Transfer reagents 4: Retro-Diels-alder routes to 3,6-Di(2-pyridyl) pyridazinonorbornadiene, a test bed for the relative dienofugacity of isobenzofuran, isoindole, and anthracene

Article abstract of DOI:10.1055/s-0033-1339879

Norbornadiene cycloadducts reacted with 3,6-di(2-pyridyl)-s-tetrazine to produce pyridazines (diene-protected alkenes), following dehydrogenation (by DDQ) of the intermediate dihydropyridazines. The title 3,6-di(2-pyridyl)- pyridazinonorbornadiene was produced under flash vacuum pyrolysis conditions by ejection of anthracene (590? °C), isobenzofuran (630°C) or isoindole (580°C) from the corresponding pyridazines, establishing the following dienofugacity order: isoindole > anthracene > isobenzofuran. Calculations of the respective retro-Diels-alder activation energies at the B3LYP/6-31G* level of theory correctly predicted the experimentally found isobenzofuran > anthracene > isoindole order. Cavity bis-3,6-di(2-pyridyl) -pyridazine (dppn) and chevron-shaped bis-dppn ligands were prepared from the title compound by coupling at the norbornene π-bond.

Full text of DOI:10.1055/s-0033-1339879

LETTER
▌2609
letter
Transfer Reagents 4: Retro-Diels–Alder Routes to 3,6-Di(2-pyridyl)pyridazi-
nonorbornadiene, a Test Bed for the Relative Dienofugacity of Isobenzofuran,
Isoindole, and Anthracene
Transfer Reagents 4: Dienofugacity
Davor Margetić,*a Douglas N. Butler,b Ronald N. Warrenerb
a
Laboratory for Physical-organic Chemistry, Division of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Bijenička c. 54,
10000 Zagreb, Croatia
Fax +385(1)4561008; E-mail: margetid@irb.hr
b
Centre for Molecular Architecture, Central Queensland University, Rockhampton, Queensland 4702, Australia
Received: 04.07.2013; Accepted after revision: 02.09.2013
isobenzofuran 17, and isoindole 19. Calculated predic-
Abstract: Norbornadiene cycloadducts reacted with 3,6-di(2-pyri-
tions conducted at a high level of theory (B3LYP/6-31G*)
dyl)-s-tetrazine to produce pyridazines (diene-protected alkenes),
were in complete accord with the experiments.
following dehydrogenation (by DDQ) of the intermediate dihydro-
pyridazines. The title 3,6-di(2-pyridyl)-pyridazinonorbornadiene
was produced under flash vacuum pyrolysis conditions by ejection
of anthracene (590 °C), isobenzofuran (630 °C) or isoindole (580
°C) from the corresponding pyridazines, establishing the following
dienofugacity order: isoindole > anthracene > isobenzofuran. Cal-
culations of the respective retro-Diels–alder activation energies at
the B3LYP/6-31G* level of theory correctly predicted the experi-
mentally found isobenzofuran > anthracene > isoindole order. Cav-
ity bis-3,6-di(2-pyridyl)-pyridazine (dppn) and chevron-shaped bis-
dppn ligands were prepared from the title compound by coupling at
the norbornene π-bond.
N
N
N
N
N
N
N
N
n
M
M
M
M
2
Lehn
dppn
(1)
self-assembly n x n grid system
bidentate
ligand
site A
bidentate
ligand
site B
Figure 1 3,6-Di(2-pyridyl)pyridazine (dppn) ligand 1
Key words: cycloadditions, heterocycles, ligands, flash pyrolysis,
alkenes
δ = 4.46
Ha
N
The ligating properties of 3,6-di(2-pyridyl)-pyridazine
(dppn, 1) are well established and examples are known
where metal complexes are formed at one or both the bi-
dentate centers (e.g., 1, Figure 1). Complexes between
dppn and copper,1 ruthenium,2 manganese,3 cobalt,4 and
nickel4,5 haveì all been reported and their structures are
supported by X-ray data in most cases. The dppn ligand
has also been attached to C60 through a short carbocyclic
frame6 or directly to C60.7 A series of rigid scaffolds con-
taining one or more end-fused dppn subunits have been
described.8 The insertion of extra pyridazine rings be-
tween the pyridyl and the pyridazine rings to form a series
of poly(bidentate) systems 2 have been reported by Lehn
and co-workers and used for the preparation of n × n mo-
lecular grids.9 The same ligand motif was used by Champ-
ness and Schröder in multimetallic complexes, where a
variety of bis-dppn ligands was synthesized by Diels–
Alder reaction of alkenes with 5.10
N
N
N
3
Figure 2 The dppn norbornadiene building block 3
Norbornene reagents have proved effective building
blocks in the ‘LEGO’-like assembly protocols leading to
functionalized scaffold systems, since each building block
can carry individual effectors and the stereoselectivity of
the fusion process can be used to control product geome-
try.11 Accordingly, when seeking a reagent for incorporat-
ing multidentate ligands into scaffold systems, the title
norbornadiene 3 was targeted as a prototype building
block, in this case to introduce the dppn ligand.
