Skeletal Reorganization of Cycloalkylamines Into Angular Azatetracyclic Scaffolds
Abstract
ABSTRACT The efficient, single‐step construction of angular azatetracyclic frameworks bearing vicinal quaternary stereocenters remains a formidable challenge in synthetic chemistry. Herein, we disclose the first borane‐catalyzed cascade reorganization of N ‐cycloalkylidenyl (CAD)‐substituted aryl cycloalkylamines that enables rapid access to these architectures. Initiated by B(C 6 F 5 ) 3 ‐mediated α ‐hydride abstraction, the reaction proceeds through an aza‐6π electrocyclization and two successive ring expansions, followed by hydride rebound, to deliver densely functionalized angular/fused azatetracycles with high diastereoselectivity. This designed cascade forges multiple C–C bonds and stereocenters in a single operation and exhibits broad substrate scope and excellent efficiency. Detailed mechanistic investigations, combining experimental results and DFT calculations, support the proposed sequence of hydride abstraction, cyclization, double ring expansion, and hydride rebound.
Article Details
Authors (8)
Yun‐Peng Wang
School of Pharmaceutical Sciences School of Chemistry and Chemical Engineering Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs State Key Laboratory of Synergistic Chem‐Bio Synthesis Shanghai Jiao Tong University Shanghai China
Wujiong Xia
State Key Lab of Urban Water Resource and Environment
Bao‐Kuan Guo
School of Pharmaceutical Sciences School of Chemistry and Chemical Engineering Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs State Key Laboratory of Synergistic Chem‐Bio Synthesis Shanghai Jiao Tong University Shanghai China
Kun Fang
Tong‐Mei Ding
School of Pharmaceutical Sciences School of Chemistry and Chemical Engineering Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs State Key Laboratory of Synergistic Chem‐Bio Synthesis Shanghai Jiao Tong University Shanghai China
Shu‐Yu Zhang
School of Pharmaceutical Sciences School of Chemistry and Chemical Engineering Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs State Key Laboratory of Synergistic Chem‐Bio Synthesis Shanghai Jiao Tong University Shanghai China
Si‐Hua Hou
School of Pharmaceutical Sciences School of Chemistry and Chemical Engineering Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs State Key Laboratory of Synergistic Chem‐Bio Synthesis Shanghai Jiao Tong University Shanghai China
Yong‐Qiang Tu
School of Pharmaceutical Sciences School of Chemistry and Chemical Engineering Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs State Key Laboratory of Synergistic Chem‐Bio Synthesis Shanghai Jiao Tong University Shanghai China