Catalytic Reduction of Oximes to Hydroxylamines: Current Methods, Challenges and Opportunities

Catalytic reduction of oximes represents a direct efficient approach to synthesize valuable hydroxylamine derivatives. However this transformation presents significant challenges: oximes are hard to reduce and, if reactive, reductive cleavage of the weak N-O bond often leads to primary amine side products. The first suitable systems involved the use of platinum-based heterogeneous catalysts with hydrogen as reductant and stoichiometric amounts of a strong Bronsted acid. More recently metal-free and transition-metal-based homogeneous catalysts have been developed, which display the highest turnovers (up to 4000). In the asymmetric variants, the E/Z-geometry of the oxime double bond affects significantly the stereoselectivity, sometimes requiring extra synthetic efforts in substrate preparation. This minireview provides an overview of the advances and limitations in catalytic oxime to hydroxylamine reduction. Emphasis is put on highlighting and comparing the practical aspects of the existing methods, such as their reaction conditions and substrate scope. Additionally, future directions for improving this young research area are suggested.

Automated summary

Catalytic reduction of oximes is an efficient method for synthesizing valuable hydroxylamine derivatives, but faces challenges such as the difficulty of reducing oximes and the complexity of their reactivity. Recent developments have focused on metal-free and transition-metal-based homogeneous catalysts with higher turnovers, yet issues with stereoselectivity and substrate preparation remain to be addressed.