Diastereoselective addition of chiral (2-lithiophenyl)acetaldehyde acetalsto various imines as key step in the asymmetric synthesis of 1-aryltetrahydroisoquinolines, Part 4

A novel asymmetric synthesis of 1-aryl-1,2,3,4-tetrahydroisoquinolines has been developed. The key step in this synthesis is the diastereoselective ad dition of homochiral (2-lithiophenyl)acetaldehyde acetals to the sulfonylim ine 25 and to the arylimines 28 and 31. The best diastereoselectivity is ob tained by addition of the bis(2-methoxypropan-2-yl)-substituted 1,3-dioxola ne 6e to benzylidene-p-anisidine (31) with an HPLC-determined diastereomeri c ratio 32c/33c = 92.1:7.9. The N-tosyl and the N-(4-methoxyphenyl) groups of the addition products 26d, 27d, 32c, and 33c are cleaved with sodium in Liquid ammonia and ammonium cerium(IV) nitrate, respectively to yield the p rimary amines 35 and 36. The acid-catalysed cyclization of the sulfonamides 26d and 27d and the carbamates 37 and 38, prepared from 35 and 36, leads t o the enantiomerically pure dihydroisoquinolines 40 and 41, respectively. D uring the cyclization of the sulfonamides 26d, 27d and the carbamates 37, 3 8 the chiral auxiliary - the diol 39 - is cleaved unchanged and can be reco vered in good yields.