Intramolecular functionalisation by a methylene radical of a 1,2-diol and a vicinal amino alcohol: models for coenzyme B-12-dependent diol dehydratase and ethanolamine ammonia lyase

Coenzyme B-12-dependent diol dehydratase converts 1,2-diols (e.g. propane-1 ,2-diol) into the corresponding aldehyde and water. The similar enzyme etha nolamine ammonia lyase transforms vicinal aminoalcohols (e.g. 2-aminoethano l) into the corresponding aldehyde and ammonia. Model systems have been dev eloped that replicate key features of the putative enzymatic mechanism, i.e . removal of a hydrogen atom from the CH2OH group of a 1,2-diol or vicinal aminoalcohol by a methylene radical derived from an alkylcobalt compound, a nd conversion of a 1,2-diol or vicinal aminoalcohol into a carbonyl compoun d and water or ammonia triggered by such a methylene radical. The models ar e based on alkyl(pyridine)bis(dimethylglyoximato)cobalt complexes [alkyl(py ridine)cobaloximes, Cbx], which were synthesised from appropriate organic p recursors using standard methodology. The complexes contain a 1,2-diol [as in 4,5-dihydroxy-2,2-dimethylpentyl(pyridine)cobaloxime] or vicinal aminoal cohol [as in 6-amino-5-hydroxy-2,2-dimethylhexyl(pyridine)cobaloxime] tethe red to the cobalt by a carbon chain. Photolysis or thermolysis of 4,5-dihyd roxy-2,2-dimethylpentyl(pyridine)cobaloxime at pH 3 or 9 gave 4,4-dimethylp entanal. It is proposed that homolysis of the Co-C bond of 4,5-dihydroxy-2, 2-dimethylpentyl(pyridine)cobaloxime induced by photolysis or thermolysis a ffords the 1,2-dihydroxy-4,4-dimethyl-1-pentyl radical via a 1,5-H shift, w hich is converted into the 4,4-dimethyl-1-oxo-2-pentyl radical, and hence 4 ,4-dimethylpentanal. The pathway for formation of the aldehyde was diagnose d using the specifically deuteriated analogue [5,5-H-2(2)]-4,5-dihydroxy-2, 2-dimethylpentyl(pyridine)cobaloxime, which gave [1,5-H-2(2)]-4,4-dimethylp entanal accompanied by 3,3-dimethylbutanal on thermolysis or photolysis at pH 3. The protected model compound 2a was hydrolysed to 6-amino-5-hydroxy-2 ,2-dimethylhexyl(pyridine)cobaloxime, which was heated at pH 3 or 9 to give 5,5-dimethylhexan-2-one and ammonia.