In principle, dehydrogenation of the dihydropyridazine 6,
formed by the Diels–Alder reaction of norbornadiene 4
with 3,6-di(2-pyridyl)-s-tetrazine (5), should yield the ti-
tle pyridazine 3 directly (Scheme 1). However, this route
is not viable owing to the rapid fragmentation of 6 at room
temperature to produce cyclopentadiene (7) together with
the 3,6-di(2-pyridyl)pyridazine (1).12 Attempts to dehy-
drogenate 6 at low temperature or to induce a prototropic
shift in the presence of acid to the retro-Diels–Alder stable
1,4-dihydro isomer prior to dehydrogenation, were not
successful.
This paper reports new retro-Diels–Alder routes for the
synthesis of dppn ligand 3 (Figure 2) and the preparation
of bis(dppn) ligands therefrom. The retro-Diels–Alder
routes to 3 have been used as a test bed for evaluating the
relative dienofugacity of cyclic dienes: naphthalene 15,
SYNLETT 2013, 24, 2609–2613
Advanced online publication: 16.10.2013
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
DOI: 10.1055/s-0033-1339879; Art ID: ST-2013-B0622-L
© Georg Thieme Verlag Stuttgart · New York

2610
D. Margetić et al.
as described for compound 14 above (Scheme 2). In these
cases, the FVP step involved the retro-Diels–Alder ejec-
tion of isobenzofuran from 16 and isoindole from 18.
These unusual dienofuges are usually the goal in FVP pro-
tocols, however, they take on the role of byproducts in this
study. Both reactions proceed satisfactorily, and it is note-
worthy that the temperature required to effect elimination
of isoindole is lower (580 °C) than that for isobenzofuran
(630 °C), a relationship which parallels the superiority of
pyrroles over furans in retro-Diels–Alder reactions.16 FVP
temperatures reported here are the lowest needed for full
conversion of transfer reagents 12, 16, and 18 to products.
In all FVP experiments involving 9–11, various amounts
of side product 8 were obtained, depending on the reaction
conditions. When the FVP experiment with 14 was car-
ried out at higher temperature (670 °C), 8 was obtained as
a sole product in 31% yield, indicating its generation from
3.
Py
Py
Py
Py
r.t.
N
N
N
N
N
N
N
r.t.
+
+
N
– N2
ref. 11
Py
Py
4
5
6
7
1
3
Scheme 1 Fragmentation of the Diels–Alder adduct of norbornene
and 5
In order to avoid this electrocyclic fragmentation, it was
necessary to remove the influence of the norbornene π-
bond in intermediate 6 and this was achieved by using a
transfer reagent13 in which one of the π-bonds of norborn-
adiene 4 has been protected as a Diels–Alder adduct
(Scheme 2). Reaction of the known anthracene adduct 914
with s-tetrazine 5 occurred on warming the two reagents
together in chloroform solution. Dinitrogen was evolved,
and the deep purple color of s-tetrazine 5 discharged as the
reaction progressed. While dihydropyridazines of type 12
are known to readily rearrange to the 1,4-isomers by a
prototropic shift, this was not a concern in the present
study since both the 1,2- and the 1,4-isomers readily un-
dergo dehydrogenation on treatment with 2,3-dichloro-
5,6-dicyano-1,4-benzoquinone (DDQ) to form the same
pyridazine 14. Demasking of the π-bond in 14 was accom-
plished by flash vacuum pyrolysis (FVP) at 590 °C (0.001
mbar), and the required pyridazino-norbornadiene 3 was
obtained in 44% yield. Compound 3 was identical with
that obtained from the photolysis of fused cyclobutatri-
azoline.15 Compounds 10 and 11 were also studied as
transfer reagents for norbornadiene and were converted
into their pyridazine derivatives 16 and 18, respectively,
The ability to use the norbornene π-bond of 3 in block
coupling protocols17 was an important objective of this
work. Reaction of two equivalents of 3 with the bisepox-
ide 20 proceeded in good yield to form the bis(dppn) scaf-
fold 21 (Scheme 3). The structure of 21 was supported by
mass spectrometry, and the stereochemistry was assigned
1
on the basis of C2v-symmetry judged by H NMR data.
