Copper-Catalyst-Controlled Site-Selective Allenylation of Ketones and Aldehydes with Propargyl Boronates

A practical and highly site-selective copper-PhBPE-catalyst-controlled allenylation with propargyl boronates has been developed. The methodology has shown to be tolerant of diverse ketones and aldehydes providing the allenyl adducts in high selectivity. The BPE ligand and boronate substituents were shown to direct the site selectivity for which either propargyl or allenyl adducts can be acquired in high selectivity. A model is proposed that explains the origin of the site selectivity

A Computational Investigation of the Ligand-Controlled Cu-Catalyzed Site-Selective Propargylation and Allenylation of Carbonyl Compounds

A copper-catalyzed site-selective propargylation/allenylation reaction toward carbonyl compounds has been mechanistically investigated using a computational approach. Different reaction pathways and catalytic cycles were investigated. Control of the site selectivity arises from a destabilizing interaction introduced by the phenyl-substituted ligand

Addressing the Configuration Stability of Lithiated Secondary Benzylic Carbamates for the Development of a Noncryogenic Stereospecific Boronate Rearrangement

A practical noncryogenic process for the Aggarwal stereospecific boronate rearrangement with chiral secondary benzylic carbamates has been developed. The use of LDA instead of <i>sec</i>-BuLi combined with an <i>in situ</i> trapping of the unstable lithiated carbamate was critical to success. Furthermore, this new process increased the substrate scope to include the versatile aryl iodide and bromide substrates. The methodology was applied to a diverse array of substrates and was demonstrated on multikilogram scale

Early Development Scale-Up of a Structurally-Challenging 5‑Lipoxygenase Activating Protein (FLAP) Inhibitor

A practical and efficient synthesis of the FLAP inhibitor <b>1</b> was developed addressing multiple scale-up and safety concerns posed by the established synthesis and utilized a resolution strategy (replacing supercritical fluid chromatography (SFC) separation) for expedient access to the key structural component of <b>1</b>: the challenging chiral quaternary center. Also highlighted are in situ IR monitoring, condensation to form the 1,2,4-oxadiazole ring, and an efficient Suzuki-Miyaura coupling

Development of New <i>P</i>‑Chiral <i>P</i>,π-Dihydrobenzooxaphosphole Hybrid Ligands for Asymmetric Catalysis

A new family of <i>P</i>-chiral <i>P</i>,π-hybrid ligands was prepared from the dihydrobenzooxaphosphole core. These new ligands were demonstrated to be both sterically and electronically tunable at the substituents on the phosphorus atom <i>and</i> the π-system of the ligand. Application of these new ligands to the catalytic asymmetric addition of boronic acids to imine electrophiles was shown to proceed with high levels of enantioinduction