Chiral aziridination of α,β-unsaturated esters and ketones using N-nitrenes in the presence of trifluoroacetic acid

Abstract

Aziridination of various α,β-unsaturated esters and α,β-unsaturated ketones has been studied using the N-nitrene generated by oxidation of 3-amino-2-(1,2,2-trimethylpropyl)quinazolin-4(3H)-one (1) with lead tetra-acetate in dichloromethane at room temperature. The stereoselectivity of this aziridination is greatly increased by the addition of trifluoroacetic acid before the oxidation of the aminoquinazolinone (1). The presence of trifluoroacetic acid has two additional advantages in these aziridinations: (a) it allows the reaction to be carried out at –60 °C with the expected increase in stereoselectivity; and (b) the alkene can be used in molar equivalent amounts with little loss of yield of aziridine. For example, aziridination of methyl acrylate (1.1 mol equiv.) at –60 °C with the N-nitrene derived from compound (1)(1 mol equiv.) gave the aziridine stereoisomers (5)(ratio 23:1) in 65% isolated yield.