As a fast-growing research field in modern organic chemistry, the crossdehydrogenative coupling (CDC) has seen considerable development in its scope of application, uptake into industry, and understanding of its mechanism to functionalize the tetrahydroisoquinoline (THIQ) scaffold. Among the vast number of possibilities offered by the CDC coupling, the metal-free oxidative α-cyanation and alkynylation reactions have emerged as powerful strategies in the synthesis of diverse and potentially bioactive THIQs. Even though transition-metal catalyzed CDC reactions have undoubtedly made significant progress in THIQ chemistry, general and selective protocols for the metal-free oxidative α-cyanation and alkynylation reactions of THIQs are urgently needed. Thereby, this critical discussion is aimed to highlight the recent progress in this field of CDC reactions where Csp3-H bonds are activated without metal catalysts to introduce the CN and the alkynyl groups into the THIQ core.