Direct formation of α-dione blocks from o-benzoquinone cycloadditions and their value in the synthesis of fused quinoxalines, 1,10-phenanthrolines and pteridines

Article abstract of DOI:10.1055/s-1998-3135

o-Benzoquinone reacts with norbornadiene to yield a mixture of exo and endo stereoisomeric bridged α-diones which are condensed with vic-diamines (o-phenylenediamines, 5,6-diamino uracil or 5,6-diaminophenanthroline) to produce the corresponding heterocyclic fused-norbornenes; other rod or angled molrac α-dione blocks and heterocycles derived therefrom are described which open new avenues for macrostructure development via block coupling protocols.

Full text of DOI:10.1055/s-1998-3135

590
LETTERS
SYNLETT
Direct Formation of α−Dione BLOCKs from o-Benzoquinone Cycloadditions and their Value
1
in the Synthesis of Fused Quinoxalines, 1,10-Phenanthrolines and Pteridines
Ronald N. Warrener,* Martin R. Johnston, Austin C. Schultz, Mirta Golic, Mark A. Houghton, Maxwell J. Gunter
a
a
a
a
a
b
a
Centre for Molecular Architecture, Central Queensland University, Rockhampton, Queensland, 4702, Australia
Fax: +61 7 4930 9917; E-mail: r.warrener@cqu.edu.au
b
Department of Chemistry, University of New England, Armidale, NSW, 2351, Australia
Fax: +61 2 6773 3268; E-mail: mgunter@metz.une.edu.au
Received 24 November 1997
Abstract: o-Benzoquinone reacts with norbornadiene to yield a mixture
of exo and endo stereoisomeric bridged α-diones which are condensed
with vic-diamines (o-phenylenediamines, 5,6-diamino uracil or 5,6-
diaminophenanthroline) to produce the corresponding heterocyclic
fused-norbornenes; other rod or angled molrac α-dione BLOCKs and
heterocycles derived therefrom are described which open new avenues
for macrostructure development via BLOCK coupling protocols.
implicit in the two step oxidation regime. Accordingly, we have
explored the role of o-benzoquinones 1-3 to produce bridged α-diones
directly from a cycloaddition step and report our findings herein. The
conversion of the bridged α-diones so formed to quinoxalines,
1,10-phenanthroline and pteridine BLOCKs is also reported with the
extension to porphyrin chemistry in this area being dealt with in the
7
accompanying letter.
8
There are now several successful strategies for the construction of rigid,
In our original report some years ago, on the reaction of o-chloranil 2
2
polyalicyclic structures adorned with effector groups. While serial
with norbornadiene 4, only the two major isomers 5a and 9 were
characterised; more careful investigation now reveals that all six isomers
5a-10a are produced (NMR analysis: 5>>7>8>>6; 9>>10);
significantly, both exo and endo products are obtained (Scheme 1). The
α-dione products 5a-8a condense with vic-diamines and this offers
A-BLOCKs in a variety of new molecular architectures and their reaction
3
cycloaddition strategies have dominated this field, the recent work on
the condensation of α-diones with phenylene diamines as a linking
technique in molecular wire production has opened up a new avenue for
4
advancement in cavity and rod construction based on BLOCK chemistry.
A very recent report on the use of molrac α-diones for production of
5
11
functionalised porphyrin and 1,10-phenanthroline systems, prompts us
with o-phenylene-diamines 17 and 18 to give quinoxalines 12a-15a
to describe our own advancements in this field based on vic-diamine
condensations with α-diones to form BLOCKs and their attendant
assembly protocols.
(Scheme 2) has been used for their characterisation. The structural
assignments were made on the basis of H NMR chemical shift data for
proton Ha to distinguish between 12a (δ=2.00) and 13a (δ=-0.67)
(Scheme 2) and the ability of adduct 15a (but not 14a) to form a
photo-cage compound (16).
1
The separate reaction of the α-dione 5a and several o-phenylene
diamines 17-20 to form the corresponding fused quinoxalines 21-24
(Scheme 3) has been investigated under thermal or high pressure
conditions (Table 1); the high pressure conditions are new and were
developed to accommodate the reaction of heat-sensitive compounds.
We had used the two step approach involving cis-hydroxylation of
alkenes followed by oxidation, to prepare α-diones in some of our
6
earlier work on photochemistry, but considered that the availability of a
direct method for bridged α-dione production would avoid limitations
Scheme 3

