thrinan, homoerythrinan, isopavine and pavine alkaloids using an aromatic cyclization of the sulfonium ion in situ

tetrahydroisoquinolines, 1,2,3,4-tetrahydroquinolines, 2,3,4,5-tetrahydro-1H-3-benzazepines, 2-quinolones, erythrinan, homoerythrinan, isopavine and pavine alkaloids using an aromatic cyclization of the sulfonium ion in situ formed from a sulfinyl precursor (Pummerer reaction). The aromatic cyclization in the reaction using trifluoroacetic anhydride (TFAA) smoothly proceeded at room temperature when the reactive center of the cyclizing benzene ring was activated by an electron-donating group. Furthermore, we found that the Pummerer substrate, which lacks an electrondonating group on the cyclizing benzene ring, requires boron trifluoride diethyl etherate (BF3·Et2O) as an additive reagent to induce the aromatic cyclization. Thus, the investigations demonstrated that the Pummerer-type cyclization reaction is highly effective and widely applicable for the construction of sixand seven-membered nitrogen heterocycles. In order to expand the utility of this methodology, we designed a synthesis of 1,2,3,4-tetrahydroisoquinoline and 1,2,4,5-tetrahydro-3H-3-benzazepine derivatives bearing a phenyl group on the nitrogen-containing ring. The compounds are expected to have some biological activities. For example, 3-substituted 1,2,3,4-tetrahydroisoquinolines are known to possess phencyclidine-like effects. Although the synthesis of 2-substituted 3-benzazepine derivatives was achieved by multi-steps using a ring expansion reaction of 1-substituted 1,2,3,4-tetrahydroisoquinoline derivatives as a key step, a simple and short-step method has not been developed. The route via the Pummerer-type cyclization reaction shown in Chart 1 should provide a convenient method for preparing nitrogen heterocycles bearing a phenyl group because all the starting materials are readily available.