Asymmetric synthetic processes for the preparation of aminosulfone compounds

摘要

Processes for synthesizing aminosulfone compounds are provided. The processes provided herein utilize asymmetric reduction reactions, e.g., asymmetric hydrogenation, of protected or unprotected enamine or ketone substrates. Aminosulfone compounds obtained using methods provided herein are useful in production or synthesis of sulfone group containing isoindoline based compounds.

主权项

1. A process for preparing an enantiomerically enriched compound of Formula (I): or a salt, solvate, isotopologue, or polymorph thereof, wherein R1 and R2 are each independently hydrogen, halogen, substituted or unsubstituted (C1-C6)alkyl, substituted or unsubstituted (C1-C6)alkoxy, (C3-C18)cycloalkyl, (C3-C6)cycloalkoxy, cyano, —CF3, or (C3-C18)cycloalkyl-(C1-C6)alkoxy, or an isotopologue thereof; and R3 is (C1-C6)alkyl, or an isotopologue thereof; comprising the step of reducing an enamine of Formula (II): or a salt or isotopologue thereof, via hydrogenation in the presence of (1) a metal catalyst and a chiral ligand, or (2) a chiral metal catalyst/ligand complex to form the compound of Formula (I) with an enantiomeric excess of at least 10%.