Palladium-Catalyzed Synthesis of Tetrahydroisoquinolines

Significance

Kuwano and co-workers report the palladium-catalyzed [4+2] cycloaddition of o-[(trimethylsilyl)methyl]benzyl carbonates 1 (as formal xylylene precursors) with N-tosyl imines 2 to give tetrahydroisoquinolines 3. A marked improvement in the reaction rate was observed, albeit with decreased yields, on addition of KF to activate the C-Si bond. Both EDGs and EWGs were tolerated on the imine fragment, although no reaction was observed for electron-deficient substrates in the absence of KF. Carbonates 4 bearing substituents on the aromatic ring participated efficiently in the reaction to give the regioisomeric products 5 and 6. Increased regioselectivity was observed with a larger group (R^² = Ph) over a smaller one (R^² = Me).