α‐C–H Functionalization of Benzylamines: A Crucial Yet Challenging Transformation

The functionalization of benzylamines continues to be a long-standing interest for organic chemists. This moiety can be found as core structural building block in many pharmaceutical and agrochemical compounds. The suitable application of this core structure not only lies with biological importance but also of great importance from strategic overview. In this review, various strategic implications of functionalizing the α-C─H bond of benzylamines will be thoroughly discussed. Non-directed functionalization mostly involves radical pathway in α-C─H functionalization in benzylamines. The inherent inertness of this α-C─H bond can be directly reasoned to the low acidity due to the presence of adjacent N atom. SET combined with HAT process was demonstrated to generate the desired benzylic radical, which leads to benzylic arylation in benzylamines. Radical carbonyl chemistry was involved in SET process to result in α-C─H alkylation. Umpolung chemistry on benzylamines leads to diverse functionalization on α-C─H bond. Stereoselective α-C─H addition to aldehydes generates chiral amines catalyzed by organocatalysts and enzyme catalysts in separate reports following a nucleophilic addition pathway. Another important transformation of α-C─H bonds is attributed to the C─H bond activation triggered by directed transition-metal catalysis.