Synthesis and reactivity of 1,4-ethano-1,5-naphthyridine derivatives using microwave activation or flow chemistry

Abstract

The design of some novel disubstituted 3,4-dihydro-2H-1,4-ethano-1,5-naphthyridine derivatives is reported under classical and flow methodologies. The series were developed from quinuclidinone, which afforded versatile platforms bearing one lactam function in position C-2 that was then used to create C–N bond using the Chan-Lam coupling reaction or in situ C–O bond activation via palladium-catalyzed cross-coupling reactions. The conditions were optimized, and a wide range of boronic acids were used to determine the scope and limitations of each method. To complete this study, a flow Suzuki-Miyaura process was established to afford polyfunctionalized 1,4-ethano-1,5-naphthyridine derivatives in high yields with a very efficient process (10 min.).