7402
J. Am. Chem. Soc. 1997, 119, 7402-7403
Scheme 1
Highly Selective Lewis Acid Catalyzed Diels-Alder
Reactions of Acyclic (Z)-1,3-Dienes
William R. Roush* and David A. Barda
Department of Chemistry, Indiana UniVersity
Bloomington, Indiana 47405
ReceiVed April 4, 1997
Acyclic (Z)-1,3-dienes are widely regarded as exceptionally
poor substrates for Diels-Alder reactions.1,2 Exceptions to this
generalization are oxygenated and other heteroatom-substituted
(Z)-1,3-dienes, which undergo cycloaddition reactions with a
range of conventional and hetero dienophiles.1-5 (Z)-1,3-Dienes
have also been successfully employed in intramolecular Diels-
Alder reactions,6-13 especially recently in the taxane series.14-18
However, scattered reports of successful thermal19-21 and Lewis
acid catalyzed22-29 Diels-Alder reactions of (Z)-1,3-dienes
suggested to us that the prospects of using these compounds as
intermediates in organic synthesis might not be as bleak as has
been widely assumed. We are most pleased, therefore, to report
herein the first extensive study of Lewis acid catalyzed Diels-
Alder reactions of (Z)-1,3-dienes 1-4, which in most cases
proceed with excellent regio- and high endo-selectivity (Scheme
1).
We began by exploring the Diels-Alder reactions of diene
1 with R-acetoxyacrolein (5a).28,30 Thus, treatment of 1 with
3.8 equiv of 5a and 1.2 equiv of SnCl4 in a 3:1 mixture of
toluene and CH2Cl2 at -78 °C for 1 h provided endo-
cycloadduct 6a in 90% yield with 96:4 selectivity (Table 1, entry
1). Encouraged by this exciting result, we explored the reactions
of 1 with a range of other dienophiles, including R-bromoac-
rolein (5b), methacrolein (5c), acrolein (5d), methacryloyl
chloride (5e), and acryloyl chloride (5f) (Table 1, entries 2-6).
These reactions were performed in toluene using MeAlCl2 as
the Lewis acid catalyst (typically 1.1 equiv, although recently
we have found that substoichiometric amounts of the Lewis acid
may be employed (cf., entries 10, 17, 18, 19)). The reactions
with 5b, 5d, and 5f were complete within 1 h at -78 °C and
provided cycloadducts 6b, 6d, and 6h, respectively, in excellent
yield and generally with excellent endo-selectivity (entries 2,
4, and 6). It should be noted that the reaction with acryloyl
chloride (5f) was quenched with MeOH and Et3N, thereby
providing methyl ester 6h as the major product. The reactions
with methacrolein (5c; entry 3) and methacryloyl chloride (5e;
entry 5) were more sluggish and required longer reaction times
or higher temperatures for complete reaction. The reaction with
methacryloyl chloride (entry 5) provided a 4:1 mixture of the
endo- and exo-lactones 10 and 11.
(1) Fringuelli, F.; Taticchi, A. Dienes in the Diels-Alder Reaction; John
Wiley & Sons: New York, 1990.
(2) Oppolzer, W. In ComprehensiVe Organic Synthesis; Trost, B. M.,
Ed.; Pergamon Press: Oxford, 1991; Vol. 5; pp 315-399.
(3) Petrzilka, M.; Grayson, J. I. Synthesis 1981, 753.
(4) Roberge, G.; Brassard, P. J. Org. Chem. 1981, 46, 4161.
(5) Danishefsky, S. Acc. Chem. Res. 1981, 14, 400.
(6) House, H. O.; Cronin, T. H. J. Org. Chem. 1965, 30, 1061.
(7) Borch, R. F.; Evans, A. J.; Wade, J. J. J. Am. Chem. Soc. 1975, 97,
6282.
(8) Oppolzer, W.; Fehr, C.; Warneke, J. HelV. Chim. Acta 1977, 60, 48.
(9) Boeckman, R. K., Jr.; Alessi, T. R. J. Am. Chem. Soc. 1982, 104,
3216.
(10) Pyne, S. G.; Hensel, M. J.; Fuchs, P. L. J. Am. Chem. Soc. 1982,
104, 5719.
(11) Yoshioka, M.; Hakai, H.; Ohno, M. J. Am. Chem. Soc. 1984, 106,
1133.
(12) Corey, E. J.; Jardine, P. D. S.; Rohloff, J. C. J. Am. Chem. Soc.
1988, 110, 3672.
(13) Deslongchamps, P. Aldrichimica Acta 1991, 24, 43.
(14) Jackson, R. W.; Shea, K. J. Tetrahedron Lett. 1994, 35, 1317.
(15) Alaimo, C. A.; Coburn, C. A.; Danishefsky, S. J. Tetrahedron Lett.
1994, 35, 6603.
(16) Rubenstein, S. M.; Williams, R. M. J. Org. Chem. 1995, 60, 7215.
(17) Winkler, J. D.; Kim, H. S.; Kim, S. Tetrahedron Lett. 1995, 36,
687.
(18) Jenkins, P. R. Pure Appl. Chem. 1996, 68, 771.
(19) Nicolaou, D. C.; Hwang, C.-K.; Sorensen, E. J.; Clairborne, C. F.
J. Chem. Soc., Chem. Commun. 1992, 1117.
(20) Okada, K.; Kondo, M.; Tanino, H.; Kakoi, H.; Inoue, S. Heterocycles
1992, 34, 589.
(21) Stokes, H. L.; Richardson, B. M.; Wright, M. W.; Vaughn, S. M.;
Welker, M. E. Organometallics 1995, 14, 5520.
(22) Brocksom, T. J.; Constantino, M. G. J. Org. Chem. 1982, 47, 3450.
(23) Gassman, P. G.; Singleton, D. A. J. Am. Chem. Soc. 1984, 106,
7993.
(24) Gassman, P. G.; Singleton, D. A. Tetrahedron Lett. 1987, 28, 5969.
(25) Gassman, P. G.; Singleton, D. A.; Wilwerding, J. J.; Chavan, S. P.
J. Am. Chem. Soc. 1987, 109, 2182.
(26) Bonnert, R. V.; Jenkins, P. R. Tetrahedron Lett. 1987, 28, 697.
(27) Engler, T. A.; Sampath, U.; Velde, D. V.; Takusagawa, F.
Tetrahedron 1992, 48, 9399.
(28) Funk, R. L.; Yost, J. K., III J. Org. Chem. 1996, 61, 2598.
(29) Murahashi, S.-I.; Naota, T.; Miyaguchi, N.; Noda, S. J. Am. Chem.
Soc. 1996, 118, 2509.
Buoyed by the success achieved with the Diels-Alder
reactions of 1, we explored the analogous reactions of the
isomeric diene 2. A basic tenet of the Diels-Alder reaction is
that the stereochemical diversity of the reaction can be doubled
simply by changing the stereochemistry of the diene component.
While there are scattered reports of success along these lines
with simple dienes such as (Z)- and (E)-2,4-pentadiene,20,22 our
results with 1 and 2 clearly demonstrate the ability to do so
with complex, highly functionalized substrates. The SnCl4 or
MeAlCl2 catalyzed Diels-Alder reactions of 2 and dienophiles
5a-d provided cycloadducts 7a-d in 84-97% yield and with
(30) Syntheses of dienes 1-3 and details of the stereochemical assign-
ments for cycloadducts 6-8 are provided in the Supporting Information.
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