Enantioselective CuH-Catalyzed Anti-Markovnikov Hydroamination of 1,1-Disubstituted Alkenes

Enantioselective synthesis of β-chiral amines has been achieved via copper-catalyzed hydroamination of 1,1-disubstituted alkenes with hydroxylamine esters in the presence of a hydrosilane. This mild process affords a range of structurally diverse β-chiral amines, including β-deuterated amines, in excellent yields with high enantioselectivities. Furthermore, catalyst loading as low as 0.4 mol% could be employed to deliver product in undiminished yield and selectivity, demonstrating the practicality of this method for large-scale synthesis.National Institutes of Health (U.S.) (Award GM58160

Ligand-Controlled Asymmetric Arylation of Aliphatic α-Amino Anion Equivalents

A palladium-catalyzed asymmetric arylation of 9-aminofluorene-derived imines using a chiral dialkylbiaryl phosphine as the supporting ligand has been developed. This transformation allows for enantioselective access to a diverse range of α-branched benzylamines.National Institutes of Health (U.S.) (Award GM58160)Amgen Inc

Rapid and Efficient Trifluoromethylation of Aromatic and Heteroaromatic Compounds Using Potassium Trifluoroacetate Enabled by a Flow System

The trifluoromethylation of aryl/heteroaryl iodides has been demonstrated using a flow system, thus enabling a rapid rate of reaction. A broad spectrum of trifluoromethylated compounds was prepared in good to excellent yields using CF[subscript 3]CO[subscript 2]K as the trifluoromethyl source. The process has the advantage of short reaction times and uses convenient [CF[subscript 3]] sources.Novartis (Firm)National Institutes of Health (U.S.) (GM46059

Diamine ligands in copper-catalyzed reactions

The utility of copper-mediated cross-coupling reactions has been significantly increased by the development of mild reaction conditions and the ability to employ catalytic amounts of copper. The use of diamine-based ligands has been important in these advances and in this perspective we discuss these systems, including the choice of reaction conditions and applications in the synthesis of pharmaceuticals, natural products and designed materials.National Institutes of Health (U.S.) (Grant GM-58160

Palladium-Catalyzed Intramolecular C-H Difluoroalkylation: Synthesis of Substituted 3,3-Difluoro-2-oxindoles

The synthesis of 3,3-difluoro-2-oxindoles through a robust and efficient palladium-catalyzed C-H difluoroalkylation is described. This process generates a broad range of difluorooxindoles from readily prepared starting materials. The use of BrettPhos as the ligand was crucial for high efficiency. Preliminary mechanistic studies suggest that oxidative addition is the rate-determining step for this process.National Institutes of Health (U.S.) (GM46059)Japan Society for the Promotion of Science (Fellowship

Dialkylbiaryl phosphines in Pd-catalyzed amination: a user's guide

Dialkylbiaryl phosphines are a valuable class of ligand for Pd-catalyzed amination reactions and have been applied in a range of contexts. This perspective attempts to aid the reader in the selection of the best choice of reaction conditions and ligand of this class for the most commonly encountered and practically important substrate combinations.National Institutes of Health (U.S.) (Grant GM-58160

Mild Palladium-Catalyzed Cyanation of (Hetero)aryl Halides and Triflates in Aqueous Media

A mild, efficient, and low-temperature palladium-catalyzed cyanation of (hetero)aryl halides and triflates is reported. Previous palladium-catalyzed cyanations of (hetero)aryl halides have required higher temperatures to achieve good catalytic activity. This current reaction allows the cyanation of a general scope of (hetero)aryl halides and triflates at 2–5 mol % catalyst loadings with temperatures ranging from rt to 40 °C. This mild method was applied to the synthesis of lersivirine, a reverse transcriptase inhibitor.National Institutes of Health (GM46059)National Institutes of Health (GM108294

Palladium-Catalyzed Hydroxylation of Aryl and Heteroaryl Halides Enabled by the Use of a Palladacycle Precatalyst

A method for the hydroxylation of aryl and heteroaryl halides, promoted by a catalyst based on a biarylphosphine ligand tBuBrettPhos (L5) and its corresponding palladium precatalyst (1), is described. The reactions allow the cross-coupling of both potassium and cesium hydroxides with (hetero)aryl halides to afford a variety of phenols and hydroxylated heteroarenes in high to excellent yield.National Institutes of Health (U.S.) (GM58160)Croucher Foundation (Postdoctoral Fellowship

Palladium-Catalyzed Amination of Unprotected Five-Membered Heterocyclic Bromides

An efficient method for the palladium-catalyzed amination of unprotected bromoimidazoles and bromopyrazoles is presented. The transformation is facilitated by the use of our newly developed Pd precatalyst based on the bulky biarylphosphine ligand tBuBrettPhos (L4). The mild reaction conditions employed allow for the preparation of a broad scope of aminoimidazoles and aminopyrazoles in moderate to excellent yields.National Institutes of Health (U.S.) (Award GM58160)Astellas USA Foundation (Fellowship)Japan Society for the Promotion of Science (Young Scientist Research Fellowship

Enantioselective Synthesis of α-Aminosilanes by Copper-Catalyzed Hydroamination of Vinylsilanes

The synthesis of α-aminosilanes by a highly enantio- and regioselective copper-catalyzed hydroamination of vinylsilanes is reported. The system employs Cu-DTBM-SEGPHOS as the catalyst, diethoxymethylsilane as the stoichiometric reductant, and O-benzoylhydroxylamines as the electrophilic nitrogen source. This hydroamination reaction is compatible with differentially substituted vinylsilanes, thus providing access to amino acid mimics and other valuable chiral organosilicon compounds.National Institutes of Health (U.S.) (Award GM58160