Gary D. Crouse

Stereocontrolled preparation of precursors to all primary prostaglandins from butadiene

Abstract Four key precursors to the primary prostaglandins have been prepared in efficient fashion from butadiene. In addition to its simplicity, the new approach capitalizes on the pivotal role of a single precursor molecule, allows for early resolution, and results in placement of four contiguous chiral centers about a cyclopentane ring without initial benefit of a stereodirecting group. Butadiene is cyclodimerized to cis2-1,5-cyclooctadiene which is transformed in four steps to cis3-1,4,7-cyclononatriene. Monoepoxidation and base-promoted ring opening of this medium ring hydrocarbon gives cis3-2,4,7-cyclononatrien-l-ol which isomerizes exclusively to aldehyde 8 in the presence of potassium hydride at room temperature. The derived carboxylic acid is easily resolved and iodolactonized to 2, the key intermediate from which 1, 19, 21, and 22 are readily obtainable in few laboratory steps.

Relative kinetic ordering of [1,3]-hydrogen migration, anionic oxy-cope rearrangement, and base-accelerated dehydration in tertiary cyclononatrienyl alkoxides

Abstract The reactivity exhibited by 1-methyl- and 1-ethyl- cis 3 -2,4,7-cyclononatrienol toward KH under various conditions has been examined.