Direct Catalytic Asymmetric Synthesis of Pyrazolidine Derivatives

Direct Catalytic Asymmetric Synthesis of Pyrazolidine Derivatives

Author: Saskia Neubacher

Pyrazolidines and pyrazolines represent important structural motifs in pharmaceutically active compounds. Armando Córdova, Stockholm University, Sweden, and coworkers efficiently make pyrazolidine derivatives accessible by developing a highly chemo- and enantioselective catalytic cascade transformation between di-1,2-N-protected hydrazine derivatives and α,β-unsaturated aldehydes.

The transformation is catalyzed metal-free by chiral amines and proceeds via a direct aza-Michael/hemiaminal cascade sequence. It delivers functional 3-hydroxypyrazolidine derivatives with 98–99 % ee in one step and is a direct entry to other pyrazolidine derivatives in two steps, such as 5-allylsubstituted pyrazolidines via a subsequent Lewis acid-mediated allylation reaction. Essential for 1,4-selectivity is the use of a di-1,2-N-protected hydrazine derivative, since monoprotected hydrazine as the dinitrogen source predominantly leads to hydrazone formation.



ChemistryOpen
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