June 1998
SYNLETT
591
12
The thermal reaction of 3,6-di(tertbutyl)-o-benzoquinone 3 with NBD
4 stood in stark contrast with o-benzoquinones 1 and 2, since no α-
diones were formed. The dominant product (>95%) was the dioxene 11
(Scheme 1), resulting from exo-attack onto the norbornadiene, with only
very minor amounts of the endo-product corresponding to 10 being
observed.
Linking two α-dione BLOCKs together was achieved via reaction with
1,2,4,5-tetraminobenzene 25 which produced both syn and anti
stereoisomers 26 (characterised as a mixture). The norbornene π-
systems in these products are available for further coupling or
functionalisation and this is illustrated by conversion to the bis-dpp
compounds 28 on treatment of mixture 26 with 3,6-di(2'-pyridyl)-
s-tetrazine 27 in the presence of DDQ using our standard methodology
Smooth condensation at the α−dione chromophore of 5b occurred with
vic-diamines to produce the corresponding heterocycle, eg, reaction of
5b with 5,6-diaminouracil 30 afforded the pteridine-fused product 31,
while 5,6-diamino-1,10-phenanthroline 19 produced the ligand-
containing BLOCK 32 (Scheme 5). Both 31 and 32 can serve as
9
(Scheme 4).
13
14
A-BLOCKs in ACE or s-tetrazine coupling procedures.
Our next objective was to establish that cyclobutene epoxide B-BLOCKs
could be produced in this series and this was explored by conversion of
A-BLOCK 5b to the related cyclobutene-1,2-diester B-BLOCK 33 under
15
Mitsudo conditions (Scheme 6). Unfortunately, no epoxidation
conditions could be found to convert 33 to an epoxide without affecting
the α-dione chromophore. Accordingly, the α-dione moiety in 5b was
protected as the quinoxaline 12b and subjected to ruthenium-catalysed
15
cycloaddition of dimethyl acetylene dicarboxylate to furnish the
cyclobutene-1,2-diester 34, which proved to be amenable to
t
nucleophilic epoxidation ( BuO H, MeLi) and formed the cyclobutene
2
epoxide 35, which is a B-BLOCK suitable for ACE coupling.
The presence of the chlorine groups in the α-dione BLOCKs was
undesirable in some applications, so we investigated the reaction of
other o-benzoquinones 1 and 3 with norbornadiene. Conducting the
oxidation of catechol 29 in a mixture of acetonitrile and norbornadiene
(co-solvent and reagent) and using PhI(OAc) as oxidant, allowed
2
10
efficient generation and trapping of the o-benzoquinone without any
evidence of self dimerisation products (Scheme 5). The major product
was the yellow-coloured α-dione 5b which could be isolated in
11
crystalline form
and proved to be more stable than its
tetrachloro-derivative 5a, which is prone to hydrate one of the α-dione
carbonyl groups. Stereoisomeric α-diones 6b-8b were only identified
spectrometrically; none of the dioxene regiomers corresponding to 9 and
10 was observed in this cycloaddition. The structure of 5b was
1
supported by H NMR spectroscopy where the lack of vicinal H, H-
proton coupling supported the exo-stereochemistry of the product and
the chemical shifts of the bridging methylene resonances in the derived
quinoxaline 12b (δ 2.02; no shielding by the heteroaromatic ring) and
13b (δ -0.67; strong upfield shielding by the heteroaromatic ring) was
definitive.
In conclusion, the role of o-benzoquinone cycloadditions to furnish
polyalicyclic α-diones has been established and these have been
condensed with vic-diamines to furnish new building BLOCKs. The
potential of such α-dione BLOCKs in porphyrin chemistry is discussed in

