3810
J . Org. Chem. 1998, 63, 3810-3811
rings.8 The starting dienes 2a -d were readily prepared in
Diels-Ald er Rea ction s of
2-(N-Acyla m in o)-1,3-d ien es. Atyp ica l
Regioselectivity a n d En d o/Exo Selectivity
78-87% yield by the Pd(PPh3)4-mediated cross-coupling of
tributyl(vinyl)tin and (N-acylamino)enol triflates 3 (eq 1).
In turn, the requisite triflates 3 were prepared in excellent
yield from N-acylated lactams 4 by the recently published
procedure.9,10
J ae Du Ha, Chul Hyun Kang, Kenneth A. Belmore, and
J in Kun Cha*
The Diels-Alder reactions of these dienecarbamates were
then investigated. Relatively unreactive dienophiles such
as ethyl (E)-crotonate or crotonaldehyde failed to undergo
the thermal (up to 180 °C) Diels-Alder reaction. On the
other hand, (E)-1-nitro-1-heptene afforded the cycloadducts,
albeit in modest yields, at 180 °C (toluene, sealed tube).
Ethyl acrylate and N-phenylmaleimide were found to react
efficiently in refluxing benzene or toluene. The results are
summarized in Table 1.11 The observed product distribu-
tions given in Table 1 are kinetic in origin, since pure
individual cycloadducts remain unchanged when resubjected
to the identical reaction conditions.
Department of Chemistry, University of Alabama,
Tuscaloosa, Alabama 35487
Received April 1, 1998
Given the unparalleled synthetic utility of the Diels-Alder
reaction in the formation of functionalized six-membered
rings, it is hardly surprising that the large body of imagina-
tive conceptual advances and synthetic applications contin-
ues to exploit the inherent control of regiochemistry and
stereochemistry. Of particular importance is the develop-
ment of the heteroatom-substituted dienes (e.g., those
containing siloxy substituents), which provide the otherwise
inaccessible functionality arrays, in addition to enhanced
reactivity. Extension has also been made to use of amino-
substituted dienes. For example, general synthetic utility
of the Diels-Alder reaction of 1-(N-acylamino)-1,3-buta-
dienes has been well demonstrated in the pioneering work
by Overman and Oppolzer,1,2 which complements that of the
corresponding (N,N-dialkylamino)dienes.3,4 In contrast, re-
gioisomeric N,N-dialkyl-2-amino-1,3-dienes have found scant
use in the Diels-Alder reaction, and a recent theoretical
study suggested that these cross-conjugated compounds
would function as poor dienes in cycloadditions.5 In fact,
only a few examples are known, and these are limited to
use of â-nitrostyrenes as the dienophiles, for which a
stepwise polar mechanism has been proposed.6 Little is
known about the reactivity of the analogous 2-(N-acylamino)-
1,3-dienes.7 Herein, we report the novel features of the
Diels-Alder reactions of 1,3-dienes 2, which afford an
expeditious assembly of octahydroquinolines 1.
Structures for the cycloadducts were determined by 1H
1
NMR analysis (1H, H COSY and difference NOE measure-
ments).12 A characteristic feature is that the C-2 siloxymeth-
yl substituent occupies the pseudoaxial position to minimize
A(1,2) and A(1,3) strain as indicated by observation of a nuclear
Overhauser effect on the siloxymethylene signal on irradia-
tion of the H-4a proton.13
Most striking is the anomalous regiochemical preference
in favor of the 1,3-regioisomers (with respect to the N-
acylamino function). This unexpected meta regioselectivity
(entries 2-7) is opposite to the prediction based on consid-
eration of either the HOMO diene-LUMO dienophile in-
teraction or a two-step process involving a 1,4-addition to
the dienophile and subsequent closure of the vinyl acylim-
monium ion. Also, conspicuously atypical is the unusual
lack of endo selectivity. Moreover, it appears to be depend-
ent on the dienophiles. For example, the Diels-Alder
reactions with ethyl acrylate show no endo/exo selectivity
(entries 3, 5, and 7), but those of (E)-1-nitro-1-heptene with
the sterically more demanding dienes 2b,c show the procliv-
ity toward the exo products 8a and 10a (entries 4 and 6 vs
entry 2). On the other hand, the reactions of N-phenylma-
leimide display exclusive endo preference to afford 5a and
(3) For example, see: (a) Hu¨nig, S.; Kahanek, H. Chem. Ber. 1957, 90,
238. (b) Dauben, W. G.; Kozikowski, A. P. J . Am. Chem. Soc. 1974, 96, 3664.
