合成路线1

Ethyl 3-oxocyclohexanecarboxylate (I) was protected as the ethylene ketal (II) and its ethyl ester group was subsequently hydrolyzed to carboxylic acid (III). After activation of acid (III) as the mixed anhydride (IV) with isobutyl chloroformate, coupling with 4-phenyl-1,2,3,6-tetrahydropyridine (V) gave amide (VI). Reduction of amide (VI) to the corresponding amine (VII) was accomplished by treatment with LiAlH4 in the presence of AlCl3. Addition of phenylmagnesium bromide to the ketone (VIII), obtained by acidic hydrolysis of ketal (VII), provided the tertiary alcohol (IX). Dehydration of alcohol (IX) by means of trifluoroacetic acid gave rise to a mixture of isomeric cyclohexene derivatives (X) and (XI), which were separated by column chromatography. The racemic 3-cyclohexenyl isomer (XI) was then resolved via formation of the salts with (R)-1,1'-binaphthyl-2,2'-diyl hydrogen phosphate to furnish the title (R)-(+)-enantiomer.