Asymmetric synthesis of 4-hydroxy-3-phenyltetrahydroisoquinolin derivatives using enantiopure sulfinimines (N-sulfinyl imines)

Addition of lateral lithiated amides and phthalide anions to enantiopure su lfinimines (N-sulfinyl imines) represents a new approach for the asymmetric synthesis of 3-substituted isoquinolones and 3-substituted 4-hydroxy isoqu inolones, respectively, important chiral building blocks for isoquinoline a lkaloid synthesis. In one example 3-phenylisoquinolone (-)-15b was prepared in >95% ee by treatment of amide ion 10b with sulfinimine (S)-(+)-11 and s ubsequent deprotection of the N-sulfinyl auxiliary and cyclization. Oxaziri dine-mediated hydroxylation of the anion of 16 afforded 4-hydroxy isoquinol one 19, which was transformed into 4-hydroxy-3-phenyltetrahydroisoquinoline (-)-22. In another approach 22 was prepared more directly by addition of p hthalide ion 26 to (S)(+)-11, creating the two stereogenic centers simultan eously. The selectivity proved to be highly counterion dependent.