C1 Functionalization\nof β‑Carboline via\nKnochel–Hauser Base-Directed Metalation and Negishi Coupling

The synthesis of C1-functionalized\nβ-carbolines from <i>N</i>-Boc norharman is described.\nSubstitution is realized by\nemploying the Knochel–Hauser base (TMPMgCl·LiCl) followed\nby transmetalation with ZnCl<sub>2</sub> and subsequent Negishi cross-coupling\nof the resulting organozinc species. A variety of aryl or heteroaryl\nbromides participated in this one-pot reaction sequence, allowing\nfor rapid diversification of the β-carboline scaffold in moderate\nto excellent yields. The reaction protocol has been applied to the\nsynthesis of natural alkaloids nitramarine, nitraridine, eudistomin\nU, and perlolyrine.