Enantioselective 1,3-Dipolar Cycloaddition Reaction of Nitrones with α-(Acyloxy)acroleins Catalyzed by Dipeptide-Derived Chiral Tri- or Diammonium Salts

Abstract

Organoammonium salts of dipeptide-derived chiral triamines or diamines with TfOH catalyzed the enantioselective 1,3-dipolar cycloaddition reactions of α-acyloxyacroleins with nitrones to give the corresponding adducts in good yields (up to 96%) and with high diastereo- and enantioselectivities (up to 89% ee). Although α-(p-methoxybenzoyloxy)acrolein is rather unstable under the reaction conditions, α-(3-pyrroline-1-carbonyloxy)acrolein is stable enough to be smoothly converted into the corresponding adducts with the aid of the chiral organoammonium salt catalysts.

Key words

acyloxyacroleins - 1,3-dipolar cycloaddition - isoxazolidines - nitrones - organocatalysis - asymmetric catalysis

• References and Notes

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pK _a (CD₃CO₂D) of TfOH: –0.74; pK _a (CD₃CO₂D) of C₆F₅SO₃H: 9.2. See:
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• 15 (3S,4R)-2-Benzyl-4-formyl-3-phenylisoxazolidin-4-yl 2,5-Dihydro-1H-pyrrole-1-carboxylate; Typical Procedure To a solution of triamine 1a (3.2 mg, 0.0105 mmol) and TfOH (2.6 μL, 0.0295 mmol) in CHCl₃ (0.15 mL) was added a solution of nitrone 4a (21.5 mg, 0.10 mmol) and acrolein 3 (34.5 mg, 0.206 mmol) in CHCl₃ (0.30 mL) at 0 °C. The resulting solution was stirred at 0 °C for 48 h and then the reaction was quenched with sat. aq NaHCO₃. The mixture was extracted with EtOAc, and the combined organic layers were washed with brine. The organic layer was dried (Na₂SO₄) and filtered. The solvent was removed in vacuo and the crude product was purified by column chromatography (silica gel, hexane–EtOAc) to give a white solid; yield: 21.9 mg (0.0579 mmol, 58% yield). This product was converted into the corresponding alcohol by reduction with NaBH₄ in MeOH at r.t.
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