The use of cobalt-mediated cycloisomerisation of ynedinitriles in the synthesis of pyridazinohelicenes

Article abstract of DOI:10.1002/chem.201402312

A cobalt-mediated [2+2+2] cycloisomerisation of ynedinitriles to helical pyridazines in good to high yields was developed. The construction of the pyridazine nucleus from one alkyne and two nitrile units is proposed to follow either a conventional organometallic mechanism or to be triggered by a single-electron transfer from a Co^II species. Various [5]-, [6]- and [7]helicene pyridazines were prepared.

Full text of DOI:10.1002/chem.201402312

DOI: 10.1002/chem.201402312
Full Paper
&
Helical Structures
The Use of Cobalt-Mediated Cycloisomerisation of Ynedinitriles in
the Synthesis of Pyridazinohelicenes
[a]
[a]
[a]
[a]
[a]
ˇ
ˇ ˇ
ˇ
ˇ
Serghei Chercheja, Jirꢀ Klꢀvar, Andrej Jancarꢀk, Jirꢀ Rybꢁcek, Simon Salzl,
[a]
[a]
[a]
[a]
ˇ
ˇ
Jꢁn Tarꢁbek, Lubomꢀr Pospꢀsil, Jana Vacek Chocholousovꢁ, Jaroslav Vacek,
Radek Pohl, Ivana Cꢀsarovꢁ, Ivo Stary,* and Irena G. Starꢁ*
[a]
[b]
[a]
[a]
ˇ
´
Dedicated to R. Zahradnꢀk on the occasion of his 85th birthday
Abstract: A cobalt-mediated [2+2+2] cycloisomerisation of
ynedinitriles to helical pyridazines in good to high yields
was developed. The construction of the pyridazine nucleus
from one alkyne and two nitrile units is proposed to follow
either a conventional organometallic mechanism or to be
triggered by a single-electron transfer from a CoII species.
Various [5]-, [6]- and [7]helicene pyridazines were prepared.
Introduction
Results and Discussion
Transition-metal-catalysed [2+2+2] cycloisomerisation of al-
kynes to form benzene derivatives, originally invented by
Reppe et al. in 1948,[1] has attained a considerable attention
due to its exceptional synthetic usefulness and versatility.[2] The
value of this methodology has been further underscored by
the introduction of the co-cycloisomerisation of nitriles with
two alkynes by Wakatsuki et al. in 1973[3] and Bçnnemann
et al. in 1974[4] thus enabling an effective de novo synthesis of
pyridine derivatives.[5] Until the recent report by Snyder et al.
that appeared during this study,[6] complementary [2+2+2] co-
cycloisomerisation of one alkyne and two nitrile units to afford
pyridazine (i.e., 1,2-diazine) derivatives has not yet been de-
scribed.[7] However, the formation of pyridazines (in our case
embedded in helicene scaffolds) by cobalt-mediated intramo-
lecular cycloisomerisation of ynedinitriles is feasible as we
report here.
In connection with the increasing interest in (hetero)helicene
chemistry[2a,8] as well as the simplified synthesis of dibenzoheli-
cenes, which we have developed recently,[9] we considered the
first energetics of intramolecular [2+2+2] (co-)cycloisomerisa-
tion of alkynes/nitriles 1–3 to form dibenzo[5]helicene 4 and
its pyridine or pyridazine congeners 5 and 6, respectively
(Table 1). The results showed that all three processes should be
Table 1. Calculated free energy differences in intramolecular [2+2+2]
(co-)cycloisomerisation of alkynes/nitriles 1–3 to form the carbohelicene
4, pyridohelicene 5, or pyridazinohelicene 6.
