Α-hydroxy Phosphonates Research Articles

Ru(II)-Catalyzed Enantioselective Transfer Hydrogenation of α-Ketophosphonates: Straightforward Access to Valuable Chiral α-Hydroxy Phosphonates.

Asymmetric transfer hydrogenation (ATH) is arguably one of the most powerful tools for the synthesis of chiral compounds. Despite tremendous advances in this field, the reduction of α-ketophosphonates remains largely unexplored. Herein, we report an efficient Ru-catalyzed ATH on a broad range of α-ketophosphonates. Compared with existing methods, our approach offers as advantages mild conditions, operational simplicity, limited waste generation, broad substrate scope (26 examples), good to excellent yields (75-93%), and excellent levels of stereoinduction (from 90% to >99% ee).

Constructive On-DNA Abramov Reaction and Pudovik Reaction for DEL Synthesis.

Organophosphonic compounds are distinctive among natural products in terms of stability and mimicry. Numerous synthetic organophosphonic compounds, including pamidronic acid, fosmidromycin, and zoledronic acid, are approved drugs. DNA encoded library technology (DELT) is a well-established platform for identifying small molecule recognition to target protein of interest (POI). Therefore, it is imperative to create an efficient procedure for the on-DNA synthesis of α-hydroxy phosphonates for DEL builds.

Green synthesis of α-hydroxy phosphonates containing unsaturated organochalcogenyl moiety

A simple and efficient protocol for the chemoselective synthesis ofα-hydroxy phosphonates containing unsaturated alkoxy/phenoxy or organosulfanyl moiety has been developed. This approach was performed by Pudovik reaction from readily available organochalcogenyl enals and dialkyl phosphites in a solvent-free system, using 0.25 equiv. CaO as a catalyst at room temperature, which provided the target phosphonates in high yields.

The sequential C–H oxidation/asymmetric phosphonylation of primary alcohols to synthesize α-hydroxy phosphonates

A new strategy for the sequential C–H oxidation/asymmetric phosphonylation of primary alcohols has been developed. It involves a combination of Cu(I)/TEMPO/NMI (N-methylimidazole) oxidation, under an air atmosphere, with chiral Al (salalen)-catalyzed enantioselective addition. Various primary alcohols, including benzylic alcohols, allylic alcohols, propargylic alcohols, alkyl alcohols, and other alcohols containing oxygen-, sulfur-, and nitrogen-heterocycles were smoothly converted into chiral α-hydroxy phosphonates with good yields and high enantioselectivities. Inhibitor of CD45 and a plant growth regulator can be easily synthesized by this new method.

Diethyl (2-(4-Phenyl-1H-1,2,3-triazol-1-yl)benzyl) Phosphate

Here we describe a full structural elucidation of the diethyl (2-(4-phenyl-1H-1,2,3-triazol-1-yl)benzyl) phosphate. This compound is a common by-product present in the synthetic protocols to access the α-hydroxy phosphonate compounds through of a Phospha-Brook rearrangement. Thus, a complete NMR structural characterization of this rearrangement by-product was performed by 1H, 13C{1H}, 31P{1H}, COSY, HSQC, and HMBC NMR experiments. Additionally, we have demonstrated that the 1H-31P HMBC is a 2D heteroatom NMR experiment which combines the simple identification by 31P chemical shift with the detection sensitivity by 1H spectrum in a practical procedure.

Enantioselective vinylogous aldol reaction of acylphosphonates with 3-alkylidene oxindoles.

A simple strategy for yielding chiral tertiary α-hydroxy phosphonates that integrates two highly biologically relevant scaffolds namely 3-alkylidene-2-oxindoles and phosphonates has been described. The hydrogen bonding ability of the bifunctional thiourea catalyst allows simultaneous dual activation of a vinylogous oxindole nucleophile and an acylphosphonate electrophile, affording hydroxyphosphonato-3-alkylidene-2-oxindoles as aldol adducts in high yields (up to 92%) with excellent stereocontrol (up to 99% ee).

Cinchona-Diaminomethylenemalononitrile Organocatalyst for the Highly Enantioselective Hydrophosphonylation of Ketones and Enones.

The use of diaminomethylenemalononitrile (DMM) organocatalyst to promote the challenging 1,2-hydrophosphonylation of simple ketones and enones, which are also called α,β-unsaturated ketones, is proposed and validated. This reaction provided the corresponding chiral α-hydroxy phosphonates in high to excellent yields and with enantioselectivity up to 96% ee.

Sodium Dodecylphosphonate: an Efficient Anionic Surfactant for the Green Synthesis of α-Hydroxy Phosphonates in Micellar Media

A simple and green synthesis of α-hydroxy phosphonates has been performed by reaction between aldehydes and triethyl phosphite using sodium dodecylphosphonate as anionic surfactant in micellar media under reflux conditions. The novel structures were recognized by 1H NMR, 13C NMR and 31P-NMR. The employ of green media, clean reaction profiles, simple experimental and work up procedures and high yields are some of the unique features of this process.

