EXPLOITATION OF DIFFERENTIAL REACTIVITY OF THE CARBON-CHLORINE BONDS IN 1,3-DICHLOROISOQUINOLINE - ROUTES TO NEW N,N-CHELATE LIGANDS AND 1,3-DISUBSTITUTED ISOQUINOLINES

Under Pd(PPh(3))(4) catalysis, coupling of arylboronic acids to the 1- position of 1,3-dichloroisoquinoline takes place, leading exclusively to 1-aryl-3-chloroisoquinolines. This regiochemistry is demonstrated b y the crystal structure of 3-chloro-1-(8-methoxy-1-naphthyl)isoquinoli ne. The 3-chloro group; may be modified by nickel-catalysed reaction w ith Grignard reagents or direct nucleophilic displacement with LiSCH(2 )Ph. Attempted lithiation of the 3-position is not successful (either deprotonation or complex reactivity results). Under zinc reduction in the presence of NiCl2-PPh(3) and NaI, the 1-aryl-3-chloroisoquinolines furnish 3,3'-biisoquinolines in good yield.