Serendipitous synthetic entrée to tetradehydro analogues of cobalamins

Tetradehydrocorrin macrocycles occupy a saturation level halfway between that of octadehydrocorrins and corrins (e.g., cyanocobalamin). While octadehydrocorrin chemistry is relatively well understood, few studies have been done on more reduced macrocycles owing to synthetic limitations. The reaction of a 2,3-dihydro-1,3,3-trimethyldipyrrin (Western half) bearing a 7-(4-iodophenyl) group and a 1-(dimethoxymethyl)-9-bromo-2,3-dihydro-3,3- dimethyldipyrrin (Eastern half) bearing a 7-p-tolyl group in the presence of Ga(OTf)₃ afforded the corresponding B,D-tetradehydrocorrin (1) in 24% yield. Use of a Western half bearing a 7-(4-ethylphenyl) group afforded the B,D-tetradehydrocorrin (2) in 29% yield. Each tetradehydrocorrin bears a 1-methyl group at the A-D ring junction (and hence is enantiomeric), a geminal dimethyl group in each pyrroline ring, and distinct substituents at the 7- and 17-positions; characterization included ¹H and ¹³C NMR spectroscopies, absorption spectroscopy, mass spectrometry, and X-ray crystallography (2 only). Treatment of 1 or 2 with CoCl₂ afforded the cobalt chelate as a mixture of stereoisomers containing an apical methoxide or hydroxide ligand. The cobalt-tetradehydrocorrin was characterized by absorption spectroscopy, mass spectrometry, infrared spectroscopy and electrochemistry. The cobalt chelate was smoothly titrated with THF, pyridine, and KCN or Bu ₄NCN. While the assignment of the oxidation state of the cobalt remains provisional, the use of natural abundance versus isotopically substituted solvents or titrants (CD₃OD, K¹³CN) enabled clear identification of the apical ligands. The facile access to stable, synthetically tailored B,D-tetradehydrocorrins should open the door to fundamental studies of simple surrogates of cyanocobalamin.