Palladium‐Catalyzed C(sp3)−H Arylation of Primary Amines Using a Catalytic Alkyl Acetal to Form a Transient Directing Group

Autor: St John‐Campbell, Sahra, Ou, Alex K., Bull, James A.
Přispěvatelé: Engineering & Physical Science Research Council (EPSRC), The Royal Society
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Zdroj: Chemistry (Weinheim an Der Bergstrasse, Germany)
ISSN: 1521-3765
0947-6539
Popis: C−H Functionalization of amines is a prominent challenge due to the strong complexation of amines to transition metal catalysts, and therefore typically requires derivatization at nitrogen with a directing group. Transient directing groups (TDGs) permit C−H functionalization in a single operation, without needing these additional steps for directing group installation and removal. Here we report a palladium catalyzed γ‐C−H arylation of amines using catalytic amounts of alkyl acetals as transient activators (e.g. commercially available (2,2‐dimethoxyethoxy)benzene). This simple additive enables arylation of amines with a wide range of aryl iodides. Key structural features of the novel TDG are examined, demonstrating an important role for the masked carbonyl and ether functionalities. Detailed kinetic (RPKA) and mechanistic investigations determine the order in all reagents, and identify cyclopalladation as the turnover limiting step. Finally, the discovery of an unprecedented off‐cycle free‐amine directed ϵ‐cyclopalladation of the arylation product is reported.
Databáze: OpenAIRE
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