Synthesis of Colibactin Pyrrolidono[3,4-d]pyridones via Regioselective C(sp3)-H Activation.

The synthesis of pyrrolidono[3,4-d]pyridones of relevance to putative genotoxic colibactin structures featuring a doubly conjugated 1,6-Michael acceptor system is reported. We investigated and implemented a highly selective Pd-catalyzed C(sp3)-H activation reaction as a key step and further functionalized the pyridone core. Evaluating the role of this structural unit of relevance to colibactin, we found that this structure displayed a high degree of stability toward both acidic conditions and nucleophiles.