Asymmetric Three-Component Reaction to Assemble the Acyclic All-Carbon Quaternary Stereocenter via Visible Light and Phosphoric Acid Catalysis
Zong‐Wang Qiu, Liang Long, Zhiqiang Zhu, Hong‐Fu Liu, Han‐Peng Pan, Ai‐Jun Ma, Jin‐Bao Peng, Yongheng Wang, Hao Gao, Xiang‐Zhi Zhang
Abstract
Chiral acyclic all-carbon quaternary stereocenters are widely present in natural products and pharmaceuticals. However, their introduction remains a challenging topic in the synthetic research community. Here, we report an efficient metal-free method for the construction of acyclic all-carbon quaternary chiral centers sited at the α-position of an aldehyde or ketone moiety. This is achieved via a well-designed reaction cascade involving arylalkynes, benzoquinones, and electron-rich (hetero)arenes and the use of visible light and phosphoric acid catalysis. Notably, the asymmetric catalytic visible-light-induced Paternò–Büchi cycloaddition/electrocyclic ring-opening/α-selective arylation of α,β-unsaturated carbonyl compound cascades is achieved. Moreover, the reaction works well for a broad range of these three components (>70 examples). Furthermore, the rich chemistry embedded in the products provides a variety of synthetically useful building blocks that are otherwise difficult to access. Lastly, the origin of enantioselectivity was investigated by density functional theory, revealing that CH/π interactions play a crucial role in the stereocontrol of the reaction.