Processes for the preparation of isoindole compounds and isotopologues thereof

A process for the preparation of an enantiomerically enriched or enantiomerically pure aminosulfone compound of Formula (III):

• or a salt stereoisomer, or isotopologue 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, (C3-C18)cycloalkyl-(C1-C6)alkoxy, or an isotopologue thereof;
• R3 is (C1-C6)alkyl, or an isotopologue thereof;
• Y1 is hydrogen or deuterium;
• and
• Y2 and Y3 are both hydrogen or both deuterium;
• wherein not all of Y1, Y2, and Y3 are hydrogen;
• comprising the step of
• (a) reducing an enamine of Formula (II):
• or a salt or isotopologue thereof, via hydrogenation with hydrogen gas or deuterium gas, in a solvent, and in the presence of (1) a metal catalyst and a chiral ligand or (2) a chiral metal catalyst/ligand complex to form an enantiomerically enriched or enantiomerically pure aminosulfone of Formula (III), or a salt or isotopologue thereof, wherein deuterium gas or a solvent containing exchangeable deuterium for proton-deuterium exchange or both is used.