Dual Catalytic C(sp <sup>2</sup> )–H Activation of Azaheterocycles toward C–N Atropisomers
Juntao Sun, Yiyao Hu, Wen‐Ji He, Chen-Xi Liao, Shenghua Yang, Quynh Nguyen Wong, Peng Liu, Keary M. Engle
Abstract
We describe a Pd II -catalyzed enantioselective C(heteroaryl)–H activation method enabled by a chiral transient directing group ( c TDG) to gain access to C–N atropisomers. Reversible condensation between the aldehyde-containing substrate and a chiral amino acid facilitates coordination of the metal catalyst and subsequent atroposelective C–H activation. Various N -heterocycles, including 2-imidazolone, indole, pyrrole, and 2-pyridone, and diverse alkene coupling partners participate in the reaction in moderate to good yields and enantioselectivity. The utility of this method is demonstrated by several downstream transformations that rapidly build up the molecular complexity. Organometallic synthesis, H/D exchange experiments, and density functional theory (DFT) calculations shed light on the critical role of the c TDG in enhancing the regio- and atroposelectivity.