10.1002/adsc.201800120
Advanced Synthesis & Catalysis
literature,[9] a proposed reaction mechanism is depicted in Scheme
General Procedure for 8: A solution of 1 (0.2 mmol, 1.0 equiv)
and Cs2CO3 (0.04 mmol, 0.02 equiv) and amine 7 (0.24 mmol, 1.2
equiv) in DMF was stirred at 80 C. The reaction was stopped
after 3 h and the mixture was extracted with EtOAc for 3 times.
The organic layer was washed with brine and dried over
anhydrous Na2SO4. After filtration, the filtrate was concentrated
under reduced pressure and the residue was purified by flash
column chromatography on silica gel (eluent: petroleum ether /
ethyl acetate = 4 / 1) to afford the product 8 in good to excellent
yield.
4. In the presence of
a base catalyst, propargyl-allenyl
isomerization followed by enolization of 1a provides an
iminoenolate intermediate I, which may undergo a 7-exo-dig
cyclization to afford a 1,4-benzoxazepine anion II. Then epoxide
anion III was formed via 6π-electrocyclization process, which
was not very stable to undergo expoxide ring-opening with the
assistance of methanol or indol, delivering an allyl alcohol
intermediate IV. Walk rearrangement process reported by Cui’s
group[9a,b,c] dose not take place from the intermediate III, because
dearomatization of phenyl ring is thermodynamically unfavorable
in this case. Meanwhile, methoxyl or indol anion is generated,
which probably assists the construction of the 3-substituted
quinoline scaffold along with the regeneration of a base catalyst.
o
Supporting Information Available
Detailed descriptions of experimental procedures and their
spectroscopic data as well as the crystal structures are presented in
the Supporting Information. CCDC 1588718 (3ce), CCDC
1587921 (8ab), 1811105 (8ak) contain the supplementary
crystallographic data for this paper. These data can be obtained
free of charge from The Cambridge Crystallographic Data Center
Acknowledgements
We are grateful for the financial support from the National Basic
Research Program of China (973)-2015CB856603, the Strategic
Priority Research Program of the Chinese Academy of Sciences,
Grant No. XDB20000000 and sioczz201808, and the National
Natural Science Foundation of China (20472096, 21372241,
21572052, 20672127, 21421091, 21372250, 21121062, 21302203,
and 20732008).
Scheme 4. Proposed reaction mechanism.
References
In summary, we have developed a simple and convenient
access to 3-functionalized quinoline scaffolds through base-
catalyzed cascade reaction of ortho-(propargylamino)aryl ketones
with primary alcohols, secondary amines including various N-
heterocycles and thiols via 1,4-benzoxazepine intermediates. The
reactions exhibit broad substrate scope, good yield and functional
group tolerance. Moreover, bimolecular reactions providing
compounds containing two quinoline units were also available
under the standard reaction conditions. Further extension of the
scope and the potential utilization are currently under
investigation.
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General Procedure for Synthesis of 3 and 8
General Procedure for the Preparation of 3: 1 (0.2 mmol, 1.0
equiv) and NaOH (0.04 mmol, 0.02 equiv) were dissolved in dry
DMSO (2.0 mL), then primary alcohols 2 (0.24 mmol, 1.2 equiv)
was added dropwise and the resulting reaction mixture was stirred
o
at room temperature (25 C). The reaction was stopped after 3 h
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and the mixture was extracted with EtOAc for 3 times. The
organic layer was washed with brine and dried over anhydrous
Na2SO4. After filtration, the filtrate was concentrated under
reduced pressure and the residue was purified by flash column
chromatography on silica gel (eluent: petroleum ether / ethyl
acetate = 10 / 1) to afford the product 3 in good to excellent yield.
4
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