Asymmetric Synthesis of 2H‐Azirines with a Tetrasubstituted Stereocenter by Enantioselective Ring Contraction of Isoxazoles

Highly strained 2H‐azirines with a tetrasubstituted stereocenter were synthesized by the enantioselective isomerization of isoxazoles with a chiral diene–rhodium catalyst system. The effect of ligands and the coordination behavior support the proposed catalytic cycle in which the coordination site is fixed in favor of efficient enantiodiscrimination by a bulky substituent of the ligand. In silico studies also support the existence of a rhodium–imido complex as a key intermediate for enantiodiscrimination. Coping well under the strain: Highly strained 2H‐azirines with tetrasubstituted stereocenters were synthesized with high enantioselectivity by the N−O bond‐cleaving isomerization of isoxazoles in the presence of a chiral diene–rhodium catalyst (see scheme). This asymmetric ring contraction of isoxazoles proceeded under mild reaction conditions to give 2‐alkoxycarbonyl 2H‐azirines with various substituents, including halogen groups.