Synthesis of Isoindoles and Isoquinolines via 1,3-Dipolar Cycloaddition and Electrocyclization

Key words

isoindoles - isoquinolines - azides - 1,3-dipolar cycloaddition - electrocyclization

Significance

Reported is a two-step sequence for the synthesis of isoindoles from α-azido carbonyl compounds containing a 2-alkenylaryl unit via 1,3-dipolar cycloaddition of azide onto the tethered alkene. It was also realized that the synthesis of dihydroisoquinolines can be achieved from the same starting mesylate by reacting it with NaN₃, then with base (K₂CO₃) in EtOH (as proton source) followed by 6π-electrocyclization under dilution in toluene. Some of the dihydroisoquinolines gave the corresponding isoquinoline derivatives under aerial oxidation.

Comment

Due to their high fluorescent and electroluminescent properties, isoindoles and their ­derivatives are important for light-emitting devices (B.-X. Mi et al. Chem. Mater. 2003, 15, 3148). They also serve as highly reactive dienophiles for cycloaddition reactions (S. Duan, D. K. Sinha-­Mahapatra, J. W. Herndon Org. Lett. 2008, 10, 1541). The substitution pattern is very well studied, but the starting material (mesylate) was prepared through a four-step sequence which could be a drawback of this method.