Communications
doi.org/10.1002/ejoc.202001643
in chlorobenzene, which were the best conditions in our
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[9e]
previous study
(Scheme 3). However, the starting material
remained and undesired 6-endo-dig product 2a or desired 7-
exo-dig product 3a was not detected along with the formation
of a ketone by alkyne hydration.
We introduced two methoxy groups to enhance the
nucleophilic nature of the arene moiety (Table 1). To our
delight, the gold-catalyzed reaction of 1b proceeded at room
temperature to give the desired 7-exo-dig product 3b and
isomerized product 4b as a mixture in moderate yield (Entry 1).
We pleased to find that NHC ligands were effective for the
present cycloisomerization (Entries 2 and 3). When IPr was used,
the 7-exo-dig product 3b was obtained in excellent yield, which
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was isomerized to 4b by acidic treatment using HNTf
2
[10]
Scheme 2. Our previous work and concept of this work
(Entry 2). In contrast, in the case of ICy, the formation of 3b
[
7]
could not be detected and 4b was the only product (Entry 3).
We chose IPrAuCl as an optimum catalyst because of its stability
and readily availability.
dig-selective cycloisomerization of nitrogen-tethered biphenyl-
containing alkynes for the synthesis of dibenzazepines and
dibenzazocines (Scheme 2b). While some reports have disclosed
that the regioselectivity was changed by the substituent at the
Under the conditions for Entry 2 in Table 1, the substituents
on the ortho-phenylene tether were investigated (Table 2). All
products were isolated and characterized as endo olefins 4 after
acidic treatment. Both electron-donating and -withdrawing
substituents could be tolerated to give the corresponding
cycloadducts (Entries 1–8). In particular, the reaction of sterically
hindered 4-Me-substituted substrate 1j also gave the corre-
[4b,5]
alkyne termini,
we anticipated that the reaction pathway
could be controlled by the choice of internal or terminal alkyne.
[
11]
sponding product 4j in high yield, which had axial chirality.
Results and Discussion
Next, we examined the effect of the aromatic ring and
protecting group of the nitrogen (Scheme 4). When 3-meth-
oxyphenyl was introduced in place of a 3,5-dimethoxyphenyl
group, the reaction of 1k proceeded to give exo olefin 3k as an
First, we subjected 2-propargylamino-N-tosylbiphenyl (1a) to
gold(I)-catalyzed cycloisomerization using AgSbF as a silver salt
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inseparable mixture with
a small amount of unknown
product(s). When PPh was used as a ligand, product 3k could
3
be isolated in moderate yield without formation of regioisomer
3
k’ (eq. (1)). The reaction of NH-free substrate 1l gave 6-endo-
dig product 2l along with aromatization, yet in low yield, and 7-
exo-dig product could not be detected at all (eq. (2)). This result
indicated that the electron-withdrawing effect of a tosyl group
suppressed 6-endo-dig cyclization.
The results using internal alkynes are shown in Table 3.
When the reaction of Ph-substituted alkyne 5a was conducted
under the optimal conditions, starting material 5a was
Scheme 3. Cationic gold-catalyzed reaction of biphenyl 1a.
[a]
Table 1. Screening of reaction conditions.
[
a]
Table 2. Scope of substituents on phenylene-tether.
[b]
[b]
Entry
L
Yield of 3b [%]
Yield of 4b [%]
[
c]
[c]
1
2
3
PPh
IPr
ICy
3
21
21
ca. 98 (N.D.)
N.D.
trace (>99)
>99
[b]
[b]
Entry
R
Yield [%]
Entry
R
Yield [%]
1
2
3
4
1-F (1c)
2-Me (1d)
2-Cl (1e)
91 (4c)
94 (4d)
97 (4e)
>99 (4f)
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6
7
8
3-Me (1g)
3-CF (1h)
3-i-Pr (1i)
4-Me (1j)
94 (4g)
95 (4h)
88 (4i)
90 (4j)
[
(
a] Reaction conditions: 1 a (0.05 mmol), LAuCl (10 mol%), AgSbF
10 mol%), PhCl (0.5 mL), r.t., 1 h. [b] Isolated yield. The yield after the
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treatment of HNTf (10 mol%) is shown in the in parentheses. [c] The NMR
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2-CF (1f)
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yields were measured using 1,1,2,2-tetrachloroethane as an internal
standard. IPr: 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene, ICy: 1,3-
dicyclohexylimidazol-2-ylidene.
[a] Reaction conditions: 1 (0.05 mmol), IPrAuCl (10 mol%), AgSbF
(10 mol%), PhCl (0.5 mL), r.t., then HNTf (ca. 5 mg). [b] Isolated yield.
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Eur. J. Org. Chem. 2021, 1688–1692
1689
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