Synthesis, Transformations, And Comparative Studies of Porphyryl Acrylic Acids and Their Homologues

Abstract

The reactivity of porphyryl acrylates and their homologues was studied systematically and to establish their potential as building blocks for the synthesis of novel tetrapyrroles. A new synthetic approach for multifunctional porphyrins was developed using alpha,beta-unsaturated acyl porphyrins as versatile building blocks with yields of 44-95%. The reaction of acyl chlorides generated in situ with ethyl diazoacetate in the presence of PPh(3) led to the corresponding phosphazine, which was quickly self-transformed into a novel porphyrin beta-keto ester system in up to 78% yield. Comparative studies of the next homologue of acrylic porphyrins, i.e., those bearing an additional CH(2) group next to the double bond of the alpha,beta-unsaturated fragment, showed that these can undergo rearrangement reactions via vinylketenes to yield both regioisomers. Depending on the reaction conditions, this method gives regioselectively access to either a rearrangement product or the product of esterification reactions in yields of 81% or 57%, respectively. Enyne metathesis of novel propargyl esters with allyl porphyrins provided an easy access to 1,3-disubstituted butadienes in up to 76% yield.

Stirring the porphyrin alphabet soup—functionalization reactions for porphyrins

“…First we were interested in gaining access to the homologues of the acrylic porphyrins described in Scheme 7, i.e., those bearing an additional CH 2 group next to the double bond of the α,β-unsaturated 450 fragment. 47 As outlined in Scheme 10 esters of type 86 could be obtained in very good yield from the allylporphyrin 85 via metathesis with Grubbs II catalyst. The allylporphyrins are easily accessible through Suzuki reactions and have proven versatile precursors for 455 our investigations.…”

“…However, such reactions gave the acroleinylporphyrin 90 (for a similar transformation see Scheme 12). 47 The acrylic esters also proved to be good precursors for versatile boron containing porphyrin synthons. 55 Crossmetathesis with Grubbs I catalysts gave porphyrins with mono and disubstituted unsaturated boronyl residues 88 in good yields and complete E-stereoselectivity.…”

“…Since porphyrin 365 carboxylic acids are frequently used in bioconjugate chemistry we investigated the chemistry of acrylic acid derivatives of porphyrins in some detail (Scheme 7 and 10). 47 Porphyrins with one or two acroleinyl groups were prepared from 60 via Heck reactions in with methyl acrylate in 80-95 % yield. These can saponified in high 370 yield to the acids 62 and then to the acyl chlorides 63.…”

“…375 Next we investigated the chemistry of the unknown porphyryl β-keto esters. 47 Our approach utilized the reaction of 63 with ethyl diazoacetate in the presence of PPh 3 . 48a This yields the phosphazine 65 (70 %).…”

mTHPC – A drug on its way from second to third generation photosensitizer?

“…Chemically there are still problems in preparing porphyrin bioconjugates. Suitable and general synthetic methods for the "linker" chemistry remain to be optimized [91]. Likewise the development of photocleavable porphyrin bioconjugates, which would offer the potential of an in vivo pro-drug activation, are still in a developmental stage [92].…”