Nitronaphthalenes as Diels-Alder dienophiles

Article abstract of DOI:10.1016/S0040-4039(00)01436-2

1-Nitronaphthalene, 2-nitronaphthalene and 1,3-dinitronaphthalene react with Danishefsky diene as normal electron demand Diels-Alder dienophiles to give hydroxyphenanthrene derivatives as principal products in reasonable yields. The aromatization is an ex

Full text of DOI:10.1016/S0040-4039(00)01436-2

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 8079–8082
Nitronaphthalenes as Diels–Alder dienophiles
Elisa Paredes, Betina Biolatto, Mar´ıa Kneeteman and Pedro M. Mancini*
´
Laboratorio Fester, Area de Qu´ımica Orga´nica, Departamento de Qu´ımica, Facultad de Ingenier´ıa Qu´ımica,
Universidad Nacional del Litoral, Santiago del Estero 2829, 3000 Santa Fe, Argentina
Received 28 August 2000; accepted 29 August 2000
Abstract
1-Nitronaphthalene, 2-nitronaphthalene and 1,3-dinitronaphthalene react with Danishefsky diene as
normal electron demand Diels–Alder dienophiles to give hydroxyphenanthrene derivatives as principal
products in reasonable yields. The aromatization is an expected behavior in thermal reactions involving
nitro-substituted compounds. However, it was possible to isolate the primary cycloadducts when using
1,3-dinitronaphthalene, although in very low yields. Other less reactive dienes do not undergo cycloaddi-
tion. © 2000 Elsevier Science Ltd. All rights reserved.
The Diels–Alder (D–A) reaction is one of the most useful methods in preparative organic
chemistry. It provides the chemist with one of his best tools for the rapid preparation of cyclic
compounds having a six-membered ring, in a one-step inter- or intramolecular reaction. This
reaction can establish large numbers of stereochemical centers in one synthetic step and thus it
has had great utility in natural product synthesis.
While a great effort has been dedicated to the development and use of aromatic compounds
as dienes for the D–A reaction, in general their use as dienophiles has been considered less
probable, mainly because aromatic and heteroaromatic compounds have proved to be relatively
unreactive as dienophiles.
Recently we reported the high dienophilicity of N-tosyl-3-nitroindole in a normal D–A reaction.1
The compounds involved as the diene partner were very reactive [(N-acetyl-N-propylamino)-1,3-
butadiene,1 Danishefsky diene2]. We have continued exploring this reaction using nitronaphthale-
nes as dienophiles. 1-Nitronaphthalene has proven to be only reactive with anthracene at 300°C.3
Naphthalene itself behaves as a dienophile in an inverse demand reaction with hexachlorocyclo-
pentadiene.4 Despite this behavior, naphthalene and its derivatives have usually been forced to
behave as dienes under hyperbaric or thermal conditions. The nitronaphthalenes used in this work
were 1-nitronaphtalene 1, 2-nitronaphthalene, and 1,3-dinitronaphthalene 5.
The reaction conditions included both elevated temperatures (80–150°C) and high pressure (12
kbar) (only for 1), evaluating different diene:dienophile molar ratios, solvents and times of reaction
* Corresponding author. Fax: 54-342-4571162; e-mail: pmancini@fiqus.unl.edu.ar
0040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)01436-2