Further support followed from the low-field chemical
shift of the methano bridge protons Hd (δ = 2.82 ppm),
typical of its proximity to the oxa bridge and from NOE
correlations between endo protons Hb and Hc.
Reaction of pyridazinonorbornadiene 3 with the s-tetra-
zine 5 gave the dihydropyridazine 22, oxidation of which
(DDQ) furnished 23 (23% yield), a new chevron-shaped
bis(dppn) ligand with multichelating centers. It is note-
worthy that the bridgehead proton Ha in product 23 is even
Py
N
DDQ
N
5
N
N
N
– N2
Py
9
N
14
12
loss of
anthracene
FVP
590 °C
44%
transfer
reagents for
norbornadiene
N
Py
N
loss of
15
isobenzofuran
O
Py
O
5
Py
O
17
N
+
3
DDQ
N
630 °C, 31%
10
16
Py
8
N
loss of
isoindole
Py
H
N
N
5
H
N
Py
NH
19
DDQ
11
580 °C, 48%
18
Scheme 2 Flash vacuum pyrolysis of transfer reagents 9–11
Synlett 2013, 24, 2609–2613
© Georg Thieme Verlag Stuttgart · New York

LETTER
Transfer Reagents 4: Dienofugacity
2611
statement to be made about the relative dienofugacity of
isobenzofuran with isoindole. The fact that nitrogen het-
erocycle 19 is a superior dienofuge than its oxygen coun-
terpart 17 parallels the relationship in the five-membered
heterocyclic ring systems where pyrrole is superior to fu-
ran.16
δ = 2.82
Hd
N
O E
O E
Ha
N
N
N
N
E
N
E
N
E
Hb
Hc
N
21
NOE
In conclusion, transfer methodology was employed to de-
liver the dppn ligand building block 3 by flash vacuum py-
rolysis. This synthetic strategy was used for protection of
a carbon–carbon double bond by diene-masking groups.
Dienofugacitiy of dienes obtained from flash vacuum
pyrolysis precursors of 3 was established in the relative
order isobenzofuran > anthracene > isoindole.
E
E
E
76%
O
E = CO2Me
O
20
3
– N2
5
δ = 6.62
N
N
Ha
Acknowledgment
N
N
N
DDQ
23%
N
N
N
N
N
This work was supported in part by ARC small and CQU Merit
grants and Ministry of Science, Education, and Sport of Republic of
Croatia (project No. 098-0982933-3218).
N
N
N
N
N
N
22
23
Scheme 3 Cycloaddition of norbornadiene building block 3
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synlett.SnuIpofoiprmntgirStanoIuifpog
r
t
iornat
further downfield (δ = 6.62 ppm) than those in 21 (δ =
4.31 ppm), owing to the influence of two dppn ring sys-
tems.
References and Notes
(1) (a) Wang, W. J.; Wang, S. S. Synth. Methods 1993, 56, 1950.
(b) De Munno, G.; Bruno, G. Acta Crystallogr., Sect. C:
Cryst. Struct. Commun. 1984, 40, 2022.
(2) (a) Atfah, A.; Tuhl, A. H.; Akasheh, T. S. Polyhedron 1991,
10, 1485. (b) Golka, A.; Craig, D. C.; Paddon-Row, M. N.
Aust. J. Chem. 1994, 47, 101.
(3) Andrew, J. E.; Blake, A. B.; Fraser, L. R. J. Chem. Soc.,
Dalton Trans. 1975, 800.
(4) Andrew, J. E.; Ball, P. W.; Blake, A. B. J. Chem. Soc., Chem.
Commun. 1969, 143.
Transition-state energies have been computed for the retro-
Diels–Alder reactions represented by systems TS12,
TS16, and TS18 (Figure 3). In this series, it could be pre-
dicted that isoindole would be lost in preference to isoben-
zofuran (3.2 kcal/mol), whereas the elimination of
anthracene fell between these systems. It is known that
transition-state energies are influenced by the stereo-
chemistry, so comparisons between loss of anthracene in
TS12 with the heteroaromatics from TS16 or TS18 may
be open for challenge. However, the fact that TS16 and
TS18 have the same stereochemistry allows a definitive
(5) Wang, J.-S.; Sheu, C.-F.; Lee, J.-S. Acta Crystallogr., Sect.
