Electroreductive Intramolecular Coupling of Aromatic β- and γ-Imino Esters: A New Synthetic Method for N-Alkoxycarbonyl-2-aryl-3-ones and cis-2-Aryl-3-ols of Pyrrolidines and Piperidines

Abstract

The electroreduction of aromatic beta- and gamma-imino esters prepared from beta-alanine and GABA in the presence of chlorotrimethylsilane and subsequent N-alkoxycarbonylation of the resulting five- and six-membered cyclized amines gave mixed ketals of N-alkoxycarbonyl-2-arylpyrrolidin-3-ones and 2-arylpiperidin-3-ones, respectively. The best result of the electroreductive intramolecular coupling was achieved using Bu(4)NClO(4) as a supporting electrolyte and a Pb cathode in THF. Acid hydrolysis of the mixed ketals afforded N-alkoxycarbonyl-2-arylpyrrolidin-3-ones and 2-arylpiperidin-3-ones in good yields. The reduction of these ketones with NaBH(4) in methanol afforded the corresponding N-alkoxycarbonyl-cis-2-arylpyrrolidin-3-ols and cis-2-arylpiperidin-3-ols diastereospecifically.