Lewis Acid Enabled Copper-Catalyzed Asymmetric Synthesis of Chiral ß-Substituted Amides.

Here we report that readily available silyl- and boron-based Lewis acids in combination with chiral copper catalysts are able to overcome the reactivity issues of unactivated enamides, known as the least reactive carboxylic acid derivatives, toward alkylation with organomagnesium reagents. Allowing unequaled chemo-reactivity and stereocontrol in catalytic asymmetric conjugate addition to enamides, the method is distinguished by its unprecedented reaction scope, allowing even the most challenging and synthetically important methylations to be accomplished with good yields and excellent enantioselectivities. This catalytic protocol tolerates a broad temperature range (-78 °C to ambient) and scale up (10 g), while the chiral catalyst can be reused without affecting overall efficiency. Mechanistic studies revealed the fate of the Lewis acid in each elementary step of the copper-catalyzed conjugate addition of Grignard reagents to enamides, allowing us to identify the most likely catalytic cycle of the reaction.

Synthesis of ferrocene tethered open and macrocyclic bis-beta-lactams and bis-beta-amino acid derivatives.

New bioorganometallic ferrocene derivatives are synthesized through a Diversity Oriented Synthesis strategy. Easily available ferrocene bisimines have been transformed into open ferrocenyl bis-beta-lactams. These compounds have demonstrated to be versatile synthons used in further transformations into new ferrocene bis-beta-amino acids. Carefully selected substituents submitted to ring closing metathesis (RCM) and Cu-catalyzed oxidative alkyne coupling conditions have also allowed the conversion of open substrates into ferrocenic macrocyclic bis-beta-lactams.