Novel Three-Component Reaction Yielding Seven-Membered Rings

Significance

A novel three-component reaction between aldehydes, diamines, and β-keto esters has been developed. Differing from the expected reactivity of the β-keto ester, the reaction takes place at the γ-position and not the α-position. This is particularly noteworthy for those cases in which the α-position is unsubstituted (R³ = H). An explanation of this behavior is the possible equilibrium shift from the enamine to the enol/enamine form of the reaction intermediate, facilitated by an intra­molecular hydrogen bond. The reaction proceeds under cata­lysis of a variety of acids, giving the seven-membered-ring products in moderate to good yields. The authors report only single diastereo­mers to be found when the γ-position of the β-keto ester bears a substituent.