ARTICLE IN PRESS
JID: CCLET
[m5G;June 5, 2021;14:6]
X. Huang, Y. Xu, J. Li et al.
Chinese Chemical Letters xxx (xxxx) xxx
Scheme 5. Mechanistic studies.
Scheme 3. Substrate scope of N-phenylbenzimidamides.
Scheme 4. Ten-fold-scale synthesis of aminoisoquinolines.
substituted reactants gave the two regioselective products (3la-
3ma). Delightfully, the product was isolated in 90% yields when
reactant with a thiophene ring was used. Moreover, substituent
with naphthalene was also suitable for the reaction, albeit in a
58% yield. Furthermore, when tert-butyl is replaced by other alkyl
groups such as benzyl, isopropyl and n-butyl, this cascade pro-
cedure could also convert to generate corresponding products in
42%–46% yields (3sa-3ua). However, the reaction failed to work
when N-phenylbenzimidamide was added.
Scheme 6. Plausible reaction mechanism.
transforms into a rhodacyclic intermediate A by C-H activation.
Subsequently, the insertion of 2a with intermediate A results in the
formation of seven-member intermediate B. Then, intermediate B
undergoes reductive elimination to generate intermediate C releas-
ing the Cp∗Rh (I). The rhodium complexe D is obtained from oxida-
tive addition of intermediate C and Cp∗Rh (I). Finally, the rhodium
complexe D generates aminoisoquinoline with the formation of the
carbonate anion through β-oxygen elimination.
Due to the inert reactivity of N-phenylbenzimidamide, a se-
ries of reaction conditions were examined for realization of the
conversion by employing vinylene carbonate (see Supporting in-
formation for details). Fortunately, we obtained the expected N-
phenylisoquinolin-1-amine successfully and confirmed the opti-
mal conditions that the reaction proceeded in 60% yield with
[Cp∗RhCl2]2 (5 mol%), AgOAc (20 mol%) and ZnSO4·7H2O (20 mol%)
as catalytic system in chlorobenzene (2.0 mL) at 140°C for
24 h under Ar (Scheme 3). The electron-donating and electron-
withdrawing groups were all compatible in 45%–66% yields with-
out obvious electrical effect. Unfortunately, when the benzene ring
was replaced by thiophene ring or naphthalene, we did not ob-
serve obvious products.
In conclusion, we developed
a novel method to construct
aminoisoquinolines derivatives via Rh(III)-catalyzed C-H activa-
tion/annulation by coupling benzamidines with vinylene carbonate
as an acetylene surrogate. In this work, we realized the transfor-
mations of phenyl and alkyl-substituted benzamidines in good to
moderate yields under different conditions, which was applied for
larger scale.
In order to explore whether the strategy could be applied for
large scale, we enlarged the amount of 1a (2 mmol) and 2a
(4 mmol) under the optimized conditions (Scheme 4). The result
disclosed the transformation was less efficient in the yield of 55%.
To further explore the experimental mechanism, we completed
some mechanistic experiments. The H/D exchange experiment was
carried out by using 1b with CD3OD at 100 °C for 2 h, which
showed that 42% deuterium incorporation was estimated at ortho-
position by 1H NMR indicating C-H bond cleavage of the transfor-
mation was reversible (Scheme 5a). When equimolar amounts of
1b and 1e were added in intermolecular competition experiment,
the 3ba and 3ea were obtained in a ratio of 1.5:1, which indicated
that electron-donating group was more effective (Scheme 5b).
Based on the above experiments and related literature, a plau-
sible mechanism is presented in the Scheme 6. First, benzamidine
Declaration of competing interest
The authors declare that they have no known competing finan-
cial interests or personal relationships that could have appeared to
influence the work reported in this paper .
Acknowledgment
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