Synthetic Pathway to trans -A 2 B 2 -Porphyrins: From Oxime-Substituted Dipyrromethanes to Functionalized Macrocycles

An unprecedented approach to trans-A₂B₂-porphyrins from α-oxime-functionalized dipyrromethanes has been disclosed. Initially aimed at BODIPY synthesis, the process serendipitously yielded porphyrins with photophysical properties suitable for use as photosensitizers in photodynamic therapy (PDT), as mirrored by its Φ_Δ values, which ranged from 66% to 86%. This unexpected discovery paves the way for innovative synthetic approaches to macrocycles via DDQ-mediated metal-free C(sp³)-C(sp²) cross-coupling reactions. The synthesis under batch reaction conditions was successfully transposed to the more sustainable continuous-flow synthesis. Furthermore, meso-oxime-functionalized trans-A₂B₂-porphyrins were also obtained via the classic [2 + 2]-type reaction between meso-oxime-functionalized dipyrromethanes and aldehydes.