Asymmetric induction in the Neber rearrangement of simple ketoxime sulfonates under phase-transfer conditions: experimental evidence for the participation of an anionic pathway.
Phase-transfer catalysis has been successfully utilized for the Neber rearrangement of simple ketoxime sulfonates. For instance, treatment of (Z)-1a with p-toluenesulfonyl chloride (1.2 equiv), tetrabutylammonium bromide (5 mol %) and MeOH (10 equiv) in toluene-50% KOH aqueous solution (volume ratio = 3:1) at 0 degrees C for 2 h, and subsequent benzoylation followed by acidic hydrolysis afforded the protected alpha-amino ketone 2a in 80% isolated yield. On the basis of this finding, asymmetric Neber rearrangement with ketoxime (Z)-1a was examined under phase-transfer conditions using structurally rigid, C(2)-symmetric chiral quaternary ammonium bromide 3 as catalyst. The desired 2a was obtained in 80% yield and 51% ee. This represents the first experimental demonstration of the substantial involvement of anion pathway in the Neber rearrangement of simple ketoxime sulfonates. Importantly, the reaction with (E)-1a under otherwise similar conditions afforded racemic 2a in 61% yield. Moreover, enhanced enantioselectivity (63% ee) was observed in the rearrangement of the oxime sulfonate derived from (Z)-1b, and notably, use of mesitylene in place of toluene further increased the enantioselectivity to 70% ee. Our approach provides not only a new mechanistic insight but also an opportunity for extending the full synthetic utility of this classical yet useful rearrangement.
Ooi
Takashi
T
Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo, Kyoto 606-8502, Japan.
Takahashi
Makoto
M
Doda
Kanae
K
Maruoka
Keiji
K
D000476:Alkanesulfonates / Q000737:chemistry*; D000838:Anions; D002384:Catalysis; D007659:Ketones / Q000737:chemistry*; D010091:Oximes / Q000737:chemistry*; D013237:Stereoisomerism
D000476:Alkanesulfonates; D000838:Anions; D007659:Ketones; D010091:Oximes