Enantioselective process

A process for hydrogenation of oximes of formula (I) in the presence of an iridium catalyst and an acid to produce a hydroxylamine of formula (II):

• wherein the position labelled with the asterisk is an asymmetric center and one stereoisomer of hydroxylamine of formula (II) is produced in excess;
• R1 and R2 are each independently C1-C8alkyl, C1-C8hydroxyalkyl, C1-C8cyanoalkyl, C1-C6alkoxyC1-C8alkyl, C1-C8haloalkyl, C2-C6alkenyl, C3-C8cycloalkyl, phenyl, phenylC1-C3alkyl, phenylsulfonylC1-C3alkyl, C1-C6alkoxycarbonyl, a bridged carbocyclyl, heterocyclyl or heteroaryl, wherein the cycloalkyl, phenyl, heterocyclyl and heteroaryl moieties are each optionally substituted with 1 to 5 groups selected from hydroxyl, halogen, C1-C6alkyl, C3-C8cycloalkyl, C1-C6haloalkyl, C1-C6alkoxy, phenyl, heteroaryl, C1-C6alkoxycarbonyl, acylamino, amido, cyano, nitro, azido, and C2-C6alkenyl;
• or a single group selected from pinacolborane, phenylsulfonyl, phenylC1-C3alkyl, or phenylC1-C3alkoxy;
• R3 is hydrogen, C1-C8alkyl, C1-C8hydroxyalkyl, C1-C8cyanoalkyl, C1-C6alkoxyC1-C8alkyl, C1-C8haloalkyl, C2-C6alkenyl, C3-C8cycloalkyl, phenylC1-C3alkyl, heterocyclylC1-C3alkyl or heterobicyclylC1-C3alkyl, wherein the cycloalkyl and heterocyclyl moieties are each optionally substituted with 1 to 5 groups selected from hydroxyl, halogen, C1-C6alkyl, C3-C8cycloalkyl, C1-C6haloalkyl, C1-C6alkoxy, phenyl, heteroaryl, C1-C6alkoxycarbonyl, acylamino, amido, cyano, azido, nitro and C2-C6alkenyl;
• and wherein R1 and R2 cannot be the same;
• or
• R1 and R2 together with the carbon atom to which they are attached may form a 4- to 9-membered saturated or partially saturated asymmetric cycloalkyl or asymmetric heterocyclyl ring, wherein the heterocyclic moiety is a non-aromatic monocyclic ring which comprises 1, 2 or 3 heteroatoms, wherein the heteroatoms are individually selected from N, O and S;
• or
• R1 and R3 together with the carbon and oxygen atoms to which they are respectively attached, may form a 5- to 8-membered non-aromatic heterocyclyl ring, or an 8- to 10-membered partially saturated heterobicyclyl;
• wherein the iridium catalysts of formula (IIIa) and (IIIb) are:
• Wherein
• represents an optionally substituted cyclopentadienyl ligand;
• represents a bidentate chelating ligand comprising at least one carbon atom which coordinates to iridium and at least one nitrogen atom which coordinates to iridium;
• X represents an anionic group;
• Y represents a neutral ligand;
• and
• Z represents an anionic group.