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Abstract
A new route for the synthesis of enantioenriched 5-oxo-trans -octahydroisoquinolines is reported. Key steps are a Suzuki coupling reaction and a pinacol-terminated N-acyliminium ion cyclization.
A mild Suzuki coupling procedure allowed benzyl vinylcarbamate to react with 9-BBN and the organoborate product to be coupled with various aryl iodides, aryl bromides and an alkenyl triflate in the presence of a palladium catalyst to yield the corresponding aminoethylated products. Using this procedure, synthesis of enantioenriched homoallylic carbamates for the key cyclization was accomplished starting from commercially available cyclohexenones in 4 steps in good overall yields.
These homoallylic carbamates were transformed into α-hydroxycarbamates and α-ethoxycarbamates, which underwent an N-acyliminium ion cyclization upon treatment with mesyl chloride or BF3.OEt 2. Enantioenriched 5-oxo-trans-octahydroisoquinolines bearing various functional groups at the C-1 position were synthesized in 7 linear steps from cyclohexenones. This is shorter than the previously reported sequence for preparing these 5-oxohydroisoquinolines from cyclohexenone. This methodology is expected to be applicable toward the synthesis of complex organic molecules of biological interest bearing an isoquinoline ring system.
