Synthesis and Properties of Ring-Deactivated Deuterated (Hydroxymethyl)pyrroles

A sequence, based on a Mitsunobu displacement at the hydroxymethyl position of deuterium-labeled, N -substituted 2-(hydroxymethyl)pyrroles, is reported as a general procedure to determine the ability of the N -substituent to deactivate the heterocycle. An S N 2 mechanism, in this reaction, has been shown to be favored over reaction via an azafulvenium intermediate, by employing N -(trifluoromethyl)sulfonyl as the deactivating group. Deuterium-labeling studies have demonstrated that suppression of contributions to the reaction from an azafulvenium intermediate is less effective with other deactivating groups, and the order for deactivation is triflyl > mesyl > BOC ≈ acetyl. The attachment of an electron-withdrawing group onto the nitrogen of a 2-formyl[ formyl - d ]pyrrole has also been shown to allow reduction to give a 2-(hydroxymethyl[ methylene - d 1 ])pyrrole of high configurational purity. The utility of the N -triflyl group to deactivate a pyrrole was demonstrated with the preparation of deuterium-labeled porphobilinogen precursor.