Enantioselective Synthesis of (S)-2,3,9,10,11-Pentamethoxyhomoprotoberberine, and (S)-O-Methylkreysigine Using an Asymmetric Addition to an Isoquinoline Ring

Total synthesis of (S)-2,3,9,10,11-pentamethoxyhomoprotoberberine (7) was carried out using an asymmetric nucleophilic addition of a silyl enol ether to 5,8-dibromo-6,7-dimethoxyisoquinoline (1) in the presence of an acid chloride derived from alanine.The addition proceeded in high diastereoselectivity to give a 1-substituted 1,2-dihydroisoquinoline (2), which was converted to the target alkaloid in short steps.One of the intermediates was readily transformed to a product (8) which was known as a precursor for synthesis of O-methylkreysigine (9).D-(-)-tartaric acid, was converted to the alkaloid in 4 steps.However, it was reported that the starting material was proved to racemize easily, thus the product obtained from this process showed only moderate stereoselectivity.