Enantioselective 1,3-dipolar cycloaddition of nitrile imines to α-substituted and α,β-disubstituted α,β-unsaturated carbonyl substrates:: A method for synthesizing dihydropyrazoles bearing a chiral quaternary center

Dihydropyrazoles bearing a chiral quaternary center at the 5-position have been prepared by enantioselective 1,3-dipolar cycloaddition of nitrile imines to alpha-substituted- and alpha,beta-disubstituted-alpha,beta-unsaturated carbonyl substrates. Use of alpha,beta-unsaturated carbonyl substrates with a 1-benzyl-5,5-dimethylpyrazolidin-3-one auxiliary in conjunction with MgI2, and a bisoxazoline ligand derived from (1R,2S)-(+)-cis-1-amino-2-indanol 6 proved optimal to obtain chiral dihydropyrazoles with high enantio-selectivity (up to 99% ee).