A Novel Synthesis of Substituted 1-Benzyloctahydroisoquinolines by Acid-Catalyzed Cyclization ofN-[2-(Cyclohex-1-enyl)ethyl]-N-styrylformamides

Abstract

The acid-catalyzed cyclization of N-[2-(cyclohex-1-enyl)ethyl]-N-styrylformamides 1–5 gave access to 1-benzyl-2-formyloctahydroisoquinolines 6–10. The reactions were performed in the presence of the Lewis acid 9-borabicyclo[3.3.1]non-9-yl triflate. The cyclization of enamide 1 was also studied with Brønsted acid catalysts, such as triflic acid and the heterogeneous catalyst tungstophosphoric acid supported on silica gel. In all cases the 1,2,3,4,5,6,7,8-octahydroisoquinoline formed was accompanied by minor concentrations of one, two, or three isomeric octahydroisoquinolines. 1-Benzyl-2-formyloctahydroisoquinoline (6) could also be prepared from N-[2-(cyclohex-1-enyl)ethyl]formamide (11) by reaction with phenylacetaldehyde in a mixture of acetic acid and trifluoroacetic acid. The octahydroisoquinolines 6, 8, 10 as model compounds, were converted into the corresponding N-formylmorphinans.