合成路线1

A stereoselective synthesis of sertraline has been described: The silylation of 1,2-dihydronaphthalen-1(R)-ol (I) with tert-butyldiphenylsilyl chloride (TBDPS-Cl) gives the corresponding silyl ether (II), which is brominated with Br2 and triethylamine (TEA) in dichloromethane yielding the 4-bromo-compound (III). The condensation of (III) with 3,4-dichlorophenyltrimethyltin (IV), by means of a palladium catalyst affords the silylated phenylnaphthalenol (V), which is deprotected with TBAF and acetic acid to provide 4-(3,4-dichlorophenyl)-1,2-dihydronaphthalen-1(R)-ol (VI). The regioselective hydrogenation with H2 over chiral iridium or rhodium catalysts gives the (1R-trans)-tetrahydronaphthol (VII), which is treated with diphenylphosphoryl azide (DPPA) and DBU in THF yielding the (1S-cis)-azide (VIII). The reduction of (VIII) with H2 over Pd/C in ethanol affords the corresponding amine (IX), which is treated with ethyl chloroformate to give the expected carbamate (X). Finally, this compound is reduced with LiAlH(OMe)3 in THF. 2,4-Dichlorophenyltrimethyltin (IV) is prepared by reaction of 3,4-dichlorophenol (XI) with triflic anhydride in pyridine/CH2Cl2 to give triflate (XII), which is converted to (IV) by reaction with hexamethylditin and Pd(PPh3)4 in THF. The silylated naphthalenol (V) can also be obtained by condensation of (III) with the phenylboronic acid (XIII) in the presence of a palladium catalyst.