[a]
Entry
Transformation
X
Y
DG [kcalmolꢀ1
]
[a] Dr. S. Chercheja,+ J. Klꢀvar,+ A. Jancarꢀk, Dr. J. Rybꢁcek, S. Salzl,
ˇ ˇ
ˇ
1
2
3
1!4
2!5
3!6
CH
CH
N
CH
N
N
ꢀ122.7
ꢀ90.5
ꢀ37.8
ˇ
ˇ
Dr. J. Tarꢁbek, Prof. Dr. L. Pospꢀsil, Dr. J. Vacek Chocholousovꢁ, Dr. J. Vacek,
Dr. R. Pohl, Dr. I. Stary´, Dr. I. G. Starꢁ
Institute of Organic Chemistry and Biochemistry
Academy of Sciences of the Czech Republic
Flemingovo nꢁm. 2, 166 10 Prague 6 (Czech Republic)
E-mail: stara@uochb.cas.cz
[a] Free-energy differences DG were calculated by DFT (B3LYP/cc-pVTZ) in
vacuo.
stary@uochb.cas.cz
exergonic (Table 1, entries 1–3). However, the released free
energy DG gradually decreases when going from carboheli-
cene 4 to pyridohelicene 5 and pyridazinohelicene 6 thus indi-
cating a significantly lower energy gain from the transforma-
tion of nitrile units than from alkyne ones. It is worth noting
that until recently unknown [2+2+2] cycloisomerisation of
ynedinitrile to form the pyridazine heterocycle was still a mod-
ˇ
[b] Dr. I. Cꢀsarovꢁ
Department of Inorganic Chemistry
Faculty of Science
Charles University in Prague
Hlavova 2030/8, 128 43 Prague 2 (Czech Republic)
[+] These authors contributed equally to this work.
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201402312.
Chem. Eur. J. 2014, 20, 1 – 7
1
ꢂ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
&
&
These are not the final page numbers! ÞÞ

Full Paper
erately exergonic reaction even though the inspected pyridazi-
nohelicene 6 contains inherent torsional strain.
Next, we investigated the effect of substituents at the a-posi-
tion relative to the nitrile group on cyclisation under the afore-
mentioned conditions (entries 2–4). The ynedinitriles 9b–d
bearing alkyl substituents were found to be reactive enough
to provide the tetrahydro[5]helicene pyridazines 10b–d in
high yields regardless of the substituent bulkiness (Me, n-Pr,
iPr) or their number (adjacent quaternary carbon centres were
tolerated). However, the substrates 9b–d required a longer re-
action period than the unsubstituted 9a as well as the repeat-
ed addition of [Co(CO)2(Cp)] to replenish the decomposed cat-
alyst. The phenyl-substituted ynedinitrile 9e underwent cyclisa-
tion to provide the tetrahydro[5]helicene pyridazine 10e in
moderate yield as its formation was accompanied by unidenti-
fied side products (entry 5). The attempt at cyclising the sub-
strate 9 f containing the methoxycarbonyl groups along with
the acidic hydrogen atoms was unsuccessful as a complex mix-
ture of products was formed (entry 6). Apparently, the pres-
ence of the acidic a-hydrogen atoms in the substrate was det-
rimental to the formation of the desired tetrahydro[5]helicene
pyridazine 10 f. This reasoning was supported by the reactivity
of the ethoxycarbonyl-phenyl-substituted ynedinitrile 9g lack-
ing acidic a-hydrogen atoms, which made it possible to obtain
the tetrahydro[5]helicene pyridazine 10g in good yield
(entry 7).
For the sake of testing the hypothesis of [2+2+2] co-cyclo-
isomerisation of one alkyne and two nitriles to obtain pyridazi-
nohelicenes and, at the same time, expecting a high energy
barrier to join nitrogen atoms, we tried to pursue intramolecu-
lar cyclisation of the easily accessible ynedinitrile 7 by employ-
ing
a
high-temperature flow chemistry methodology
(Scheme 1). To our delight, pyridazino[5]helicene 8 was formed
in reasonable yield.[10] Actually, the transformation consisted of
two elemental steps: cobalt-mediated [2+2+2] cycloisomerisa-
tion of ynedinitrile and acetic acid elimination.
