Reductive Arylation of Nitroarenes with Chloroarenes: Reducing Conditions Enable New Reactivity from Palladium Catalysts

Abstract

Palladium-catalyzed C–N bond forming reactions are a key tool in modern synthetic organic chemistry. Despite advances in catalyst design enabling the use of a variety of aryl (pseudo)­halides, the necessary aniline coupling partner is often synthesized in a discrete reduction step from a nitroarene. An ideal synthetic sequence would avoid the necessity of this step while maintaining the reliable reactivity of palladium catalysis. Herein, we describe how reducing conditions enable new chemical steps and reactivity from well-studied palladium catalysts, resulting in a new, useful transformation: the reductive arylation of nitroarenes with chloroarenes to form diarylamines. Mechanistic experiments suggest that under reducing conditions, BrettPhos-palladium complexes catalyze the dual N-arylation of typically inert azoarenesgenerated via the in situ reduction of nitroarenesvia two distinct mechanisms. Initial N-arylation proceeds via a novel association-reductive palladation sequence followed by reductive elimination to yield an intermediate 1,1,2-triarylhydrazine. Arylation of this intermediate by the same catalyst via a traditional amine arylation sequence forms a transient tetraarylhydrazine, unlocking reductive N–N bond cleavage to liberate the desired product. The resulting reaction allows for the synthesis of diarylamines bearing a variety of synthetically valuable functionalities and heteroaryl cores in high yield.

Aminations of Aryl Halides Using Nitroaromatics as Coupling Partners: Overcoming the Hydrodehalogenation Pathway under a Hydrogen Atmosphere in Water

“…The low yields were most likely due to unwanted homocoupling or Miyaura borylation. Recently, Akana-Schneider and Weix reported a similar protocol in the HFIP/DMF solvent system to enable C–N cross-coupling . In their work, the reaction proceeds through an alternative reductive pathway where the nitroarene-derived diazo compound reacts with aryl halides in the presence of stoichiometric Mn, HFIP, and Pd catalyst.…”

Dual role of nitroarenes as electrophiles and arylamine surrogates in Buchwald–Hartwig-type coupling for C–N bond construction

“…20 Very recently, Weix and co-workers have impressively demonstrated a reductive arylation of nitroarenes with chloroarenes through an azoarene intermediate using manganese powder as a reductant. 21 Despite these remarkable advances, 15–22 requiring aryl halides or aryl boronic acids limits their broad applications in C(sp 2 )–N bond formation (Scheme 1b).…”

Pd/NHC catalyzed reduction and coupling of nitroaromatics for the synthesis of diarylamines

“…1b ). 8 Under reducing conditions, palladium–phosphine complexes catalyze the dual N -arylation of typically inert azoarenes generated via the in situ reduction of nitroarenes. Kazemnejadi and coworkers described a one-pot synthetic approach to diarylamines through bimetallic nickel–palladium catalyzed sequential reduction of nitroarenes to aromatic amines and further C–N coupling with haloarenes ( Fig.…”