Conjugate Addition of Carbon Acids to β,γ-Unsaturated α-Keto Esters: Product Tautomerism and Applications for Asymmetric Synthesis of Benzo[a]phenazin-5-ol Derivatives

A correlation between the equilibrium ratio of tautomeric products generated by the asymmetric Michael reactions of cyclic carbon acids with beta,gamma-unsaturated alpha-keto esters and the chemical shift of the alpha-proton in starting nucleophilic substrates was revealed which makes equilibration predictable. New tetrahydropyran-fused benzo[a]phenazins were enantioselectively (up to 99% ee) synthesized from beta,gamma-unsaturated alpha-keto esters and benzo[a]phenazin-5-ol, a powerful anti-cancer agent sAJM589. Facile recyclability of catalyst Ia in the catalytic reactions was demonstrated.