9500
M. P. D. Mahindaratne et al. / Tetrahedron 61 (2005) 9495–9501
or Lewis acid solution (1.5 equiv) and treated with
cyclopentadiene (3 equiv) under specified conditions. The
mixture was stirred for 24 h at room temperature (unless
otherwise specified) and the reaction was quenched by
heterogeneous removal of unreacted cyclopentadiene with
ethyl acetate (2!5 mL). The aqueous layer was then treated
with HCl (10%, 1.5 equiv), extracted with ethyl acetate (2!
5 mL), and dried over anhydrous sodium sulfate. Removal
of solvent in vacuo left behind a slightly yellow solid (2;
GM08194) and The Welch Foundation (#96-086). B.Q.,
A.R., and E.R. are indebted to the NIGMS MBRS-RISE
(GM 60655) for partial support. NIGMS MBRS MARC-
U*STAR support (GM 07717) for B.Q. is also gratefully
acknowledged. We also appreciate discussions with Dr.
Ghezai Musie on the interpretation of the transition metal
results and Dr. Robert E. Lyle for helpful comments on this
manuscript.
1
MZH) that exhibited a forest of signals in H NMR (satd
NaHCO3 in D2O) and was not further characterized. The
solid was suspended in water (5 mL) and heated to 70 8C for
24 h. The resulting clear solution was extractively (ethyl
acetate) processed as described above to yield 3a as a
colorless oil (54%). For spectral observation, an aliquot was
removed from ethyl acetate extract and the major endo
isomer was enriched via silica gel chromatography, which
exhibited proton and carbon NMR signals that were
identical to reported values of 3a.19 1H NMR (CDCl3): d
1.28 (br d, JZ8.3 Hz, 1H), 1.40 (ddd, JZ2.4, 4.4, 11.72 Hz,
1H), 1.45 (ddt, JZ2.4, 8.3, 2.0 Hz, 1H), 1.92 (ddd, JZ3.4,
9.3, 11.7 Hz, 1H), 2.92 (br s, 1H), 3.00 (dt, JZ9.3, 3.9 Hz,
1H), 3.23 (br s, 1H), 6.00 (dd, JZ2.9, 5.4 Hz, 1H), 6.21 (dd,
JZ3.4, 5.9 Hz, 1H), 10–12 (br s, 1H); 13C NMR (CDCl3): d
29.1 (t), 42.5 (d), 43.3 (d), 45.7 (d), 49.7 (t), 132.4 (d), 137.9
(d), 181.4 (s).
References and notes
1. Current address: Chemical Diversity, Inc., San Diego, CA,
92121.
2. (a) Nicolaou, K. C.; Snyder, S. A. Proc. Natl. Acad. Sci. U.S.A.
2004, 101, 11929–11936. (b) Corey, E. J. Angew. Chem., Int.
Ed. 2002, 41, 1650–1667. (c) Tietze, L. F.; Modi, A. Med. Res.
Rev. 2000, 20, 304–322.
3. (a) Singleton, D. A.; Merrigan, S. R.; Beno, B. R.; Houk, K. N.
Tetrahedron Lett. 1999, 40, 5817–5821. (b) Morgan, K. M.
Annu. Rep. Prog. Chem. Sect. B: Org. Chem. 2004, 100,
335–350.
4. For other examples of auxiliaries specifically developed for
aqueous Diels–Alder transformations see: (a) Fringuelli, F.;
Matteucci, M.; Piermatti, O.; Pizzo, F.; Burla, M. C. J. Org.
Chem. 2001, 66, 4661–4666. (b) Waldmann, H. Liebigs Ann.
Chem. 1989, 231–238. (c) Waldmann, H.; Braun, M. Gazz.
Chim. Ital. 1991, 121, 277–284. (d) Yu, L.; Li, J.; Ramirez, J.;
Chen, D.; Wang, P. G. J. Org. Chem. 1997, 62, 903–907.
5. For a general discussion of aqueous Diels–Alder cyclo-
additions, see: Otto, S.; Engberts, J. B. F. N. Pure Appl.
Chem. 2000, 72, 1365–1372.
