Communication
Organic & Biomolecular Chemistry
Notes and references
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Scheme 4 A plausible reaction mechanism.
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EG at 120 °C to verify the Boc removal effect of EG, and
phenylethylamine (11) was obtained in 55% yield after
8 hours, which indicated that EG was essential for the
deprotection of the Boc group to promote intramolecular
cyclization.
On the basis of these results, a plausible mechanism is pre-
sented in Scheme 4. Initially, a Pd-catalyzed regioselective
Heck reaction was performed through oxidative addition,
migratory insertion, and the β-H elimination process to
provide 3a.8a,11 Then the Boc group of 3a was removed by an
attack of EG at a high enough temperature. Subsequently,
intramolecular cyclization and double bond isomerization
gave the product 4a.
In conclusion, we have developed a new approach for con-
structing 1-substituted-4-methylisoquinolines, starting from
2-acylphenyl triflates/halide and N-Boc allylamine, based on a
one-pot Pd-catalyzed Heck reaction and intramolecular
cyclization. The efficiency and substituent tolerance of this
procedure have been fully demonstrated by synthesizing a
wide range of functionalized 4-methylisoquinolines. Moreover,
three isoquinoline derivatives from 1-phenyl-4-methylisoquino-
line have been synthesized, which can be used in the further
synthesis of complicated structures. The high efficiency and
simple manipulation render this one-pot reaction an attractive
method in organic synthesis.
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Acknowledgements
This work was financially supported by the National Natural
Science Foundation of China (NSFC; no. 81102322), PUMC
Youth Fund (no. 3332013072) and the Fundamental Research
Funds for the Central Universities.
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