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saccharin (NBSA) was found to possess a significantly weaker
NÀBr bond (48 vs. 62 kcalmolÀ1 in NBS, Figure 1B), which
would be more amenable to visible-light photolysis (400–
700 nm, 40–70 kcalmolÀ1). Indeed, when a solution of NBSA
and benzene (1.5 equiv) in CH2Cl2 was exposed to ambient
light[11] under ambient temperature, an imidation reaction oc-
curred smoothly and the expected adduct was isolated in 73%
yield. In sharp contrast, no reaction was observed with other
N-halogen imides, such as N-bromosuccimide (NBS) and N-bro-
mobenzosuccimide (PNBS) (Figure 1B). The photolytic nature
of the reaction can be verified by the following experimental
observations: 1) no reaction in the dark, 2) the reaction was
stopped by protection from light and restarted by exposure to
light (Figure 2, and Schemes S1–S2 in the Supporting Informa-
was sufficient to deliver a decent yield of imidation adduct
(61%). The use of 1.5 equivalents of benzene was found to
give better yield (73%). A gram-scale reaction with 1.5 equiva-
lents of benzene worked equally well to give a 69% yield. A
plethora of substituted arenes were explored (Scheme 1).
Mono- and disubstituted benzenes, either electron-withdraw-
ing or -donating, can be applied to give the imidated adducts
(3b–m). The observed regioselectivity is generally para- and
ortho- directing, consistent with substitute effect typically ob-
served in radical aromatic substitution reactions (Figure 3).[12]
The steric effect would also contribute in the regioselective
control as reflected by the generally favored para-selectivity. In
the cases with tert-butylbenzenes, the sterically controlled pro-
cess becomes dominant with the major imidation site remote
to the bulky tert-butyl group (3 f and 3j). In an extreme con-
text, the regioselectivity is even reversed with 1-bromo-4-tert-
butylbenzene compared with that of 1-bromo-4-methylben-
zene (3j vs. 3i). Polyarenes, such as naphthalene, anthracene,
and phenanthrene, are also workable to give single imidation
adducts (3n–p). Notably, the reactions with biphenyls occurred
exclusively para to the phenyl moiety (the substituted one)
(3q and 3r) and no other regioisomers were detected. It
should also be noted that the current reaction didn’t work well
with highly electron-rich arenes/heteroarenes, such as phenols
and anilines.[13]
The catalyst-free imidation reaction has also been tested
with heteroarenes. In this regard, N-Boc-pyrrole (tert-butoxycar-
bonyl) and N-Boc-indoles worked well in the reactions to give
the desired adducts in high yields (Scheme 1, 4a–4e), al-
though their N-methylated derivatives worked poorly. Pyridine,
(benzo)thiophene, and benzofuran are also applicable to the
present conditions to furnish imidated adducts in moderate to
high yields (4 f, g).
Figure 2. Light-responsive behaviors by in-situ monitoring the consumption
of NBSA at 1228 cmÀ1
.
tion), 3) the addition of a typical radical species, such as
2,2,6,6-tetramethylpiperidine N-oxide (TEMPO), shut down the
reaction, which indicated the radical nature of the reaction,
and 4) indeed, a radical species was detected in a solution of
NBSA only or in the reaction mixture under ambient light irra-
diation (see Scheme S3 in the Supporting Information). Consis-
tent with their inertness in the reactions, no radical species
was detected with NBS and PNBS under visible-light irradiation
(see Scheme S3 in the Supporting Information). The UV/Vis
spectroscopy of NBSA has also been examined in CH2Cl2 either
alone or in the presence of benzene (1.0 equiv), showing peak
absorption at 288 nm, which tails above 400 nm (e400 =30,
e450 =12) (see Scheme S4 in the Supporting Information). No
change of absorption in the visible light range was observed
in the presence of benzene. A 405 nm laser light resource has
also been examined in the reactions, which shows comparable
results with that by ambient light or LED blue-light irradiation
(see Scheme S2 in the Supporting Information). It seems weak
absorption in the visible-light range may ensure a steady and
controllable generation of the active radical species, and thus
facilitate a chemoseletive reaction. Similarly, the known UV
photolytic imidation with NBS has also been performed at the
weak-absorption range of NBS (e300 =13).[9f]
In all the examined cases in Scheme 1, no brominated
arenes/heteroarenes byproducts have been identified. In the
reactions with toluenes, benzyl bromides can be isolated from
the reaction mixture, and the benzyl bromination with bromo
radical by the Goldfinger or Bloomfield mechanism may com-
pete with the imidyl radical addition pathway in these cases.[14]
Fortunately, the benzyl bromide byproducts can be easily sepa-
rated from the major imidation adducts (e.g. 3e, 3g, and 3h).
On the basis of previous knowledge as well as our own ex-
perimental observations, the homolytic radical substitution
pathway can be proposed. Accordingly, the reaction is initiated
by visible-light photolysis of NBSA to generate saccharin N rad-
ical and Br radical (Scheme 2, step 1). The critical N radical ad-
dition to arene leads to a cyclohexadienyl-type radical inter-
mediate Int-1 (Scheme 2, step 2), which undergoes rearomati-
zation to give the imidation adduct (Scheme 2, step 3). Mecha-
nistically, three rearomatization pathways can be conceived
(Scheme 2). The first one is the radical propagation route
(Scheme 2, pathway I), in which the cyclohexadienyl-type radi-
cal reacts with N-bromo saccharine to generate the final prod-
uct together with a new N radical and HBr. In the radical
quenching route II (Scheme 2, pathway II), Br radical recom-
bines with Int-1 to give intermediate Int-2, and the following
HBr elimination affords the final product; the third one is the
The scope of this mild imidation protocol was next investi-
gated. In the reaction of benzene, a 1:1 arene/NBSA mixture
Chem. Eur. J. 2014, 20, 14231 – 14234
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