Organocatalysis was shown to facilitate conjugate additions to vinylogous esters and amides for the first time. Subsequent elimination of a β-alcohol or amine provided π-conjugated β-substituted enones. Remarkably, nucleophile addition to the electron-rich vinylogous substrates is more rapid than classical enones, forming monosubstituted products. A doubly organocatalytic (organic diol and methyl aniline) conjugate addition synthesized the products directly from alkynyl ketones. Both of these catalytic transformations are orthogonal to transition metal catalysis, allowing for good yields, easily accessible or commercially available reagents, high selectivity, reagent recovery and recyclability, facile scalability, and exceptional functional group tolerance.

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Two key factors bear on reaction rates for the conjugate addition of alkenyl boronic acids to heteroaryl-appended enones: the proximity of inductively electron-withdrawing heteroatoms to the site of bond formation and the resonance contribution of available heteroatom lone pairs to stabilize the developing positive charge at the enone β-position. For the former, the closer the heteroatom is to the enone β-carbon, the faster the reaction. For the latter, greater resonance stabilization of the benzylic cationic charge accelerates the reaction. Thus, reaction rates are increased by the closer proximity of inductive electron-withdrawing elements, but if resonance effects are involved, then increased rates are observed with electron-donating ability. Evidence for these trends in isomeric substrates is presented, and the application of these insights has allowed for reaction conditions that provide improved reactivity with previously problematic substrates.