Tetrahedron Letters
Ruthenium catalyzed desymmetrization of diazabicyclic olefins
to access heteroaryl substituted cyclopentenes through C–H
activation of phenylazoles
P. S. Aparna a,b, , B. Prabha a, Praveen Prakash a, E. Jijy a, R. Luxmi Varma a,b, K. V. Radhakrishnan a,b,
⇑
a Organic Chemistry Section, Chemical Sciences and Technology Division, National Institute for Interdisciplinary Science and Technology (CSIR), Trivandrum 695019, India
b Academy of Scientific and Innovative Research (AcSIR), New Delhi 110001, India
a r t i c l e i n f o
a b s t r a c t
Article history:
The first ruthenium catalyzed redox-neutral C–H activation strategy for the ring-opening of diazabicyclic
olefins via C–H bond cleavage of phenyl azoles is reported. The developed method offers a novel route to
functionalized cyclopentenes by employing less-expensive ruthenium catalyst and readily accessible bio-
logically significant heteroarenes. The present protocol is a merger of the C–H activation of phenyl substi-
tuted heteroaromatics and subsequent b-nitrogen elimination of diazabicyclic olefins.
Ó 2013 Elsevier Ltd. All rights reserved.
Received 26 October 2013
Revised 30 November 2013
Accepted 9 December 2013
Available online 12 December 2013
Keywords:
Ruthenium
Cyclopentene
Bicyclic olefin
C–H activation
Pyrazole
Transition metal catalyzed direct carbon–carbon bond forma-
tion via cleavage of inert C–H bonds represents a proficient
atom-economical and environmentally friendly strategy in organic
synthesis.1 Notably, C–H bond activation of various substrates
mediated by less-expensive ruthenium catalysts have recently
been emerged as a powerful and promising synthetic tool.2
[RuCl2(p-cymene)]2 catalyzed direct functionalization reactions of
substituted arenes with various alkenes as well as alkynes have
been independently investigated by Ackermann et al.,3 Dixneuf
and co-workers,4 Jeganmohan and co-workers,5 and Miura and
co-workers.6 for the synthesis of many valuable scaffolds. Acker-
mann et al. reported a Ru catalyzed regioselective direct alkylation
of 2-phenyl pyridines and 1-phenylpyrazoles with alkyl halides
through C–H bond activation.3g Later, the same group demon-
strated the first ruthenium-catalyzed oxidative annulation of al-
kynes with 1H-pyrazoles by C–H/N–H bond functionalizations.3j
Miura and co-workers reported the direct alkenylation of 1-phen-
ylpyrazoles with alkenes under ruthenium catalysis.7 At the same
time, Dixneuf, Bruneau and co-workers described the Ru catalyzed
dehydrogenative alkenylation of N-arylpyrazoles5f and 2-phenyl
oxazolines5e under air. Jeganmohan et al. reported a ruthenium
catalyzed alkenylation of ortho C–H bond of aryl carbamates with
alkynes to afford substituted alkene derivatives.5h Even though,
very limited number of reports are available on the rhodium cata-
lyzed C–H activation/ring-opening of strained systems8,9 there
have been no reports for the ruthenium catalyzed ring-opening
of strained bicyclic olefins via C–H activation of substituted arenes.
Metal catalyzed synthetic transformations of versatile synthons,
diazanorbornenes10 via ring-opening reactions11–16 have been well
investigated with various organometallic reagents, aryl iodides,
and soft nucleophiles for the preparation of a variety of biologically
significant substituted cyclopentenes.17 Recently, we have devel-
oped a rhodium catalyzed oxidative coupling of salicylaldehydes
with diazabicyclic alkenes for the synthesis of cyclopentene fused
chromanone derivatives by a one-pot ring opening-ring closing
strategy.18 A recent work on Rh(III)-catalyzed ring-opening of diaz-
abicycles through the C–H activation of arenes was reported by Cui
et al.8 Compared to palladium and rhodium catalyzed ring-opening
reactions of diazanorbornenes, detailed investigations under
ruthenium catalysis remain less explored. Very recently, Simon
and Darses demonstrated a ruthenium catalyzed co-dimerization
of bicyclic alkenes and Michael acceptors to provide the exo-(E) ad-
ducts (Scheme 1).19 To the best of our knowledge there has been no
report on the C–N bond cleavage of diazabicyclic olefins via C–H
activation of phenyl substituted heteroarenes by employing less-
expensive ruthenium catalyst. Herein we wish to report the first
ruthenium catalyzed ring-opening of diazabicyclic olefins via C–
H activation of phenylazoles to access functionalized cyclopentene
derivatives in a redox neutral fashion.
⇑
Corresponding author. Tel.: +91 471 2515420; fax: +91 471 2491712.
Tel.: +91 471 2515420; fax: +91 471 2491712.
E-mail
addresses:
(K.V. Radhakrishnan).
0040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
Aparna
