Following a minor re-optimization of the reaction parameters and modification of the experimental setup (see Supplementary Information, Sections S7.1-S7.3), we discovered that crude peptides, synthesized using Rink Amide resin via SPPS, could be readily engaged in the photocatalytic alkylation (Figure ). Illustratively, heptapeptide P1 was subjected to LSF, yielding the corresponding homoproline-containing analogue 59 in a 28% isolated yield after 21 steps from resin loading (74% LCAP for the decarboxylative alkylation step, with LCAP defined as LC Area % of the product peak in the ultra-performance liquid chromatography (UPLC) chromatogram of the reaction crude. See Supplementary Information, Section 7.5). Highlighting the efficacy of our method, a 28% yield robustly demonstrates the potential of our cross-electrophile coupling for synthesizing complex structures with high selectivity and notable yield conservation. Similarly, a late-stage incorporation of a benzylic unit was accomplished efficiently, demonstrating utility in the context of lipophilicity modulation (60) (72% LCAP for the decarboxylative alkylation step, See Supplementary Information, Section 7.6). To our delight, a derivative of afamelanotide-a therapeutic peptide indicated for patients affected by erythropoietic protoporphyria-was also successfully engaged in the protocol, affording derivative 61 in an overall 9% yield from resin loading (71% LCAP for the decarboxylative alkylation step. See Supplementary Information, Section 7.7). Figure . Scope of the cross-electrophile coupling of peptide RAEs and benzenesulfonyl hydrazones on resin. Reaction conditions: RAE (0.03 mmol, 1 equiv.), Sulfonyl Hydrazone (3 equiv.), Hantzsch ester (4.5 equiv.) and EYNa2 (0.30 equiv.) in CH2Cl2 (33 mM). For full experimental details, see the Supplementary Information.