Experimental and Computational Studies of Palladium-Catalyzed Spirocyclization via a Narasaka–Heck/C(sp<sup>3</sup> or sp<sup>2</sup>)–H Activation Cascade Reaction
Wan‐Xu Wei, Yuke Li, Yating Wen, Ming Li, Xuesong Li, Cui‐Tian Wang, Hongchao Liu, Yu Xia, Bo‐Sheng Zhang, Rui-Qiang Jiao, Yong‐Min Liang
Abstract
The first synthesis of highly strained spirocyclobutane-pyrrolines via a palladium-catalyzed tandem Narasaka–Heck/C(sp3 or sp2)–H activation reaction is reported here. The key step in this transformation is the activation of a δ-C–H bond via an in situ generated σ-alkyl-Pd(II) species to form a five-membered spiro-palladacycle intermediate. The concerted metalation-deprotonation (CMD) process, rate-determining step, and energy barrier of the entire reaction were explored by density functional theory (DFT) calculations. Moreover, a series of control experiments was conducted to probe the rate-determining step and reversibility of the C(sp3)–H activation step.