Scheme 1. The test [2+2+2] cycloisomerisation of ynedinitrile 7 to pyridazi-
no[5]helicene 8: [Co(CO)2(Cp)] (2.0 equiv), flow reactor, 2508C, 100 bar, flow
rate: 0.5 mLminꢀ1, residence time: 16 min, THF.
To explore further the scope and limitations of this new re-
action, we turned our attention to the other substrates 3, 7
and 11–16 (Table 3). Carrying out the in-flask cyclisation of the
ynedinitrile 7, the pyridazino[5]helicene 8 was obtained in
a lower yield than achieved by employing the flow reactor
(Table 3, entry 1). Here, surprisingly, more side products were
formed. We hypothesised that the premature acetic acid elimi-
nation took place producing (di)enynedinitrile(s) comprising of
E double bond(s), which cannot cyclise under the reaction con-
ditions. In contrast, the oxygen-containing ynedinitrile 11 was
found to be the most reactive substrate in this study as it un-
derwent cyclisation catalysed by [Co(CO)2(Cp)] (0.1 equiv)
within less than one hour to deliver pyridazinohelicene 17 in
high yield (entry 2). Placing methyl groups in a-positions rela-
tive to nitrile units resulted in a diminished reactivity of 12 and
lower yield of 18 but cyclisation was still catalytic with respect
to cobalt (entry 3). Next, we turned to the substrate 13 with
more conformational freedom (entry 4). However, it did not
provide the expected product 19 apparently due to entropic
factors. Reintroducing a conformational restriction by inserting
a biphenyl-2,2’-diyl tether on one side and a geminally disub-
stituted tether on the other side of the alkyne unit in 14, the
desired cyclisation promoted by increased rigidity along with
Thorpe–Ingold effect[11] proceeded delivering pyridazine 20 in
moderate yield (entry 5). In the context of the recently devel-
oped simplified preparation of dibenzohelicenes and their
functionalised derivatives,[12] we attempted the synthesis of
their pyridazine analogues. Indeed, the ynedinitrile 3 afforded
the dibenzo[5]helicene pyridazine 6 but the yield was only
modest owing to substrate polymerisation (entry 6). In con-
trast, cyclisation of 3 performed in the flow reactor utilising
heat-shock conditions for a limited period of time (2508C,
16 min) proved to be more effective in giving the desired
Demonstrating the proof of the concept, we embarked on
developing an in-flask cyclisation protocol (to avoid the utilisa-
tion of a flow reactor) as well as exploring the reactivity of the
closely related alkyne dinitriles 9a–g (Table 2). After an initial
screening of suitable reaction conditions, we found that the
model ynedinitrile 9a underwent [Co(CO)2(Cp)]-mediated cycli-
sation (Cp=cyclopentadienyl) to the tetrahydro[5]helicene pyr-
idazine 10a in high yield under milder reaction conditions
than originally applied in the flow reactor (Table 2, entry 1).
The structure of 10a was unequivocally assigned by a single-
crystal analysis (see Figure S1 in the Supporting Information).
Table 2. In-flask cobalt-mediated [2+2+2] cycloisomerisation of ynedi-
nitriles 9a–g to form tetrahydrohelicene pyridazines 10a–g.
Entry
Product[a]
R1
R2
[Co] [equiv]
t [h]
Yield [%][b]
1
2
3
4
5
6
7
10a
10b
10c
10d
10e
10 f
10g
H
n-Pr
iPr
Me
Ph
H
H
H
Me
H
1.1
2.0
2.0
3.0
2.0
1.0
1.3
3
18
18
18
9
96
91[c]
95[c]
95
51[c]
0
76[c]
CO2Me
CO2Et
H
Ph
4
6
[a] Reactions were conducted under argon in distilled p-xylene; race-
mates were formed. [b] Isolated. [c] A 1:1 mixture of diastereomers was
formed (by 1H NMR spectroscopic analysis of the crude reaction mixture).
&
&
Chem. Eur. J. 2014, 20, 1 – 7
www.chemeurj.org
2
ꢂ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÝÝ These are not the final page numbers!

