SYNTHESIS OF THE PENTACYCLIC SKELETON OF THE ASPIDOSPERMA ALKALOIDS USING RHODIUM CARBENOIDS AS REACTIVE INTERMEDIATES

A series of diazo amido keto esters prepared from N-alkenyl-substitute d 3-carbalkoxy-2-piperidone derivatives was treated with rhodium(II) a cetate. Attack of the amido carbonyl oxygen at the resultant rhodium c arbenoid center produced a transient push-pull carbonyl ylide dipole w hich underwent an intramolecular dipolar cycloaddition reaction. A rel ated annulation sequence was used to prepare the pentacyclic skeleton of the aspidosperma family of alkaloids. Synthesis of the required dia zo imide was carried out from 3-carboxy-3-ethyl-2-piperidone and N-met hyl-3-indoleacetic acid. Treatment of the diazo imide with rhodium(II) acetate afforded a transient 1,3-dipole which subsequently underwent cycloaddition across the indole pi-bond. The resulting cycloadduct is the consequence of endo cycloaddition with respect to the dipole which is fully in accord with the lowest energy transition state. The cyclo adduct was converted in three steps into desacetoxy-4-oxo-6,7-dihydrov indorosine. The stereochemistry of the final product was established b y a X-ray crystallographic study.