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 alpha,beta-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 a,p-unsaturated ester function played important roles in the asymmetric induction and (4S,5S)-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. ((c) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008).