Synthesis of Isoxazolines from Nitroalkanes via a [4+1]‐Annulation Strategy

A novel access to isoxazolines was developed using the [4+1]‐annulation of α‐keto‐stabilized sulfur ylides with N,N‐bis(siloxy)enamines derived from aliphatic nitro compounds. The resulting 5‐keto‐substituted isoxazolines were shown to be convenient precursors of polysubstituted 3‐hydroxypyrrolidines via the one‐pot catalytic N−O hydrogenolysis/intramolecular reductive amination sequence. Application of this approach to the formal synthesis of Merck's potent NK₁ receptor antagonist was demonstrated.

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