C: Cryst. Struct. Commun. 1999, 55, 1806.
(6) Warrener, R. N.; Elsey, G. M.; Houghton, M. A. J. Chem.
Soc., Chem. Commun. 1995, 1417.
(7) Miller, G. P.; Tetreau, M. C.; Olmstead, M. M.; Lord, P. A.;
Blach, A. L. Chem. Commun. 2001, 1758.
(8) Warrener, R. N.; Elsey, G. M.; Danka, I. V.; Butler, D. N.;
Pekos, P.; Kennard, C. H. L. Tetrahedron Lett. 1994, 35,
6745.
(9) (a) Baxter, P. N. W.; Lehn, J.-M.; Fischer, J.; Youinou, M.-
T. Angew. Chem., Int. Ed. Engl. 1994, 33, 2284. (b) Bassani,
D. M.; Lehn, J.-M.; Baum, G.; Fenske, D. Angew. Chem.,
Int. Ed. Engl. 1997, 36, 1845. (c) Semenov, A.; Spatz, J. P.;
Moller, M.; Lehn, J.-M.; Sell, B.; Schubert, D.; Weidl, C. H.;
Schubert, U. S. Angew. Chem. Int. Ed. 1999, 38, 2457.
(d) Baxter, P. N. W.; Lehn, J.-M.; Baum, G.; Fenske, D.
Chem. Eur. J. 2000, 6, 4510.
(10) Thébault, F.; Blake, A. J.; Wilson, C.; Champness, N. R.;
Schröder, M. New J. Chem. 2006, 30, 1498.
(11) (a) Warrener, R. N.; Butler, D. N.; Margetić, D.; Pfeffer, F.
M.; Russell, R. A. Tetrahedron Lett. 2000, 41, 4671.
(b) Warrener, R. N.; Butler, D. N.; Russell, R. A. Synlett
1998, 566. (c) Warrener, R. N.; Schultz, A. C.; Butler, D. N.;
Wang, S.; Mahadevan, I. B.; Russell, R. A. Chem. Commun.
1997, 1023.
(12) (a) Sauer, J.; Heinrichs, G. Tetrahedron Lett. 1966, 7, 4979.
(b) Wilson, W. S.; Warrener, R. N. J. Chem. Soc., Chem.
Commun. 1972, 211.
Figure 3 B3LYP/6-31G* optimized transition states and activation
energies for the retro-Diels–Alder transition states TS12, TS16, and
TS18 corresponding to the loss of anthracene, isobenzofuran, and
isoindole
© Georg Thieme Verlag Stuttgart · New York
Synlett 2013, 24, 2609–2613

2612
D. Margetić et al.
(13) (a) Warrener, R. N.; Wang, J. M.; Weerasuria, K. D. V.;
Russell, R. A. Tetrahedron Lett. 1990, 31, 7069.
(b) Warrener, R. N.; Russell, R. A.; Solomon, R.; Pitt, I. G.
Tetrahedron Lett. 1987, 28, 6503. (c) Butler, D. N.; Officer,
D. L.; Pitt, I. G.; Warrener, R. N.; Russell, R. A. Tetrahedron
Lett. 1987, 28, 6507.
(14) Butler, D. N.; Barrette, A.; Snow, R. A. Synth. Commun.
1975, 5, 101.
(15) Margetić, D.; Butler, D. N.; Warrener, R. N. Aust. J. Chem.
2000, 53, 959.
(d, J = 8.0 Hz, 1 H, CH2), 2.37 (s, 2 H, Hendo), 2.92 (s, 2 H,
bridgehead-C), 3.68 (br s, 1 H, NH), 4.23 (s, 2 H, Hbridgehead-N),
H
6.25 (s, 2 H, =CH), 7.02–7.06 (m, 2 H, HAr), 7.13–7.16 (m,
2 H, HAr). 13C NMR (75 MHz, CDCl3): δ = 43.0 (Cendo), 49.1
(Cbridgehead-C), 55.1 (CH2), 63.0 (Cbridgehead-N), 119.3 (=CH),
125.8 (CArH), 136.2 (CArH), 153.1 (CArq). ESI-HRMS: m/z
calcd for C15H15N1 [M]+: 209.1204; found: 209.1195.
