A formal synthesis of reserpine: hydrindane approach to the Woodward’s ring-E precursor

A new synthetic approach to a functionally and stereochemically embellished cyclohexanoid, corresponding to the Woodward’s ring-E intermediate 24 of the complex indole alkaloid reserpine 1 is delineated. Our scheme emanates from a readily available endo-tricyclo[5.2.1.02,6]decane system from which cis-hydrindane and cyclohexanoid moieties are sequentially extracted. The strategy outlined here exploits the propensity of the endo-tricyclo[5.2.1.02,6]decane and cis-hydrindane systems to react from the convex face to generate the requisite stereochemical pattern. Since 24 has been previously elaborated to the natural product, the present effort constitutes a formal synthesis of rac-reserpine.