Asymmetric Synthesis of Amino-Bis-Pyrazolone Derivatives via an Organocatalytic Mannich Reaction

A new
series of N-Boc ketimines derived from pyrazolin-5-ones
have been used as electrophiles in asymmetric Mannich reactions with
pyrazolones. The amino-bis-pyrazolone products are obtained in excellent
yields and stereoselectivities by employing a very low loading of
1 mol % of a bifunctional squaramide organocatalyst. Depending on
the substitution at position 4 of the pyrazolones, the new protocol
allows for the generation of one or two tetrasubstituted stereocenters,
including a one-pot version combing the Mannich reaction with a base-mediated
halogenation.