Catalytic asymmetric synthesis of meta benzene isosteres.

Although aromatic rings are common elements in pharmaceutically active compounds, the presence of these motifs brings several liabilities with respect to the developability of a drug. Nonoptimal potency, metabolic stability, solubility and lipophilicity in pharmaceutical compounds can be improved by replacing aromatic rings with non-aromatic isosteric motifs. Moreover, whereas aromatic rings are planar and lack three-dimensionality, the binding pockets of most pharmaceutical targets are chiral.

Stereospecific Phosphination and Thioetherification of Organoboronic Esters.

Alkyllithium-activated organoboronic esters are found to undergo stereospecific phosphination with copper chloride and chlorophosphines. They also react with thiolsulfonate electrophiles under copper catalysis. These reactions enable stereospecific phosphination and thiolation of organoboronic esters, which are further applied in preparation of chiral ligands and biologically active molecules.

Site-Selective Activation and Stereospecific Functionalization of Bis(boronic Esters) Derived from 2-Alkenes: Construction of Propionates and Other 1,2-Difunctional Motifs.

Non-directed regioselective activation of bis(boronic esters), followed by functionalization, is reported. A bulky activator is shown to selectively activate the less hindered boronic ester enabling it to undergo stereospecific cross-coupling to a variety of electrophiles. This steric-based regioselectivity provides a simple and efficient method to prepare highly functionalized, enantiomerically enriched products starting from simple alkenes.

1,2-Diborylsilanes: Catalytic Enantioselective Synthesis and Site-Selective Cross-Coupling.

A Pt-catalyzed enantioselective hydrosilylation of ()-1,2-diborylethylene provides a 1,2-diboryl-1-silylalkane that can be used in catalytic cross-coupling reactions. Depending on the catalyst employed and the cross-coupling reaction conditions, the coupling can occur at either α or β relative to the silane center.

Substrate Plasticity Enables Group-Selective Transmetalation: Catalytic Stereospecific Cross-Couplings of Tertiary Boronic Esters.

Activation of enantiomerically enriched tertiary alkylboronic esters with adamantyllithium generated enables stereoretentive boron-to-copper transmetalation. The resulting alkylcopper species can undergo cross-coupling reactions with an array of electrophiles to furnish synthetically useful compounds bearing quaternary stereocenters. DFT calculations of the transmetalation process provide insights for reactivity and selectivity.