Alkylthio Unit as an α-Pyrrole Protecting Group for Use in Dipyrromethane Synthesis

The synthesis of porphyrin precursors requires the successive introduction of substituents at the pyrrole
α- and α‘-positions (2- and 5-, respectively). An α-pyrrole substituent that serves as a temporary masking
agent and is not deactivating would greatly facilitate such syntheses, particularly for β-(3,4)-unsubstituted
pyrroles, but has heretofore not been available. A series of α-RS groups (R = Me, Et, n-decyl, Ph) have
been investigated in this regard, including the determination of the kinetics of substitution at the pyrrolic
3-, 4-, and 5-positions and the application to dipyrromethane formation. The RS group was readily
introduced into the pyrrole α-position by the reaction of 2-thiocyanatopyrrole (prepared from pyrrole,
ammonium thiocyanate, and iodine) and the corresponding Grignard reagent RMgBr. Each 2-alkylthio
group activated the pyrrole ring toward deuteration at the 3- or 5- (vs 4-) position. The dipyrromethane
synthesis was carried out using a 2:1 ratio of 2-(RS)pyrrole/benzaldehyde with a catalytic amount of
InCl3 at room temperature in the absence of any solvent. The α-RS group was removed by
hydrodesulfurization using Raney nickel or nickel complexes. This stoichiometric synthesis using the
α-RS-protected pyrrole is in contrast to the traditional synthesis that employs an aldehyde and 25−100
mol equiv of pyrrole. Six meso-substituted dipyrromethanes were prepared by the reaction of
2-(n-decylthio)pyrrole/aldehyde/InCl3 (2.2:1:0.2 ratio) followed by hydrodesulfurization. Other reactions
of the 1,9-bis(RS)dipyrromethane include oxidation to give (i) the 1,9-bis(RS)dipyrrin or (ii) the 1,9-bis(RSO2)dipyrromethane, which underwent subsequent complexation with dibutyltin dichloride. In
summary, under mild reaction conditions, the 2-alkylthio group is readily introduced to the pyrrole nucleus,
directs electrophilic substitution to the 5-position, and is readily removed as required for elaboration of
porphyrinic precursors.