ORGANIC
LETTERS
2009
Vol. 11, No. 6
1197-1200
Study of Very Reactive Tautomeric
Phenol Dienones as Dienes in
Diels-Alder Reactions
Yves L. Dory,* Andre´e-Lucie Roy, Pierre Soucy, and Pierre Deslongchamps*
De´partement de Chimie, Institut de Pharmacologie de Sherbrooke, UniVersite´ de
Sherbrooke, 3001 12e AVenue nord, Sherbrooke (Que´bec) J1H 5N4, Canada
yVes.dory@usherbrooke.ca; pierre.deslongchamps@usherbrooke.ca.
Received November 19, 2008
ABSTRACT
Masked ortho-benzoquinones are very reactive as diene partners in Diels-Alder reactions. Careful exploration of the orbital factors that
govern their surprising behavior shows that their LUMO is almost as electron demanding as that of o-benzoquinone itself. Methyl substituents
at either end of their diene system influence the activation energy through modification of the reaction pathway being more or less asynchronous.
The Diels-Alder (DA) reaction, although old, is still widely
studied because of its broad use in organic synthesis and its
interest in terms of fundamental understanding of its mech-
anism.1 It is commonly accepted that the frontier molecular
orbitals (FMO) theory helps in rationalizing the outcome of
“normal” electron demand DA reactions (electron-rich diene/
electron-poor dienophile). On the other hand, inverse electron
demand cases are not as easily explained.1c In particular,
their kinetics are not related to the FMO energy gap (diene
LUMO/dienophile HOMO). In this letter, we disclose
experimental and theoretical data concerning an electron-
poor diene that reacts nearly as fast as electron-rich dienes.
Masked o-benzoquinone (MOB), a tautomeric phenol, is
formally a cisoid dienone.2 Its reactivity can be modulated
by substituent patterns in a controllable way. It is a highly
valuable synthon for organic chemists.3
Both related isomeric dienones 1 and 2 (Scheme 1) were
prepared from the same aldehyde synthon 7. Aldehyde 7 was
reduced to alcohol 8 that was immediately protected as its
benzylidene ketal 9.4 Subsequent SN2 attack of the remaining
phenolate onto methyl bromoacetate yielded ester 10 in 45%
overall yield. Hydrogenation of 10 over palladium and under
acidic conditions gave lactone 11 quantitatively. Diene 1 was
finally obtained by sequential treatment of 11 with NaOH
(2) (a) Berney, D.; Deslongchamps, P. Can. J. Chem. 1969, 47, 515.
(b) Be´langer, A.; Berney, D. J. F.; Borschberg, H.-J.; Brousseau, R.;
Doutheau, A.; Durand, R.; Katayama, H.; Lapalme, R.; Leturc, D. M.; Liao,
C.-C.; MacLachlan, F. N.; Maffrand, J.-P.; Marazza, F.; Martino, R.;
Moreau, C.; Saint-Laurent, L.; Saintonge, R.; Soucy, P.; Ruest, L.;
Deslongchamps, P. Can. J. Chem. 1979, 57, 3348. (c) Liao, C.-C.; Wei,
C.-P. Tetrahedron Lett. 1989, 30, 2255. (d) Magziak, D.; Meek, S. J.; Pettus,
T. R. R. Chem. ReV. 2004, 104, 1383. (e) Liao, C.-C. Pure Appl. Chem.
2005, 77, 1221.
(3) (a) Liao, C.-C.; Peddinti, R. K. Acc. Chem. Res. 2002, 35, 856. (b)
Reeder, M. D.; Srikanth, G. S. C.; Jones, S. B.; Castle, S. L. Org. Lett.
2005, 7, 1089.
(1) (a) Takao, K.-I.; Munakata, R.; Tadano, K.-I. Chem. ReV. 2005, 105,
4779. (b) Dory, Y. L.; Hall, D.; Deslongchamps, P. Tetrahedron 1998, 54,
12279. (c) Spino, C.; Pesant, M.; Dory, Y. Angew. Chem., Int. Ed. 1998,
37, 3262. (d) Kong, S.; Evanseck, J. D. J. Am. Chem. Soc. 2000, 122, 10418.
(e) Houk, K. N.; Gonza´lez, J.; Li, Y. Acc. Chem. Res. 1995, 28, 81.
(4) Deslongchamps, P.; Be´langer, A.; Berney, D. J. F.; Borschberg, H.-
J.; Brousseau, R.; Doutheau, A.; Durand, R.; Katayama, H.; Lapalme, R.;
Leturc, D. M.; Liao, C.-C.; MacLachlan, F. N.; Maffrand, J.-P.; Marazza,
F.; Martino, R.; Moreau, C.; Ruest, L.; Saint-Laurent, L.; Saintonge, R.;
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10.1021/ol8026768 CCC: $40.75
Published on Web 02/19/2009
2009 American Chemical Society