A two-step reaction sequence for the syntheses of tetrahydronaphthalenes

Article abstract of DOI:10.1021/ol0477879

(Chemical Equation Presented) A cobalt(I)-catalyzed Diels-Alder reaction of a boron-functionalized enyne is the key step in a two-step reaction cascade interconnecting four simple starting materials to obtain polycyclic multifunctionalized products in goo

Full text of DOI:10.1021/ol0477879

ORGANIC
LETTERS
2005
Vol. 7, No. 2
251-253
A Two-Step Reaction Sequence for the
Syntheses of Tetrahydronaphthalenes
Gerhard Hilt,* Steffen Lu2ers, and Konstantin I. Smolko
Fachbereich Chemie, Philipps-UniVersita¨t Marburg, Hans-Meerwein-Strasse,
35032 Marburg, Germany
hilt@chemie.uni-marburg.de
Received October 28, 2004
ABSTRACT
A cobalt(I)-catalyzed Diels−Alder reaction of a boron-functionalized enyne is the key step in a two-step reaction cascade interconnecting four
simple starting materials to obtain polycyclic multifunctionalized products in good yields and with a very high degree of diastereoselectivity.
Atom-economic multicomponent reactions for the fast and
efficient diversity-oriented synthesis of a large number of
Scheme 1
structurally complex molecules have always been of general
interest. Recent progress in this field illustrates the elegance
and the synthetic usefulness of such a synthetic strategy.1
On the basis of our cobalt(I)-catalyzed Diels-Alder reac-
tion employing alkynyl boron derivatives and 1,3-dienes for
the generation of dihydroaromatic building blocks,2 we inves-
tigated a reaction sequence where four components are inter-
connected with each other. The acyclic 1,3-diene (isoprene
1), which was mostly used in this study, could be reacted
with the boron-functionalized enyne derivative (2) under mild
reaction conditions using our cobalt(I) catalyst system to
generate the boron-functionalized 1,3-diene (3) (Scheme 1).
Then this key intermediate 3 was converted in a thermal
Diels-Alder reaction with an activated dienophile (4) to a
highly substituted boron-functionalized 1,4-diene (5) contain-
ing an allyl boron subunit. Consequently, the allylboration
of an aldehyde (6) led to dihydroaromatic derivatives (7)3
that could be oxidized with DDQ to the corresponding mul-
tiply substituted tetrahydronaphthalene derivatives (8). By
this reaction sequence four mostly commercially available
starting materials can be interconnected to a complex product
with diverse functional groups generating five new carbon-
(1) (a) Balme, G.; Bossharth, E.; Monteiro, N. Eur. J. Org. Chem. 2003,
4101. (b) Ugi, I.; A. Do¨mling, A.; Werner, B. J. Heterocycl. Chem. 2000,
37, 647. (c) Weber, L.; Illgen, K.; Almstetter, M. Synlett 1999, 366.
carbon bonds with up to four new stereogenic centers (one
(2) Hilt, G.; Smolko, K. I. Angew. Chem. 2003, 115, 2901; Angew. Chem.,
Int. Ed. 2003, 42, 2795.
of them quaternary).
10.1021/ol0477879 CCC: $30.25
© 2005 American Chemical Society
Published on Web 12/18/2004

Table 1. Results for the Two-Step Synthesis of Tetrahydronaphthalenes
a Isolated as dihydroaromatic compound of type 7i. The DDQ oxidation procedure led to low yields of the aromatic compound and to some decomposition
products. b Isolated as a mixture of stereoisomers of products 8m.
Within this study we focused our attention not on the
generation of the boron-functionalized dihydroaromatic build-
ing block 32 but on the unusual thermal Diels-Alder reaction
of the highly substituted 1,3-diene subunit in 3 with activated
dienophiles and the following allylboration of the aldehyde
(6) with the pentasubstituted allyl boron subunit in 5.4
Especially interesting is the possibility to perform the
reactions sequentially without tedious purifications of the
intermediates. After filtration over a small amount of silica
gel and remvoval of the solvent in vacuo the crude products
were directly used in the next synthetic steps. The final
products of type 8 were isolated by recrystallization to give
acceptable to good yields. The results of these four compo-
nent conversions are summarized in Table 1.
As expected the boron functionalized dihydroaromatic
compounds (3) could only be reacted in thermal Diels-Alder
252
Org. Lett., Vol. 7, No. 2, 2005

