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Cite this: DOI: 10.1039/c0xx00000x
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Scheme 3. Plausible mechanism of the base-mediated C2-homocoupling.
was briefly examined by means of electron paramagnetic
resonance. While no signal was observed for KOt-Bu in MeTHF,
addition of heterocyclic N-oxides resulted in formation of
paramagnetic species that were detected by EPR (Figure S1 in the
Supporting Information). The shape of the signal indicated that
several paramagnetic species may be present in the solution. The
the N-oxides and potassium tert-butoxide.
5
45
Financial support by the Welch Foundation (AX-1788),
NIGMS (SC3GM105579), UTSA, and the NSF (CHE-1455061)
is gratefully acknowledged. JLB is supported by the IFARHU,
SENACYT, and Ministry of Economic and Finance (DIPRENA-
DPIP-10866-2013) of Panama. Mass spectroscopic analysis was
10 signal for the mixture of quinoline N-oxide and KOt-Bu persisted 50 supported by a grant from the NIMHD (G12MD007591).
for several weeks, pointing to significant stability of the radical
Notes and references
a Department of Chemistry, The University of Texas at San Antonio, San
Antonio, TX 78249, United States. E-mail: oleg.larionov@utsa.edu
b Centre for Biodiversity and Drug Discovery, Institute for Scientific
55 Research and High Technology Services (INDICASAT-AIP), City of
Knowledge, Panama City, Republic of Panama.
species. An EPR signal was also detected for 2,2'-
biquinoline/KOt-Bu system, indicating that a radical anionic
species similar to that observed by Jutand and Li for the 1,10-
15 phenanthroline/KOt-Bu system14 can also be formed in this case.
Further investigation by Tuttle and Murphy showed that
deprotonation of DMF, azines, and other C–H acidic compounds
by KOt-Bu generates carbanions that can serve as electron donors
in the KOt-Bu-mediated processes.15 It is possible that
20 deprotonation of DMF or the C2–H of N-oxide 1 leads to the
generation of carbanions 2416 and 25 that, upon an SET reduction
of N-oxide 1,15 will produce radical anion 26 and radical 27. An
addition of radical anion 26 to N-oxide 1 can produce distonic
radical anion 28 that, after the recombination with radical 27
25 gives rise to intermediate 29. Base-mediated elimination17 of
ROH and hydroxide can then produce 2,2'-biquinoline (2).
Production of intermediate 29 can be further assisted by the
radicals generated from AIBN. In addition, an SET reduction of
anion radical 28 can produce dianion 30 that is converted to 2,2'-
30 biquinoline (2) via a stepwise base-mediated elimination of
hydroxide anion. In MeTHF, hydrogen abstraction from the
solvent by radical 27 produced from anion 25 can contribute to
the regeneration of N-oxide 1. Small amounts of oxygen can arise
from decomposition of tert-butyl peroxide formed in a reaction of
35 KOt-Bu with N-oxide 1 that also produces quinoline (3).
Formation of oxygen was previously observed in a reaction of
DMDO with N-oxides.18 Quinoline (3) may also arise from
reduction of N-oxide 1 with anions 24 and 25.
c Department of Biotechnology, Acharya Nagarjuna University,
Nagarjuna Nagar, India.
† Electronic Supplementary Information (ESI) available: Experimental
60 procedures and characterization data. See DOI: 10.1039/b000000x/
1
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In conclusion, we have developed an efficient base-mediated
40 C2-homocoupling of heterocyclic N-oxides. The reaction
proceeds directly to N-heterobiaryls that are isolated in good to
excellent yields. Preliminary mechanistic studies point to
involvement of radical anionic intermediates that are formed from
8
9
K. Inamoto, Y. Araki, S. Kikkawa, M. Yonemoto, Y. Tanaka, Y.
Kondo, Org. Biomol. Chem., 2013, 11, 4438.
10 Generation of oxygen was confirmed by the oxidation of
leucomethylene blue by the evolved gas. O. Impert, A. Katafias, P.
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