Cyclopenta[c]pyrans from 6-oxo-6H-1,3,4-oxadiazines

Article abstract of DOI:10.1039/a807233g

Prepared in a three-step sequence including acid-catalysed cycloaddition of cyclopentadiene to 6-oxo-6H-1,3,4-oxadiazines, dehydrogenation with DDQ of the dihydro-α-pyrones formed and reduction of the resulting α-pyrones with DIBAL-H, 1,4-disubstituted cy

Full text of DOI:10.1039/a807233g

Cyclopenta[c]pyrans from 6-oxo-6H-1,3,4-oxadiazines†
Manfred Christl,*a Notker Bien,a Gabriele Bodenschatz,a Erich Feineis,a Joachim Hegmann,a Carola
Hofmann,a Stefan Mertelmeyer,a Joachim Ostheimer,a Frank Sammtleben,a Susanne Wehner,a Eva-Maria
Peters,b Karl Peters,b Matthias Pfeifferc and Dietmar Stalkec
a Institut für Organische Chemie, Universität Würzburg, Am Hubland, D-97074 Würzburg, Germany.
E-mail: christl@chemie.uni-wuerzburg.de
b Max-Planck-Institut für Festkörperforschung, Heisenbergstrabe 1, D-70569 Stuttgart, Germany
c Institut für Anorganische Chemie, Universität Würzburg, Am Hubland, D-97074 Würzburg, Germany
Received (in Liverpool, UK) 15th September 1998, Accepted 29th September 1998
R1
R1
R1
Prepared in a three-step sequence including acid-catalysed
cycloaddition of cyclopentadiene to 6-oxo-6H-1,3,4-oxadi-
azines, dehydrogenation with DDQ of the dihydro-a-
pyrones formed and reduction of the resulting a-pyrones
with DIBAL-H, 1,4-disubstituted cyclopenta[c]pyrans are
shown to undergo electrophilic substitution; the molecular
structures of 1-(4-anisyl)-4-phenylcyclopenta[c]pyran and
4-isopropyl-1-phenylcyclopenta[c]pyran-7-carbaldehyde
have been determined by single crystal X-ray diffraction
studies.
O
O
O
cyclopentadiene
(cat.)
N
N
+
O
O
O
CH2Cl2
–10 to 0 °C
R2
R2
R2
6
7
8
R1
R2
Ph
Ratio 7:8 Yield (%)
a
b
c
d
e
f
Ph
Ph
Ph
Pri
Pri
Pri
8:1
69
73
80
84
85
80
Iridoids with a cyclopenta[c]pyran skeleton occur widely.2 For
example, plagiolactone 1 is a constituent of the defence
secretion produced by the larvae of Plagiodera versicolora3a
and viburtinal 2 was obtained by hydrolysis of the esters
4-MeOC6H4
CO2Me
Ph
4-ClC6H4
4-MeOC6H4
10:1
<1:>20
5:1
>5:<1
>5:<1
Me
Me
Scheme 1
Y
H
O
X
R1
R1
Ph
Br
O
H
O
O
O
O
O
Y
Br
Me
CHO
O
O
O
1
2
3 X = Y = H
4 X = But, Y = H
5 X = But, Y = Ph
R2
9a–f
R2
CO2Me
11
10a–d
extracted from the leaves of Viburnum tinus.4a One synthesis
for each of these compounds is known.3b,4b
10c, we added bromine to 8c and treated the resulting dibromide
11 with DBU, giving rise to a 1:8 mixture of 9c and 10c in 81%
overall yield.
To our surprise, the a-pyrones 9 and 10 were directly
transformed to the target compounds 12 by DIBAL-H (Scheme
2). The low yield of 12c has its origin in the attack of the reagent
at the ester group. Applying 4 equiv. of DIBAL-H afforded the
alcohol 12g (36% yield). An effect analogous to that of DIBAL-
H could be achieved by AlMe3, which converted 9a/10a into the
methyldiphenylcyclopenta[c]pyran 13 (50%).
We report here on a simple route to compounds having the
bicyclic systems of 1 and 2 as well as to aldehydes that differ
from 2 only by the substituents in the six-membered ring.
Hitherto, only three cyclopenta[c]pyrans without an acceptor
substituent have been described: the parent heterocycle 3, its
tert-butyl derivative 45 and its tert-butyldiphenyl derivative 5.6
No reactions were performed with 3–5. Being 10p-electron
systems, they should be aromatic7 and thus amenable to
electrophilic substitution.
The non-catalysed reaction of diphenyl-1,3,4-oxadiazin-
6-one 6a with cyclopentadiene proceeded unsatisfactorily.
However, as in the case of norbornene,8 the presence of TFA led
to a strong acceleration of the desired cycloaddition with
subsequent formation of the regioisomeric dihydro-a-pyrones
7a and 8a. Eleven further oxadiazinones9 were utilised. Scheme
1 summarises the best results. We had shown previously that the
methyl oxooxadiazinecarboxylate 6c reacts rapidly with cyclo-
pentadiene in the absence of a catalyst.10 On treatment with
triflic acid, the resulting g-oxoketene now cyclised smoothly to
give pure exo-8c.
R1
12a (53%)
12b (44%)
12c (9%)
12d (40%)
12e (38%)
12f (28%)
DIBAL-H
9/10
CH2Cl2
–78 °C
O
R2
Ph
Ph
Me
O
O
The next step was the conversion of 7 and 8 into the a-
pyrones 9 and 10, respectively, with DDQ with yields ranging
from 27 (10c) to 76% (9b/10b). In order to improve the yield of
CH2OR
Ph
12g R = H
13
12h R = SiMe3
† Cycloadditions of 6H-1,3,4-oxadiazin-6-ones (4,5-diaza-a-pyrones). Part
17. For Part 16, see ref. 1.
Scheme 2
Chem. Commun., 1998, 2387–2388
2387

