Buttressing Salicylaldehydes: A Multipurpose Directing Group for C(sp³)−H Bond Activation

Abstract

A palladium-catalyzed reaction of primary amines with iodoarenes produces γ-arylated primary amines. A bulky salicylaldehyde, which is marked as easily available, installable, removable, and recoverable, plays a key role in directing palladium to site-selectively activate the C-H bond located γ to the amino group.

Transient Ligand‐Enabled Transition Metal‐Catalyzed C−H Functionalization

“…In this process, 5‐substituted trifluoromethyl‐ and nitro‐2‐pyridone were identified as the optimal X‐type ligands by acting as an internal base to accelerate the C−H bond cleavage step, which can significantly improve the efficiency of the δ‐arylation of alkyl amines (Scheme b) . In 2016, the use of a stoichiometric amount of 3,5‐di‐ tert ‐butylsalicylaldehyde ( L37 ) as a precursor to form the removable and recoverable directing group for the γ‐arylation of free primary amines has also been reported by Murakami and co‐workers (Scheme c) …”

Site‐Selective γ‐C(sp3)−H and γ‐C(sp2)−H Arylation of Free Amino Esters Promoted by a Catalytic Transient Directing Group

“…used 8‐formylquinoline; Murakami et al. used salicylaldehydes; Ge et al. used a catalytic amount of glycoylic acid; and Yu et al.…”

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

“…Very recently, transient directing groups (TDGs) have been applied to the functionalization of C(sp 3 )−H bonds, particularly arylation of aldehyde and ketone substrates via endo ‐imines formed in situ with amine additives . The use of exo ‐imine directing groups for C−H functionalization of primary amines remains rare, with examples using palladium catalysis . In 2016 Dong used stoichiometric 8‐formylquinoline to form an imine which effected arylation with bisaryliodonium salts .…”

“…Yu reported catalytic 2‐hydroxynicotinaldehyde as a highly effective directing group, compatible with propylamine as well as α‐ and β‐branched amines . In 2017 Murakami used a stoichiometric salicaldehyde in separate imine formation and hydrolysis steps, completed in a one‐pot sequence . While preparing this manuscript, Young reported the use of carbon dioxide to promote C−H arylation of primary and secondary aliphatic amines …”