5,8-Di(2-pyridyl)-6,7-diaza-1α,2β,3α,10α,11β,12α-
octacyclo[10.6.6.13,10.02,11.04,9.013,18.019,24]pentacosa-
4,6,8,13,15,17,19,21,23-nonaene (14)
(16) Warrener, R. N.; Margetić, D.; Sun, G. Tetrahedron Lett.
2001, 42, 4263.
(17) (a) Warrener, R. N.; Margetić, D.; Russell, R. A. Synlett
1998, 585. (b) Warrener, R. N.; Margetić, D.; Amarasekara,
A. S.; Butler, D. N.; Mahadevan, I. B.; Russell, R. A. Org
Lett. 1999, 1, 199.
A solution of alkene 9 (300 mg, 1.11 mmol) in CHCl3 (10
mL) was treated with s-tetrazine (260 mg, 1.11 mmol) and
refluxed overnight. To this mixture, DDQ (480 mg, 2.11
mmol) was added and refluxed overnight. Insoluble material
was removed by filtration, and the residual liquid was
washed with 3 M NaOH (3×), then with H2O, dried
(MgSO4), and the solvent was removed under vacuum to
afford 14 as a brown-colored powder (303 mg, 58.8%, mp
270–272 °C). 1H NMR (300 MHz, CDCl3): δ = 0.23 (d,
J = 10.7 Hz, 1 H, CH2), 1.08 (d, J = 10.7 Hz, 1 H, CH2), 2.26
(s, 2 H, Hendo), 4.24 (s, 2 H, Hbridgehead-C), 4.46 (s, 2 H,
Hbridgehead-2.2.2), 6.99–7.01 (m, 2 H, Ar), 7.19–7.22 (m, 2 H,
HAr), 7.24–7.27 (m, 2 H, HAr), 7.34–7.39 (m, 4 H, HAr), 7.87
(dd, J = 6.4, 1.3 Hz, 2 H, HAr), 8.51 (dt, J = 7.1, 0.8 Hz, 2 H,
HAr), 8.85 (d, J = 4.4 Hz, 2 H, HAr). 13C (NMR (75 MHz,
CDCl3): δ = 41.2 (CH2), 46.1 (Cbridgehead-norb), 46.8 (Cendo),
48.8 (Cbridgehead-anthrac), 123.3, 123.9, 124.0, 125.2, 126.0,
126.8, 137.1, 142.7 (CArq), 145.4 (CArq), 149.6, 151.1 (CArq),
151.8 (CArq), 156.2 (CArq). ESI-HRMS: m/z calcd for
C33H24N4 [M]+: 476.2001; found: 476.2001.
(18) Warrener, R. N.; Margetić, D.; Amarasekara, A. S.; Russell,
R. A. Org. Lett. 1999, 1, 203.
(19) The NMR spectra were recorded in CDCl3 solutions
containing TMS as internal standard on a Bruker AMX-300
or a Bruker Avance DPX-400 NMR spectrometer fitted with
a gradient quattro nucleus probe. Melting points were
determined using a Gallenkamp digital melting point
apparatus and are uncorrected. The high-resolution mass
spectra were recorded on a Micromass Platform II single
quadrupole AutoSpec instrument (ESMS, electrospray mass
spectrometry in CH2Cl2). Radial chromatography was
carried out with a chromatotron, model No. 79245T, using 1
mm plates with silica gel 60F254 as the stationary phase. FVP
experiments were conducted under vacuum (0.001 mbar) in
an 600 × 10 mm Pyrex tube packed with broken glass and
heated by a horizontally mounted ‘Thermolyne’ model
21100 tube furnace. Products were collected at the end of the
furnace on the cooler part of the tube. Volatile products were
condensed in a liquid nitrogen trap. New compounds were
isolated by radial chromatography and gave satisfactory
spectroscopic and analytical data (accurate mass).
Compound 9 was prepared by a previously published
procedure14 by reaction of anthracene and norbornadiene.
