Synthesis of meso-Substituted ABCD-Type Porphyrins by Functionalization Reactions

Considerable progress has been made in recent years in the search for synthetic methods leading to functionalized porphyrins, especially for modification of either the beta- or meso positions. For the latter, total synthesis based on condensation methods or partial synthesis through functionalization of preformed porphyrin have emerged as possible methods. The increasing number of possible technical and medicinal applications for unsymmetrically meso-substituted porphyrins requires straightforward methods for the preparation of the so-called ABCD-porphyrins, i.e., porphyrins with up to four different meso substituents. Here, we describe new strategies for the synthesis of ABCD-type porphyrins based on porphyrin reactions with organolithium reagents and the use of Pd-catalyzed coupling reactions. With the whole repertoire of contemporary functionalization methods, a comprehensive analysis and comparison of the various strategies for A-, AB-, A(2)B-, ABC-, A(2)BC- and ABCD-type porphyrins is given. In addition, we report on the synthesis of new functionalized derivatives for some of these porphyrin classes. In practical terms and taking an applied-science-oriented approach, the synthesis of unsymmetrically meso-substituted porphyrins is best accomplished by a combination of well-developed condensation methods with subsequent functionalization. by organolithium compounds or transition-metal-catalyzed coupling protocols. The methods described are suitable for the preparation of porphyrins for many divergent applications ranging over amphiphilic porphyrins for photodynamic therapy, push-pull systems for optical applications and chiral systems useful in catalysis to donor-acceptor systems suitable for electron-transfer studies.