An Enantioselective Access to 1-Alkyl-1,2-Dihydroisoquinolines and 1-Alkyl-, 3-Alkyl-, and 1,3-Dialkyl-1,2,3,4-tetrahydroisoquinolines

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New chiral isoquinolinium salt derivatives 1, 2 or 3 have been treated with Grignard reagents to give as major products, 1-substituted 1,2-dihydroisoquinolines 4a − f, oxazolidine derivatives 10a − f or 21, respectively, 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-dihydroisoquinoline 4b and the minor oxazolidine 11b . Reduction of all these intermediates gave chiral 1-substituted 1,2,3,4-tetrahydroisoquinolines such as base 8 . The enantioselective synthesis of the natural alkaloid (−)-salsonidine in three steps and 38% overall yield from salt 3 is described as an application. Reduction of salt 2 gave a new oxazolidine derivative 15 which is a practical intermediate for the synthesis of 3-alkyl 1,2,3,4-tetrahydroisoquinolines 17a,b, while oxazolidines such as 10 are convenient precursors of 1,3-disubstituted tetrahydroisoquinolines, as illustrated by a synthesis of 1,3-dimethyl tetrahydroisoquinoline 20 .