SYNTHESIS OF 6,8-DIOXABICYCLO(3.2.1)OCTANES; UTILIZATION AND STUDIES OF PHOSPHINOTHIOIC AMIDES

Ozonolysis of 3-acetoxy-1-ethyl-4,6-dimethyl-1-cyclohexene, readily available from the corresponding enone, in a participating solvent followed by a reductive workup (Me(,2)S) produced 2-acetoxy-3,5-dimethyl-6-oxooctanal. Chemoselective reduction of the aldehyde using tert-butylamine borane and hydrolysis of the acetate produced multistriatin in 58% yield from the allylic acetate. Similar methodology was also used to prepare frontalin (3 steps, 49% overall yield) and brevicomin (4 steps, 32% overall yield) from the appropriately substituted allylic acetates.;It was found that the erythro:threo diastereoselectivity of the nucleophilic addition described above was sensitive to changes in solvent polarity, nature of the counterion, and carbonyl structure. Finally it was demonstrated that by using amidine bases in the decomposition of (beta)-hydroxythiophosphinates improved yields of the corresponding alkenes could be achieved.;Endo-brevicomin was stereospecifically synthesized from (Z)-methyl 5-octenoate. The methodology used to generate the requisite alkene involved the nucleophilic addition of a thionophosphorous-stabilized carbanion to methyl 5-oxopentanoate. The intermediate alcohols were isolated, purified, and stereospecifically decomposed (cis cycloelimination) to the corresponding alkenes. The decomposition was achieved by activation of the phosphorous center toward nucleophilic addition of the oxygen to form the phosphorane for cycloelimination of the alkene by alkylation of the intermediate adducts at sulfur with iodomethane.