Synthesis of 4H-Chromenes by an Enantio-selective Oxa-Michael-Aldol Reaction

Significance

Based on a previous result (X. Zhang, S. Zhang, W. Wang Angew. Chem. Int. Ed. 2010, 49, 1481), an enantioselective oxa-Michael-aldol cascade between (2-hydroxy-­phenyl)-2-oxoacetates 2 and ynals 1, involving an unprecedented iminium-allenamine activation mode to form chiral 4H-chromenes 3 is reported. After screening of different diarylprolinol silyl ether analogues I-III, the scope of the oxa-Michael-­aldol cascade was established. The process exhibits a broad substrate tolerance in 1 (aliphatic and aromatic ynals bearing EDGs and EWGs), and generates a quaternary stereogenic center with high enantioselectivity in all cases. Moreover, various phenols 2 bearing EDGs and EWGs on the ­aromatic part are tolerated. However, a poor enantioinduction was observed for 2, R^² = Cl. The (R) absolute configuration of 3 was established by
X-ray crystal structure analysis.