AN ENANTIOSELECTIVE ACCESS TO 1-ALKYL-1,2-DIHYDROISOQUINOLINES AND 1-ALKYL-1,2,3,4-TETRAHYDROISOQUINOLINES, 3-ALKYL-1,2,3,4-TETRAHYDROISOQUINOLINES, AND 1,3-DIALKYL-1,2,3,4-TETRAHYDROISOQUINOLINES

New chiral isoquinolinium salt derivatives 1, 2 or 3 have been treated with Grignard reagents to give as major products, 1-substituted 1,2-d ihydroisoquinolines 4a-f, oxazolidine derivatives 10a-f or 21, respect ively, in good yield and in moderate to good diastereoisomeric excess. The stereochemistry of these new derivatives has been elucidated, in particular, by X-ray crystallographic studies of 1,2-dihydroisoquinoli ne 4b and the minor oxazolidine 11b. Reduction of all these intermedia tes gave chiral 1-substituted 1,2,3,4-tetrahydroisoquinolines such as base 8. The enantioselective synthesis of the natural alkaloid (-)-sal sonidine in three steps and 38% overall yield from salt 3 is described as an application. Reduction of salt 2 gave a new oxazolidine derivat ive 15 which is a practical intermediate for the synthesis of 3-alkyl 1,2,3,4-tetrahydroisquinolines 17a,b, while oxazolidines such as 10 ar e convenient precursors of 1,3-disubstituted tetrahydroisoquinolines, as illustrated by a synthesis of 1,3-dimethyl tetrahydroisoquinoline 2 0.