Synthetic polymers with extraordinary properties shape our modern life. However, the current production of polymers, mostly derived from fossil resources, follows an unsustainable model, overlooking their adverse outcomes and their end-of-life fate. An immense and growing accumulation of polymer waste is leading to a global plastic pollution crisis, presenting serious health and environmental concerns. While enhanced waste management and recycling can contribute to addressing these pressing challenges, the development of bio-based sustainable polymers derived from renewable resources with intrinsically embedded degradability can also play a crucial role. Carefully designed degradable polymers have been developed for advanced applications, such as controlled drug delivery, tissue engineering, and chemical recycling. To this end, the creation of bio-based polymers whose degradation can be selectively activated by external stimuli is of great significance. Over the past couple of decades, self-immolative polymers (SIPs) that undergo end-to-end depolymerization in response to specific stimuli, have been gaining increasing attention. Due to their selective and amplified responses to stimuli, SIPs are currently recognized as an emerging class of materials for a range of applications such as sensing, 18, 23 nanolithography, controlled release, and recyclable plastics. Current syntheses of SIPs rely on either stepgrowth polymerization of precursors containing self-immolative spacers (Figure ) or chain-growth polymerization to obtain backbones with low ceiling temperature. With the exception of a recent report from our group, 31 end-capping has typically been performed in situ. Both synthetic approaches involve non-ambient conditions (i.e., high or ultralow temperature), moisture sensitivity, and difficulty in modular end-functionalization. Moreover, the stepgrowth approach generally necessitates the use of protecting or activating groups within the monomers and thus generates side products, compromising atom economy (Figure ). Therefore, it is highly desirable to develop highly efficient strategies to readily access functionalizable SIPs under ambient conditions. The radical-mediated thiol-ene addition reaction has emerged as a versatile click process for surface and polymer functionalization, polymer and network synthesis, and the formation of complex materials and bioconjugates. For example, Hawker et al. described the synthesis of dendrimers using thiol-ene click chemistry to construct the backbone and functionalize the peripheral groups. Additionally, polythioethers were effectively constructed via thiolene click polyaddition of α,ω-alkylene thiols. Motivated by these designs and recent reports on self-immolative elimination to generate thiols, we report the synthesis of bio-based SIPs with varying stimuli-sensitive end-caps via thiol-ene click chemistry (Figure ). These SIPs exhibit selective depolymerization upon stimuli-mediated end-cap removal. First, a polymer based on lignin-derived syringaldehyde was prepared, with a three-carbon spacer between the thioether and carbonate. A bifunctional monomer, M1 with allyloxycarbonyl (Al) and benzyl thiol moieties was synthesized (Scheme 1). Then, UVactuated thiol-ene polymerization in the presence of photoinitiator 2,2-dimethoxy-2-phenylacetophenone (DMPA) was conducted to generate polymer Al-P1, whose chemical structure was confirmed using 1 H and 13 C NMR spectroscopy (Figure ; Figures ). Size exclusion chromatography (SEC) in THF showed a number average molar mass (Mn) of ~5.8 kg/mol and a dispersity (Ð) of 2.84, typical for a step-growth polymerization(Figure and Table ). The high thiol end-group fidelity for Al-P1 was verified by the successful polymer-polymer coupling with acrylate-terminated poly(ethylene glycol) (PEG-Acrylate) through thiol-Michael addition click reaction to afford Al-P1-b-PEG (Figure ; Figure ). With both Al-P1 and Al-P1-b-PEG in hand, their degradation profiles were evaluated upon end-cap cleavage of the allyloxycarbonyl with tetrakis(triphenylphosphine)palladium(0) (Pd(0)) under different conditions in the presence of N-methylaniline (NMA) as the allyl group scavenger and the base 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) to promote the deprotonation of generated thiol moieties. Note that nucleophilic NMA can also trap the reactive quinone methides generated during 1,6-elimination. However, the degradation of these polymers discontinued after removal of Al and only one 1,6-elimination with generation of one new thiol moiety, as revealed by 1 H NMR spectroscopy, regardless of the conditions (i.e., different fractions of D2O in DMSO-d6; Figures ). These results indicated that the cyclization reaction of the thiol group on the carbonate to obtain a six-membered ring product was unfavorable, impeding further depolymerization. Motivated by this observation and previous reports on self-immolative linkers, we synthesized small molecule model compounds with two-and three-carbon spacers between sulfur and the carbonyl group (Scheme 1b) to elucidate the effect of spacer length on the cyclization reaction.