Reductive Arylation of Nitroarenes with Chloroarenes: Re-ducing Conditions Enable New Reactivity from Palladium Catalysts

05 May 2023, Version 1
This content is a preprint and has not undergone peer review at the time of posting.

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 neces-sary aniline coupling partner is often synthesized in a discrete reduc-tion 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 typi-cally inert azoarenes—generated via the in situ reduction of ni-troarenes—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, un-locking 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.

Keywords

palladium
C-N bond formation
reductive
mechanism

Comments

Comments are not moderated before they are posted, but they can be removed by the site moderators if they are found to be in contravention of our Commenting Policy [opens in a new tab] - please read this policy before you post. Comments should be used for scholarly discussion of the content in question. You can find more information about how to use the commenting feature here [opens in a new tab] .
This site is protected by reCAPTCHA and the Google Privacy Policy [opens in a new tab] and Terms of Service [opens in a new tab] apply.