(+)-6-hydroxy-morphinan or (+)-6-amino-morphinan derivatives

A process for preparing a (+)-morphinan compound of Formula (IV), the process comprising:

• (a) contacting a compound of Formula (III) with a secondary amine of formula NHR8R9 and an acid catalyst to form an intermediate enamine compound;
• and
• (b) contacting the intermediate enamine compound with an alkali metal cyanoborohydride to form the compound of Formula (IV) according to the following reaction scheme:
• wherein:
• R1 is chosen from hydrocarbyl and substituted hydrocarbyl;
• R3 and R4 are independently chosen from hydrogen, hydrocarbyl, and substituted hydrocarbyl;
• R5 and R6 are independently chosen from hydrogen, hydrocarbyl, substituted hydrocarbyl, halogen, {—}OH, {—}NH2, and {—}OR7;
• R7 is chosen from hydrocarbyl and substituted hydrocarbyl;
• R8 and R9 are independently chosen from acyl, acyloxy, alkyl, cycloalkyl, alkoxy, hydroxy alkyl, alkenyl, aryl, aryloxy, substituted alkyl, substituted cycloalkyl, substituted alkenyl, substituted aryl, and together R8 and R9 form a ring or ring system chosen from carbocyclic, substituted carbocylic, heterocyclic, substituted heterocylic, and a combination thereof;
• provided that when one of R8 or R9 is benzyl, then the other of R8 or R9 is other than C1-C6 alkyl or C6-C12 aryl;
• Y is chosen from hydrogen, hydroxy, protected hydroxy, alkoxy, and acyloxy;
• and
• Z is chosen from hydroxy, protected hydroxy, alkoxy, and acyloxy.