Chiral Squaramide‐Catalyzed Asymmetric Synthesis of N,O‐Acetals From Pyrazolinone Ketimines

Abstract

Quinine-derived bifunctional squaramide catalyzed the asymmetric addition of different alcohols to pyrazolone-derived Boc-ketimines, providing chiral pyrazolones containing a tetrasubstituted stereocenter bearing a new N,O-acetal motif. The products were isolated in satisfactory yields (up to 91%) and with moderate levels of enantioselectivity (up to 79:21 er) by using 5 mol% of the chiral squaramide catalyst across a broad substrate scope. Importantly, enantioenriched N,O-aminals can be efficiently recovered from the mother liquors by a simple recrystallization. The reaction was extended to other nucleophiles, thiophenol and N-methylaniline, providing the corresponding N,S- and N,N-acetals in moderate to good yield but low enantioselectivity.