Pot-Economic Organocatalytic Asymmetric Synthesis of the Corey Lactone

Key words

Corey lactone - amine catalysis - Michael addition - cascade reaction - asymmetric synthesis

Significance

Hayashi and co-workers report an organocatalytic domino Michael/Michael reaction of α,β-unsaturated aldehydes and ethyl (E)-4-oxopent-2-enoate that uses a diphenylprolinol silyl ether as catalyst. The desired cyclopentanones were obtained in good to excellent yields and with excellent diastereo- and enantioselectivities. The newly developed formal (3+2) cycloaddition was applied as the key step in a concise and highly stereoselective route towards the Corey lactone.

Comment

Due to its importance as a crucial intermediate for the synthesis of various prostaglandin hormones, efficient, selective, and practical routes toward the Corey lactone are desirable. The authors have developed a time-efficient organocatalytic protocol consisting of seven steps in a single reaction vessel that furnishes enantiopure Corey lactone. The required silyl acrylaldehyde is accessible through an atom-economic trimerization of ethyne, carbon monoxide, and dimethyl(phenyl)­silane (I. Matsuda, A. Ogiso, S. Sato, Y. Izumi J. Am. Chem. Soc. 1989, 111, 2332).