Recent advancements in metal-free C–C bond formation via C–H bond functionalization†

In modern synthetic organic chemistry, C–H bond activation has attracted the attention of researchers for various organic transformations, including C–C and C–X (X = N, O, S, and P) bond formation and heterocycle construction. For the purpose of C–C bond formation or annulation, C–H bond functionalization is more advantageous than conventional cross-coupling reactions owing to the non-requirement of pre-functionalized substrates, less waste generation, higher atom economy, low operational cost and direct incorporation of the desired functional group. Earlier, it was considered that transition metals and their coordinating directing groups are crucial for performing C–H activation reactions. Later, the hazardous effect of the metals on the environment and human health introduced metal-free organic reactions in the synthetic chemistry toolbox. Metal-free organic transformations are gradually becoming more preferred by both industry and academia for construction of bioactive molecules considering their advantages such as low operational cost, less number of steps for the synthesis, low risk of metal contamination-associated hazards, and less possibility of error in the results of biological evaluations. For achieving the mentioned advantages, two different sustainable practices (i.e., metal-free approaches and C–H bond activation) were combined into a new approach of sustainable synthesis, entitled “metal-free C–H bond activation approach”. Although the C–H bond activation strategy is itself a sustainable approach, one or more sustainable approaches were also incorporated for synergism in the C–H functionalization protocol. In this review, we focus on metal-free C–C bond formation reactions carried out via a C–H activation approach. This review covers metal-free C–H alkylation, alkenylation, arylation, carbonylation, carbamoylation, alkynylation and cyanation reactions with emphasis on their reaction mechanisms.