Regiospecific Functionalization of the Monoterpene Ether 1,3,3-Trimethyl-2-oxabicyclooctane (1,8-Cineole). Synthesis of the Useful Bridged γ-Lactone 1,3-Dimethyl-2-oxabicyclooctan-3-->5-olide

Article abstract of DOI:10.1021/jo00384a023

The regiospecific functionalization at C-5 and difuctionalization at C-5/C-8 and C-5/C-10 of the monoterpene 1,3,3-trimethyl-2-oxabicyclo<2.2.2>octane (1) is described.Chromyl acetate oxidation of 1 afforded 1,3,3-trimethyl-2-oxabicyclo<2.2.2>octan-5-one (6) in 60percent yield along with 28percent of unreacted 1 and minor amounts of exo-1,3,3-trimethyl-2-oxabicyclo<2.2.2>octan-5-ol acetate (9), 1,3,3-trimethyl-2-oxabicyclo<2.2.2>octane-5,8-dione (13), exo-8-acetoxy-1,3,3-trimethyl-2-oxabicyclo<2.2.2>octan-5-one (16), 1,3,3-trimethyl-2-oxabicyclo<2.2.2>octane-5,7-dione (14), and orcinol (15).On digestion with oxalic or phthalic acid, ketone 6 was converted into a mixture of piperitenone (20), 3-methyl-2-cyclohexenone (22), acetone, and traces of isopiperitenone (21), while 60percent sulfuric acid at room temperature yielded 20 as the sole reaction product.Oxidation of 6 with chromyl acetate yielded diketone 13, which decomposed into orcinol (15) on digestion with either boiling water or a 2.5percent sodium bicarbonate solution.Sodium borohydride or lithium aluminum hydride reduction of 6 gave stereospecifically exo-1,3,3-trimethyl-2-oxabicyclo<2.2.2>octan-5-ol (7) while reduction with sodium-ethanol or aluminum isopropoxide in isopropyl alcohol (equilibrium conditions) yielded a 3:2 mixture of the alcohols 7 and 8, respectively.Treatment of 7 with phosphoryl chloride produced 1,3,3-trimethyl-2-oxatricyclo<2.2.2.0^5,8>octane (25) together with minor amounts of the chlorocineoles 10 and 11.Pyrolysis of the methyl xanthate of 7 yielded 1,3,3-trimethyl-2-oxabicyclo<2.2.2>oct-5-ene (2).Photolysis of 7 in the presence of mercuric oxide and iodine or iodosylbenzene diacetate and iodine gave the tricyclic diether 29, which was quantitatively converted into the bridged γ-lactone 30 by oxidation with ruthenium tetraoxide.Oxidation of 29 with chromyl acetate yielded a 1:1 mixture of 30 and the formate lactone 31.Lithium aluminum hydride reduction of 30 produced diol 37, which was converted into menthofuran (44) in five steps.