Some observations on the enantio- and diastereo-selective synthesis of 1-substituted-1,2,3,4-tetrahydroisoquinolines

Abstract

Several approaches to the synthesis of optically active 1-aryl- 1,2,3,4- tetrahydroisoquinoline alkaloids, cryptostylines (1,3) from dihydroisoquinoline precursors 5,6,11 and 12 have been tried. Reductions of the 1-aryldihydroisoquinoline and the 1- methyl analogue 7 as well as of their methiodides 6 and 9 with yeast are unsuccessful. Reduction of the quaternary salts 6, 11,12 and 9 with sodium tris- acyloxyborohydrides gives the tetrahydroisoquinoline alkaloids 1-3 and 10, respectively, in unsatisfactory enantiomeric excess. (±) Norcryptostyline 4 is resolved with (-) and (+) tartaric acid into (-) S and (+)R enantiomers 14 and 17, respectively, which are converted to their emphorsulphonyl derivatives 15 and 16. Reaction of camphorsulphonyl homoveratryl amine 13 with piperonal affords a mixture of 16 and 15 in the ratio of 4:3, whereas camphorsulphonylation of racemic 4 gives 16 much in excess of 15(4:1).