Organic Letters
Letter
Scheme 6b).17b The third synthesis based on the N-acyliminium
chemistry starting from available anhydride or corresponding
carboxylic acid, which was developed by Daich et al. (Scheme
6c).2c While these three precedents utilized harsh conditions
(240 or −78 °C) or multistep operations, we now show a concise
two-step synthesis by integrating our N-alkylation/amidation
cascade reaction with radical cyclization. Thus, the cascade
reaction of isoquinoline (2a) and o-bromotoluene (3m) afforded
N-benzylisoquinolinone 4m (Scheme 6d),18 which was readily
converted to isoindolo[2,1-b]isoquinolin-7(5H)-one (1) and its
dihydro analogue (1′) in 30 and 23% yield, respectively, by
repeating the radical cyclization developed by Daich. It is worth
noting that many other analogues of isoindolo[2,1-b]-
isoquinolin-7(5H)-ones could be rapidly assembled by this
new two-step procedure using readily available starting materials.
In conclusion, we have developed an efficient and practical
iodine-catalyzed oxidative functionalization of azaarenes with
benzylic C−H bonds via an N-alkylation and amidation cascade,
which was integrated into the concise, two-step synthesis
isoindolo[2,1-b]isoquinolin-7(5H)-one (1). This method uti-
lizes unfunctionalized azaarenes and methylarenes as starting
materials and proceeds under metal-free conditions with good to
excellent yields, avoiding the use of expensive noble metal
catalysts and generation of halide and metal wastes; thus, it is a
“green” pathway for the construction of isoquinolinone. Further
application of this strategy to other functionalizations of
azaarenes is ongoing in our laboratory.
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ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
General information, experimental procedures, detailed
optimization, mechanistic experiments, compound char-
acterization data, and copies of NMR spectra (PDF)
AUTHOR INFORMATION
Corresponding Author
■
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported by the Xiangtan University “Academic
Leader Program” (11QDZ20), New Teachers’ Fund for Doctor
Stations, Ministry of Education (20124301120007), and Hunan
Provincial Excellent Young Scientist Foundation (13B114).
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