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Asymmetric Synthesis of Rubiginones A 2 and C 2 and Their 11‐Methoxy Regioisomers
Author(s) -
Carreño M. Carmen,
Somoza Álvaro,
Ribagorda María,
Urbano Antonio
Publication year - 2007
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200600809
Subject(s) - sulfoxide , aromatization , chemistry , sulfone , enantioselective synthesis , structural isomer , stereoselectivity , cycloaddition , stereochemistry , ring (chemistry) , medicinal chemistry , domino , cascade reaction , organic chemistry , catalysis
Abstract Convergent enantioselective syntheses of angucyclinone‐type natural products rubiginones A 2 ( 2 ) and C 2 ( 1 ) and their 11‐methoxy regioisomers 3 a and 3 b have been achieved by using two domino processes from a common enantiomerically pure 1‐vinylcyclohexene 4 . Key steps in the synthesis of this diene were the stereoselective conjugate addition of AlMe 3 on (S S )‐[( p ‐tolylsulfinyl)methyl]‐ p ‐quinol ( 9 ) and the elimination of the β‐hydroxy sulfoxide fragment, after oxidation to sulfone, to recover a carbonyl group. The first domino sequence comprised Diels–Alder reaction with a sulfinyl naphthoquinone followed by sulfoxide elimination. An efficient opposite regioselection in the cycloaddition step was achieved in the convergent construction of the tetracyclic skeleton using a sulfoxide at C‐2 or C‐3 of the dienophiles 5 or 6 , derived from 5‐methoxy‐1,4‐naphthoquinone. The second domino process, triggered by oxygen and sunlight, allowed the transformation of the initial tetracyclic adducts into the final products after B ring aromatization, silyl deprotection and C‐1 oxidation.