I. APPROACHES TO A STEREOSELECTIVE SYNTHESIS OF PROSTAGLANDINS AND PROSTAGLANDIN ANALOGS. II. A NEW PREPARATION OF METHYLACETYLENES AND TERMINAL ACETYLENES

I. Two sequences have been investigated for the preparation of potentially useful synthetic precursors to prostanoid systems. Each sequence utilizes dicyclopentadiene 1 or functionalized dicyclopentadienes as readily available sources of carbons 6 through 13 of the prostanoid skeleton and involves a series of selective functional group transformations, a controlled ring fragmentation, and a critical endo-to-exo equilibration. The products, norbornane 4 and norbornene 6, appear to be single stereoisomers having the requisite polyfunctionality and stereochemistry for elaboration to prostaglandins and/or prostaglandin analogs.; ; Sequence A employs an Eschenmoser-Tanabe fragmentation of epoxy ketone 3, prepared from 1 by either of two moderate-yield approaches. After subsequent functional group manipulation (including an endo-to-exo equilibration) trans-1,2-disubstituted norbornane 4 was generated in modest overall yield.; Sequence B employs a Marshall fragmentation of the spiro-fused tetracyclic acyl-1,3-dithiane 5, which was readily prepared from 1 via hydroxymethylene ketone 2. Subsequent manipulations (including an endo-to-exo equilibration) generated trans-5,6-disubstituted 2-norbornene 6 in 19% overall yield (from 1). This sequence offers excellent promise for efficient, stereocontrolled synthesis of C-9/C-11 modified analogs of E, F, and H series prostaglandins as well as of natural E and F prostaglandins.; II. A new method for the preparation of methylacetylenes and terminal acetylenes has been demonstrated on three model systems:; ; 2-Alkyl-1,3-dithianes (from the corresponding aldehydes and propanedithiol) have been converted to 2-acyl-2-alkyl-1,3-dithianes 7 (R' = H or CH(,3)) by standard procedures and, subsequently in high yield, to acetylenes 9 by the action of methyllithium on the intermediate hydrazones 8.