Stereoselective Synthesis of Enantiopure Pyrrolo[3,4-c]pyrazoles

Significance

Nitrilimines bearing stereocenters in tethers derived from inexpensive, commercially available l-alanine, l-phenylalanine and (S)-2-phenylglycine methyl esters undergo intramolecular [2+3] cycloaddition to give a series of chiral 2,3,3a,4,5,6-hexahydro-pyrrolo[3,4-c]pyrazoles in moderate to high chemical yields and with high to complete diastereoselectivity. The observed high stereoselectivity has been rationalized on the basis of the two transition states shown in which the lower is predicted to be less favored. The absolute configuration of the products was determined by ¹H NMR spectroscopy and supported by AM1 semi-empirical calculations.