R1
Ph
Ph
similar to those of benzene and the corresponding ones of
azulene.11 Also C(4a)–C(7a) and C(7)–C(7a) resemble each
other closely (144.5–145.1 pm), but are significantly shorter
and longer than the respective bonds of azulene (ca. 150 and
140 pm). Unlike its effect in the five-membered ring, the formyl
group causes remarkable changes of several bond lengths in the
pyran subunit.
Me
O
O
CHO
CHO
14a,d,e,f
R2
15
In the UV–VIS spectra (MeCN) of 12a,b and 13 the
absorption maxima at longest wavelengths are found at
437–450 nm (log e 3.13–3.20). As compared to those of 12a and
13, the absorptions of the aldehydes 14a and 15 show hardly any
shift in the wavelengths, but an increase of the molar extinction
coefficient (log e 3.73, 3.82). The methyl carboxylate 12c
absorbs at the longest wavelength (490 nm, log e 2.95).
We thank the Deutsche Forschungsgemeinschaft as well as
the Fonds der Chemischen Industrie for financial support, and
Degussa AG for gifts of chemicals.
R1
R1
O
O
NO2
R2
R2
CF3CO
16a,d,g
17a,g
The availability of compounds 12 and 13 made us try
electrophilic substitutions. Formylation with DMF/POCl3 at 0
°C furnished mainly the aldehydes 14 and 15 (61–84%). TFAA/
NEt3 at 20 °C produced the trifluoromethyl ketones 16a,d,g (74,
46, 11%). In the case of 16g, the alcohol 12g had to be
transformed to the TMS ether 12h prior to trifluoroacetylation.
Nitration was achieved with tetranitromethane/Py at 0 °C giving
rise to the products 17a,g (56, 38%).
The cyclopenta[c]pyrans 12 and 13 are orange to deep red,
rather sensitive compounds, which could be purified by
chromatography on basic alumina of activity IV. Only the
crystalline products (12a,b,c, 13) were persistent at room
temperature, whereas the oils and solutions could only be stored
at 230 °C for a short time.
Notes and references
‡ Crystal data for 12b: C21H16O2, M = 300.34, orthorhombic, space group
Pbca, a = 1269.4(2), b = 735.97(9), c = 3245.4(6) pm, V = 3.0320(8)
nm3, Z = 8, Dc = 1.316 Mg m23, F(000) = 1264, l = 71.073 pm, T = 193
K [shock-frozen crystal (0.5 3 0.5 3 0.1 mm) in a drop of oil], m = 0.084
mm21. Data were collected on an Enraf-Nonius CAD4 diffractometer using
Mo-Ka radiation. A total of 3009 reflections were measured in the scan
range of 6.4 @ 2q @ 41.7°, of which 1587 were independent (Rint = 0.073).
The structure was solved by direct methods (SHELXS-97) and refined by
full-matrix least-squares (SHELXL-97). R1 = 0.076, wR2 (all data) =
0.239.
For 14d: C18H16O2, M = 264.32, orthorhombic, space group Pbca, a =
1555.4(3), b = 969.3(2), c = 1898.0(4) pm, V = 2.862(1) nm3, Z = 8, Dc
