3ai) in good yields
(44−87%). In general, aliphatic α-keto acids (3ab, 3ac)
provided slightly lower yields compared with aromatic α-keto
acids (3aa and 3ad−3ai). To our delight, N-methacryloyl-2-
arylbenzoimidazoles bearing various electron-donating groups
or electron-withdrawing groups could react with 2a to give the
corresponding target products (3aj−3as) in 76−92% yields.
Specifically, when N-phenylacryloyl-2-phenylbenzoimidazole
1t was employed as a substrate to react with 2a under the
standard conditions, the corresponding product 3at was given
in 70% yield. Next, the scope of the 2-aryl indoles was
investigated. Halosubstituted indole derivatives, including F-,
Cl-, and Br-bearing indoles, could afford the desired indolo-
[2,1-a]isoquinoline derivatives 3bd−3bf in moderate yields
(61−66%). Moreover, −Me, −CF3, and −CN on the indole
ring could also be compatible to provide the corresponding
products (3bc, 3bg−3bl) in 51−81% yields. Additionally,
when we used 3,3-dimethyl-2-oxobutyric acid as the acyl
radical precursor, the unexpected products (3au and 3bj) were
obtained in 68 and 47% yields, respectively. In this process, the
a
Reaction conditions: 4 or 6 (0.2 mmol), 2 (0.4 mmol), 4CzIPN (5
mol %), and BPO (3 equiv) in CH3CN (2.5 mL) with the irradiation
of a blue LED at room temperature under N2. Isolated yields are
given.
Subsequently, the scope of various substituted N-arylpropio-
lamides 4 and α-keto acids 2 was further surveyed. The desired
products (5a−5o) were afforded in 50−80% yields.
Furthermore, when methylthiolated alkynones 6 were
employed to react with both aliphatic and aromatic α-keto
acids, the corresponding products, thioflavones 7a−7i, were
synthesized in good yields (69−84%).
To our satisfaction, the approach was also suitable for the
construction of acylated heterocycles, including quinoxalin-
2(1H)-one (9), acylated quinolone (11), chroman-4-one (13),
and isoquinoline (15) (Scheme 4). Importantly, the strategy
was well tolerated by the phenol group to give the desired
product 15,11 an analog of Roxadustat, which is an oral drug to
regulate erythropoiesis and iron metabolism.
2977
Org. Lett. 2021, 23, 2976−2980
Zhu, Hu-Lin
