Despite the efficiency and robustness of the widely used copper-catalyzed 1,3-dipolar cycloaddition reaction, the use of copper as a catalyst is often not attractive, particularly for materials intended for biological systems. The use of photo-initiated thiol-ene as an alternative click reaction to synthesize model networks is investigated here. Poly(N-isopropylacrylamide) precursors were synthesized by reversible addition fragmentation chain transfer (RAFT) polymerization and were designed to have trithiocarbonate moieties as end groups. This structure design provides opportunity for subsequent end-group modifications in preparation for thiol-ene click. Two reaction routes have been proposed and studied to yield thiol and ene moieties. The advantages and disadvantages of each reaction path were investigated to propose a simple but efficient route to prepare copper-free click hydrogels. (c) 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 4626-4636