[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 β- and γ-carboline cores. The choice of the catalyst strongly affects the β/γ ratio. Spectroscopic features of the γ-isomer are distinctly different from those of the naturally occurring isoperlolyrine.