Rational Synthesis of β-Substituted Chlorin Building Blocks

Chlorins bearing synthetic handles at specific sites about the perimeter of the macrocycle constitute valuable building blocks. We previously developed methodology for preparing meso-substituted chlorin building blocks and now present methodology for preparing several complementary β-substituted chlorin building blocks. The chlorins bear one or two β substituents, one meso substituent, a geminal dimethyl group to lock in the chlorin hydrogenation level, and no flanking meso and β substituents. The synthesis involves convergent joining of an Eastern half and a Western half. New routes have been developed to two β-substituted bromo-dipyrromethane monocarbinols (Eastern halves). A new β-substituted Western half was prepared following the method for preparing an unsubstituted Western half (3,3-dimethyl-2,3-dihydrodipyrrin). Chlorin formation is achieved by a two-flask process of acid-catalyzed condensation followed by metal-mediated oxidative cyclization. β-Substituted chlorins have been prepared in 18−24% yield bearing a 4-iodophenyl group at the 8-position, a 4-iodophenyl group or a 4-[2-(trimethylsilyl)ethynyl]phenyl group at the 12-position, and a 4-iodophenyl group and a 4-[2-(trimethylsilyl)ethynyl]phenyl group at diametrically opposed β-positions (2, 12). The latter building block makes possible the stepwise construction of linear multi-chlorin architectures. The chlorins exhibit typical absorption and fluorescence spectra. A systematic shift in the absorption maximum (637−655 nm for the free base chlorins, 606−628 nm for the zinc chlorins) and intensity of the chlorin Q_y band (ε up to 79 000 M^-1 cm^-1) is observed depending on the location of the substituents. The characteristic spectral features and location of substituents in defined positions make these chlorins well suited for a variety of applications in biomimetic and materials chemistry.