Oxidative C-C bond cleavage of N-alkoxycarbonylated cyclic amines by sodium nitrite in trifluoroacetic acid

Oxidative carbon-carbon bond cleavage of N-alkoxycarbonylated cyclic amines was accomplished by NaNO2 in TFA to afford ω-amino carboxylic acid in high yield. Optically active 3-hydroxypiperidine derivatives and 3-pipecolinate, were converted to enantiomerically pure (R)-4-amino-3-hydroxybutanoic acid (GABOB) and (S)-2-pyrrolidone-4-carboxylate, respectively. It is well known that trifluoroacetic acid (TFA) acts as an efficient medium for oxidation of hydrocarbons. Recently, we found that efficient oxidation of adamantanes to 1-adamantanols was catalyzed by sodium nitrite (NaNO2) under oxygen atmosphere in TFA. In addition, 2 equiv of NaNO2 in TFA oxidized acyclic and cyclic secondary alcohols to the corresponding ketones and α,ω-dicarboxylic acid, respectively. In the latter case, oxidative cleavage of cyclic secondary alcohols occurred between the α-carbon and the β-carbon. We report herein that this oxidizing agent works well as demonstrated by a unique reaction of N-alkoxycarbonylated cyclic amines 1 which reacted with NaNO2 to afford the ring-opened products 2 and its application to preparation of optically active compounds 3e and 4 (Eq. 1). 1 2 ( )n N CO2R α β NaNO2 ( )n N CHO CO2H CO2R (1) HO2C N CHO OAc 3e N O CO2Et 4 H2O in TFA CO2Bn CHO A typical example for the oxidative carbon-carbon (C-C) bond cleavage is shown in Eq. 2. The oxidation of 1a (1 mmol) was carried out in TFA (5 mL) containing NaNO2 (2 mmol) and H2O (10 mmol) under aerobic condition. The oxidation smoothly proceeded