Methods of asymmetrically synthesizing enantiomers of casodex, its derivatives and intermediates thereof

A method of asymmetrically synthesizing an enantiomer of an acylanilide or a derivative thereof comprising:

• (a) contacting a compound having a ring structure, said compound having the structure of Formula IV:
• wherein
• R1 is alkyl having up to 4 carbons;
• R2′ is alkylene having up to 6 carbon atoms;
• R9 is hydrogen, or straight, branched or cyclic alkyl;
• R10 is straight or branched alkyl, aryl, or R11X34, where R11 is alkyl and X4 is alkyl, halogen or aryl;
• and
• X3 is a leaving group;
• wherein said compound of Formula IV, when opened, provides a substituent having the structure of Formula I:
• wherein
• R1 is alkyl having up to 4 carbons;
• R2 is alkyl having up to 6 carbon atoms;
• and
• R3 is CH2OR4 where R4 is hydrogen or benzyl, C(O)CH3, or C(O)OR5 where R5 is hydrogen or alkyl;
• with a compound having a structure of Formula II:
• R7—R6—X1H Formula II
• wherein
• R6 is a direct link or alkylene having up to 6 carbon atoms;
• R7 is alkyl, alkenyl, hydroxyalkyl or cycloalkyl each of up to 6 carbons;
• or R7 is phenyl which bears one, two or three substituents independently selected from hydrogen, halogen, nitro, carboxy, carbamoyl and cyano, and alkyl, alkoxy, alkanoyl, alkylthio, alkylsulphinyl, alkylsulphonyl, perfluoroalkyl, perfluoroalkylthio, perfluoroalkylsulphinyl, perfluoroalkylsulphonyl, alkoxycarbonyl and N-alkylcarbamoyl each of up to 4 carbon atoms, and phenyl, phenylthio, phenylsulphinyl and phenylsulphonyl;
• or R7 is naphthyl;
• or R7 is a 5- or 6-membered saturated or unsaturated heterocyclic which contains one, two or three heteroatoms selected from oxygen, nitrogen and sulfur, which heterocyclic may be a single ring or may be fused to a benzo-ring, and which heterocyclic is unsubstituted or bears one or two halogen, cyano or amino, or alkyl, alkoxy, alkylthio, alkylsulphinyl or alkylsulphonyl each of up to 4 carbon atoms, or oxy or hydroxy substituents, or which if sufficiently saturated may bear one or two oxo substituents;
• and
• X1 is oxygen, sulfur, sulphinyl (—SO—), sulphonyl (—SO2—), imino (—NH—) or alkylimino (—NR8—) where R8 is alkyl having up to 6 carbon atoms;
• under conditions sufficient to provide a compound having the structure of Formula III:
• wherein X2is oxygen, sulfur, sulphinyl (—SO—), sulphonyl (—SO2—), imino (—NH—), oxidized imino alkylimino (—NR8—) where R8 is alkyl having up to 6 carbon atoms, or oxidized alkylimino;
• and
• (b) treating the compound of Formula III under conditions sufficient to provide a pure enantiomer of an acylanilide or a derivative thereof.