Bridging C−H Activation: Mild and Versatile Cleavage of the 8‐Aminoquinoline Directing Group

Abstract

8-Aminoquinoline has emerged as one of the most powerful bidentate directing groups in history of C-H activation within the last decade. However, cleavage of its robust amide bond has shown to be challenging in several cases, thus jeopardizing the general synthetic utility of the method. To overcome this limitation, we herein report a simple oxidative deprotection protocol. This transformation rapidly converts the robust amide to a labile imide, allowing subsequent cleavage in a simple one-pot fashion to rapidly access carboxylic acids or amides as final products.

Synthesis and antimicrobial evaluation of novel analogues of dehydroabietic acid prepared by C H-Activation

“…[22] Indeed, and in contrast to our disappointing results aforementioned, ozonolysis and treatment with hydrochlorid acid resulted smoothly in the formation of novel aryl analogues 11 of dehydroabietyl amide with simultaneous hydrolysis of the methylester in 9d (Scheme 3). It is worth mentioning that ozonolysis occurs with remarkably high selectivity for the aminoquinoline and neither oxidation of the electron-poor/electron-rich aryl moieties nor modification of the carbon skeleton of DHAA-amides 9 was observed.…”

A comprehensive overview of directing groups applied in metal-catalysed C–H functionalisation chemistry

“…If difficulties are met, additional steps such as N -methylation 379 – 382 or N -Boc 383 – 387 protection might be helpful in some cases for the deprotection of the DG under basic conditions. More recently, it has been demonstrated that oxidative cleavage 388 (ozonolysis followed by hydrolysis) as well as Ni- 389 , 390 and Co-catalysis 387 were also good alternatives for instance although so far less commonly used compared to classical acid and basic conditions.…”

Iron-Catalyzed C–H Functionalizations under Triazole-Assistance

“…This approach presented a notable advantage with respect to recent removal protocols of the AQ DG that required the use of hazardous chemicals such as ozone and dimethylsulfide (DMS) (Scheme 23c) [73]. More recently, iron-catalyzed, triazole-assisted C-H functionalization methodologies have been exploited in the presence of propargyl acetates 40 for the synthesis of highly decorated isoquinolone derivatives [72].…”

“…The synthetic utility of the methodology was additionally demonstrated by a simple electrochemical cleavage of the TAH DG that delivered NH-free isoquinolone 42a in high yield and chemoselectivity (Scheme 23b). This approach presented a notable advantage with respect to recent removal protocols of the AQ DG that required the use of hazardous chemicals such as ozone and dimethylsulfide (DMS) (Scheme 23c) [73]. Detailed mechanistic studies were conducted submitting deuterium-labelled benzamides 37 to the optimized reaction conditions.…”