4.1.3. Naphthalen-1-yl bicyclo[2.2.1]hept-5-ene-2-car-
boxylate (3b, mixture of stereoisomers). The stereo-
isomeric mixture of carboxylic acid 3a (34.5 mg,
0.25 mmol) was dissolved in CH2Cl2 (1.0 mL) and treated
with 1-naphthol (39.6 mg, 1.1 equiv), DMAP (7.6 mg, 25%
mol) and DIC (34.7 mg, 1.1 equiv). After 6 h stirring, the
mixture was washed with brine (2!1 mL), dried over
anhydrous sodium sulfate, and the solvent was evaporated
under reduced pressure. The crude residue was flash
chromatographed in a 5!0.5 cm plug of silica gel (5%
ethyl acetate in hexanes) prior to stereochemical analysis by
chiral phase HPLC (Regis Pirkle Type 1, RR; 95:5 hexanes/
isopropanol, 1.0 mL/min). For analytical purposes the endo
product was enriched by gradient normal phase chromato-
graphy (hexanes to 20% ethyl acetate/hexanes) to yield 3b
as a light yellow solid. MpZ56–58 8C; 1H NMR (CDCl3): d
1.39 (br d, JZ8.3 Hz, 1H), 1.54 (ddt, JZ2.4, 8.3, 2.0 Hz,
1H), 1.64 (ddd, JZ2.9, 3.9, 11.7 Hz, 1H), 2.07 (ddd, JZ3.4,
9.3, 11.7 Hz, 1H), 2.99 (br s, 1H), 3.37 (dt, JZ9.3, 3.9 Hz,
1H), 3.50 (br s, 1H), 6.17 (dd, JZ2.9, 5.9 Hz, 1H), 6.30 (dd,
JZ2.9, 5.9 Hz, 1H), 7.18 (d, JZ7.3 Hz, 1H), 7.41 (t, JZ
7.8 Hz, 1H), 7.47 (m, 2H), 7.68 (d, JZ8.3 Hz, 1H), 7.82
(ddd, JZ1.5, 2.5, 7.3 Hz, 1H), 7.87 (ddd, JZ1.5, 2.4,
7.3 Hz, 1H); 13C NMR (CDCl3): d 29.4 (t), 42.6 (d), 43.7
(d), 46.1 (d), 49.8 (t), 117.9 (d), 121.1 (d), 125.3 (d), 125.6
(d), 126.2 (d), 126.3 (d), 126.9 (s), 127.9 (d), 132.3 (d),
134.6 (s), 138.3 (d), 146.7 (s), 173.1 (s); HRMS (m/z): Calcd
for C18H16O2 264.115030, found 264.115050; MS (m/z):
264 (40), 144 (100), 121 (44), 115 (22), 93 (24), 55 (38); IR
(cmK1): 3062, 2962, 2942, 2871, 1749, 1595, 1388, 1338,
1258, 1224, 1127, 1106, 1013.
6. Lakner, F. J.; Negrete, G. R. Synlett 2002, 643–645.
7. For a recent report on the effect of alkali cation on an aqueous
aza-Diels–Alder cycloaddition see: Loncaric, C.; Manabe, K.;
Kobayashi, S. Chem. Commun. 2003, 574–575.
8. For a Diels–Alder cycloaddition study of the cations impact in
organic solvents see: Jung, D. Y.; Park, D. H.; Kim, S. H.;
Kim, Y. H. J. Phys. Org. Chem. 2004, 17, 1017–1022.
9. (a) Chu, K. S.; Negrete, G. R.; Konopelski, J. P.; Lakner, F. J.;
Woo, N.-T.; Olmstead, M. M. J. Am. Chem. Soc. 1992, 114,
1800–1812. (b) Seebach, D.; Lamatsch, B.; Amstutz, R.; Beck,
´
A. K.; Dobler, M.; Egli, M.; Fitzi, R.; Gautschi, M.; Herradon,
B.; Hidber, P. C.; Irwin, J. J.; Locher, R.; Maestro, M.;
Maetzke, T.; Mourin˜o, A.; Pfammatter, E.; Plattner, D. A.;
Schickli, C.; Schweizer, W. B.; Seiler, P.; Stucky, G.; Petter,
W.; Escalante, J.; Juaristi, E.; Quintana, D.; Miravitlles, C.;
Molins, E. Helv. Chim. Acta 1992, 75, 913–934. (c) Juaristi,
´ ´ ´
E.; Lopez-Ruiz, H.; Madrigal, D.; Ramırez-Quiros, Y.;
Escalante, J. J. Org. Chem. 1998, 63, 4706–4710.
10. Johnson, F. Chem. Rev. 1968, 68, 375–413.
11. MM2 calculations were performed using Chem3D Pro 5.0 on a
Mac G3. Both s-trans structures exhibited significant out-of-
plane distortions at the sigma bond connecting the vinyl and
carbonyl groups.
12. This sequence was recently conducted in a single-pot
synthesis: Mahindaratne, M. P. D.; Quin˜ones, B. A.; Recio
III, A.; Rodriguez, E. A.; Lakner, F. J.; Negrete, G. R.
ARKIVOC 2005 (vi), in press.
Acknowledgements
13. In this report, the term ‘endo diastereoselectivity’ will be used
to describe the cycloaddition diastereoselectivity values for
This work was supported by grants from the NIGMS (S06