Full Paper
The reaction mechanism of
the [2+2+2] cycloisomerisation
of ynedinitriles to pyridazinoheli-
cenes has not yet been investi-
gated. It might follow the con-
ventional organometallic route
of alkyne/nitrile [2+2+2] (co-)cy-
cloisomerisation;[13] however, al-
ternative mechanisms should
also be considered (vide infra).
The ynedinitrile cyclisation ex-
hibited the following features:
Table 3. Cobalt-mediated [2+2+2] cycloisomerisation of ynedinitriles 3, 7 and 11–16 to form pyridazinoheli-
cenes 6, 8 and 17–22.
Entry
Ynedinitrile
[Co(CO)2(Cp)] [equiv], t[a]
Pyridazine
Yield [%][b]
36 (52)[c]
1
2.0 equiv, 18 h
1) [Co(CO)2(Cp)] is gradually oxi-
dised if oxygen can diffuse
into the reaction vessel. First,
2
0.1 equiv, 45 min
95
a
[CoII(Cp)Ln] complex is
formed (proved by EPR spec-
troscopy, see below), which
might be catalytically active
(see the complex
A
in
3
4
0.2 equiv, 4 h
65[d]
Scheme 3). However, in the
presence
oxygen,
of
excessive
original
the
[Co(CO)2(Cp)] is gradually de-
stroyed through [CoII(Cp)Ln]
2.0 equiv, 18 h
0 (0)[c,e]
to
a black precipitate of
[(C5H5CoO3)x].[14]
2) [Co(CO)2(Cp)] can act as a cat-
alyst only if sufficiently reac-
tive ynedinitriles, such as 11,
are subjected to cyclisation
(cyclisation has to be faster
than the [Co(CO)2(Cp)] de-
composition).
5
2.0 equiv, 18 h
50
3) In addition to [Co(CO)2(Cp)],
also [Co(CO)(Cp)(fum)] (fum=
dimethyl fumarate;[15] similar-
ly active) or cobaltocene
[Co(Cp)2] (less active) mediate
6
2.1 equiv, 6 h
35 (80)[c]
the
cyclisation
reaction.
[CoCl2-
[Co(Cp*)2]
(dppe)][16]
and
(Cp*=1,2,3,4,5-
pentamethylcyclopentadiene,
dppe=1,2-bis(diphenylphos-
phino)ethane) are inactive
along with the complexes of
Rh, Ni and Ru.[17]
7
7.0 equiv, 72 h
84[f]
4) On a time scale of 1H NMR
spectrometry, no intermedi-
ates of cyclisation can be de-
product 6 in good yield. More complex and less reactive ynedi-
nitriles 15 and 16 were successfully cyclised upon applying in-
vessel conditions to give the dibenzo[6]helicene pyridazine 21
and dibenzo[7]helicene pyridazine 22, respectively, in good
yields (entries 7 and 8).[12]
tected (only signals of ynedinitrile 9a, [Co(CO)2(Cp)] and
the gradually formed tetrahydro[5]helicene pyridazine 10a
can be seen if cyclisation is carried out in an NMR tube at
110 8C).
5) Heating the ynedinitrile 9a with [Co(CO)2(Cp)] in p-xylene
containing oxygen traces above 908C, the in situ EPR spec-
Chem. Eur. J. 2014, 20, 1 – 7
www.chemeurj.org
3
ꢂ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
&
&
These are not the final page numbers! ÞÞ

Full Paper
ed redox processes might also
be considered (Scheme 3). Here,
Table 3. (Continued)
the
inactive
precatalyst
[Co(CO)2(Cp)] is first oxidised by
oxygen to the catalytically active
[CoII(Cp)Ln]+
Entry
Ynedinitrile
[Co(CO)2(Cp)] [equiv], t[a]
Pyridazine
Yield [%][b]
paramagnetic
Xꢀspecies A, which coordinates
one (or two) nitrile group(s) of
ynedinitrile (here 9a) to form
the CoII intermediate B. Then the
nitrile group reduction takes
place being triggered by the
single-electron transfer from the
CoII centre to the coordinated
ynedinitrile ligand. It generates
the valence tautomeric CoIII com-
plex C,[19] which as a carbon-cen-
tred radical undergoes the cas-
8
7.0 equiv, 72 h
83[f]
[a] Reactions were conducted in a reaction vessel in p-xylene at 1408C under argon (unless noted otherwise);
racemates were formed. [b] Isolated. [c] The reaction was conducted in the flow reactor (THF, 2508C, 100 bar,
flow rate: 0.5 mLminꢀ1, residence time: 16 min). [d] A 1:1 mixture of diastereomers was formed (by 1H NMR
spectroscopic analysis of the crude reaction mixture). [e] At 250–3208C. [f] A minor amount (ca. 5%) of the
starting material remained unreacted.