reactions with quite reactive and sterically less hindered
dienophiles (4) to give the compounds of type 5. These
reactions gave rise to allylic boron reagents (5) in good
yields. Acrylic esters proved to be not very reactive under
the chosen reaction conditions. However, stronger activated
and sterically also less hindered dienophiles, such as N-
phenylmaleimide, (E)-1,2-dicyanoethylene, or maleic anhy-
dride, easily react with 3. The desired products of type 8
from the latter dienophiles could be isolated in acceptable
to good yields after performing the whole reaction sequence.
Thereby the naphthalene backbone bearing functional groups
prone to further functionalization could be generated selec-
tively. Very electron poor and sterically not hindered
dienophiles, such as tetracyanoethylene (TCNE) or acetylenic
dicarboxylic ester (entries 11 and 14), should favor a fast
thermal Diels-Alder reaction. Surprisingly, only traces of
the desired intermediates of type 5 could be found in these
cases. These dienophiles preferentially react in a redox
reaction under electron transfer with the electron rich
dihydroaromatic compound 3 to dehydrogenated aromatic
products.5
anhydride were much more successful. These could be
reacted with a wide range of aliphatic, olefinic, and aromatic
aldehydes (6).6 The following DDQ oxidation under standard
conditions generated the aromatic four-component reaction
products (8). The pure products were obtained by column
chromatography over a small plug of silica and subsequent
recrystallization. The NMR data of the crude products
showed a high level of diastereoselectivity during the Diels-
Alder conversions of 3 with 4 and the allylboration reaction
with the aldehyde 6. As could be ascertained by X-ray
analysis of the product of entry 4, the thermal Diels-Alder
reaction to the intermediate of type 5 took place with a high
endo-selectivity (>95:5). The boronic ester functionality and
the imido group were in trans relation to each other.7 The
following well-described allylboration takes also place in a
highly diastereoselective fashion. Therefore the products 7
and 8 are generated in a very high degree of diastereose-
lective purity (>95:5).
Within this study we were able to show that the dihy-
droaromatic boronic esters can be used as a synthetic
platform not only in Suzuki coupling reactions2 but also in
Diels-Alder reaction sequences. The highly substituted and
functionalized products of the reaction sequence are gener-
ated in acceptable to very good yields taking into account
that four synthetic steps were involved. Five new C-C bonds
from four simple components are formed in this process.
Tedious workup of all of the intermediates is not necessary,
and the final products are obtained by recrystallization.
On the other hand, a sterically more hindered boron-
functionalized 1,3-diene (3) (entry 10) leads to a drastic
decrease in reactivity. The corresponding cycloadduct of type
5 could only be detected in traces.
The reactions of the pentasubstituted allyl boron subunit
in the cycloadducts of type 5 generated from N-phenylma-
leimide, (E)-1,2-dicyanoethylene, fumaric ester, and maleic
Acknowledgment. This work was supported by the
Deutsche Forschungsgemeinschaft and the Fonds der Che-
mischen Industrie. We thank Dr. Klaus Harms for the X-ray
analysis and Frank Schmidt for isolating the single crystal
(product of entry 4) and repeating partially the reaction
sequence.
(3) (a) Toure, B. B.; Hall, D. G. Angew. Chem. 2004, 116, 2035; Angew.
Chem., Int. Ed. 2004, 43, 2001. (b) Deligny, M.; Carreaux, F.; Toupet, L.;
Carboni, B. AdV. Synth. Catal. 2003, 345, 1215. (c) Gao, X.; Hall, D. G.
Tetrahedron Lett. 2003, 44, 2231. (d) Toure, B. B.; Hoveyda, H. R.; Tailor,
J.; Ulaczyk-Lesanko, A.; Hall, D. G. Chem. Eur. J. 2003, 9, 466. (e) Deligny,
M.; Carreaux, F.; Carboni, B.; Toupet, L.; Dujardin, G. Chem. Commun.
2003, 276. (f) Lallemand, J.-Y.; Six, Y.; Ricard, L. Eur. J. Org. Chem.
2002, 503. (g) Vaultier, M.; Truchet, F.; Carboni, B.; Hoffmann, R. W.;
Denne, I. Tetrahedron Lett. 1987, 28, 4169.
(4) For the Diels-Alder reactions with highly substituted 1,3-dienes
see: (a) Schmittel, M.; Von Seggern, H. J. Am. Chem. Soc. 1993, 115,
2165. (b) Wehbe, M.; Lepage, L.; Lepage, Y.; Platzer, N. Bull. Soc. Chim.
Fr. 1987, 309. (c) Majo, V. J.; Suzuki, S.; Toyota, M.; Ihara, M. J. Chem.
Soc., Perkin Trans. 1 2000, 3375. (d) Phansavath, P.; Aubert, C.; Malacria,
M. Tetrahedron Lett. 1998, 39, 1561. (e) Tjepkema, M. W.; Wilson, P. D.;
Audrain, H.; Fallis, A. G. Can. J. Chem. 1997, 75, 1215. (f) Dai, W.-M.;
Lau, C. W.; Chung, S. H.; Wu, Y. D. J. Org. Chem. 1995, 60, 8128. (g)
Graziano, M.; Iesce, M. R.; Cermola, F. Synthesis 1994, 149. (h) Nicolaou,
K. C.; Hwang, C. K.; Sorensen, E. J.; Clairborne, C. F. J. Chem. Soc.,
Chem. Commun. 1992, 1117. (i) Bonnert, R. V.; Jenkins, P. R. Tetrahedron
Lett. 1987, 28, 697. (j) Erman, W. F.; Stone, L. C. J. Am. Chem. Soc. 1971,
93, 2821.
Supporting Information Available: Experimental pro-
cedures and full characterization of the compounds 8a-h,
7i, and 8l. This material is available free of charge via the
Internet at http://pubs.acs.org.
OL0477879
(6) Generally the allylboration of the aldehydes was performed at 40
°C. The conversion with paraformaldehyde was performed successfully at
100 °C in a thick-walled glass tube; compare to: (a) Kalinin, A. V.; Scherer,
S.; Snieckus, V. Angew. Chem. 2003, 115, 3521; Angew. Chem., Int. Ed.
2003, 42, 3399. (b) Hoffmann, R. W.; Menzel, K.; Harms, K. Eur. J. Org.
Chem. 2002, 2603.
(5) As main product of the reactions, the corresponding aromatic boronic
ester (2-(2-isopropenyl-5-methylphenyl)-4,4,5,5-tetramethyl-1,3,2-diox-
aborolan was isolated.
(7) The X-ray data were deposited in the CCDC data bank (CCDC
246015).
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