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Guanidine‐Catalyzed Asymmetric Synthesis of 2,2‐Disubstituted Chromane Skeletons by Intramolecular Oxa‐Michael Addition
Author(s) -
Saito Noriko,
Ryoda Akemi,
Nakanishi Waka,
Kumamoto Takuya,
Ishikawa Tsutomu
Publication year - 2008
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.200800089
Subject(s) - chemistry , moiety , intramolecular force , guanidine , enantioselective synthesis , stereochemistry , michael reaction , enantiomer , catalysis , alkyl , aryl , asymmetric carbon , asymmetric induction , hydroxymethyl , medicinal chemistry , organic chemistry
The guanidine‐catalyzed 6‐ exo ‐ trig ‐type intramolecular asymmetric oxa‐Michael addition of α,β‐unsaturated esters with a 2‐hydroxyaryl moiety at the C‐5 carbon has been examined for the construction of chromane skeletons with a quaternary carbon chiral center. The bulkiness of the alkyl group and the E / Z geometry of the α,β‐unsaturated ester function played important roles in the asymmetric induction and (4 S ,5 S )‐2‐[( R )‐1‐hydroxymethyl‐2‐phenylethylimino]‐1,3‐dimethylimidazolidine (or its enantiomer) carrying aryl pendants at the 4‐ and 5‐positions was found to be the most effective catalyst among 18 chiral guanidines examined. In this way, the Z isomer of the less bulky methyl ester was subjected to the cyclization reaction, affording chiral chromane in up to 83 % yield with 76 % ee . (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)