New efficient total syntheses of derivatives of protoporphyrin‐IX bearing deuteriated methyl groups

New total syntheses of hemins which are regioselectively deuteriated in the 1,5 (2), 5 (3) or 8 (4) methyl groups are described. Syntheses of hemins 2 and 3 follow the progression from pyrromethane 12 to t‐butyl tripyrrene‐carboxylate hydrobromide (17 and 30) and then to a,c‐biladiene dihydrobromide (19 and 31), but for reasons of economy in use of labeled monopyrroles, the o,c‐biladiene dihydrobromide 40 for hemin 4 is approached in an initially “clockwise” manner by synthesis of a benzyl tripyrrene‐carboxylate hydrobromide 37 from the pyrromethane 5. Cyclization of the a,c‐biladienes (19, 31, and 40) was accomplished by brief heating in dimethylformamide in the presence of copper(II) chloride.