UPDATES
and 11). The most interesting results were observed when in the presence of electron-donating and elec-
when the reaction was performed in different atmos- tron-deficient substituents at the ortho-, meta-, and
pheres (air vs. Ar). While synthesis in the Ar para-positions in the phenyl ring, provided the desired
atmosphere resulted in hydroxyl-containing quinoxa- products in moderate to good yields (Table 2, 3b–3h,
lin-2(1H)-one 4a as the major product (entry 5), 65–82%). The reaction yield decreased when we
synthesis in air resulted in acylated product 3a as the carried out the reaction with trifluoromethyl substituted
major product (entries 12–14). Further improvement in α-oxocarboxylic acid (3i, 57%). Moreover, with 2-(4-
the yield of acylated product 3a was observed when nitrophenyl)-2-oxoacetic acid, the reaction did not take
we decreased the amount of the catalyst under air place (3j). The main reason for this might be that the
atmosphere (entry 13, 79%).
strong electron-withdrawing group decreased the addi-
We then explored the scope of the synthesis of tion susceptibility of acyl radicals to quinoxalin-2(1H)-
[2d,e,10]
quinoxalin-2(1H)-ones. Various quinoxalin-2(1H)-ones ones.
and α-oxocarboxylic acids 2 provided the desired Heteroaromatic ring- or naphthyl-containing sub-
1
acylated products 3 in moderate to good yields in air strates provided the desired products in moderate to
atmosphere (Table 2). Various α-oxocarboxylic acids, high yields (3k–3m, 57–86%). Other heteroarenes
such as quinoline, isoquinoline, 2H-indazole, and
quinoxaline did not provide the desired products in this
transformation (for details, see the Supporting Infor-
Table 2. Substrate scope: synthesis of acylated quinoxalin-
[a]
mation). Next, we employed an alkyl substituted α-
oxocarboxylic acid, tert-butylglyoxylic acid was found
to be suitable substrate in this reaction (3n, 62%).
Quinoxalinones 1 bearing substituents on the aromatic
ring, such as chloro and dimethyl groups, produced the
corresponding products, but only at relatively low
yields (3o: 59%, 3p: 44%). Other amine protecting
groups, including phenyl, benzyl, and alkyl groups,
were tolerant under the reaction conditions, producing
the desired products in good to high yields (3q–3t,
2(1H)-ones.
66–89%). However, unprotected quinoxalinones did
not provide the desired products (not shown).
Next, the substrate scope for the synthesis of
hydroxyl-containing quinoxalin-2(1H)-ones was ex-
plored (Table 3).
Similar to the results achieved with the acylated
quinoxalin-2(1H)-ones, various quinoxalin-2(1H)-ones
1
and α-oxocarboxylic acids 2 provided the desired
products 4 in moderate to high yields (48–95%).
However, no desired products were obtained with alkyl
substituted α-oxocarboxylic acids in the reaction (not
shown), which may be due to the lack of the stability
of the radical intermediates. Quinoxalinones 1 bearing
dimethyl groups on the aromatic ring produced the
corresponding products in good to high yields (Table 3,
4
o–4s: 72–95%). However, relatively low yields were
observed with 2-thiopheneglyoxylic acid (4m, 48%)
and 7-chloro-1-methylquinoxalin-2(1H)-one (4n,
49%).
To gain a mechanistic insight into this reaction, we
performed control experiments (Scheme 2). When
TEMPO (2,2,6,6-tetramethyl-1-piperidinyloxy) was
employed as a radical inhibitor, no reaction was
observed, indicating that the reaction mechanism
[11]
includes a radical pathway. Moreover, the fact that
no desired product was observed in the presence of
[
a]
Reactions conducted on 0.5 mmol scale.
[b]
1
Reaction conducted on 6.5 mmol scale. Yields are of the
isolated products after column chromatography. For details,
see the Supporting Information.
NaN , a well-known strong singlet oxygen ( O )
3
2
1
quencher, proves that O is involved in this trans-
formation under air atmosphere (Scheme 2, a).
2
[12,13]
Adv. Synth. Catal. 2021, 363, 1443–1448
1445
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