Practical and Scalable Kinetic Resolution of BINOLs Mediated by a Chiral Counterion.

BINOLs are valuable and widely used building blocks, chiral ligands, and catalysts that are effective across a remarkable range of different chemical transformations. Here we demonstrate that an ammonium salt catalyzed kinetic resolution of racemic BINOLs with benzyl tosylate proceeds with s up to 46. This is a scalable and practical process that can be applied across >30 different C2 - and non-C2 -symmetric BINOLs. Implementation of this method enables the enantioselective synthesis of a wide range of BINOL derivatives with over 99:1 e.r.

Chromophore Activation of α,ß-Unsaturated Carbonyl Compounds and Its Application to Enantioselective Photochemical Reactions.

The first law of photochemistry, as described by Theodor von Grotthuß and John W. Draper, states that only the light absorbed by the irradiated matter can effect photochemical change. Consequently, the photochemical behavior of a molecule can be controlled by bringing its absorbance properties in line with the emission of the light source. A compound with a chromophore that only absorbs light at short wavelengths will not be excited by light of longer wavelengths. If one can reversibly modify the photophysical properties of a compound with a chemical activator, then it is possible to photoexcite only the activated species. For α,ß-unsaturated carbonyl compounds, the use of Lewis acids, Brønsted acids, or the formation of the respective iminium ions can bring about the desired chromophore activation to catalyze a photochemical reaction at a given wavelength. In this Minireview, the concept of chromophore activation will be illustrated, and examples of its implementation in enantioselective catalysis will be discussed.

Catalytic enantioselective synthesis of atropisomeric biaryls by a cation-directed O-alkylation.

Axially chiral biaryls, as exemplified by 1,1'-bi-2-naphthol (BINOL), are key components of catalysts, natural products and medicines. These materials are synthesized conventionally in enantioenriched form through metal-mediated cross coupling, de novo construction of an aromatic ring, point-to-axial chirality transfer or an atropselective transformation of an existing biaryl. Here, we report a highly enantioselective organocatalytic method for the synthesis of atropisomeric biaryls by a cation-directed O-alkylation. Treatment of racemic 1-aryl-2-tetralones with a chiral quinidine-derived ammonium salt under basic conditions in the presence of an alkylating agent leads to atropselective O-alkylation with e.r. up to 98:2. Oxidation with DDQ gives access to C2-symmetric and non-symmetric BINOL derivatives without compromising e.r. We propose that the chiral ammonium counterion differentiates between rapidly equilibrating atropisomeric enolates, leading to highly atropselective O-alkylation. This dynamic kinetic resolution process offers a general approach to the synthesis of enantioenriched atropisomeric materials.

A Counterion-Directed Approach to the Diels-Alder Paradigm: Cascade Synthesis of Tricyclic Fused Cyclopropanes.

An approach to the intramolecular Diels-Alder reaction has led to a cascade synthesis of complex carbocycles composed of three fused rings and up to five stereocenters with complete stereocontrol. Computational analysis reveals that the reaction proceeds by a Michael/Michael/cyclopropanation/epimerization cascade in which size and coordination of the counterion is key.