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Diasteroselektive Hydroxyalkylierungen in 1‐Stellung von Tetrahydroisochinolinen und Synthese von Aporphin‐, Protoberberin‐ und Phthalid‐Alkaloider
Author(s) -
Seebach Dieter,
Isabelle M. P. Huber,
Max A. Syfrig
Publication year - 1987
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.19870700517
Subject(s) - chemistry , aporphine , saponification , stereochemistry , phthalide , nuclear magnetic resonance spectroscopy , medicinal chemistry , organic chemistry , alkaloid
Diastereoselective Hydroxyalkylations in Position 1 of Tetrahydroisoquinolines and Synthesis of Aporphine, Protoberberine, and Pathalide Alkaloids Unsubstituted and 6,7‐dialkoxy‐ N ‐pivaloyl‐tetrahydroisoquinolines 1 – 3 are converted to 1‐bromomagnesium derivatives by sequential treatment with t ‐BuLi (−75°/THF) and MBr 2 .OEt 2 . Addition of the metalated tetrahydroisoquinolines to aliphatic or aromatic aldehydes occurs with relative topicity ul ( Scheme 2 ). The 1‐hydroxyalkylated 2‐pivaloyl‐tetrahydroisoquinolines a of u ‐configuration thus obtained (14 examples) can be converted to free aminoalcohols c of either l ‐or u ‐configuration ( 9 examples; Scheme 3 ). The depivaloylation with retention (→ u‐c ) is best achieved by heating in EtOH/KOH, the conversion to 1 ‐aminoalcohols l ‐c by treatment with CF 3 COOH/(CF 3 CO) 2 O (→ l ,‐pivalates l ‐b), followed by alkaline saponification or by LiAlH 4 reduction of the esters. The configuration of the products is assigned by 1 H‐NMR spectroscopy, by X‐ray crystal structure analysis, by chemical correlation, and by comparison of the chemical properties of the l ‐ and the u ‐isomers. The diastereoselective hydroxybenzylation of the tetrahydroisoquinoline is used for short syntheses of ushinsunine/oliveroline ( Scheme 4 ), β‐hydrastine, and ophiocarpine/epiopliocarpine ( Scheme 6 ; aporphine, phthalide, and protoberberine alkaloids, respectively).