Formal [4+2] Cycloadditions Promoted by a Chiral Amine Urea Catalyst

Significance

The enantioselective synthesis of spiro[cyclohexane-1,3′-indoline]-2,4′-dione derivatives was accomplished, using urea 1 as a bifunctional catalyst for the formal [4+2] cycloaddition between γ,δ-unsaturated β-keto esters and methyleneindolinones. The authors suggest that the Brønsted acidic moiety of the catalyst activates the indolinone, whereas the Brønsted basic side interacts with the β-keto ester. The preorganized substrates now undergo two subsequent Michael additions to give the desired products in mainly high yields and high enantioselectivities for a variety of differently substituted substrates.