[2+2+2] Cycloadditions of Alkynylynamides - A Total Synthesis of Perlolyrine and the First Total Synthesis of Isoperlolyrine

The total syntheses of the carboline alkaloids perlolyrine and isoperlolyrine are reported. Key-steps of the syntheses are Negishi coupling reactions on alkynylynamides and their metal-catalyzed [2+2+2] cycloadditions with nitriles to form the beta- and gamma-carboline cores. The choice of the catalyst strongly affects the beta/gamma ratio. Spectroscopic features of the gamma-isomer are distinctly different from those of the naturally occurring isoperlolyrine.