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Diastereoselective Addition of Chiral (2‐Lithiophenyl)acetaldehyde Acetals to Various Imines as Key Step in the Asymmetric Synthesis of 1‐Aryltetrahydroisoquinolines, Part 4
Author(s) -
Wünsch Bernhard,
Nerdinger Sven
Publication year - 1999
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/(sici)1099-0690(199902)1999:2<503::aid-ejoc503>3.0.co;2-i
Subject(s) - chemistry , diastereomer , acetaldehyde , yield (engineering) , enantioselective synthesis , medicinal chemistry , cerium , ammonium nitrate , organic chemistry , stereochemistry , catalysis , ethanol , materials science , metallurgy
A novel asymmetric synthesis of 1‐aryl‐1,2,3,4‐tetrahydroisoquinolines has been developed. The key step in this synthesis is the diastereoselective addition of homochiral (2‐lithiophenyl)acetaldehyde acetals to the sulfonylimine 25 and to the arylimines 28 and 31 . The best diastereoselectivity is obtained by addition of the bis(2‐methoxypropan‐2‐yl)‐substituted 1,3‐dioxolane 6e to benzylidene‐ p ‐anisidine ( 31 ) with an HPLC‐determined diastereomeric 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 primary 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 to the enantiomerically pure dihydroisoquinolines 40 and 41 , respectively. During the cyclization of the sulfonamides 26d , 27d and the carbamates 37 , 38 the chiral auxiliary – the diol 39 – is cleaved unchanged and can be recovered in good yields.