trum arises consisting of two parts at giso =2.1020 and
2.0034, thus indicating the formation of paramagnetic spe-
cies with not solely carbon-centred spin density. The EPR
spectra of the separated solution and black precipitate
show that the signal at giso =2.1020 belongs to a soluble
paramagnetic CoII complex (see Figure S2 in the Supporting
Information) and the single-line EPR spectrum at giso
=
2.0034 to paramagnetic black precipitate.
The conventional organometallic mechanism encompassing
a [CoI(Cp)Ln] catalytic species might seem to be disfavoured by
kinetic factors since reductive elimination in the theoretical in-
termediate A or, alternatively, Diels–Alder cycloaddition form-
ing the intermediate B should lead to the joining of two nitro-
gen atoms with lone electron pairs (Scheme 2). However, we
did not acquire any evidence to rule out this reaction pathway.
In contrast, a metal-free formal [2+2+2] cycloisomerisation
mechanism might be excluded since the studied ynedinitriles
(except for 13 and 14) lack a hydrogen atom at the a-position
to the alkyne unit that is necessary for the initial ene reac-
tion.[18]
Intriguingly, a radical-type mechanism for [2+2+2] cyclo-
isomerisation of ynedinitriles that involves two cobalt-mediat-
Scheme 3. Proposed radical-type mechanism for [2+2+2] cycloisomerisation
of ynedinitriles (exemplified by cyclisation of 9a to 10a; the counteranion is
not shown for clarity).
cade radical cyclisation C!D!E closing two carbocycles.
Upon forming the CoIII intermediate E (a nitrogen-centred radi-
cal), this species undergoes intramolecular homolytic substitu-
tion reaction (SHi)[20] on nitrogen being accompanied by the
(now reversed) single-electron transfer from the ylideneazanide
ligand to the CoIII centre. It finalises the pyridazine ring closure
by connecting nitrogen atoms. Before entering the next cata-
lytic cycle, however, A can also deteriorate to a catalytically in-
active black precipitate due to excessive oxygen. Despite the
fact that we identified an in situ generated CoII species by
Scheme 2. Simplified conventional organometallic mechanism for [2+2+2]
cycloisomerisation of ynedinitriles.
&
&
Chem. Eur. J. 2014, 20, 1 – 7
www.chemeurj.org
4
ꢂ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÝÝ These are not the final page numbers!

Full Paper
[3] a) Y. Wakatsuki, H. Yamazaki, J. Chem. Soc. Chem. Commun. 1973, 280a;
b) Y. Wakatsuki, H. Yamazaki, Tetrahedron Lett. 1973, 14, 3383–3384.
[4] H. Bçnnemann, R. Brinkmann, H. Schenkluhn, Synthesis 1974, 575–577.
[5] For recent reviews, see: a) A. V. Gulevich, A. S. Dudnik, N. Chernyak, V.
Gevorgyan, Chem. Rev. 2013, 113, 3084–3213; b) K. Tanaka, Heterocycles
2012, 85, 1017–1043; c) M. R. Shaaban, R. El-Sayed, A. H. M. Elwahy, Tet-
rahedron 2011, 67, 6095–6130; d) B. Heller, M. Hapke, Chem. Soc. Rev.
