Communication
ChemComm
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Scheme 4 Potential synthetic applications of hydroxy-substituted 3.
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3a by molecular oxygen (Scheme 3).21 Alternatively, dihydrophen-
anthridin-7(5H)-ones 4a can be converted to dihydrophen-
anthridin-7(8H)-ones 5a through base-catalyzed isomerization.
Finally, in order to highlight the synthetic potential of this
new strategy, selected transformations of the generated hydroxyl-
substituted phenanthridines were conducted (Scheme 4). Phenan-
thridine 3a was readily converted to the triflate 7a by triflation with
Tf2O in high yield. Reductive cleavage of the O-triflate group with
Pd(PPh3)2Cl2 and HCOOH provided the 9-phenylphenanthridine
8a in good yield. The Suzuki coupling reaction of triflate 7a with
4-methoxylphenylboronic acid afforded the 7-(4-methoxyphenyl)-9-
phenylphenanthridine 9a in excellent yield. Furthermore, the
9-methylphenanthridine 3p could be readily converted to the tricyclic
9-methylphenanthridine-7,10-dione 11p, which is the structural
motif existing in natural products calothrixin A and B.22
In conclusion, the first example of organocatalyzed aerobic
oxidative Robinson annulation was successfully developed for
the expedient one-pot synthesis of phenanthridine derivatives
from easily available starting materials under mild metal-free
conditions. This unprecedented domino transformation, featuring
successive construction of two rings and three C–C bonds in a
single operation, represents a new strategy for the general
construction of these tricyclic scaffolds. On the basis of control
experiments, a multistep reaction mechanism is proposed involving
Michael addition, intramolecular isocyanide electrophilic cyclization,
intramolecular aldol condensation, dehydration, deacylation and
aerobic oxidative aromatization. Furthermore, this domino reaction
is amenable to gram scale syntheses, and the 7-hydroxyl group on
the phenanthridines can be used as a handle for further diversity.
Financial support of this research provided by the NSFC
(21672034) and the Natural Science Foundation of Jilin Province
(20160101330JC) is greatly acknowledged.
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Notes and references
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