synthesis investigations in terpenes

Abstract

The thesis, entitled "Synthetic Investigations in Terpenes", consists of two chapters. Chapter I describes briefly the isolation, elucidation of the structure, determination of the absolute configuration and the reported syntheses of valeranone along with our stereoselective total synthesis of (dl)-valeranone and one of its isomers, in which the isopropyl group is in cis-relationship with the angular methyls, starting from 9?-acetoxy-10?-methyl-??-octalone-3 (1). Our initial plan for the introduction of an alkoxycarbonyl group at 9?-hydroxy-10?-methyl-??-octalone-3 (2) and 9?-acetoxy-10?-methyl-??-octalone-3 (1) by condensation with diethyl carbonate and magnesium methyl carbonate respectively led to the formation of 2-carbethoxy-4-methyl-?-tetralol (3) and 2-carboxyl-4-methyl-?-tetralol (4) respectively by rearrangement, instead of the expected 2-carbethoxy-9?-hydroxy-10?-methyl-??-octalone-3 and 2-carbomethoxy-9?-acetoxy-10?-methyl-??-octalone-3 respectively. Acetoxy-cis-3?,10?-dimethyldecalone-3 (5) was prepared by the copper-catalysed conjugate addition of methylmagnesium iodide to the ??-enone (1). The condensation of cis-dimethyldecalone-3 (5) with a large excess of diethyl carbonate in presence of sodium hydride afforded, in place of 2-carbethoxy-9?-acetoxy-5?,10?-dimethyl-decalone-3, 2-carbethoxy-cis-5?,10?-dimethyl-9?-ethoxycarbonyl-oxyd-decalone-3 (6) by trans-esterification. Reduction of the 3-keto group in the compound (6), its thioketal followed by desulphurisation, furnished 2-carbethoxy-cis-5?,10?-dimethyl-9?-ethoxycarbonyl-oxyd-decalin (7) which on interaction with an excess of either methylmagnesium iodide or methyllithium gave 2?-hydroxyisopropyl-cis-5?,10?-dimethyl-9?-hydroxydecalin (8), the latter reaction giving higher yields. Oxidation of the diol (8) gave 2?-hydroxy-isopropyl-cis-5?,10?-dimethyldecalone-9 (9). Dehydration and hydrogenation of the compound (9) afforded 2?-isopropyl-cis-5?,10?-dimethyldecalone-9 (dl-valeranone) (10) and 2?-isopropyl-cis-5?,10?-dimethyldecalone-9 (11). There is an appendix to Chapter I. Prior to the copper-catalysed conjugate addition of methylmagnesium iodide to the ??-enone (1), the addition of hydrogen cyanide to 10?-methyl-??-octalone-3 (12) to obtain trans-10-methyl-5-cyanodecalone-3 (13) and cis-10-methyl-3-cyanodecalone-3 (14) was initially studied as a model. Configurations were assigned to the isomers (13 and 14) on the basis of IR spectra of their corresponding hydrolysed products. Similar addition of hydrogen cyanide to 10?-methyl-9?-hydroxy-??-octalone-3 (2) afforded trans-10?-methyl-9?-hydroxy-5-cyanodecalone-3 (15) and cis-10?-methyl-9?-hydroxy-5-cyanodecalone-3 (16), configurations of which were proved by their conversion into trans and cis-ketonitriles (13 and 14) respectively. Chapter II describes the isolation, determination of the structure and absolute configuration of carissone and also the reported syntheses. This has been followed by an account of the synthesis of epicarissone ethylene thioketal (8). 3-keto-10-methyl-??-hexahydronaphthalene (1) and 3-keto-4,10-dimethyl-??-hexahydronaphthalene (2) were prepared from the corresponding 10-methyl-??-octalone-3 (3) and 4,10-dimethyl-??-octalone-3 (4) by dehydrogenation with chloranil. Addition of hydrogen cyanide to the ??-dienone (2) gave 5-keto-7?-cyano-4,10-dimethyl-??-octahydronaphthalene (5) which on methanolysis afforded 5-keto-7?-carbomethoxy-4,10-dimethyl-??-octahydronaphthalene (6). Protection of the 3-carbonyl group of the compound (6) as the ethylene thioketal (7) followed by treatment with an excess of methylmagnesium iodide gave epicarissone ethylene thioketal (8), whose configuration was assigned on the basis of the non-identity of its IR spectrum with that of the natural carissone ethylene thioketal.