The formation of new bonds through C-C bond formation is of utmost importance in the synthesis of
biologically privileged scaffolds and therapeutic drugs. In recent years, extensive efforts has been done to improve the
intermolecular and intramolecular cross-coupling reaction in the simple, mild, efficient, economical, and eco-friendly
manner via transition metal-free or organocatalytic direct C-H bond activation methodology. The traditional crosscoupling era continuously shifted to metal-free, organocatalytic, or metal-free cross-dehydrogenative coupling strategies
to fast-track the reactions and diminishing the typical purification processes. Therefore, recent advances on the transitionmetal-free, organocatalytic inter- and intra-molecular cross-coupling reactions have been introduced and discussed in the
present article. In view of the reaction mechanism, organocatalytic cross-coupling reactions undergo through the radical
pathways, radical anionic intermediate which is completely different from traditional transition metal-catalyzed reactions.
The exploration of transition metal-free organocatalyzed cross-couplings for direct C-H arylation of arenes has grown
significantly, thereby, improving the formation of a wide range of aryl-aryl /aryl-heteroaryl/ heteroaryl-heteroaryl
In the survey, transition metal-free/organocatalytic cross-coupling reactions showed a higher efficiency under simple and
mild conditions than the comparative transition metal-catalyzed cross-coupling reactions. However, the higher
regioselectivity and chemoselectivity are still far ahead in organocatalytic cross-coupling reactions due to their specific
intrinsic mechanistic pathway. The tuning of many parameters such as oxidative states, ligands coordination, and counter
anions, etc., which results in the specific direct C-H functionalization with flexible methodology are missing in the
transition metal-free cross-coupling reactions. The highly systematic transition metal-catalyzed chemistry is still playing a
dominant role over transition metal-free chemistry in organic synthesis. The organocatalyzed transition-metal-free
conditions should be more efficient, chemoselective, and regioselective for further potential development and applications
in organic synthesis. For the endless pursuit of sustainable chemistry and green chemistry, such transition-metalfree/organocatalytic reactions should be never ceased. Additional curious attention and interest have been developed so
far, and chemists are showing their eagerness and talents to uncover the hidden treasure of green chemistry.
In this review article, we highlighted the developments of various transition metal-free/organocatalytic C-H bond
activation reactions which further encourages the advancement in the development of sustainable C-C coupling reactions
and their further applications towards the synthesis of biologically privileged scaffolds and drug molecules.