Chiral Squaramide‐Catalyzed Asymmetric Synthesis of <i>N,</i> 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.