Asymmetric Vinylogous Aldol Reaction via H‑Bond-Directing Dienamine Catalysis

The enantioselective direct vinylogous aldol reaction of 3-methyl 2-cyclohexen-1-one with α-keto esters has been developed. The key to success was the design of a bifunctional primary amine-thiourea catalyst that can combine H-bond-directing activation and dienamine catalysis. The simultaneous dual activation of the two reacting partners results in high reactivity while securing high levels of stereocontrol

Asymmetric Vinylogous Aldol Reaction via H‑Bond-Directing Dienamine Catalysis

The enantioselective direct vinylogous aldol reaction of 3-methyl 2-cyclohexen-1-one with α-keto esters has been developed. The key to success was the design of a bifunctional primary amine-thiourea catalyst that can combine H-bond-directing activation and dienamine catalysis. The simultaneous dual activation of the two reacting partners results in high reactivity while securing high levels of stereocontrol

Relative Tendency of Carbonyl Compounds To Form Enamines

Equilibria between carbonyl compounds and their enamines (from <i>O</i>-TBDPS-derived prolinol) have been examined by NMR spectroscopy in DMSO-<i>d</i>₆. By comparing the exchange reactions between pairs (enamine A + carbonyl B → carbonyl A + enamine B), a quite general scale of the tendency of carbonyl groups to form enamines has been established. Aldehydes quickly give enamines that are relatively more stable than those of ketones, but there are exceptions to this expected rule; for example, 1,3-dihydroxyacetone acetals or 3,5-dioxacyclohexanones (2-phenyl-1,3-dioxan-5-one and 2,2-dimethyl-1,3-dioxan-5-one) show a greater tendency to afford enamines than many α-substituted aldehydes