Aryl halides are an indispensably important class of compounds owing to their role as precursors in the synthesis of organometallic reagents and nucleophilic substitution reactions. In addition, with the advent of cross‐coupling chemistry, the importance of aryl halides has increased tremendously, and they are therefore classified as the core building blocks in organic synthesis. With the recent advances in the area of transition‐metal‐catalyzed C−H functionalization, metal‐catalyzed C−H halogenation has emerged as a modern tool in organic synthesis. This focus review highlights the significant developments in the area of directed C−H halogenation reactions, particularly in the last two years.
Site selectivity is an inherent challenge in C–H functionalization reactions. The most intensively sought‐after approaches have involved the employment of Lewis‐basic coordinating groups to direct a metal to a proximal site, in the process generating a metallacycle capable of further organometallic reactivity. In the recent years considerable effort has been directed towards the development of new transformations involving transition‐metal‐mediated C–H functionalization directed by weakly coordinating groups. This microreview focuses on the role and utility of amides and anilides in directed, proximal C–H bond functionalization reactions.
A new approach for the regioselective functionalization of the C-3-position of quinolines is described. The method utilizes heteroatom guided regioselective C-3 palladation followed by arylation via transmetalation with aryl boronic acids to yield 3-aryl-N-acyl-1,2-dihydroquinolines. In a one-pot sequence, N-deacylation followed by aromatization leads to important 3-arylquinolines in good yields.
Electron‐deficient aromatic heterocycles, such as pyridine, quinoline, and isoquinoline, occupy a vast and rapidly expanding area of chemistry because of the obvious application of their derivatives in medicine, agriculture, polymers, and other fields. These heterocycles are rather poorly reactive towards electrophilic metalation by C−H activation and oxidative C−H activation mechanisms. The catalytic C−H functionalization of electron‐ deficient heterocycles remains a challenge for the synthetic chemistry community. This Focus Review highlights significant developments made in the area of transition‐metal‐catalyzed C−H functionalization of π‐deficient heterocycles.
A palladium-catalyzed, ortho-selective C-H halogenation methodology is reported herein. The highlight of the work is the highly selective C(sp)-H functionalization of benzyl nitriles in the presence of activated C(sp)-H bond, which results in good yields of the halogenated products with excellent regioselectivity. Along with benzyl nitriles, aryl Weinreb amides and anilides have been evaluated for the transformation using aprotic conditions. Mechanistic studies yield interesting aspects with respect to the pathway of the reaction and the directing group abilities.
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