Syntesis of subtituted succinimides by radical β-fragmentation of bicyclic carbinol amides. A new expeditious synthesis of 2-[2-(methoxycarbonyl)ethyl]-3-[(methoxycarbonyl)methyl]-3-methylsuccinimide, the ring-B imide of vitamin B12

Abstract

A mild and efficient synthesis of substituted succinimides by radical β-fragmentation of carbinol amides is described. The carbinol amides studied were generated by treatment of the corresponding α,β-unsaturated ketones with hydrogen cyanide and subsequent hydrolysis of the cyanide intermediates. Photolysis with visible light in the presence of (diacetoxyiodo)benzene (DIB) and iodine of azabicyclic carbinol amides of the types l-hydroxy-2-azabicyclo[3.3.0]octan-3-on (e.g., 4,6, and 7) and l-hydroxy-2-azabicyclo[3.2.l]octan-3-on (e.g., 16,17, and 21) led to the substituted succinimides in good yields. A novel and operationally simple synthesis of the ring-B imide 28 is described, employing this β-fragmentation reaction on the carbinol amide 7 as the key step. The transformation of the resulting succinimide 11 into the target 28 was accomplished in one step by oxidation of the primary iodide and the phenyl group with Ru04.