Studies Directed toward the Total Synthesis of Cerorubenic Acid-III. 3. A Convergent Enantioselective Approach Involving New Arrangements for the Actuation of Ring D Cyclization

Article abstract of DOI:10.1021/jo00068a021

A possible enantiocontrolled route to cerorubenic acid-III (1) is described herein.The central elements of the approach takes advantage of the ready availability of both optical antipodes of citronellol and of the tricyclic ketone 8.Although the absolute configuration of 1 is not known, its relative stereochemistry has been established by X-ray crystallography.On this basis, it is possible to match the reaction partners with the long-range view of establishing experimentally the actual configuration of 1.Assembly of the two structural halves was accomplished via a vinylstannane intermediate whose construction required utilization of an intramolecular S_N2 displacement in order to overcome the weakly nucleophilic nature of a stannyl-substituted ester enolate.The coupling reaction leading to 38 and 39 proved highly stereoselective as before, thereby setting the stage for conversion to D-seco derivatives of 1 via anionic oxy-Cope rearrangement.Although this phase of the strategy had previously been worked out on simpler systems, 38, 39, and analogs thereof isomerized with concomitant α-hydroxylation of the intermediate enolates.These conversions proceeded smoothly and efficiently.Although conditions were found that curtailed this adventitious oxygenation, the conversions proceeded so slowly that degradation was now competitive with the formation of 41 and 43.