Two dipyrromethane + dipyrromethanedicarbinol routes to a meso-substituted phlorin bearing electron-withdrawing pentafluorophenyl substituents (TpFPPhl) were investigated in an attempt to obtain a phlorinwith enhanced stability toward light and air and to explore the application of dipyrromethanecarbinolchemistry to the preparation of phlorins. For each route, a systematic survey of reaction parameters forthe two-step, one-flask reaction leading to TpFPPhl was performed. The analytical-scale reactions weremonitored for yield of TpFPPhl by HPLC. Sharp differences were observed in the yield of TpFPPhlafforded by the two synthetic routes. The most promising reaction condition (TFA catalysis, 100 mM)was performed on a preparative scale providing TpFPPhl in a yield of 45% (189 mg). The stability ofthe electron-deficient phlorin in dilute solution upon exposure to light and air was probed in a numberof solvents, and decomposition was monitored by UV-vis spectroscopy and HPLC. Many of the solutionsof TpFPPhl were found to be quite stable for periods of ~8 h, with decomposition requiring exposureperiods of several days. Taken together, this work contributes an efficient synthesis of a meso-substitutedphlorin of practical stability and provides further insights toward the adaptation of dipyrromethanecarbinolchemistry to the preparation of diverse porphyrinoids.
