Asymmetric synthesis of isoquinoline derivatives from amino acids

Reaction of isoquinolines 1 with N-arylsulfonylamino acid fluorides 2 provides a highly stereoselective access to new dihydroimidazo [2, 1-a]isoquinolin-3-ones 5 via intermediate N-acylisoquinolinium salts 3. Addition reactions to the enamine double bond, such as hydrogenation or epoxidation with dimethyldioxirane, leads to tetrahydroimidazo[2,1-a]isoquinoline-3-ones 6, 7 and oxiranes 8, respectively. Opening of the oxirane ring of the 8 with nucleophiles allows the synthesis of hydroxytetrahydroimidazo [2,1-a]isoquinolin-3-ones 10 or 12 or of the polycyclic 1,4-dioxane 13 in high stereoselectivity. The regioselectivity of the oxiran ring opening depends on the kind of nucleophile and the conditions. Reaction of dihydroisoquinoline with O-TBDMS-mandelic acid chloride 15 leads to a tetrahydrooxazolo[2,3-a]isoquinoline 17 with opposite facial selectivity as compared with dihydroimidazo [2,1-a]isoquinolin-3-ones 5. (C) Wiley-VCH Verlag GmbH Co.