Chiral Binol-Phosphate Research Articles

Atropselective Hydrolysis of Chiral Binol-Phosphate Esters Catalyzed by the Phosphotriesterase from Sphingobium sp. TCM1.

The phosphotriesterase from Sphingobium sp. TCM1 (Sb-PTE) is notable for its ability to hydrolyze a broad spectrum of organophosphate triesters, including organophosphorus flame retardants and plasticizers such as triphenyl phosphate and tris(2-chloroethyl) phosphate that are not substrates for other enzymes. This enzyme is also capable of hydrolyzing any one of the three ester groups attached to the central phosphorus core. The enantiomeric isomers of 1,1'-bi-2-naphthol (BINOL) have become among the most widely used chiral auxiliaries for the chemical synthesis of chiral carbon centers. PTE was tested for its ability to hydrolyze a series of biaryl phosphate esters, including mono- and bis-phosphorylated BINOL derivatives and cyclic phosphate triesters. Sb-PTE was shown to be able to catalyze the hydrolysis of the chiral phosphate triesters with significant stereoselectivity. The catalytic efficiency, kcat/Km, of Sb-PTE toward the test phosphate triesters ranged from ∼10 to 105 M-1 s-1. The product ratios and stereoselectivities were determined for four pairs of phosphorylated BINOL derivatives.

Halogen-Bond-Catalyzed Addition of Carbon-Based Nucleophiles to N-Acylimminium Ions.

N-acylimminium ions are an important class of synthetic intermediates to produce diverse products upon treatment with different nucleophiles. Most of the reported catalytic protocol involved moisture-sensitive Lewis acids or transition metal. Herein, we reported an organocatalytic version by using halogen-bond catalyst as mild Lewis acid through anion-abstraction strategy. A preliminary result of enantioselective version by employing a chiral BINOL-phosphate anion has also been demonstrated.

Computational Exploration of a Pd(II)-Catalyzed γ-C-H Arylation Where Stereoselectivity Arises from Attractive Aryl-Aryl Interactions.

The enantioselective Pd(II)-catalyzed γ-C-H arylation of picolinamides with a chiral BINOL phosphate ligand was explored using density functional theory (DFT). Enantioselectivity arises from attractive aryl-aryl interactions between the pseudoequatorial phenyl substituent of the substrate and the chiral BINOL phosphate ligand.

Synthesis of (R)-Modafinil via Organocatalyzed and Non-Heme Iron-Catalyzed Sulfoxidation Using H2O2 as an Environmentally Benign Oxidant

The first organocatalyzed sulfoxidation reaction towards enantioenriched (R)-modafinil (Armodafinil®), a drug against narcolepsy, is reported here. A series of chiral organocatalysts, e.g., different chiral BINOL-phosphates, or a fructose-derived N-substituted oxazolidinone ketone (Shi catalyst) were applied for the sulfoxidation reaction with environmentally friendly H2O2 as a convenient oxygen transferring agent. Furthermore, the potential of a biomimetic catalytic system consisting of FeCl3 and a dipeptide-based chiral ligand was demonstrated, which constitutes the most successful asymmetric non-heme iron-catalyzed synthesis of (R)-modafinil so far.

Mechanistic insights on cooperative asymmetric multicatalysis using chiral counterions.

Cooperative multicatalytic methods are steadily gaining popularity in asymmetric catalysis. The use of chiral Brønsted acids such as phosphoric acids in conjunction with a range of transition metals has been proven to be effective in asymmetric synthesis. However, the lack of molecular-level understanding and the accompanying ambiguity on the role of the chiral species in stereoinduction continues to remain an unresolved puzzle. Herein, we intend to disclose some novel transition state models obtained through DFT(B3LYP and M06) computations for a quintessential reaction in this family, namely, palladium-catalyzed asymmetric Tsuji-Trost allylation of aldehydes. The aldehyde is activated as an enamine by the action of a secondary amine (organocatalysis), which then adds to an activated Pd-allylic species (transition metal catalysis) generated through the protonation of allyic alcohol by chiral BINOL-phosphoric acid (Brønsted acid catalysis). We aim to decipher the nature of chiral BINOL-phosphates and their role in creating a quaternary chiral carbon atom in this triple catalytic system. The study reports the first transition state model capable of rationalizing chiral counterion-induced enantioselectivity. It is found that the chiral phosphate acts as a counterion in the stereocontrolling event rather than the conventional ligand mode.

Gold(I) Complexes of Conformationally Constricted Chiral Ferrocenyl Phosphines

The preparation of two new chiral, enantiopure, and conformationally constrained phosphocin and 1,5-diphosphocin, incorporating two ferrocenyl units, is described. The gold(I) chloride complexes of these ligands and (S)-(R)-PPF-OMe were prepared, and their structures, in solution and solid states, are compared. Abstraction of the chloride anion by the addition of silver salt of either toluenesulfonate or chiral BINOL-phosphates generates active catalysts for the intramolecular cyclization of 6-methyl-1,1-diphenylhepta-4,5-dien-1-ol, where up to 47% ee can be obtained. Match and mismatch effects between chiral ligands and counteranions are highlighted.

Chiral BINOL-derived phosphoric acids: privileged Brønsted acid organocatalysts for C–C bond formation reactions

BINOL-derived phosphoric acids have emerged during the last five years as powerful chiral Brønsted acid catalysts in many enantioselective processes. The most successful transformations carried out with chiral BINOL phosphates include C-C bond formation reactions. The recent advances have been reviewed in this article with a focus being placed on hydrocyanations, aldol-type, Mannich, Friedel-Crafts, aza-ene-type, Diels-Alder, as well as cascade and multi-component reactions.

A Highly Enantioselective Brønsted Acid Catalyst for the Strecker Reaction

An amenable route to amino acids: An optimized new chiral binol phosphate catalyst (see scheme; Ar=9-phenanthryl) for the hydrocyanation of imines provides a convenient strategy for the enantioselective synthesis of α-amino acids and diamines.

Enantioselective Brønsted Acid Catalyzed Transfer Hydrogenation: Organocatalytic Reduction of Imines

The first enantioselective Brønsted acid catalyzed reduction of imines has been developed. This new organocatalytic transfer hydrogenation of ketimines with Hantzsch dihydropyridine as the hydrogen source offers a mild method to various chiral amines with high enantioselectivity. The stereochemistry of the chiral amines can be rationalized by a stereochemical model derived from an X-ray crystal structure of a chiral BINOL phosphate catalyst. [reaction: see text]