Porphyrins with exocyclic rings. Part 25: synthesis of porphyrins with a fused cyclic ether subunit from tetrahydro-4H-pyan-4-one

A novel porphyrin system with a fused dihydropyran ring has been synthesized from commercially available 4-oxotetrahydropyran. The cyclic ketone reacted with oximes derived from acetoacetate esters in the presence of zinc dust, sodium propionate, and propionic acid at 150-155 °C to give good yields of 5-oxatetrahydroindoles. A low yield of a benzo-fused analog was also obtained using 4-oxochromanone as the starting reagent. Reaction of the b-annelated pyrroles with N-chlorosuccinimide gave the 7-chloro-derivatives and these underwent an acid catalyzed condensation with α-unsubstituted pyrroles to give dipyrrolic products linked by a dihydropyran moiety. Hydrogenolysis of a dipyrrole dibenzyl ester gave the corresponding dicarboxylic acid and this was converted into a dialdehyde by treatment with TFA-CH(OMe)3. MacDonald '2+2' condensation with two different dipyrrylmethanes under optimized conditions afforded the porphyrin ethers in 30-36% yield. This approach provides a pilot study for the synthesis of porphyrin crown ether structures. In addition, insightful results on the conformations of dihydropyran-linked dipyrroles were obtained by careful examination of their proton NMR spectra in CDCl3 and DMSO-d6.

Graphical abstractPorphyrins with a fused dihydropyran unit were prepared using a '2+2' strategy from 5-oxatetrahydroindoles. The key bicyclic pyrrole intermediates were obtained from tetrahydropyran-4-one by using a Knorr-type reaction.Download full-size image