Catalytic meta-selective C–H functionalization to construct quaternary carbon centres

Abstract

A catalytic meta-selective C-H functionalization of 2-phenylpyridines using a range of tertiary halides is described. The protocol is simple to perform and uses commercially available reagents to construct challenging quaternary carbon centres in a regioselective manner. Preliminary studies suggest the C-H functionalization proceeds through a radical process directed via a remote σ-activation.

Mechanistic insight into ruthenium catalysed meta-sulfonation of 2-phenylpyridine

“…14,15,16 In order to investigate a possible the SEAr pathway, the effect of various sulfonating reagents were subjected to study ( Table 2). Interestingly, it has recently been demonstrated that similar ruthenium complexes such as [Ru( t BuCN)6][BF4]2 can catalyse the C-H arylation of fluoroarenes and arenes with directing groups.…”

“…Once the metallacycle is formed the introduction of a functional group can be achieved at the ortho 1,2 and meta positions. Recently, new examples of meta selective catalytic C-H functionalization controlled by the catalyst have been achieved Scheme 1 using secondary 14 or tertiary 15,16 alkyl halides and bromination reagents. 1,2 Despite the great achievements in this area, the direct introduction of a functional group at the meta position remains a challenge.…”

“…We reported the first example of catalytic metafunctionalization by remote electronic activation using ruthenium catalysis. 15 Recent studies have revealed that the meta-functionalization of arenes via cycloruthenated complexes may follow a radical pathway. The innovative template assisted direct meta-C-H bond activation first reported by Yu et al involves the use of a removable tethered directing group capable of coordinating to the catalyst and directing it to the meta position.…”

“…8,9 This important switch of regioselectivity in the sulfonation of phenylpyridines from the ortho 10 to the meta position was realised by changing the catalyst from Pd(II) to Ru(II). 14,15,16 Herein, we present mechanistic studies to establish important steps and intermediates in the meta-sulfonation of phenylpyridines. 11 Other strategies involve transient mediators such as a carboxylic acid 12 or norbornene 13 that direct ortho but reveal meta-arylated products after their removal (Scheme 1a).…”

Palladium‐Catalyzed para‐Selective Alkylation of Electron‐Deficient Arenes

“…[4] Yu and co-workers also reported a meta-selective alkylation of a-aryl acetamides by cooperative palladium and norbornene catalysis to introduce primary alkyl chains. [4] Yu and co-workers also reported a meta-selective alkylation of a-aryl acetamides by cooperative palladium and norbornene catalysis to introduce primary alkyl chains.…”