Stereoselectivity in the Formation of Heterocyclic Amine Oxides

Article abstract of DOI:10.1021/jo00323a035

The stereoselectivity of the oxidation of N-alkylpiperidines was studied with the aid of the conformationally biassing 4-tert-butyl substituent.The stereoselectivity was always >95percent and showed little sensitivity to the nature of the N-alkyl substituent.The axial approach was found to be predominating stereochemical oxidation path.A brief study of the effects of solvent, temperature, and oxidant on the stereoselectivity was made.The 1,4-dimethylpiperazine system was investigated, and its oxidation at room temperature resulted in 100percent of trans-1,4-dimethylpiperazine 1,4-dioxide.A method to modulate the stereoselectivity in the formation of saturated heterocyclic amine oxides was developed by inverting the sequence of introduction of the nitrogen substituents.With cis-8-methyl-8-azabicyclo<4.3.0>nonane oxidation is preferred from that side of the molecule which is sterically more hindered.