Compounds 10 and 11 were prepared by a procedure
analogous for the benzo crown ether derivative of 10.18,19
1α,2β,3β,6β,7β,8α-15-Oxatetracyclo[6.6.1.13,6.02,7.09,14]-
hexadeca-4,9,11,13-tetraene (10)
16,19-Di(2-pyridyl)-14-oxa-1β,2β,3α,10α,11β,12β-
hexacyclo[10.6.1.13,10.02,11.04,9.015,20]icosa-4,6,8,15,17,19-
hexaene (16)
A solution of alkene 10 (430 mg, 2.05 mmol) in CHCl3 (5
mL) was treated with s-tetrazine (483 mg, 2.05 mmol) and
refluxed overnight. To this mixture, DDQ (900 mg, 4.0
mmol) was added and refluxed overnight. Insoluble material
was removed by filtration, and the residual liquid was
washed with 3 M NaOH (3×), then with H2O, dried
(MgSO4), and the solvent was removed under vacuum to
afford a brown-colored oil, which was subjected to radial
chromatography (CHCl3–MeOH = 10:1) to afford 16 as a
colorless solid (331 mg, 38.8%, mp 202–205 °C). 1H NMR
(300 MHz, CDCl3): δ = 1.81 (d, J = 9.3 Hz, 1 H, CH2), 1.93
(d, J = 9.3 Hz, 1 H, CH2), 2.86 (dd, J = 3.0, 1.6 Hz, 2 H,
Hendo), 4.63 (d, J = 1.1 Hz, 2 H, Hbridgehead-C), 5.10 (s, 2 H,
Hbridgehead-O), 7.04–7.07 (m, 2 H, HAr), 7.14–7.17 (m, 2 H,
HAr), 7.38–7.41 (m, 2 H, HAr), 7.90 (dt, J = 9.0, 1.8 Hz, 2 H,
HAr), 8.69 (d, J = 8.0 Hz, 2 H, Ar), 8.84 (dd, J = 4.7, 0.6 Hz,
2 H, Ar). 13C NMR (75 MHz, CDCl3): δ = 40.5, 50.1, 53.2
(CH2), 79.6 (Cbridgehead-O), 119.5, 112.8, 120.1, 123.4, 126.6,
139.0, 149.3, 149.6, 150.1, 155.4, 160.1. ESI-HRMS: m/z
calcd for C27H20N4O1 [M]+: 416.1637; found: 416.1638.
16,19-Di(2-pyridyl)-14-aza-1β,2β,3α,10α,11β,12β-
hexacyclo[10.6.1.13,10.02,11.04,9.015,20]icosa-4,6,8,15,17,19-
hexaene (18)
A solution of alkene 11 (870 mg, 4.16 mmol) in CHCl3 (5
mL) was treated with s-tetrazine (980 mg, 4.16 mmol) and
refluxed overnight. To this mixture, DDQ (1.589 mg, 7.0
mmol) was added and refluxed overnight. Insoluble material
was removed by filtration, and the residual liquid was
washed with 3 M NaOH (3×), then with H2O, dried
(MgSO4), and the solvent was removed under vacuum to
afford a black-colored oily residue, which was subjected to
radial chromatography (PE–EtOAc = 1:1, then the solvent
polarity was gradually increased to EtOAc) to afford 18 as a
black-colored solid (129 mg, 7.5%, mp 109–110 °C). 1H
A solution of 1,4-dihydro-1,4-epoxynaphthalene (1.0 g, 6.94
mmol) and cyclopentadiene (2.00 g, 30.3 mmol) in CHCl3 (5
mL) was heated at 70 °C for 14 h in a glass high-pressure
vessel. The solvent was removed under vacuum, and
cyclopentadiene excess was removed under high vacuum to
afford 10 as a yellow-colored oil (1.30 g, 89.2%). 1H NMR
(300 MHz, CDCl3): δ = 1.37 (d, J = 8.0 Hz, 1 H, CH2), 1.54
(dt, J = 8.0, 1.8 Hz, 1 H, CH2), 2.37 (t, J = 1.8 Hz, 2 H,
H
H
endo), 2.92 (q, J = 1.8 Hz, 1 H, Hbridgehead-C), 4.96 (s, 2 H,
bridgehead-O), 6.13 (t, J = 1.5 Hz, 2 H, =CH), 7.09 (dd, J = 5.5,
3.1 Hz, 2 H, HAr), 7.17 (dd, J = 5.5, 3.1 Hz, 2 H, HAr). 13
C
NMR (75 MHz, CDCl3): δ = 44.4 (Cendo), 49.3 (Cbridgehead-C),
53.7 (CH2), 80.2 (Cbridgehead-O), 119.0 (=CH), 126.7 (CArH),
134.7 (CArH), 148.7 (CArq). ESI-HRMS: m/z calcd for
C15H14O1 [M]+: 210.1045; found: 210.1046.
