Synthesis of pyrrolizidine, indolizidine, and quinolizidine derivatives using ruthenium-catalyzed ring-opening metathesis and ring-closing metathesis of cycloalkene-ynes

Ring-opening metathesis and ring-closing metathesis (ROM-RCM) of a cyclopentene-yne having an ester moiety was demonstrated using first-and second-generation Grubbs' catalysts. When the reaction of cycloalkene-yne was carried out in the presence of 5 mol% of a ruthenium carbene complex under an ethylene atmosphere at room temperature, ROM-RCM proceeded smoothly to give a pyrrolidine derivative in good yield, which could be converted to a pyrrolizidine derivative. Furthermore, ROM-RCM of azabicyclo[2.2.1]heptene-ynes using the second-generation Grubbs' catalyst was investigated. When an azabicycloheptene derivative was exposed to a catalytic amount of a ruthenium carbene complex, pyrrolizidine and indolizidine derivatives were obtained in good yields. The distribution of these products depends on the substituents on the alkyne. When azabicyclo[2.2.1]heptene-ynes bearing large substituents on the alkyne were treated with ruthenium catalyst 1b, a pyrrolizidine derivative was obtained as the major product. ROM-RCM of azabicyclo[2.2.2]octene-ynes with 1b afforded quinolizidine derivative 20, although the yield was moderate.