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Studies for a Variable Synthesis of Colchicinoids: Construction of Ring A on a Heptalene Moiety
Author(s) -
Meyer Markus,
AbouHadeed Khaled,
Hansen HansJürgen
Publication year - 2000
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 - 10.1002/1522-2675(20000906)83:9<2383::aid-hlca2383>3.0.co;2-0
Subject(s) - chemistry , moiety , intramolecular force , adduct , diol , stereochemistry , michael reaction , ring (chemistry) , medicinal chemistry , organic chemistry , catalysis
It is shown that heptalene‐4,5‐dicarboxylates 2 , which react with lithiated methyl sulfones mainly in a Michael fashion at C(3) ( cf. Scheme 2 ), so that the formation of 3‐sulfonylbenzo[ a ]heptalene‐2,4‐diols 5 is repressed or completely suppressed, can be transformed into corresponding pseudo‐esters 15 ( Scheme 4 ). These pseudo‐esters, on treatment with lithiated methyl sulfones, followed by addition of BuLi, furnish the 3‐sulfonylbenzo[ a ]heptalene‐2,4‐diols 5 in excellent‐to‐moderate yields without formation of Michael adducts or their follow‐up products ( cf. Scheme 5 and 6 ). The reaction of the pseudo‐ester 15a with Li[ 13 C]H 2 SO 2 Ph, followed by treatment with non‐labeled LiCH 2 SO 2 Ph and then BuLi, led to the exclusive formation of 3‐(phenylsulfonyl)‐[1‐ 13 C]benzo[ a ]heptalene‐2,4‐diol 5a* ( Scheme 9 ). This experiment demonstrates that the (phenylsulfonyl)acetyl groups at C(4) and C(5) of the heptalene core retain their individual positions in the course of the benzo[ a ]heptalene‐2,4‐diol formation. These findings are only compatible with an intramolecular rearrangement mechanism as depicted in Scheme 10 .