Palladium‐Catalyzed CH Oxidation of Isoquinoline N‐Oxides: Selective Alkylation with Dialkyl Sulfoxides and Halogenation with Dihalo sulfoxides

Abstract

A novel palladium‐catalyzed CH oxidation of isoquinoline N‐oxides has been developed for regioselectively synthesizing substituted isoquinolines. The method represents the first example of using dialkyl sulfoxides as the alkyl sources for the construction of 1‐alkylated isoquinolines. Moreover, the regioselective halogenation of isoquinoline N‐oxides is also successful using dihalo sulfoxides as the halide sources.

Direct, Catalytic, and Regioselective Synthesis of 2-Alkyl-, Aryl-, and Alkenyl-Substituted N-Heterocycles from N-Oxides

“…2 In particular, introduction of substituents in the C2-position of pyridines, quinolines and related six-membered nitrogenous heterocycles is an important strategy in heterocyclic synthesis that represents a significant synthetic challenge. 3 One of the most commonly used strategies is based on transition metal-catalyzed coupling reactions of organometallic reagents with 2-haloazines, 4 which are prepared from the corresponding N -oxides 5 (Scheme 1). However, despite its widespread use, this route has significant drawbacks.…”

Recent Advances in Catalytic Functionalization of N‐Oxide Compounds via CH Bond Activation

“…[42] A broad range of functional groups can be tolerated in this reaction. [42] A broad range of functional groups can be tolerated in this reaction.…”

Metal‐Free Synthesis of Methylene‐Bridged Bisamide via Selectfluor‐Mediated Oxidative Methylenation

“…Oxidants were often required to promote such reactions . Dimethyl sulfoxide (DMSO), as a cheap, aprotic polar and versatile solvent with low toxicity and relative stability, has been widely used as a synthon in organic synthesis such as a source of ‐Me, ‐CH, or ‐CHO . In addition, several papers have been reported on the synthesis of bisamides from primary amides using DMSO as a methylene soucre in the presence of an additional oxidant such as ammonium persulfate, cyanuric chloride, I 2 or catalysed by NiCl 2 .…”