“…[ 24 , 25 , 26 , 27 , 28 , 29 ] Notably, in recent years, click chemistry has been employed for the construction of PROTACs and fine‐tuning the properties of the designed degraders. [ 34 , 35 ] However, this synthetic strategy was mainly used for a single experiment of PROTAC synthesis and still required further product purification processes to remove the metal catalyst and ligands. [ 18 , 36 , 37 , 38 ] We reasoned that several factors are required for the successful implementation of this direct‐to‐biology strategy: i) PROTACs are heterobifunctional molecules consisting of a target protein ligand, a connecting linker, and an E3 ligand, Therefore, the fragments for PROTAC library synthesis should be readily accessible; ii) The high‐throughput synthesis of PROTACs should be conducted without the use of toxic metal catalysts and additional chemical reagents or ligands, with the goal of minimizing toxicity to biological systems; iii) The by‐products generated during synthetic steps ideally should not interfere with subsequent bioassays; for instance, by‐products like water are considered acceptable; iv) The multi‐step synthesis reactions should be highly efficient and compatible in plates without the need for further purification steps, which ensures a seamless synthesis‐bioassay process; v) Due to the critical roles that linker structures (e.g., linkage site and linker length) play in the bioactivity of degraders, [ 14 , 15 , 16 ] the linker should be stable and exhibit diversity in linkages.…”