2007, 36, 1085–1094; e) G. D. Henry, Tetrahedron 2004, 60, 6043–6061;
f) J. A. Varela, C. Saꢁ, Chem. Rev. 2003, 103, 3787–3802.
[6] C. Cai, M. A. Audet, J. K. Snyder, Heterocycles 2014, 88, 179–186.
[7] To the best of our knowledge, co-cyclisation of one alkyne and two ni-
triles leading to pyrimidine derivatives was described only once, see: Y.
Satoh, K. Yasuda, Y. Obora, Organometallics 2012, 31, 5235–5238 and
references cited therein. Cycloisomerisation of three nitriles to form
1,2,4-triazines under iron catalysis was also reported, see: E. R. F. Gesing,
U. Groth, K. P. C. Vollhardt, Synthesis 1984, 351–353.
using EPR spectroscopy, a link between its formation and role
in ynedinitrile cyclisation is still missing and further mechanis-
tic studies are required.
Conclusion
In summary, we have developed a cobalt-mediated/catalysed
[2+2+2] cycloisomerisation of ynedinitriles to pyridazine heli-
cenes in good to high yields. The de novo construction of pyr-
idazine heterocycle, which combines one alkyne unit with two
nitrile groups in such a way that two nitrogen atoms become
connected under otherwise neutral reaction conditions, is pro-
posed to obey either the conventional mechanism of alkyne/
nitrile [2+2+2] (co-)cycloisomerisation or the single-electron
transfer-triggered radical cyclisation of ynedinitrile mediated
by a [CoII(Cp)Ln] species might also operate in a cyclisation (as
indicated by indirect evidences). We applied this synthetic
methodology to the preparation of a series of helical pyrida-
zines including [5]-, [6]- and [7]helicene derivatives. We
showed by DFT calculations that [2+2+2] cycloisomerisation of
the representative ynedinitrile 3 to the dibenzo[5]helicene pyr-
idazine 6 is an exergonic reaction although being less downhill
in energy than that of the analogous triyne 1 or diynenitrile 2.
We believe that this cyclisation reaction might develop into
a useful tool for the preparation of complex pyridazines, the
importance of which has been noticed.[6,21]
[8] For recent reviews, see: a) M. Gingras, Chem. Soc. Rev. 2013, 42, 968–
1006; b) M. Gingras, G. Fꢃlix, R. Peresutti, Chem. Soc. Rev. 2013, 42,
1007–1050; c) M. Gingras, Chem. Soc. Rev. 2013, 42, 1051–1095; d) A.
Urbano, M. C. CarreÇo, Org. Biomol. Chem. 2013, 11, 699–708; e) Y.
´
Shen, C.-F. Chen, Chem. Rev. 2012, 112, 1463–1535; f) I. G. Starꢁ, I. Stary,
in Science of Synthesis Vol. 45b (Eds.: J. S. Siegel, Y. Tobe), Thieme, Stutt-
gart, 2010, pp. 885–953; g) F. Dumitrascu, D. G. Dumitrescu, I. Aron, Ar-
´
kivoc 2010, i, 1–32; h) I. Stary, I. G. Starꢁ, in Strained Hydrocarbons (Ed.:
H. Dodziuk), Wiley-VCH, Weinheim, 2009, pp. 166–176; i) A. Rajca, M.
Miyasaka, in Functional Organic Materials (Eds.: T. J. J. Mꢄller, U. H. F.
Bunz), Wiley-VCH, Weinheim, 2007, pp. 547–581.
ˇ ˇ
ˇ
ˇ
[9] A. Jancarꢀk, J. Rybꢁcek, K. Cocq, J. Vacek Chocholousovꢁ, J. Vacek, R.
ˇ
´
Pohl, L. Bednꢁrovꢁ, P. Fiedler, I. Cꢀsarovꢁ, I. G. Starꢁ, I. Stary, Angew.
Chem. 2013, 125, 10154–10159; Angew. Chem. Int. Ed. 2013, 52, 9970–
9975.
