Chiral Dihydropyrazoles via Mg(II)-Catalyzed Nitrile Imine Cycloaddition

Significance

In the presence of a MgI₂/(R,S)-CP-Indabox catalyst and a base, pyrazolidinonyl acrylates undergo 1,3-dipolar cycloaddition with hydrazonoyl halides (which are converted in situ into nitrile imines in the presence of Et₃N for X = Br, or P₁-t-Bu with X = Cl) to afford chiral dihydropyrazoles with a chiral quaternary stereocenter in good to excellent yield, and with generally excellent enantioselectivity. Substitutents are tolerated at both the α and β positions of the acrylate, with no detrimental effect towards enantioselectivity. Aromatic substitutents worked best on the hydrazonyl halide, as significant reduction of yields and enantioselectivity were observed when aliphatic substituents were present.