10.1002/anie.201904702
Angewandte Chemie International Edition
COMMUNICATION
spectra (SI for details). After coordination with azide nitrogen, α-
Fe(III)-nitrene radical intermediate (C) is formed by the loss of
dinitrogen from species (B). Upon subsequent trapping with
alkyne, the intermediate (C) produces γ-Fe(III)-vinyl radical
intermediate (D), which undergo radical addition intramolecularly
to the C=N bond to generate a new b-Fe(III)-alkyl radical
intermediate (E) where the fused five-membered ring is
constructed upon C-N bod formation. Subsequently, the beta-
Fe(III)-alkyl radical intermediate (E) proceeds b-radical scission
to break N–Fe bond and form C=N double bond, affording the
product (3) regenerating the catalytic cycle.
Keywords: Denitrogenative annulation • Fe-nitrene • catalysis •
nitrogen-heterocycles • Metalloradical
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Cl
[2]
N
N
N
N
III
Fe
Zn(0)
Ar
1
2
Zn+2
N
N
N
N
N
N
N
N
N
N
N
N
II
Fe
N
N
3
1
N
(A)
N2
active catalyst for
annulation
Ar
N
N
N
II
Fe
N
N
•
N
N
III
Fe
N
N
N
N
(B)
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Metalloradical Activation
Mechanism
(E)
N2
N
Ar
•
•
N
N
N
N
N
III
Fe
N
N
III
N
N
N
N
Fe
(C)
(D)
Ar
Scheme 5. Proposed Metalloradical Activation Mechanism
In conclusion, we have developed
a new metalloradical
activation concept for the intermolecular denitrogenative
annulation, which completely overturn the traditionally more
favored click reaction. It has been demonstrated that the
reaction proceeds via an unprecedented metalloradical
activation mechanism. The method requires commercially
available cheap Fe(TPP)Cl catalyst in combination of a catalytic
amount of Zn dust as reducing agent. This is the first report for
the denitrogenative intermolecular annulation via metal-nitrene
formation. The developed method shows a wide range of
substrate scope and functional group tolerance. The synthetic
utility of the developed method is showcased with the short
synthesis of valuable bioactive molecules.[16] We do believe that
the developed concept will have extensive impact in this area for
solving the long-standing challenging problem for the overriding
the traditional click chemistry towards intermolecular annulation.
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Acknowledgements
This
work
was
supported
by
CSIR-EMR-II
grant
(02(0259)/16/EMR-II), Ramanujan fellowship grant and DST-
SERB CRG grant (CRG/2018/000133). SR and SKD thank
CSIR for SRF and HK thanks CSIR for JRF. We thank the NMR
and mass spectrometry facility at CBMR, and the Director, for
the research facilities.
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