[10] Spectra of 8 corresponded in all respects to the structure of 7,8-di-
aza[5]helicene prepared earlier by Caronna et al. by a different method,
see: T. Caronna, F. Fontana, A. Mele, I. N. Sora, W. Panzeri, L. Viganꢅ, Syn-
thesis 1984, 413–416.
[11] For a review on the gem-disubstituent effect (Thorpe–Ingold effect),
see: M. E. Jung, G. Piizzi, Chem. Rev. 2005, 105, 1735–1766.
[12] Note, in both cases we observed incomplete substrate consumptions
despite an extended reaction period (72 h) and repeated addition of
[Co(CO)2(Cp)] (in total 7.0 equiv).
Experimental Section
Experimental details can be found in the Supporting Information.
CCDC-977705 (10a) contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge
from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
[13] N. Agenet, V. Gandon, K. P. C. Vollhardt, M. Malacria, C. Aubert, J. Am.
Chem. Soc. 2007, 129, 8860–8871.
[14] Along with the involvement of [Co(CO)2(Cp)] in the cyclisation, this
complex gradually deteriorates in a parallel reaction channel due to the
presence of oxygen traces (a standard Schlenk technique using rubber
septa was employed). Accordingly, a black precipitate is formed lacking
CO ligands and with an elemental composition of [(C5H5CoO3)x]: calcd
for C5H5CoO3, C 34.91, H 2.93, Co 34.26, O 27.90; found: C 31.52, H 2.91,
Co 35.99, O 29.58; IR (KBr): n˜ 3427 (s), 3105 (m), 1585 (s), 1517 (s), 1415
(s), 1011 (w), 864 (w), 462 cmꢀ1 (m). If this black precipitate is added to
the ynedinitrile 9a, cyclisation does not proceed. The black precipitate
was also obtained by direct oxidation of [Co(CO)2(Cp)], providing the
same elemental analysis and IR data as that from cyclisation reactions.
[15] A. Geny, N. Agenet, L. Iannazzo, M. Malacria, C. Aubert, V. Gandon,
Angew. Chem. 2009, 121, 1842–1845; Angew. Chem. Int. Ed. 2009, 48,
1810–1813.
Acknowledgements
This work was supported by the Czech Science Foundation
(207/10/2207), the Ministry of Education, Youth and Sports of
the Czech Republic (MSM0021620857) and by the Institute of
Organic Chemistry and Biochemistry, Academy of Sciences of
the Czech Republic (RVO: 61388963).
Keywords: cobalt
·
cyclization
·
helical structures
·
heterocycles · radicals
[16] [CoCl2(dppe)]/Zn/ZnI2 or [CoCl2(dppe)]/AgOTf were also inactive.
[17] Inactive complexes of Rh, Ni and Ru: [Ru(C2H4)2(Cp)], [Rh(nor)2]+BF4
ꢀ
,
[Rh(nor)2]+BF4ꢀ/(R)-H8-BINAP, [Ni(cod)2]/PPh3, [Ni(cod)2]/PCy3 and [RuCl-
(cod)(Cp*)] (nor=norbornadiene, BINAP=2,2’-bis(diphenylphosphino)-
1,1’-binaphthyl, cod=1,5-cyclooctadiene).
[1] W. Reppe, W. J. Schweckendiek, Justus Liebigs Ann. Chem. 1948, 560,
104–116.
[2] For recent reviews, see: a) Transition-Metal-Mediated Aromatic Ring Con-
struction (Ed.: K. Tanaka), Wiley, Hoboken, 2013; b) G. Domꢀnguez, J.
Pꢃrez-Castells, Chem. Soc. Rev. 2011, 40, 3430–3444; c) D. Leboeuf, V.
Gandon, M. Malacria, in Handbook of Cyclization Reactions (Ed.: S. Ma),
Wiley-VCH, Weinheim, 2010, Vol. 1, pp. 367–405; d) A. Pla-Quintana, A.
Roglans, Molecules 2010, 15, 9230–9251; e) K. Tanaka, Chem. Asian J.
