Scheme 1.

Synthesis of 1,4-Substituted Isoquinolines^a

^aReagents: (a) 4-methoxybenzenesulfonyl chloride, pyridine, rt, 1 h; (b) Boc2O, N,N-dimethylaminopyridine, MeCN, rt, 2 h; (c) mCPBA, CHCl₃, rt, 24 h; (d) 4-methoxybenzenesulfonamide or 4-fluorobenzenesulfonamide, PPh₃, PhI(OAc)₂, MeCN, 80°C, 1h; (e) CF₃CO₂H, CH₂Cl₂, 0 °C - rt, 2 h; (f) BrCH₂CO₂Et, K₂CO₃, Me₂NCHO, rt, 48 h; (g) 15% NaOH, MeOH, rt, 4 h. (h) alkyl-X or alkyl-OTf, K₂CO₃, Me₂NCHO or MeCN, rt, 18 – 48h