1α,2β,3β,6β,7β,8α-15-Azatetracyclo[6.6.1.13,6.02,7. 09,14]-
hexadeca-4,9,11,13-tetraene (11)
A solution of 1,4-dihydro-1,4-iminonaphthalene (2.0 g, 13.9
mmol) and freshly distilled cyclopentadiene (5.00 g, 75.6
mmol) in CHCl3 (10 mL) was heated at 70 °C overnight in a
glass high-pressure vessel. The solvent was removed under
vacuum and cyclopentadiene excess under high vacuum to
afford 11 as a black-colored oil (2.10 g, 72.3%). 1H NMR
(300 MHz, CDCl3): δ = 1.40 (d, J = 8.0 Hz, 1 H, CH2), 1.57
Synlett 2013, 24, 2609–2613
© Georg Thieme Verlag Stuttgart · New York

LETTER
NMR (300 MHz, CDCl3): δ = 1.68 (br s, 1 H, NH), 1.80 (d,
Transfer Reagents 4: Dienofugacity
2613
3,14,18,29-Tetra(carbomethoxy)-7,10,22,5-tetra(2-
J = 9.2 Hz, 1 H, CH2), 1.96 (d, J = 9.2 Hz, 1 H, CH2), 2.69
(m, 2 H, Hendo), 4.22 (s, 2 H, Hbridgehead-C), 4.64 (s, 2 H,
Hbridgehead-N), 6.99–7.01 (m, 2 H, HAr), 7.11–7.13 (m, 2 H,
HAr), 7.39–7.43 (m, 2 H, HAr), 7.88–7.93 (m, 2 H, HAr), 8.63–
8.77 (m, 4 H, HAr). 13C NMR (75 MHz, CDCl3): δ = 45.0
(Cendo), 48.6 (Cbridgehead-C), 53.0 (CH2), 61.8 (Cbridgehead-N),
119.5, 122.0, 123.8, 125.6, 137.0, 148.3, 149.4, 151.9,
152.9, 159.0. ESI-HRMS: m/z calcd for C27H21N5 [M]+:
415.1797; found: 415.1794.
pyridyl)-32,34-dioxa-8,9,23,24-tetraaza-1α,2β,4β,5α,12α,
13β,15β,16α,17β,19β,20α,27α,28β,30β-dodecacyclo-
[14.14.1.13,14.15,12.118,29.120,27.02,15.04,13.06,11.017,30.019,28.021,26]-
pentatriaconta-6,8,10,21,23,25-hexaene (21)
A solution of alkene 3 (100 mg, 0.336 mmol) and bisepoxide
20 (68 mg, 0.167 mmol) in THF (2 mL) was heated
overnight at 140 °C in a sealed high-pressure glass vessel.
The solvent was removed under vacuum, and the residue
was subjected to radial chromatography (PE–EtOAc = 1:1,
then the solvent polarity was gradually increased to EtOAc),
to afford 21 as a brown-colored solid (128 mg, 76%, mp
>350 °C). 1H NMR (300 MHz, CDCl3): δ = 1.34 (d, J = 9.1
Hz, 2 H, CH2), 2.00 (s, 4 H, Hendo), 2.04 (s, 2 H, CH2), 2.22
(s, 2 H, Hbridgehead), 2.42 (s, 4 H, Hendo), 2.82 (d, J = 9.1 Hz, 2
H, CH2), 3.96 (s, 12 H, CO2Me), 4.36 (s, 4 H, Hbridgehead-C),
7.39–7.41 (m, 4 H, HAr), 7.92 (dt, J = 6.1, 0.7 Hz, 4 H, HAr),
8.58 (d, J = 6.1 Hz, 4 H, HAr), 8.71 (d, J = 5.6 Hz, 4 H, HAr).
13C NMR (75 MHz, CDCl3): δ = 28.7 (CH2), 41.2, 42.3
(CH2), 45.6, 52.6, 54.1, 56.6, 89.8 (Cbridgehead-O), 122.1,
123.3, 137.4, 149.3, 149.8, 152.3, 155.0, 169.2 (C=O). ESI-
HRMS: m/z calcd for C57H48N8O10: 1004.3493 [M]+,
1027.3391 [M + Na]+, 1005.3557 [M + H]+; found:
1027.3352.
