Tosylhydrazide-promoted diastereoselective Intramolecular 1,3-dipolar cycloadditions: Synthesis of tetrahydropyrrolo[3,4-c]pyrazoles

Abstract

A very straightforward diastereoselective synthesis of tetrahydropyrrolo[3,4-c]pyrazoles by intramolecular 1,3-dipolar cycloaddition is described. The starting materials for the synthetic route are N-Boc-protected α-amino acids, which are first transformed into N-allyl-α-amino ketones through conventional methodologies. Then, a one-pot sequence that involves formation of a tosylhydrazone from the ketone, base induced decomposition of the hydrazone, and intramolecular 1,3-dipolar cycloaddition of the diazo compound generated, gives rise to the bicyclic systems with total diastereoselectivity and high preservation of the enantiomeric purity. However, the analogous process employing α-amino aldehydes lacks stereoselectivity. DFT computational modeling has been carried out to account for the different behavior of the two types of systems.