Total Synthesis of (+)‐3‐Oxacarbacyclin 2. Stereoselective Deprotonation and Completion of the Synthesis

The asymmetric synthesis of (+)‐3‐oxacarbacyclin (1) from cis‐bicyclo[3.3.0]octane‐2,5‐dione has been achieved. A notable feature in this synthesis is an asymmetric Horner‐Wadsworth‐Emmons (HWE) reaction. A further key step is the stereoselective deprotonation of a chiral bicyclic ketone, having a high local symmetry about the carbonyl group, with lithium (R,R)‐bis(phenylethyl)amide in the presence of lithium chloride. The route described also allows the synthesis of the anti‐thrombotic and anti‐metastatic prostacyclin analogs cicaprost and eptaloprost. The flexibility of this route should also provide access to further side‐chain modified analogs of 1.