592
LETTERS
SYNLETT
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the accompanying letter where ACE or s-tetrazine couplings are
addressed.
Acknowledgements. This work was supported by ARC grant
(A29532170). A.C.S thanks the Australian Government for the
provision of an UPRA Scholarship and M.G. thanks the Centre for
Molecular Architecture for a PhD Scholarship.
(7) Warrener, R.N.; Johnston M. R.; Gunter M. J. Synlett 1998, 593.
(8) Nunn, E. E.; Wilson, W. S.; Warrener, R. N. Tetrahedron Lett.
1972, 2 ,175.
References and Notes
(1) Building BLOCKs in Synthesis Part 5: for part 4, see Warrener, R.
N.; Butler, D. N.; Malpass, J. R.; Margetic, D.; Russell, R. A. Sun,
G. Synlett 1998, 588.
(9) Warrener, R. N.; Elsey, G. M.; Sankar, I. V.; Butler, D. N.; Pekos,
P.; Kennard, C. H. L. Tetrahedron Lett. 1994, 35, 6745.
(10) Benzoquinones have been generated in situ by enzymatic
oxidation of catechols and trapped using cycloaddition reactions.
Müller, G. H.; Waldman, H. Tetrahedron Lett. 1996, 37, 3833.
13
(2) Warrener, R. N.; Schultz, A. C.; Houghton, M. A.; Butler, D. N.
Tetrahedron 1997, 53, 3991. Warrener, R. N.; Wang, S.; Russell,
R. A. Tetrahedron 1997, 53, 3975. Warrener, R. N.; Wang, S.;
Russell, R. A.; Gunter, M. J. Synlett 1997, 47. Warrener, R. N.;
Wang, S.; Butler, D. N.; Russell, R. A. Synlett 1997, 44. Warrener,
R. N.; Ferreira, A. B. B.; Schultz, A. C.; Butler, D. N.; Keene, F.
R.; Kelso, L. S. Angew. Chem., Int. Ed. Engl. 1996, 35, 2485.
Warrener, R. N.; Houghton, M. A.; Schultz, A. C.; Keene, F. R.;
Kelso, L. S.; Dash, R.; Butler, D. N. Chem. Commun. 1996, 1151.
Warrener, R. N.; Ferreira, A. B. B.; Tiekink, E. R. T. Tetrahedron
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N.; Watson, W. H.; Kashyap, R. P. Tetrahedron Lett. 1995, 36,
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Commun. 1994, 1831. Warrener, R. N.; Elsey, G. M.; Sankar, I. V.;
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(11) All new compounds gave satisfactory
C NMR, MS and/or
analytical data. Representative data for selected compounds:
1
5b: m.p. 142 °C. H NMR (CDCI ) δ 1.18 (1H, d, J = 9 Hz); 2.13
3
(2H, s); 2.54 (1H, d, J = 9 Hz); 2.95 (2H, t, J = 1.8 Hz); 3.52 (2H,
t, J = 3 Hz); 6.29 (2H, t, J = 1.8 Hz); 6.36 (2H, t, J = 3 Hz).
1
9: m.p. 145 °C. H NMR (CDCI ) δ 1.89 (1H, d of t, J = 9.6 Hz,
3
d
J = 1.6 Hz); 2.26 (1H, d, J = 9.6 Hz); 3.24 (2H, t, J = 1.6 Hz); 4.21
t
(2H, d, J = 1.7 Hz); 6.19 (2H, t, J = 1.7 Hz).
1
11: m.p. 169 °C. H NMR (CDCI ) δ 1.39 (18H, s); 1.87 (2H, d of
3
t, J = 9 Hz, J = 1.5 Hz); 2.61 (2H, d, J = 9 Hz); 3.13 (2H, t, J =
d
t
1.5 Hz); 3.97 (2H, d, J = 1.8 Hz); 6.17 (2H, t, J = 1.8 Hz); 6.84
(2H, s).
1
12a: m.p. 190 °C. H NMR (CDCI ) δ 1.47 (1Η, d of t, J = 10.3
3
d
Hz, J = 0.9 Hz); 2.02 (1H, d, J = 10.3 Hz); 2.42 (2H, d, J = 0.9
t
Hz); 3.29 (2H, t, J = 1.8 Hz); 6.33 (2H, t, J = 1.8 Hz); 7.80 (2H,
m); 8.18 (2H, m).
12b: m.p. 147 °C, H NMR (CDCl ) δ 1.19 (1H, d, J = 9 Hz);
1
3
2.08 (2H, s); 2.78 (1H, d, J = 9 Hz); 2.83 (2H, s); 4.08 (2H, t, J = 3
Hz); 6.19 (2H, s); 6.59 (2H, t, J = 3 Hz); 7.63 (2H, m); 7.92 (2H,
m).
1
16: m.p. 300 °C, H NMR (CDCl ) 1.75 (1Η, d of t, J = 12 Hz, J
3
d
t
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= 1.5 Hz); 1.99 (1Η, J = 12 Hz); 2.92 (2H, d, J = 1.9 Hz); 3.30
(2H, m); 3.41 (2H, m); 7.84 (2H, m); 8.30 (2H, m). 22: m.p. 192
1
°C, H NMR (CDCl ) δ 1.45 (1H, d, J = 10 Hz); 1.99 (1H, d, J =
3
10 Hz); 2.40 (2H, s); 3.29 (2H, t, J = 1.7 Hz); 6.36 (2H, t, J = 1.7
Hz); 8.28 (2H, s).
31: m.p. 345-347 °C (dec.). H NMR (CDCl /DMSO-d = 3:1): δ
1
3
6
0.72 (1H, d, J = 8.9 Hz); 1.56 (2H, m); 2.27 (1H, d, J = 8.9 Hz);
2.34 (2H, s); 3.55-3.57 (1H, m); 3.63-3.65 (1H, m); 5.75 (2H,
brs); 6.03-6.07 (1H, m); 6.14-6.18 (1H, m); 10.96 (1H, brs); 11.16
(1H, brs).
1
32: m.p. 168 °C (dec.). H NMR (CDCl ) δ 1.28 (1H, d, J = 9
3
Hz); 2.19 (2H, s); 2.85 (1H, d, J = 9 Hz); 2.93 (2H, s); 4.32 (2H,
m); 6.21 (2H, s); 6.71 (2H, m); 7.75 (2H, dd, J = 8.2, 4.4 Hz); 9.23
(2H, dd, J = 4.4, 1.8 Hz); 9.47 (2H, dd, J = 8.2, 1.8 Hz).
1
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34: m.p. 212 °C H NMR (CDCl ) δ 1.03 (1H, d, J = 12 Hz); 1.86
3
(2H, s); 2.42 (2H, s); 2.56 (2H, s); 3.75 (6H, s); 4.23 (2H, t, J = 4
Hz); 6.54 (2H, t, J = 4 Hz); 7.60 (2H, m); 7.94 (2H, m).
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