V. P. Singh et al. / Tetrahedron Letters 53 (2012) 4591–4594
4593
works like
a NAD(P)H model for biomimetic asymmetric
hydrogenation.25
The identities of dihydrophenanthridine derivatives 12 and
phenanthridine 13 were established by spectroscopic methods
such as IR, 1H & 13C NMR, and HRMS (please see Supplementary
data). The molecular structures of 12a, 12g, and 13g were unam-
biguously confirmed by single crystal X-ray crystallographic stud-
ies26 (Fig. 3). The structure was solved by direct method and
refined by a full-matrix least-squares procedure on F2 for all
reflections in SHELXL-97 software.27 In summary, an efficient
methodology for the high yield and facile synthesis of dihydrophe-
nanthridines from Schiff’s bases has been developed. The advanta-
ges of this methodology include easy access to the starting
materials and one-pot procedure for the C–C bond formation with-
out any transition-metal catalyst. The cyclization reactions of
imines having electron-withdrawing para-substituents (e.g., NO2)
at the N-phenyl ring and electron-donating substituents (e.g.,
Me) in place of NO2 in another ring are not viable.
Acknowledgments
HBS is grateful to the Department of Science and Technology
(DST), New Delhi, for funding. P.S. thanks the Indian Institute of
Technology, Bombay for a Post Doctoral Fellowship and V.P.S.
wishes to thank IIT Bombay for a teaching assistantship.
Supplementary data
Supplementary data associated with this article can be found,
2012.06.087. These data include MOL files and InChiKeys of the
most important compounds described in this article.
References and notes
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tion of dihydrophenanthridines via intermediates 16 and 17. The
reducing reagent, NaBH4, and solvent ethanol play crucial roles in
the cyclization reaction. The role played by NaBH4/NaB(OEt)4 is
corroborated by attempting the cyclization in the absence of
NaBH4. When 14e was refluxed in ethanol in the absence of NaBH4,
no cyclization was observed. Since NaBH4 is the source of hydride
ion and which also acts as a base, the cyclization reaction of sec-
amine was attempted with NaH. The reaction gave a red intracta-
ble mixture, which could not be purified and characterized. Also
when the sec-amine was refluxed with bases Et3N/NaOH, only
the starting material was recovered. Attempted catalytic cycliza-
tion of 14e with Pd(OAc)2/Ag2SO4 in AcOH under reflux condition
did not lead to the corresponding dihydrophenanthridine.
In order to understand the mechanism of the formation of phe-
nanthridines 13f and 13g, the reduction of 11g under reflux was
monitored by TLC for 12 h. It was found that the reaction (for prod-
uct 12) was almost complete in 1 h and there was no significant
change in the intensity of the red spot for 12 up to 12 h. However,
the intensity of the minor product 13, which appeared after 1 h (a
faint yellow spot) increased with time up to 12 h. Therefore, we
presume that the minor product is obtained by the aerial oxidation
of 12. The formation of 13 is favored in the cases where N-aryl ring
is electron rich and also aromatization of phenanthridine ring may
be the driving force for the oxidation. Recently, Zhou et al. reported
that the conversion of phenanthridine into dihydrophenanthridine
is a reversible reaction and in the presence of hydrogen gas it
21. Kasturi, T. R.; Raju, G. J. J. Chem. Soc., Chem. Commun. 1982, 167.