Enantioselective Synthesis of Quaternary Δ4- and Δ5-Dehydroprolines Based on a Two-Step Formal [3+2] Cycloaddition of α-Aryl and α-Alkyl Isocyano(thio)acetates with Vinyl Ketones

A divergent synthesis of optically active quaternary Delta(4)- and Delta(5)-dehydro prolines is developed based on the first catalytic enantioselective conjugate addition of alpha-substituted isocyano( thio) acetates to vinyl ketones that is general for both alpha-aryl and alpha-alkyl isocyano( thio) acetates. The new tetrasubstituted C-N stereocenter is formed without the need of any metal salt due to a bifunctional tertiary amine/squaramide catalyst, featuring a bulky poly-aryl sidearm and an unusually short squaramide diamide H center dot center dot center dot H interatomic distance in the solid state.