| dc.description.abstract | The thesis entitled “Acid-Catalysed Cyclisation of Steroidal Seco-Diones – Total Synthesis of Racemic Copacamphor and Ylangocamphor and Their C?-Homologues” consists of three chapters. The bicyclo[3.2.1]octane ring system occurs in various naturally occurring sesquiterpenes and diterpenes. The synthetic challenges involved in constructing this framework, illustrated through selected examples, are discussed in Chapter 1.
Chapter 2 describes the synthesis of (±)-copacamphor (1e), (±)-ylangocamphor (2e), and their C?-homologues, presented in three sections:
Section A deals with the synthesis of diketones (5b, 6b, 6d) and tricyclic hydroxy ketones (7b, 7d). Condensation of 2-ethylcyclopentan-1,3-dione with vinyl carbinol—obtained via Grignard reaction of 2?,3?,4?-trimethoxypropiophenone with vinylmagnesium bromide—afforded 2-ethyl-2-[3-(2,4-dimethoxyphenyl)-5-methoxypent-2-enyl]cyclopentan-1,3-dione (seco-dione 3b). Cyclodehydration of 3b to the pentaenone 4b was unsuccessful; however, treatment of 3b with anhydrous methanolic hydrogen chloride yielded two isomeric diketones and a tricyclic hydroxy ketone. Based on PMR, IR, and mass spectra, the isomeric exo and endo structures—2-(2,4-dimethoxyphenyl)-2-(2-methoxyethyl)-5-ethylbicyclo[3.2.1]octan-6,8-dione (5b and 6b)—were assigned to the diketones. The structure 5-ethyl-3a-hydroxy-5-(2,4-dimethoxyphenyl)-octahydro-2,4-methano-1H-inden-1-one (7b) was assigned to the tricyclic hydroxy ketone based on spectral data and analogy with previously reported compounds [Kasturi et al., Tetrahedron Lett., 5059 (1972)]. Similarly, methanolic hydrogen chloride treatment of seco-dione 3d afforded the endo diketone 6d and tricyclic hydroxy ketone 7d.
Section B describes the stereospecific rearrangement of the homobrendane system to the perhydro-1,4-methanoindene system. The tricyclic hydroxy ketone 7a, obtained from acid-catalysed cyclisation of seco-dione 3a, on catalytic hydrogenation followed by Grignard reaction with methylmagnesium iodide, yielded diol 8a. Refluxing the diol with catalytic p-toluenesulfonic acid in benzene or brief treatment with BF?·Et?O afforded exclusively a tricyclic ketone. Similar transformations were observed for diols 8b–8d. Structure 9 was assigned to these tricyclic ketones based on IR, NMR, and mass spectra; X-ray crystallographic analysis of 9a and 9d confirmed these assignments.
Section C details the conversion of rearranged compound 9a, possessing a perhydro-1,4-methanoindene skeleton, to (±)-copacamphor (1e) and (±)-ylangocamphor (2e). Oxidation of the aromatic compound with RuO? afforded acid 10e, which upon esterification and subsequent Grignard reaction with methylmagnesium iodide yielded tert-alcohol 11e. Dehydration of 11e gave a mixture (7:3) of olefins (12e and 13e). Hydrogenation and separation of this mixture furnished (±)-copacamphor and (±)-ylangocamphor, whose spectral characteristics matched authentic samples. Following the same methodology, (±)-C?-homocopacamphor (1f) and (±)-C?-homoylangocamphor (2f) were synthesized from tricyclic ketone 9d.
Chapter 3 describes a convenient and efficient preparation of the strategic intermediate 14, which has been utilized in the synthesis of several sesquiterpenes of the copa and ylango series. Acid-catalysed cyclisation of triketone 15—obtained by condensation of amino compound 16 with 2-methylcyclopentan-1,3-dione—yielded 5-methyl-2-isopropylbicyclo[3.2.1]oct-2-en-6,8-dione (17), which was transformed into intermediate 14 in five steps. | |
