Aziridination of β-substituted styrene derivatives with 3-acetoxyaminoquinazolin-4(3H)-ones: probing transition state geometry from changes in diastereoselectivity

Abstract

Reaction of (S)-3-acetoxyamino-2-[1-(t-butyldimethylsilyloxy)ethyl]quinazolin-4(3H)-one 5 (Q¹NHOAc) with styrene and R(β)-substituted E-styrenes (R = SiMe₃, Me, CH₂Cl, CHCl₂) gives the corresponding aziridines diastereoselectively. The diastereoselectivity increases in the same sense from 5 ∶ 1 → 20 ∶ 1 as the electron-withdrawing character of R increases [H(Me), CH₂Cl, CHCl₂] but is accompanied by a decrease in yield of aziridine. A similar increase in diastereoselectivity is found in the reaction of 3-acetoxyamino-2-(2,3,3-trimethylpropyl)quinazolin-4(3H)-one 38 (Q⁴NHOAc) with the same β-substituted styrenes.

An explanation for these observations is offered based on a tighter, more symmetrical transition state for the aziridination of styrenes bearing the more electron-withdrawing β-substituents and is supported by SCF calculations.