Regioselective Addition of Grignard Reagents to New Lipophilic Isoquinolinium Salts Applied to the Synthesis of Stable Ethyl 1,2-disubstituted 1,2-Dihydroisoquinoline-3-carboxylates and Derivatives

New and stable ethyl 1,2-disubstituted 1,2-dihydroisoquinoline-3-carboxylates 6 and 12 a were synthesized in good yields by regioselective addition reactions of alkyl Grignard reagents to lipophilic and soluble isoquinolinium salts 4 and 11. The salts 4 and 11 were obtained quantitatively and directly from isoquinoline-3-carboxylates 1(a,b) with the corresponding alkyl halides 2 or symmetric alkyl dihalides 7 using solventless quaternization reaction conditions and were converted into the corresponding isoquinolinium perfluorobutanesulfonates 4 and 11 a by ionic metathesis.

1,2-dihydroisoquinoline - Grignard reaction - lipophilic isoquinolinium salt - ionic methathesis - solvent-free quaternization