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in order to improve the rate and/or the yields of the reaction.1,2† This allowed us to compare
not only the relative reactivity of the 1- and 2-substitution of the aromatic ring, but also the
regioselectivities and stereoselectivities in the case of successful cycloaddition.
The diene components were trans-1-methoxy-3-(trimethylsilyloxy)-1,3-butadiene diene 2
(Danishefsky diene), (1Z,3E)-1,4-dimethoxy-1,3-butadiene,5 chosen for their higher reactivity
compared to the other readily available dienes isoprene, trans-1-(N-acetyl-N-propylamino)-
1,3-butadiene, trans-1-methoxy-1,3-butadiene, which proved to be unreactive toward cyclo-
addition under the reaction conditions studied.
When 1- and 2-nitronaphthalene were reacted with the Danishefsky diene under all condi-
tions (see Table 1) the observed products were 2-hydroxyphenanthrene 4a6 and 3-hydroxy-
phenanthrene 4b,7 respectively, with traces of their regioisomers (16:1 ratio of 2-hydroxy to
3-hydroxyphenanthrene, entry 4, Table 1). These products resulted from the expected aroma-
tization of the nitro-adducts.8 Attempts to isolate the primary adducts were unsuccessful
because of their unstability. The first exploratory experiment using 1 and 2 under hyperbaric
conditions (entry 4) led to the highest yields at 2-hydroxyphenanthrene. In this case, the 75
MHz 13C NMR analysis of the crude product mixture immediately after decompression and
solvent evaporation, showed the presence of the substituted adduct 3‡ which rapidly decom-
posed to the corresponding phenanthrene. When 2-nitrosubstituted, naphthalene evidenced a
significantly lower reactivity.§ This fact, in addition to it being a strong cancer suspect agent,
persuaded us to discard this isomer for further reactions (Scheme 1).
Table 1
Diels–Alder reactions of nitronaphthalenes derivatives and Danishefsky diene
Entry
Dienophile
Diene:dienophile
ratio
Conditions
Isolated product (yield%)a
1
2
3
4
5
6
1
1
1
1
5
5
2:1
2:1
2:1
12:1
2:1
2:1
Benzene, 80°C, 6 d, ampoule
Benzene, 120°C, 3 d, ampoule
Xylene, 150°C, 6 d, reflux
Dichloromethane, 40°C, 50 h, 12 kbar 4a (76), 4b (5)
Benzene, 80°C, 6 d, ampoule
4a (traces)
4a (51)
4a (46)
10 (12), 11 (15), 8 (4), 9 (2)
10 (14), 11 (65), 8, 9 (traces)
Benzene, 120°C, 3 d, ampoule
a Based on consumed dienophile.
Scheme 1.
† Experimental conditions can be found in these references.
‡ 13C NMR (75 MHz, Cl3CD) 57.2 OMe, 76.34-C, 92.2 quat CꢀNO2.
§ This result agrees with the observed unreactivity of 2-nitronaphthalene in its reaction with anthracene at 300°C.3

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The higher reactivity expected for 1,3-dinitronaphthalene 5 is a consequence of its lower
LUMO compared to the mononitrated naphthalenes. Moreover, according to MM+ calcula-
tions, the higher electronic deficiency in this dienophile is at C4 (due to the presence of two
electronwithdrawing groups in a 1,3 relation), indicating a more favored cycloaddition pro-
cess at the C3ꢀC4 bond than at the C1ꢀC2 bond. The reaction of 5 with Danishefsky diene
(Scheme 2) led to a mixture of 2-hydroxy-10-nitrophenanthrene 10¶ and 3-hydroxy-9-nitro-
phenanthrene 11.ꢀ At higher temperatures, compound 11 is clearly the major product (Table
1, entry 6).
Scheme 2.
¶ 1H NMR (300 MHz Cl3CD+DMSOd6) l 7.28 (dd, 1H, J34=9.0 Hz, J31=2.6 Hz, 3-H), 7.51 (t, 1H, J76=J78=7.4
Hz, 7-H), 7.68 (t, 1H, J65=J67=7.4 Hz, 6-H), 7.87 (d, 1H, J87=7.2 Hz, 8-H), 7.79 (d, 1H, J13=2.6 Hz, 1-H), 8.37
(s, 1H, 9-H), 8.49 (d, 1H, J43=9.0 Hz, 4-H), 8.53 (d, 1H, J56=7.4 Hz, 5-H); 13C NMR (75 MHz, Cl3CD+DMSOd6)
l 106.1, 117.9, 121.1, 123.7, 123.7 quat, 124.1 quat, 124.7, 125.2, 126.3 quat, 128.9, 129.3, 131.4 quat, 138.5 quat,
C-NO2, 156.8 quat CꢀOH].
ꢀ 1H NMR (300 MHz Cl3CD+DMSOd6) l 7.25 (dd, 1H, J21=8.5 Hz, J24=2.4 Hz, 2-H), 7.70 (m, 2H, 6-H and
7-H), 7.9 (d, 1H, J12=8.5 Hz, 1-H), 8.02 (d, 1H, J42=2.4 Hz, 4-H), 8.47 (s, 1H, 10-H), 8.56–8.57 (m, 2H, 5-H and
8-H); 13C NMR (75 MHz Cl3CD+DMSOd6) l 105.0, 116.8, 120.1 quat, 120.9, 121.5 quat, 121.7, 124.4, 125.0, 125.9,
128.0 quat, 130.2, 132.4 quat, 140.6 quat C-NO2, 157.7 quat CꢀOH.