(c) Snowden, R. L. Tetrahedron Lett. 1984, 25, 3835.
(4) For use of 1-amino-3-siloxy-1,3-dienes, see: (a) Smith, A. B., III;
Wexler, B. A.; Tu, C.-Y.; Konopelski, J . P. J . Am. Chem. Soc. 1985, 107,
1308. (b) Schlessinger, R. H.; Pettus, T. R. R.; Springer, J . P.; Hoogsteen,
K. J . Org. Chem. 1994, 59, 3246. (c) Kozmin, S. A.; Rawal, V. H. J . Org.
Chem. 1997, 62, 5252 and J . Am. Chem. Soc. 1997, 119, 7165.
(5) Koikov, L. N.; Terent′ev, P. B.; Gloriozov, I. P.; Bundel′, Y. G. J . Org.
Chem. USSR 1984, 20, 832.
(6) For reviews, see: (a) Enders, D.; Meyer, O. Liebigs Ann. 1996, 1023.
(b) Krohn, K. Angew. Chem., Int. Ed. Engl. 1993, 32, 1582.
(7) To our knowledge, to date only two reports have appeared on the
Diels-Alder reaction of 2-(acylamino)-1,3-dienes: (a) Terada, A.; Murata,
K. Bull. Chem. Soc. J pn. 1967, 40, 1644. (b) Reference 1b; no structure was
given for the cycloadduct.
(8) Decahydroquinoline rings are present in several major classes of
alkaloids, including dendrobatid alkaloids (such as pumiliotoxin C, cis-243A,
and gephrotoxin), Lycopodium alkaloids (lycodine, lycopodine, and lycodo-
line), luciduline, etc.
(9) Ha, J . D.; Lee, D.; Cha, J . K. J . Org. Chem. 1997, 62, 4550.
(10) (a) Foti, C. J .; Comins, D. J . J . Org. Chem. 1995, 60, 2656. (b) Okita,
T.; Isobe, M. Tetrahedron 1995, 51, 3737. (c) Luker, T.; Hiemstra, H.;
Speckamp, W. N. Tetrahedron Lett. 1996, 37, 8257; J . Org. Chem. 1997,
62, 3592.
For a preliminary study, the piperidine ring system and
the benzyloxycarbonyl (Cbz) group were chosen as the
2-amino skeleton and protecting group (R1 ) benzyl),
respectively, as part of our research program directed at the
construction of suitably functionalized decahydroquinoline
(1) (a) Overman, L. E.; J essup, P. J . Tetrahedron Lett. 1977, 1253. (b)
Overman, L. E.; Clizbe, L. A. J . Am. Chem. Soc. 1976, 98, 2352 and 8295.
(c) Overman, L. E.; J essup, P. J . J . Am. Chem. Soc. 1978, 100, 5179. (d)
Overman, L. E.; Fukaya, C. J . Am. Chem. Soc. 1980, 102, 1454. (e) J essup,
P. J .; Petty, C. B.; Roos, J .; Overman, L. E. Organic Syntheses; Wiley: New
York, 1988; Collect. Vol. VI, p 95.
(11) Surprisingly, the Diels-Alder reaction of diene 2a with ethyl
acrylate gave an inseparable mixture of all four possible isomers (on the
basis of 1H and 13C NMR spectra). This lack of regiocontrol is in sharp
contrast with that of dienes 2b-d .
(12) The 1H, 1H COSY spectra of 5a , 8a , 9a ,b, 11a ,b, 14, 15a ,b, and 16
are available in the Supporting Information.
(2) (a) Oppolzer, W.; Fro¨stl, W. Helv. Chim. Acta 1975, 58, 590. (b)
Oppolzer, W.; Bieber, L.; Francotte, E. Tetrahedron Lett. 1979, 4537.
(13) For numbering, see structure 8a in Table 1.
S0022-3263(98)00593-3 CCC: $15.00 © 1998 American Chemical Society
Published on Web 05/28/1998