Communication
our delight, in halogenated solvents (chloroform, dichlorome-
thane) the reactions took place more rapidly, and almost full
conversion (entries 7 and 8; 97%) was obtained in dichloro-
ethane in 20 minutes (entry 9). The best result (full conversion
in 20 min at 258C) was achieved in toluene under the same re-
action conditions (entry 10). Besides ammonia, we tested other
bases in the transformation, and we found that K2CO3, KOtBu,
and NaOH are also effective in the reaction (entries 11–13).
With these results, we demonstrated that the more bulky
group can be transferred to the target heterocycle, and that
the N-arylation took place at 258C in 20 minutes even in the
presence of weak base, likely due to the neighboring effect of
adjacent nitrogen atoms.[19]
of electron-deficient pyridyl part was preferred over phenyl
group. When a 4-methyl group was present in the phenyl ring,
the selectivity of pyridyl group transfer increased to 8:1. With
a stronger electron-donating methoxy group in the para posi-
tion (2m), complete selectivity for pyridyl transfer was ach-
ieved. These results showed that the more electron-rich aro-
matic system enforces the transfer of the electron-poor aryl or
heteroaryl moiety.
To further explore the selectivity of the reactions, we used
several 4-methoxyphenyl(aryl)iodonium salts (2m–t) for further
studies, and we have found that the electron-rich anisyl group
enables high selectivity with the more electron-rich aryl moiety
remaining intact in the transformation. In some cases, when
the difference in electron density between the aryl rings is
smaller (4-Me-Ph (2r) and 4-F-Ph (2s)), the transfer of anisyl
group was also observed (10.5:1 and 6.3:1, respectively). When
the 2-Me-Ph group was present in the anisyliodonium salt (2t),
the reaction was selective again due to the marked ortho
effect. In further studies, we found that the thienyl group had
the strongest directing ability. This heterocyclic ring behaves
With the optimal conditions in hand, we aimed to explore
the chemoselectivity of the transformation. To fulfil this goal,
we synthesized 66 different diaryliodonium salts using the
known procedures for mechanistic studies.[20] Our collection
consisted of symmetric and unsymmetric aryl and heteroaryl
iodonium salts equipped with wide range of sterically and
electronically different substituents with different counterions
(OTfÀ, BF4À, BrÀ, CF3COOÀ, OTsÀ).
For these studies, we used 3,5-
diphenylpyrazole as the sub-
strate and the reactions were
conducted in 25 w/w% NH3 (aq.)
solution/dichloroethane at 258C.
When mesityliodonium salts
(2b–f) were used, we observed
a high preference for mesityl
group transfer (Scheme 2).[21] We
observed minor transfer of 4-
acetylphenyl (2h, 1:11.4) and
naphthyl (2g,1:17.2) groups, and
only the highly electron-deficient
4-nitrophenyl group was trans-
ferred with high ratio (2i,1:3.2).
In all the other cases, the mesityl
group was exclusively trans-
ferred to the pyrazole nitrogen
under the applied conditions.
These results showed that the
steric factors play important role
in the selectivity.
We continued the reactivity
studies with unsymmetric diary-
liodonium salts having aryl
groups with different electronic
properties (Scheme 3). The 4-ni-
trophenyl group was selectivity
transferred instead of a phenyl
ring when 2j was used, demon-
strating the strong preference
for electron-deficient aromatic
rings in the reaction. The
phenyl-3-pyridyliodonium
salt
Scheme 4. Reactivity of diaryliodonium salts. Reagents 1a (0.025 mmol, 1 equiv), 2 (0.0275 mmol, 1.1 equiv),
C2H4Cl2 (0.5 mL), 25 w/w% NH3 (aq., 0.5 mL). Indicated conversions and product ratio of N-arylated products were
(2k) provided mixture of isomers
in 2:1 ratio, in which the transfer determined by GC analysis.
Chem. Eur. J. 2015, 21, 16801 – 16806
16803
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