3,6-Di(2-pyridyl)-4,5-diaza-1α,8α-tricyclo[6.2.1.02,7]-
undeca-2,4,6,9-tetraene (3)
Compound 14 (50 mg 0.108 mmol) was subjected to FVP at
590 °C to give two fractions, one colorless solid
(anthracene) and 3 as a brown-colored solid (14 mg, 43.5%).
1H NMR (300 MHz, CDCl3): δ = 2.36 (td, J = 7.9, 1.5 Hz, 1
H, CH2), 2.41 (td, J = 7.9, 1.5 Hz, 1 H, CH2), 5.16–5.18 (m,
2 H, Hbridgehead), 6.99 (t, J = 1.9 Hz, 2 H, =CH), 7.35 (dd,
J = 6.3, 1.3 Hz, 1 H, HAr), 7.38 (dd, J = 6.3, 1.3 Hz, 1 H,
HAr), 7.88, (td, J = 8.7, 1.8 Hz, 2 H, HAr), 8.56 (td, J = 8.0,
0.9 Hz, 2 H, HAr), 8.76–8.79 (m, 2 H, HAr). These values are
consistent with those reported in the literature.14
8,11-Di(2-pyridyl)-9,10-diazabicyclo[6.4.0]undeca-
2,4,7,9,11-pentaene (8)
Compound 24 (50 mg, 0.108 mmol) was subjected to FVP at
670 °C (in this experiment pyrolysis tube was not packed
with broken glass) to give a black-colored oil, which was
subjected to radial chromatography (CHCl3–MeOH = 10:1)
to afford 8 as a brown-colored oil (9 mg, 30.6%). 1H NMR
(300 MHz, CDCl3): δ = 3.12 (d, J = 5.8 Hz, CH2, 2 H), 6.10–
6.18 (m, 1 H, =CH), 6.39 (dd, J = 7.9, 5.3 Hz, 1 H, =CH),
6.95 (dd, J = 10.5, 5.3 Hz, 1 H, =CH), 7.38–7.43 (m, 2 H,
HAr), 7.72 (d, J = 11.6 Hz, 1 H, HAr), 7.86–7.91 (m, 2 H,
HAr), 8.02 (d, J = 7.8 Hz, 1 H, =CH), 8.20 (d, J = 7.8 Hz, 1
H, HAr), 8.78 (d, J = 4.2 Hz, 2 H, HAr). 13C NMR (75 MHz,
CDCl3): δ = 30.0 (CH2), 123.7, 125.1, 125.8, 127.3, 128.9,
126.1, 130.8, 132.7, 136.2, 137.6, 149.1, 149.2, 156.4,
156.8, 157.9. ESI-HRMS: m/z calcd for C19H12N4 [M]+:
298.1218; found: 298.1198.
3,6,10,13-Tetra(2-pyridyl)-4,5,11,2-tetraaza-1α,8α-
tetracyclo[6.6.1.02,7.09,14]pentadeca-2,4,6,9,11,13-
hexaene (23)
A solution of alkene 3 (55 mg, 0.125 mmol) in CHCl3 (2 mL)
was treated with s-tetrazine (30 mg, 0.125 mmol) and
refluxed overnight. To this mixture, DDQ (227 mg, 1.0
mmol) was added and refluxed overnight. The insoluble
material was removed by filtration, and the residual liquid
was washed with 3 M NaOH (3×), then with H2O, dried
(MgSO4), and the solvent was removed under vacuum. The
residue was subjected to radial chromatography (PE–EtOAc
= 1:1), to afford 23 as a brown-colored solid (21 mg, 22.5%,
mp 302–304 °C). 1H NMR (300 MHz, CDCl3): δ = 2.99 (s,
2 H, Hendo), 6.62 (s, 2 H, Hbridgehead), 7.30–7.34 (m, 4 H, HAr),
7.82 (dt, J = 6.1, 4.2 Hz, 4 H, HAr), 8.33–8.36 (m, 8 H, HAr).
13C NMR (75 MHz, CDCl3): δ = 49.3 (Cbridgehead-C), 67.9
(CH2), 123.4, 123.9, 137.0, 149.2, 151.5, 154.3, 155.7. ESI-
HRMS: m/z calcd for C31H20N8 [M]+: 504.1811; found:
504.1815.
© Georg Thieme Verlag Stuttgart · New York
Synlett 2013, 24, 2609–2613

Copyright of Synlett is the property of Georg Thieme Verlag Stuttgart and its content may not
be copied or emailed to multiple sites or posted to a listserv without the copyright holder's
express written permission. However, users may print, download, or email articles for
individual use.