Part I: The Short, Regiospecific Synthesis Of (+,-)-estradiol. Part Ii: The Generation And Synthetic Use Of 2,3-dimethylene-2,3-dihydrofurans.

Abstract

Part I. A diisobutylaluminum hydride adduct of 5-methoxyphthalide (a protected hydroxy aldehyde) was treated with (omega)-alkenyl Grignard reagents to provide 50-67% yields of the corresponding benzene-1,2-dimethanols. These, upon treatment with 1,1'-thiobisbenzimidazole, provided a regioisomeric mixture of substituted sultines which underwent partial rearrangement to the corresponding sulfones. Thermolysis of the above mixtures at 80-180(DEGREES)C led to elimination of sulfur dioxide, providing the desired intramolecular cycloaddition products. This sequence was applied to a short, regiospecific synthesis of ((+OR-))-estradiol. Part II. All previously described methods used to generate the furan-o-quinodimethane system employ temperatures as high as 950(DEGREES)C, incompatible with most functionalities. Chapter I describes the development of a method for a mild and efficient generation of 2,3-dimethylene-2,3-dihydrofurans from silicon-containing quaternary ammonium salts, by the action of fluoride ion. Excellent yields of inter- and intramolecular cyclization products were obtained under appropriate conditions. The synthesis of the corresponding silicon precursors from readily available materials is also described. Chapter II describes efficient fluoride ion induced generations and intramolecular cyclizations of 3-substituted-2,3-dimethylene-2,3-dihydrofurans, from 2-trimethylsilylmethyl-3-furylmethyl-arylsulfones. The value of this methodology is demonstrated in the total synthesis of furanosteroids and dinordrin (an antiimplantation agent).