2009, 4, 508–518; f) B. R. Galan, T. Rovis, Angew. Chem. 2009, 121,
2870–2874; Angew. Chem. Int. Ed. 2009, 48, 2830–2834; g) T. Shibata,
K. Tsuchikama, Org. Biomol. Chem. 2008, 6, 1317–1323; h) N. Agenet, O.
Buisine, F. Slowinski, V. Gandon, C. Aubert, M. Malacria, Org. React.
2007, 68, 1–302; i) K. Tanaka, Synlett 2007, 1977–1993.
[18] For a discussion, see: K. Kral, M. Hapke, Angew. Chem. 2011, 123, 2482–
2483; Angew. Chem. Int. Ed. 2011, 50, 2434–2435.
[19] For reviews on valence tautomerism of cobalt complexes, see: a) O.
Sato, A. Cui, R. Matsuda, J. Tao, S. Hayami, Acc. Chem. Res. 2007, 40,
361–369; b) E. Evangelio, D. Ruiz-Molina, Eur. J. Inorg. Chem. 2005,
2957–2971.
[20] For examples of intramolecular homolytic substitution reactions in CoII–
CoIII catalysis, see: a) W. I. Dzik, X. Xu, X. P. Zhang, J. N. H. Reek, B. de
Bruin, J. Am. Chem. Soc. 2010, 132, 10891–10902; b) H. Lu, H. Jiang, L.
Wojtas, X. P. Zhang, Angew. Chem. 2010, 122, 10390–10394; Angew.
Chem. Eur. J. 2014, 20, 1 – 7
www.chemeurj.org
5
ꢂ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
&
&
These are not the final page numbers! ÞÞ

Full Paper
Chem. Int. Ed. 2010, 49, 10192–10196; c) A. Cos¸kun, M. Gꢄney, A.
Das¸tan, M. Balci, Tetrahedron 2007, 63, 4944–4950; d) J. D. Boyd, C. S.
Foote, D. K. Imagawa, J. Am. Chem. Soc. 1980, 102, 3641–3642.
VCH, Weinheim, 2011, pp. 1683–1776; c) M. M. Miller, A. J. DelMonte,
Prog. Heterocycl. Chem. 2011, 22, 393–425.
[21] a) T. J. Ritchie, S. J. F. Macdonald, S. Peace, S. D. Pickett, C. N. Luscombe,
MedChemComm 2012, 3, 1062–1069; b) M.-P. Cabal, Modern Heterocy-
clic Chemistry (Eds: J. Alvarez-Builla, J. J. Vaquero, J. Barluenga), Wiley-
Received: February 22, 2014
Published online on && &&, 0000
&
&
Chem. Eur. J. 2014, 20, 1 – 7
www.chemeurj.org
6
ꢂ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÝÝ These are not the final page numbers!

Full Paper
FULL PAPER
Helical pyridazines: A cobalt-mediated
[2+2+2] cycloisomerisation of ynedi-
nitriles providing pyridazine helicenes in
good to high yields was developed (see
scheme). The de novo construction of
the pyridazine nucleus from one alkyne
and two nitrile units is proposed to
follow either a conventional organome-
tallic mechanism or a radical one. Vari-
ous [5]-, [6]- and [7]helicene pyridazines
were prepared in this way.
&
Helical Structures
ˇ ˇ
S. Chercheja, J. Klꢀvar, A. Jancarꢀk,
ˇ
ˇ
J. Rybꢁcek, S. Salzl, J. Tarꢁbek, L. Pospꢀsil,
ˇ
J. Vacek Chocholousovꢁ, J. Vacek, R. Pohl,
ˇ
´
I. Cꢀsarovꢁ, I. Stary,* I. G. Starꢁ*
&& – &&
The Use of Cobalt-Mediated
Cycloisomerisation of Ynedinitriles in
the Synthesis of Pyridazinohelicenes
Chem. Eur. J. 2014, 20, 1 – 7
www.chemeurj.org
7
ꢂ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
&
&
These are not the final page numbers! ÞÞ