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Oxidative Nucleophilic Substitution (S N Ox) of the Benzylic Position as a Tunable Synthesis of Tetrahydroisoquinoline Natural Alkaloid Analogues
Author(s) -
Aubry Sylvain,
PelletRostaing Stéphane,
Lemaire Marc
Publication year - 2007
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/ejoc.200700366
Subject(s) - chemistry , tetrahydroisoquinoline , nucleophilic substitution , alkaloid , ketone , nucleophile , stereoselectivity , derivative (finance) , regioselectivity , stereochemistry , chemical synthesis , substitution reaction , organic chemistry , catalysis , in vitro , biochemistry , financial economics , economics
Abstract Synthetic investigations of 1,3‐dichloro‐5,6‐dicyanobenzoquinone‐mediated benzylic oxidation is reported for the synthesis of natural alkaloid analogues. Extensive explorations of the oxidative nucleophilic substitution of the benzylic position of β‐phenylethylamine derivatives and the synthesis of functionalized tetrahydroisoquinolines of ecteinascidin 743 precursors have been carried out. Starting from L ‐DOPA, a tunable oxazolidinone group was installed under oxidative benzylic conditions. This derivative 13 was submitted to benzylic oxidation reactions using a wide range of carboxylic acids and subsequent chemical transformations of these compounds were attempted. Moreover, an efficient synthesis of an aromatic ketone derivative 20 was achieved and gave rise to tetrahydroisoquinoline 24 through a direct Pictet–Spengler cyclisation reaction. Subsequently, 24 was transformed into functionalized α‐amino alcohols 31a and 31b , precursors of ecteinascidin 743 analogues. In addition, in order to assess the viability of our synthetic strategy, the reaction of 24 with methyl thioglycolate was performed and the stereoselectivity confirmed by X‐ray analysis of 33a . (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)