AN APPROACH TO LYSERGIC-ACID UTILIZING AN INTRAMOLECULAR ISOMUNCHNONECYCLOADDITION PATHWAY

A series of alkenyl- and alkynyl-substituted diazo imides were prepare d to demonstrate that the intramolecular cycloaddition across a transi ent isomunchnone dipole was a viable approach to the quinoline ring sy stem (rings C and D) of the ergot alkaloids. The diazo imides were syn thesized by N-malonylacylation of the appropriate amide followed by ex posure to standard diazo transfer conditions. The carbenoid intermedia te derived by treatment of the diazo imide with rhodium(II) acetate un dergoes ready cyclization onto the neighboring amide carbonyl oxygen t o generate an isomunchnone intermediate. Subsequent 1,3-dipolar cycloa ddition across the pendant olefin affords the cycloadduct in high yiel d. The stereochemical assignment of several of the cycloadducts was de duced by X-ray crystallography. The stereochemical outcome of the reac tion is the consequence of an endo cycloaddition of the neighboring pi -bond across the transient isomunchnone dipole. Exposure of the olefin ic cycloadduct to boron trifluoride etherate resulted in exclusive car bon-oxygen bond cleavage producing a transient N-acyliminium ion which undergoes rapid proton loss to afford an enamide derivative. In contr ast, exposure of the acetylenic cycloadduct to boron trifluoride ether ate resulted in exclusive carbon-nitrogen bond cleavage. The resulting oxonium ion underwent reduction with triethylsilane, producing a dihy drofuran derivative. In the absence of a reducing agent, the alkyne cy cloadduct underwent a retro Diels-Alder reaction to give a substituted furan derivative in high yield. The Rh(II) acetate catalyzed reaction of the appropriate diazo imide precursor to lysergic acid resulted in a mixture of the desired dipolar cycloadduct as well as a C-H inserti on product. Switching to rhodium(II) perfluorobutyrate as the catalyst significantly enhanced the cycloadditon pathway. The inability to car ry out a double-bond isomerization thwarted our efforts to synthesize lysergic acid.