Multiple “Click” Reactions on Porphyrins

Abstract

The concept of the 1,3-dipolar “click” alkyne-azide cycloaddition was successfully applied to ortho-benzylic fuctionalized tetraphenylporphyrins presented by JUX in 2000. As the further modification of these porphyrins is indispensable the “click” cycloaddition was optimized for these basic porphyrins in order to obtain good yields and easy working procedures. Thus, over 40 sophisticated and complex molecular structures were prepared. All of these new compounds feature the triazole ring as binding motif and could be characterized by standard chemical analytic methods. The optimized reaction conditions were determined successfully to be CuSO4*H2O as Cu(I)-source and sodium ascorbate as reducing agent. As solvent, a mixture of dichloromethane, ethanol and water delivered the best results. Very important is the addition of the sterical demanding base N,N’-diisopropylethylamine, which increases the yield enormously. Thus, diverse acetylene compounds were attached to various azidoporphyrins with different symmetries. The ortho-benzylic fuctionalized tetraphenylporphyrins synthesized turned out to be favorable precursors for this reaction class as the azido functionalized derivatives can be generated in a few easy steps which all proceed under full conversion. In this manner, tetraphenylporphyrins with up to eight azido units in the ortho-benzylic positions can be obtained easily. As acetylene compounds ethynyl ferrocene, phenyl acetylene and a dendritic ferrocene alkyne conjugate were chosen and were reacted with the different azidoporphyrins. Thus, a plenitude of triazole connected porphyrin conjugates was prepared. This modified “click” method allowed the easy attachment of new functional groups to the basic porphyrins. The yields of the less often functionalized systems (mono- and bis-substituted porphyrins) were satisfactory with around 60%, but excellent results were achieved for the highly-substituted systems (tetra- and octa-substituted porphyrins). These reactions proceeded with complete conversion, which means that the yield for each single reaction center on the porphyrin is higher than 99%. An autocatalytical mechanism and the stabilization of the catalytically active Cu(I)-species by the triazole moieties were supposed to be the reason for this excellent success. The structures of these systems were determined by NMR spectroscopy as well as by mass spectrometry. The ferrocene conjugates were also examined via cyclic voltammetry as the ferrocene unit offers interesting electrochemical behavior. Since this “click” approach turned out to work very well with the JUX porphyrins bridged porphyrins modeled on BALDWIN’S capped porphyrins were created. As bridging unit ferrocene or a dendritic compound were used and anchored to the azido groups of two different azidoporphyrins. In this way, simple- and double-capped ferrocene porphyrins as well as simple- and double-capped dendritic porphyrins were formed. The electrochemical properties of these systems were investigated via cyclic voltammetry and showed an astonishing additional oxidation step, whose origin can be found in the strained configuration of the porphyrin. The capability of the 1,3-dipolar “click” reaction with our porphyrin systems was underlined by creating oligomers consisting of different porphyrins. An array of conjugates built up of different porphyrins, ferrocene units and dendritic NEWKOME branches was generated. One approach, for instance, was the synthesis of a pentamer consisting of one porphyrin in the core and four porphyrins attached to it. A tetrakisazidoporphyrin was used as core porphyrin and four alkyne porphyrins were connected via the 1,3 dipolar SHARPLESS cycloaddition. Due to the autocatalytical process caused by the ortho-position of the azido groups this reaction gave full conversion. Other examples for synthesized oligomers are porphyrins which are linked via a ferrocenyltriazolyl bridge or dendritic ferrocenyl-bridged porphyrins. At last, a long desired approach was realized with this Cu(I)-catalyzed alkyne-azide coupling on the azidoporphyrins: the side-selective functionalization of the tetrakis and octakisazidoporphyrin. This synthesis is challenging due to a lot of isomers that can be formed when the porphyrins are not converted on every of its four or eight reaction centers. By taking the right stoichiometrically deficient proportion of the alkyne compound, the triazole units were built only on one side of the porphyrin plane. Thus, the side-selective modification was carried out successfully via the “click” approach. The side-selective functionalization can clearly be determined via the NMR spectra which prove the difference between the upper and the lower side of the porphyrin plane. Thus, hydrophilic and hydrophobic groups can be attached to the highly-substituted porphyrin in a regioselective manner. Show more