Abstract
The synergistic use of chiral bifunctional ammonium iodide catalysts in combination with simple catalytically relevant aldimines allows for an unprecedented asymmetric α-hydroxylation reaction of β-ketoesters using H2O2. The reaction proceeds via in situ formation of a hypervalent iodine species, which then reacts with the used aldimine to generate an activated electrophilic oxygen transfer reagent.
Highlights
The use of chiral quaternary ammonium salt (R4N+X−) ion pairing catalysts is one of the most versatile approaches to facilitate the noncovalent organocatalytic asymmetric control of prochiral starting materials, and numerous highly enantioselective applications have been reported.[1,2] the significance of the chiral quaternary ammonium group R4N+ for activation and control of the starting materials/reagents is well-appreciated, the influence of the achiral counteranion X− is usually less systematically addressed, as most scientists rely on the anion originating from the catalyst synthesis (i.e., Cl− or Br− for the commonly used cinchona- and Maruoka-type catalysts[1−4])
This powerful combination is more commonly documented for achiral ammonium iodides,[9,10] the catalytic utilization of in situ formed chiral quaternary ammoniumiodite or iodate species R4N+I(O)n− has so far been reported sparingly, with a handful of highly impressive examples by Ishihara’s group mainly (Scheme 1B).[11,12]
In 2016, we reported the asymmetric bifunctional ammonium iodide A1-catalyzed α-hydroxylation of βketoesters 1 using oxaziridines 2 as the O-transfer reagents (Scheme 1C).[8]
Summary
AAll reactions were run for 20 h at 0 °C using 0.1 mmol 1a (0.02 M) and 5 mol % of A unless otherwise stated. bIsolated yields. cDetermined by HPLC using a chiral stationary phase. Very surprisingly when carrying out the reaction in the presence of the aldimine 4a and H2O2 only, product 3a was obtained with an even higher enantioselectivity of 93:7 (entry 5) It is well-known that chiral iminium salts or imines can undergo in situ oxidations to oxaziridinium salts or oxaziridines, which may be utilized for asymmetric epoxidation or sulfoxidation reactions.[21,22] Quite contrary, no oxaziridine formation was observed under our conditions when using ammonium iodide catalyst A1, imine 4a, and H2O2 (this was regularly checked during all further optimization). Karl Grubmayr, who has been an inspiring (and patient) teacher to all of us, on the occasion of his 70th birthday
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