= 1.227 Mg m23, F(000) = 1120, l = 71.073 pm, T = 293 K, m = 0.08
mm21. Crystal size 0.3 3 0.2 3 0.15 mm. Data were collected on a Siemens
P4 diffractometer using Mo-Ka radiation. A total of 4663 reflections were
measured in the scan range of 3.5 @ 2q @ 55.0°, of which 1534 were
independent (Rint = 0.051). The structure was solved by direct methods and
Detailed information on the structures of 12b and 14d is
provided by X-ray analyses (Fig. 1).‡ The formyl group of 14d
is almost coplanar with the five-membered ring (angle between
their best least-squares planes 172°). Astoundingly, the CC
bond lengths in the five-membered ring of 14d hardly differ
from those of 12b. Thus, the distances C(4a)–C(5), C(5)–C(6)
and C(6)–C(7) are nearly the same (138.2–139.3 pm) and
refined by full-matrix least-squares (SHELXTL PLUS). R = 0.081, Rw
=
0.061. CCDC 182/1041.
1 T. T. Tidwell, F. Sammtleben and M. Christl, J. Chem. Soc., Perkin
Trans. 1, 1998, 2031.
2 L. J. El-Naggar and J. L. Beal, J. Nat. Prod., 1980, 43, 649; C. A. Boros
and F. R. Stermitz, J. Nat. Prod., 1990, 53, 1055.
3 (a) J. Meinwald, T. H. Jones, T. Eisner and K. Hicks, Proc. Natl. Acad.
Sci. U. S. A., 1977, 74, 2189; (b) J. Meinwald and T. H. Jones, J. Am.
Chem. Soc., 1978, 100, 1883.
4 (a) R.-P. Godeau, J.-C. Rossi and I. Fouraste, Phytochemistry, 1977, 16,
604; (b) J.-L. Brayer, J.-P. Alazard and C. Thal, J. Chem. Soc., Chem.
Commun., 1983, 257.
5 T. Kämpchen, G. Moddelmog, D. Schulz and G. Seitz, Liebigs Ann.
Chem., 1988, 855.
6 H. Kato, T. Kobayashi, M. Ciobanu, H. Iga, A. Akutsu and A. Kakehi,
Chem. Commun., 1996, 1011; H. Kato, T. Kobayashi, M. Ciobanu and
A. Kakehi, Tetrahedron, 1997, 53, 9921.
7 Review on pseudoazulenes: H.-J. Timpe and A. V. El’tsov, Adv.
Heterocycl. Chem., 1983, 33, 185.
8 M. Christl, G. Bodenschatz, E. Feineis, J. Hegmann, G. Hüttner, S.
Mertelmeyer, K. Schätzlein and H. Schwarz, J. Prakt. Chem., 1995,
337, 659.
9 Preparation of the oxadiazinone 6a: W. Steglich, E. Buschmann, G.
Gansen and L. Wilschowitz, Synthesis, 1977, 252; the other oxa-
diazinones 6, except 6e (preparation as that of 6d), have been described
in the previous papers of this series.
10 J. Hegmann, E. Ditterich, G. Hüttner, M. Christl, E.-M. Peters, K. Peters
and H. G. von Schnering, Chem. Ber., 1992, 125, 1913.
11 O. Bastiansen and J. L. Derissen, Acta Chem. Scand., 1966, 20, 1319
and references cited therein.
Fig. 1 Molecular structures of (a) 1-(4-anisyl)-4-phenylcyclopenta[c]pyran
12b and (b) 4-isopropyl-1- phenylcyclopenta[c]pyran-7-carbaldehyde 14d,
together with the atomic numbering scheme and some selected bond lengths
(pm).
Communication 8/07233G
2388
Chem Commun., 1998