Chiral oxacyclic structures such as tetrahydrofuran rings are commonly found in many bioactive compounds. Cinchona-alkaloid-thiourea L4 catalyzes the cycloetherification of ε-hydroxy-α,β-unsaturated ketones with excellent enantioselectivity, even with low catalyst loadings at room temperature. The probable activation intermediate might go through TS-1.

Scheme 6. Cycloetherification via intramolecular oxy-Michael addition reaction

The catalyst L4 can also catalyze the domino aza-Michael–Michael reactions of anilines with nitroolefin enoates to afford chiral 4-aminobenzopyrans bearing two consecutive stereogenic centers and one quaternary stereocenter (Scheme 7). The products can be isolated with high yield and enantioselectivity.

Scheme 7. Domino aza-Michael–Michael Reactions

Chiral amine L5 has been used to activate α,β -unsaturated enones with nitro alkenes toward a well-defined enamine-iminium activation mode in presence of 2-fluorobenzoic acid as an additive. The reaction affords the Diels–Alder adduct bearing three or four stereogenic centers with high enantioselectivity (Scheme 8). The extension of this process to other Michael acceptors such as N -benzyl maleimide leads to the formation of cyclohexanones with up to >99% ee.

Scheme 8. Asymmetric Domino Michael–Michael Reactions