Stereoselective synthesis of α-amino fluoroalkyl ketones and β-amino fluoroalkyl alcohols from perfluoroalkyl enol ethers

Abstract

α-Amino and α-peptidyl fluoromethyl ketones and corresponding alcohols are a very important class of protease inhibitors. However, there is no general synthesis for these compounds. Our approach is the opening of trifluoromethyl epoxyethers prepared from easily available trifluoromethyl enol ethers. Direct epoxidation of fluorinated olefins is claimed to be unsuccessful. Epoxidation of fluoroalkyl enol ethers is achieved at room temperature with MCPBA. ▪ The opening of epoxyethers by an amine proceeds as follows: ▪ in high yields, with high stereoselectivity in reduction (RS,SR), and allowing possible chiral synthesis of aminoalcohols.