Scope and limitations in sulfur ylide mediated catalytic asymmetric aziridination of imines: use of phenyldiazomethane, diazoesters and diazoacetamides

Abstract

Imine aziridination using diazo-compounds and catalytic quantities of metal salts and sulfides has been investigated. A range of imines derived from benzaldehyde bearing electron-withdrawing groups (N-Ts, N-SO₂CH₂CH₂SiMe₃ (SES), N-P(O)Ph₂, N-CO₂Bn, N-CO₂Bu^t, N-CO₂(CH₂)₂SiMe₃, N-CO₂C(CH₃)₂CCl₃) were prepared and tested in the aziridination process using Me₂S and phenyldiazomethane. High yields were obtained with all imines but diastereoselectivity varied considerably (3 ∶ 1–>10 ∶ 1). A range of N-SES imines were tested with stoichiometric amounts of sulfides and high yields were obtained with both aromatic and aliphatic imines. These imines were subsequently tested with stoichiometric and sub-stoichiometric loadings of enantiomerically pure 1,3-oxathiane 3 with Rh₂(OAc)₄ and with Cu(acac)₂. Good yields and high enantioselectivities (89–95%) were observed with Rh₂(OAc)₄, although a small reduction in enantiomeric excess was observed with Cu(acac)₂ (85–95%) especially when sub-stoichiometric amounts of sulfide were employed. The same sulfide was also tested with a range of electron-withdrawing groups on the imine nitrogen and in all cases good yields and high enantioselectivities were maintained. Improved diastereoselectivity was observed with carbamate groups.

The aziridination process was extended to include diazoester and diazoacetamides with a range of N-Ts imines, and again good yields were obtained although diastereoselectivity varied according to the diazo-compound employed. Although the 1,3-oxathiane 3 could not be employed with these more stable diazo-compounds, (R,R)-2,5-dimethylthiolane 5 was found to be a suitable chiral catalyst and gave moderate enantio- and diastereoselectivities. Rationales for the origin of the diastereoselectivity and enantioselectivity are provided.