S. R. Surasani et al. / Tetrahedron Letters 50 (2009) 773–775
775
CSIR and V.S.R. thanks MHRD, New Delhi, for the award of research
fellowships.
O
(δ 3.07)
Hg
(δ 2.29)
(δ 1.92)
Hf
He
References and notes
O
(δa 3.49)
(δ 6.02)
Hb
a
c
OMe
Cl
1. (a) Liao, C.-C. Pure Appl. Chem. 2005, 77, 1221–1234; (b) Magdziak, D.; Meek, S.
J.; Pettus, T. R. R. Chem. Rev. 2004, 104, 1383–1429; (c) Liao, C.-C.; Peddinti, R. K.
Acc. Chem. Res. 2002, 35, 856–866; (d) Quideau, S.; Pouysegu, L. Org. Prep. Proc.
Int. 1999, 31, 617–680; (e) Singh, V. Acc. Chem. Res. 1999, 32, 324–333.
2. Tamura, Y.; Yakura, T.; Haruta, J.; Kita, Y. J. Org. Chem. 1987, 52, 3927–3930.
3. Liao, C.-C.; Chu, C.-S.; Lee, T.-H.; Rao, P. D.; Ko, S.; Song, L. D.; Shiao, H.-C. J. Org.
Chem. 1999, 64, 4102–4110.
Hd
(δ 3.25)
OMe
8c
Figure 1.
4. (a) Patrick, T. B.; Yu, H.; Taylor, D.; Gorrell, K. J. Fluorine Chem. 2004, 125, 1965–
1966; (b) Lai, C.-H.; Shen, Y.-L.; Wang, M.-N.; Rao, N. S. K.; Liao, C.-C. J. Org. Chem.
2002, 67, 6493–6502; (c) Yen, C.-F.; Peddinti, R. K.; Liao, C.-C. Org. Lett. 2000, 2,
2909–2912; (d) Bonnarme, V.; Bachmann, C.; Cousson, A.; Mondon, M.; Gessen,
J.-P. Tetrahedron 1999, 55, 433–448; (e) Becker, H. D.; Bremholt, T.; Adler, E.
Tetrahedron Lett. 1972, 4205–4208.
5. Fryatt, T.; Botting, N. P. J. Label. Compd. Radiopharm. 2005, 48, 951–969.
6. Spectral data for MOB 4: 1H NMR (CDCl3, 500 MHz): d 6.82 (d, J = 8.5 Hz, 1H), 6.49
(d, J = 3.0 Hz, 1H), 6.39 (dd, J = 8.5, 3.0 Hz, 1H), 3.81 (s, 3H), 3.86 (s, 3H); 13C NMR
(CDCl3, 125 MHz): d 187.4, 181.6, 158.6, 137.2, 134.4, 107.6, 56.2. MOB 5: 1H
NMR (CDCl3, 500 MHz): d 6.78 (dd, J = 10.5, 2.0 Hz, 1H), 6.44 (d, J = 2.0 Hz, 1H),
6.05 (d, J = 10.5 Hz, 1H), 3.39 (s, 6H); 13C NMR (CDCl3, 125 MHz): d 192.8, 141.3,
131.0, 130.7, 126.5, 92.1, 50.1. MOB 6: 1H NMR (CDCl3, 500 MHz): d 6.99–6.96
(m, 2H), 5.80 (d, J = 9.5 Hz, 1H), 3.37 (s, 6H); 13C NMR (CDCl3, 125 MHz): d 192.8,
146.9, 143.9, 126.3, 93.3, 91.1, 50.2.
7. General procedure: Method A: To a solution of 4-halo-2-methoxyphenol (1 mM)
and dienophile (25 mM) in anhydrous methanol (4 mL) was added a solution of
DAIB (1.1 mM) in anhydrous methanol (6 mL) over a period of 30 min at 0 °C
under nitrogen atmosphere. After 10 min, the ice bath was removed and the
contents were allowed to stir at room temperature for the time specified in
Table 1. After the reaction was complete, the reaction mixture was concentrated
using a rotary evaporator under reduced pressure, and the residue was purified
by silica gel column chromatography with 10% ethyl acetate in hexanes to
furnish the cycloadduct.
four isomers, only the one possessing ortho regiochemistry (EWG is
adjacent to octenone carbonyl function) and endo stereochemistry
(EWG is anti to octenone carbonyl function) was formed in this
study. The regiochemistry of these cycloadducts was deduced from
1H–1H decoupling NMR experiments. The assigned stereochemis-
try is based on the coupling constants between He–Hg and Hf–Hg.
For instance, these J values for the adduct 8c are 10.0 and 6.0 Hz,
respectively. The larger J value for He–Hg reveals the cis orientation
of the protons, He and Hg, thus confirming the endo stereochemis-
try of the [4+2] cycloadduct (Fig. 1). The endo stereochemistry of
cycloadduct 9c was further confirmed by the two-dimensional
rotational frame nuclear Overhauser effect spectroscopy (ROESY)
measurements.8 The observed regio- and stereoselectivities are in
accordance with the literature precedents.3,4b,9
In conclusion, bicyclo[2.2.2]octenones derivatives bearing halo-
gen substituents are accessed in a highly regio- and stereoselective
manner from the corresponding 4-halo-guaiacols. We have dem-
onstrated for the first time that the title 4-halo-orthobenzoquinone
monoketals (X = F, Cl, I) are sufficiently stable for isolation and
characterization.
Method B: To a solution of 4-halo-2-methoxyphenol (1 mM) and dienophile
(25 mM) in anhydrous methanol (4 mL) was added a solution of DAIB (1.1 mM)
in anhydrous methanol (6 mL) over a period of 1 h at 50 °C under nitrogen
atmosphere. The stirring was continued for 1 h at 50 °C for the reaction to reach
completion, and then the products were purified as in method A.
8. Details will be published in full account.
Acknowledgements
9. (a) Gao, S.-Y.; Ko, S.; Lin, Y.-L.; Peddinti, R. K.; Liao, C.-C. Tetrahedron 2001, 57,
297–308; (b) Katayama, S.; Hiramatsu, S.; Aoe, K.; Yamauchi, M. J. Chem. Soc.,
Perkin Trans. 1 1997, 561–576; (c) Schultz, A. G.; Dittami, J. P.; Lavieri, F. P.;
Salowey, C.; Sundararaman, P.; Szymula, M. J. Org. Chem. 1984, 49, 4429–4440.
We gratefully acknowledge financial support from the Depart-
ment of Science and Technology, New Delhi. S.R.S. and N.B. thank