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

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.