Enantioselective Synthesis of α-Secondary and α-Tertiary Piperazin-2-ones and Piperazines by Catalytic Asymmetric Allylic Alkylation

The asymmetric palladium-catalyzed decarboxylative allylic alkylation of differentially N-protected piperazin-2-ones allows the synthesis of a variety of highly enantioenriched tertiary piperazine-2-ones. Deprotection and reduction affords the corresponding tertiary piperazines, which can be employed for the synthesis of medicinally important analogues. The introduction of these chiral tertiary piperazines resulted in imatinib analogues which exhibited comparable antiproliferative activity to that of their corresponding imatinib counterparts

The Enantioselective Synthesis of Eburnamonine, Eucophylline, and 16′-epi-Leucophyllidine

A synthetic approach to the heterodimeric bisindole alkaloid leucophyllidine is disclosed herein. An enantioenriched lactam building block, synthesized through palladium-catalyzed asymmetric allylic alkylation, served as the precursor to both hemispheres. The eburnamonine-derived fragment was synthesized through a Bischler–Napieralski/hydrogenation approach, while the eucophylline-derived fragment was synthesized by Friedländer quinoline synthesis and two sequential C−H functionalization steps. A convergent Stille coupling and phenol-directed hydrogenation united the two monomeric fragments to afford 16′-epi-leucophyllidine in 21 steps from commercial material

Asymmetric Synthesis of Quaternary Stereocenters via Metal Enolates

The strategy of using chiral metal enolate intermediates in a diverse variety of asymmetric transformations has allowed the generation of quaternary stereocenter-bearing products that are otherwise difficult to access. Many classic transformations including aldol, Mannich, conjugate addition, alkylation, and pericyclic-type reactions, as well as allylic alkylation and α-arylation/alkenylation, have been adapted to proceed through chiral metal enolate intermediates, allowing the asymmetric synthesis of many complex products in both an intermolecular and intramolecular manner. These transformations have proven useful in the synthesis of natural products and may also be applied to the synthesis of novel pharmaceuticals and other compounds of interest in the future. This review includes work done up to and including the year 2014

Asymmetric Synthesis of Quaternary Stereocenters via Metal Enolates

The strategy of using chiral metal enolate intermediates in a diverse variety of asymmetric transformations has allowed the generation of quaternary stereocenter-bearing products that are otherwise difficult to access. Many classic transformations including aldol, Mannich, conjugate addition, alkylation, and pericyclic-type reactions, as well as allylic alkylation and α-arylation/alkenylation, have been adapted to proceed through chiral metal enolate intermediates, allowing the asymmetric synthesis of many complex products in both an intermolecular and intramolecular manner. These transformations have proven useful in the synthesis of natural products and may also be applied to the synthesis of novel pharmaceuticals and other compounds of interest in the future. This review includes work done up to and including the year 2014