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In this reaction system it was possible to isolate a small amount of products 8 and 9** derived
by hydrolysis of the enol ethers 6 and 7, considered to be precursors of the isolated aromatic
compounds. An endo approach in both addition processes leads to a cis arrangement of nitro
and methoxy groups, consistent with only minor steric repulsions in the transition state.
In the reactions of 1-nitronaphthalene and 1,3-dinitronaphthalene with (1Z,3E)-1,4-
dimethoxy-1,3-butadiene (similar conditions than cited in Table 1), no cycloaddition products
were observed. In these cases, we noted only the presence of the corresponding N-naphthyl-
pyrrole, e.g. 1-nitronaphthalene yields 1-(1%-naphthyl)-pyrrole.††
Conclusions. It has been demonstrated that naphthalene, when substituted at positions 1- or
2- with a nitro group (strong electron withdrawing), can undergo cycloaddition on the C1ꢀC2
bond with Danishefsky’s diene. The substitution at the 1-position proved to be better in the
ability to induce the dienophilic behavior of the aromatic compound. When 1,3-dinitrosubsti-
tuted, naphthalene produced higher yields of products by addition to the C3ꢀC4 bond, due to
the higher dienophilicity of this position. Compared with our former results using N-tosyl-3-
nitroindol, nitronaphthalene demonstrates a lower reactivity because of its higher aromaticity.
Acknowledgements
This work was supported by grants from the Universidad Nacional del Litoral. The help
rendered by Prof. Dr. M. Gonzalez Sierra, in the NMR studies and facilities is greatly
appreciated. E. Paredes is very grateful to Prof. Dr. Th. Eicher for his advice.
References
1. Biolatto, B.; Kneeteman, M.; Mancini, P. Tetrahedron Lett. 1999, 40, 3343–3346.
2. Biolatto, B.; PhD Dissertation, Facultad de Ingenier´ıa Qu´ımica, Universidad Nacional del Litoral, 1999.
3. Hurd, C. D.; Juel, L. H. J. Am. Chem. Soc. 1955, 77, 601–606. This result could not be reproduced in our
laboratory.
4. Danish, A. A.; Silverman, M.; Tajima, Y. A. J. Am. Chem. Soc. 1954, 76, 6144–6149.
5. Guillam, A.; Toupet, L.; Maddaluno, J. J. Org. Chem. 1998, 63, 5110–5122.
6. Dannenberg, H.; Meyer, E. Chem. Ber. 1969, 102, 2384–2391.
7. Morley, J. A.; Woolsey, N. F. J. Org. Chem. 1992, 57, 6487–6495.
8. Danishefsky, S.; Prisbilla, M. P.; Hiner, S. J. Am. Chem. Soc. 1978, 100, 2918–2920.
** Compound 8 1H NMR (300 MHz, Cl3CD) l 3.44 (s, 3H OMe), 4.45 (dd, 1H, J10a-1=10.7, 5.46 Hz, 10a-H), 4.97
1
(t, 1H, J43=3.05 Hz, 4-H); 13C NMR (75 MHz Cl3CD) l 90.2 quat CꢀNO2; 204.8 CꢁO; compound 9 H NMR (300
MHz Cl3CD): l 5.31 (brt, 1H, J12=6.10 Hz, 1-H); 5.57 (d, 1H, J4a4=9.32 Hz, 4a-H). The separation was achieved
by preparative TLC, which leads to the lower proportion or rate of aromatization.
†† 1H NMR (300 MHz Cl3CD) l 6.40 (t, 2H, J32=J34=J45=2.2 Hz, 3-H and 4-H), 6.98 (t, 2H, J23=J54=2.2 Hz,
2-H and 5-H), 7.42–7.52 (m, 7H, 3%-H, 5%-H, 6%-H, 7%-H), 7.74 (d, 1H, J43=8.42 Hz, 4%-H), 7.84 (d, 1H, J23=7.96 Hz,
2%-H), 7.88 (d, 1H, J87=8.68 Hz, 8%-H); 13C NMR (75 MHz Cl3CD) l 109.1, 123.2, 123.3, 125.3, 126.5, 126.9, 127.8,
128.1, 129.9 quat 9%-C, 134.3 quat 10%-C, 138.3 quat CꢀN. We observed similar products in the reactions of
nitronaphthalenes and the above cited dienes, with improved yields at higher temperature.