Collect. Czech. Chem. Commun. 2001, 66, 1257-1268
https://doi.org/10.1135/cccc20011257

Tetrahydrocannabinol Revisited: Synthetic Approaches Utilizing Molybdenum Catalysts

Andrei V. Malkov* and Pavel Kočovský*

Department of Chemistry, University of Glasgow, Glasgow G12 8QQ, U.K.

References

1a. Nakanishi K., Goto T., Ito S., Natori S., Nozoe S.: Natural Products Chemistry, Vol. 2, p. 151. Academic Press, New York 1975.
1b. For earlier syntheses, see: Crombie L., Crombie W. M. L., Palmer C. J., Jamieson S. V.: Tetrahedron Lett. 1983, 24, 3129. <https://doi.org/10.1016/S0040-4039(00)88114-9>
1c. Crombie L., Crombie W. M. L., Jamieson S. V., Palmer C. J.: J. Chem. Soc., Perkin Trans. 1 1988, 1243. <https://doi.org/10.1039/p19880001243>
1d. Crombie L., Crombie W. M. L., Firth D. F.: J. Chem. Soc., Perkin Trans. 1 1988, 1251. <https://doi.org/10.1039/p19880001251>
1e. Crombie L., Crombie W. M. L., Tuchinda P.: J. Chem. Soc., Perkin Trans. 1 1988, 1255. <https://doi.org/10.1039/p19880001255>
1f. Crombie L., Crombie W. M. L., Firth D. F.: J. Chem. Soc., Perkin Trans. 1 1988, 1263. <https://doi.org/10.1039/p19880001263>
1g. For recent synthetic studies, see, e.g.: Kachensky D. F., Hui R. A. F.: J. Org. Chem. 1997, 62, 7065. <https://doi.org/10.1021/jo970969e>
1h. Mahadevan A., Siegel C., Martin B. R., Abood M. E., Beletskaya I., Radan R. K.: J. Med. Chem. 2000, 43, 3778. <https://doi.org/10.1021/jm0001572>
2. Kočovský P., Ahmed G., Šrogl J., Malkov A. V., Steele J.: J. Org. Chem. 1999, 64, 2765. <https://doi.org/10.1021/jo9821675>
3a. Malkov A. V., Baxendale I. R., Mansfield D. J., Kočovský P.: Tetrahedron Lett. 1997, 38, 4895. <https://doi.org/10.1016/S0040-4039(97)01052-6>
3b. Malkov A. V., Baxendale I. R., Mansfield D. J., Kočovský P.: J. Org. Chem. 1999, 64, 2737. <https://doi.org/10.1021/jo9821776>
4a. Malkov A. V., Davis S. L., Mitchell W. L., Kočovský P.: Tetrahedron Lett. 1997, 38, 4899. <https://doi.org/10.1016/S0040-4039(97)01053-8>
4b. Malkov A. V., Davis S. L., Baxendale I. R., Mitchell W. L., Kočovský P.: J. Org. Chem. 1999, 64, 2751. <https://doi.org/10.1021/jo982178y>
5. Malkov A. V., Spoor P., Vinader V., Kočovský P.: J. Org. Chem. 1999, 64, 5308. <https://doi.org/10.1021/jo990372u>
6a. Doyle G.: Inorg. Chem. 1971, 10, 2348. <https://doi.org/10.1021/ic50104a059>
6b. van den Bergen A., Murray K. S., West B. O.: Aust. J. Chem. 1972, 25, 705.
7. Note that the (E)-isomer cannot cyclize, would remain in the reaction mixture unreacted, and could then be separated from the product by chromatography owing to a sufficiently different polarity. Two equivalents of citral were employed in this and the subsequent experiments.
8. The yield is calculated with respect of olivetol.
9a. Taylor E. C., Lenard K., Shvo Y.: J. Am. Chem. Soc. 1966, 88, 367. <https://doi.org/10.1021/ja00954a039>
9b. Razdan R. K., Dalzell H. C., Handrick G. R.: J. Am. Chem. Soc. 1974, 96, 5860. <https://doi.org/10.1021/ja00825a026>
10. This mechanism has been proposed earlier by another group for conventional Lewis acids: Kane V. V., Razdan R. K.: Tetrahedron Lett. 1969, 591. <https://doi.org/10.1016/S0040-4039(01)87756-X>
11. For the first asymmetric synthesis of (+)-1 based on the construction of the cyclohexene ring via the Diels–Alder addition catalyzed by (bisoxazoline)Cu(II), see: Evans D. A., Shaughnessy E. A., Barness D. M.: Tetrahedron Lett. 1997, 38, 3193. <https://doi.org/10.1016/S0040-4039(97)00609-6>
12a. Malkov A. V., Bella M., Langer V., Kočovský P.: Org. Lett. 2000, 2, 3047. <https://doi.org/10.1021/ol006111k>
12b. Malkov A. V., Baxendale I. R., Fawcett J., Russel D. R., Langer V., Mansfield D. J., Valko M., Kočovský P.: Organometallics 2001, 20, 673. <https://doi.org/10.1021/om000850n>
12c. Malkov A. V., Spoor P., Vinader V., Kočovský P.: Tetrahedron Lett. 2001, 42, 509. <https://doi.org/10.1016/S0040-4039(00)02007-4>
13a. Rickards R. W., Watson W. P.: Aust. J. Chem. 1980, 33, 451. <https://doi.org/10.1071/CH9800451>
13b. Rickards R. W., Roennenberg H.: J. Org. Chem. 1984, 49, 572. <https://doi.org/10.1021/jo00177a044>
14. Note that the regiochemistry of the oxirane ring-opening is controlled by the stereoelectronic effect, so that it occurs in a diaxial fashion.
15. For a similar strategy, see: Stoss P., Merrath P.: Synlett 1991, 553. <https://doi.org/10.1055/s-1991-20793>
16. Owing to the non-stereoselective epoxidation of limonene, the overall yield of 21 cannot exceed ≈50%.
17. The structure of these and other products (vide infra) was deduced form their 2D NMR spectra and from the comparison of their GC MS characteristics with the known data. See refs9,10 and the following: Petrzilka M., Häflinger W., Sikemeier C.: Helv. Chim. Acta 1969, 52, 1102. <https://doi.org/10.1002/hlca.19690520427>