Transition-Metal-Free Direct Arylation: Synthesis of Halogenated 2‑Amino-2′-hydroxy-1,1′-biaryls and Mechanism by DFT Calculations

• Published in: Journal of the American Chemical Society Vol. 135; no. 19; pp. 7086 - 7089
• Main Authors: Gao, Hongyin, Ess, Daniel H, Yousufuddin, Muhammed, Kürti, László
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 15-05-2013
• Subjects: Halogenation; Hydrocarbons, Aromatic - chemical synthesis; Hydrocarbons, Aromatic - chemistry; Models, Molecular; Stereoisomerism
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja400897u

A transition-metal-free, regioselective direct aryl–aryl bond-forming process for the synthesis of halogenated 2-amino-2′-hydroxy-1,1′-biaryls that are currently either inaccessible or challenging to prepare using conventional methods is disclosed. The addition of ArMgX to an o-halonitrobenzene at low temperature generates a transient N,O-biarylhydroxylamine that rapidly undergoes either [3,3]- or [5,5]-sigmatropic rearrangement in one-pot to form a 2-amino-2′-hydroxy-1,1′-biaryl or 1-amino-1′-hydroxy-4,4′-biaryl, respectively. The periselectivity is controlled by the choice of solvent and temperature. This direct arylation process is also readily scalable (1–10 mmol). DFT calculations suggest that from the N,O-biarylhydroxylamine intermediate there is a low-energy stepwise pathway that involves initial Mg-mediated N–O bond cleavage followed by pathway branching toward either [3,3]- or [5,5]-rearrangement products via C–C bond formation and rearomatization.