Synthesis and Reactivity of 1,4‐Ethano‐1,5‐Naphthyridine Derivatives Using Microwave Activation or Flow Chemistry

The design of some novel disubstituted 3,4‐dihydro‐2 H ‐1,4‐ethano‐1,5‐naphthyridine derivatives is reported under classical and flow methodologies. The series are developed from quinuclidinone, which afford versatile platforms bearing one lactam function in position C ‐2 that is 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 are optimized and a wide range of boronic acids are used to determine the scope and limitations of each method. To complete this study, a flow Suzuki–Miyaura process is established to afford polyfunctionalized 1,4‐ethano‐1,5‐naphthyridine derivatives in high yields with a very efficient process (10 min).