Guanidine‐Catalyzed Asymmetric Synthesis of 2,2‐Disubstituted Chromane Skeletons by Intramolecular Oxa‐Michael Addition

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)