Chiral Bicyclic Bridgehead Phosphoramidite (Briphos) Ligands for Asymmetric Rhodium-Catalyzed 1,2- and 1,4-Addition

A complementary solution for Rh-catalyzed enantioselective 1,2- and 1,4-arylation with two structurally related chiral ligands is reported. A chiral bicyclic bridgehead phosphoramidite (briphos) ligand derived from 1-aminoindane was efficient for the 1,2-arylation of <i>N</i>-sulfonyl imines, while that derived from 1,2,3,4-tetrahydro-1-naphthylamine was efficient for 1,4-arylation of α,β-unsaturated cyclic ketones. For α,β-unsaturated <i>N</i>-tosyl ketimines, the briphos derived from 1-aminoindane was found to selectively provide γ,γ-diaryl <i>N</i>-tosyl enamines with high yields and stereoselectivities

Rhodium-Catalyzed Asymmetric 1,4-Addition of α,β-Unsaturated Imino Esters Using Chiral Bicyclic Bridgehead Phosphoramidite Ligands

A chiral bicyclic bridgehead phosphoramidite (briphos) prepared from 1-aminoindane is a highly efficient and selective ligand for rhodium­(I)-catalyzed asymmetric 1,4-addition of arylboronic acids to α,β-unsaturated <i>N</i>,<i>N</i>-dimethyl-sulfamoyl imino esters at ambient temperature. This transformation provides a new class of chiral (<i>Z</i>)-γ,γ-diaryl-α,β-dehydroamino esters with excellent yield and enantioselectivity

Rhodium-Catalyzed Asymmetric 1,4-Addition of α,β-Unsaturated Imino Esters Using Chiral Bicyclic Bridgehead Phosphoramidite Ligands

A chiral bicyclic bridgehead phosphoramidite (briphos) prepared from 1-aminoindane is a highly efficient and selective ligand for rhodium­(I)-catalyzed asymmetric 1,4-addition of arylboronic acids to α,β-unsaturated <i>N</i>,<i>N</i>-dimethyl-sulfamoyl imino esters at ambient temperature. This transformation provides a new class of chiral (<i>Z</i>)-γ,γ-diaryl-α,β-dehydroamino esters with excellent yield and enantioselectivity

Synthesis of α‑(4-Oxazolyl)amino Esters via Brønsted Acid Catalyzed Tandem Reaction

A one-step, Brønsted acid catalyzed tandem reaction for the synthesis of α-(4-oxazolyl)­amino esters was developed. 4-Nitrobenzenesulfonic acid was found to be an efficient catalyst for the coupling of ethyl 2-oxobut-3-ynoates with amides to provide various α-(4-oxazolyl)­amino esters. The experimental and X-ray crystallographic data suggest that a series of bond-forming reactions including imine formation, intermolecular Michael addition, and intramolecular Michael addition are involved to generate both the oxazole and amino acid functionalities

2,2′-Dihydroxybenzil: A Stereodynamic Probe for Primary Amines Controlled by Steric Strain

A rational approach for generating 1,1′-binaphthalene-like axial chirality of a small organic receptor, 2,2′-dihydroxybenzil is presented. The receptor combines with 2 equiv of monodentate primary amines to form a diimine, of which axial chirality is controlled by steric strain with moderate (1.4:1) to good (4.7:1) stereoselectivity. The observed circular dichroism (CD) spectra have been closely simulated by TD-DFT computations and can be used for determining the absolute chirality and enantiomeric excess of primary amines

An Enantioselective Cross-Dehydrogenative Coupling Catalysis Approach to Substituted Tetrahydropyrans

An enantioselective cross-dehydrogenative coupling (CDC) reaction to access tetrahydropyrans has been developed. This process combines <i>in situ</i> Lewis acid activation of a nucleophile in concert with the oxidative formation of a transient oxocarbenium electrophile, leading to a productive and highly enantioselective CDC. These advances represent one of the first successful applications of CDC for the enantioselective couplings of unfunctionalized ethers. This system provides efficient access to valuable tetrahydropyran motifs found in many natural products and bioactive small molecules

An Enantioselective Cross-Dehydrogenative Coupling Catalysis Approach to Substituted Tetrahydropyrans

An enantioselective cross-dehydrogenative coupling (CDC) reaction to access tetrahydropyrans has been developed. This process combines <i>in situ</i> Lewis acid activation of a nucleophile in concert with the oxidative formation of a transient oxocarbenium electrophile, leading to a productive and highly enantioselective CDC. These advances represent one of the first successful applications of CDC for the enantioselective couplings of unfunctionalized ethers. This system provides efficient access to valuable tetrahydropyran motifs found in many natural products and bioactive small molecules

Palladium-Catalyzed Dehydrative Cross-Coupling of Allylic Alcohols and <i>N</i>‑Heterocycles Promoted by a Bicyclic Bridgehead Phosphoramidite Ligand and an Acid Additive

A mild and efficient dehydrative cross-coupling reaction between allylic alcohols and <i>N</i>-heterocycles using palladium catalysis is reported. A bicyclic bridgehead phosphoramidite (briphos) ligand together with Pd­(dba)₂ is a highly efficient catalyst, and an acid additive involved in the rate-determining step promotes the catalytic cycle. The coupling reaction of allylic alcohols with <i>N</i>-heterocycles including imidazoles, benzimidazoles, and triazole proceeds under mild reaction conditions with high yields using Pd/briphos and pentafluorophenol

Bicyclic Bridgehead Phosphoramidite (Briphos) Ligands with Tunable π‑Acceptor Ability and Catalytic Activity in the Rhodium-Catalyzed Conjugate Additions

A new type of bicyclic bridgehead phosphoramidites (briphos) is reported, where the geometrical constraints significantly enhance the π-acceptor ability compared with its monocyclic analogs. The briphos is shown to be highly efficient and tunable for Rh­(I)-catalyzed conjugate additions of aryl boronic acids to α,β-unsaturated ketones and <i>N</i>-tosyl ketimines