Base-controlled reaction of α,β-unsaturated trifluoromethyl ketone and dialkyl phosphite

Base-controlled selective reactions of α,β-unsaturated trifluoromethyl ketones with dialkyl phosphites were achieved. In the presence of DABCO, the Pudovik reaction took place readily to give the corresponding α-hydroxy phosphonates in high yields under mild conditions. While using DBU as base, the Phospha-Brook rearrangement of α-hydroxy phosphonates formed in the reaction occurred to afford phosphates as final products.

Compositional Effect in AuPd Bimetallic Nanoparticles Towards Product Selectivity during Aerobic Oxidation of α-Hydroxy Esters and Phosphonates

Aerobic oxidation of α-hydroxy esters and phosphonates for direct formation of α-keto esters and α-keto phosphonates was explored using Au nanoparticle based catalytic systems. Alloying Au with Pd resulted in high activity and selectivity for the aerobic oxidation reaction under base and solvent free conditions. The formation of desired α-keto esters and α-keto phosphonates as sole products were highly dependent on the composition of the alloy nanocatalyst. Addition of a secondary oxidizer such as tert-butylhydroperoxide (TBHP) significantly enhanced the yield of the products at shorter reaction time under mild reaction conditions.

ChemInform Abstract: Efficient Synthesis of β‐Lactam Containing α‐Hydroxy Phosphonates Using Tartaric Acid and Fumaric Acid as Mild Catalysts.

ABSTRACTA short and efficient protocol for the synthesis of β-lactam containing α-hydroxy phosphonate esters using inexpensive catalysts such as tartaric acid and fumaric acid is described.

Efficient synthesis of β-lactam containing α-hydroxy phosphonates using tartaric acid and fumaric acid as mild catalysts

ABSTRACTA short and efficient protocol for the synthesis of β-lactam containing α-hydroxy phosphonate esters using inexpensive catalysts such as tartaric acid and fumaric acid is described.

RAFT copolymerization of a phosphorus-containing monomer with α-hydroxy phosphonate and methyl methacrylate

RAFT copolymerization of a phosphorus-containing monomer with α-hydroxy phosphonate PHMA and MMA was successfully conducted and the resultant well-defined copolymer material shows good superior flame-retardant properties and hydrophilicity.

ChemInform Abstract: Asymmetric Hydrogenation of α‐Keto Phosphonates with Chiral Phosphine—Phosphoramidite Ligands.

Abstract Rh-catalyzed asymmetric hydrogenation of challenging α-keto phosphonates has been developed. With a new chiral phosphine–phosphoramidite ligand, a wide range of α-keto phosphonates were hydrogenated to afford the corresponding ( R )-α-hydroxy phosphonates with moderate to good enantioselectivities (up to 87% ee).

ChemInform Abstract: C—H Hydroxylation of Phosphonates with Oxygen in [bmIm]OH to Produce Quaternary α‐Hydroxy Phosphonates.

A highly efficient and mild [bmIm]OH-catalyzed α-hydroxylation of phosphonates using O2 as the oxygen source is described. The employment of ionic liquid under mild reaction conditions makes this transformation green and practical. Especially, this reaction provided a novel and convenient methodology for the construction of quaternary α-hydroxy phosphonates.

Asymmetric hydrogenation of α-keto phosphonates with chiral phosphine–phosphoramidite ligands

Rh-catalyzed asymmetric hydrogenation of challenging α-keto phosphonates has been developed. With a new chiral phosphine–phosphoramidite ligand, a wide range of α-keto phosphonates were hydrogenated to afford the corresponding (R)-α-hydroxy phosphonates with moderate to good enantioselectivities (up to 87% ee).

Synthesis of Quaternary α‐Hydroxy Phosphonates via Direct Hydroxylation of Phosphonate Compounds

AbstractIt was found for the first time that Cs2CO3 serves as highly efficient catalyst for the direct hydroxylation reactions of phosphonates under mild conditions. This reaction provides an efficient approach to quaternary α‐hydroxy phosphonates, which possess intriguing biological activities and are widely used in many areas.

Asymmetric Synthesis of Tertiary α-Hydroxy Phosphonic Acid Derivatives under Aerobic Oxidation Conditions

The copper-catalyzed asymmetric α-hydroxylation of β-ketophosphonates, using in situ generated nitrosocarbonyl compounds as electrophilic source of oxygen, is reported. The reaction merges aerobic oxidation and Lewis acid catalysis. α-Aminoxy-β-ketophosphonates were synthesized in high yields (up to 97% yield) and high enantioselectivities (up to >99% ee).

C-H hydroxylation of phosphonates with oxygen in [bmIm]OH To produce quaternary α-hydroxy phosphonates.

A highly efficient and mild [bmIm]OH-catalyzed α-hydroxylation of phosphonates using O2 as the oxygen source is described. The employment of ionic liquid under mild reaction conditions makes this transformation green and practical. Especially, this reaction provided a novel and convenient methodology for the construction of quaternary α-hydroxy phosphonates.

The catalytic aerobic synthesis of quaternary α-hydroxy phosphonates via direct hydroxylation of phosphonate compounds

A highly efficient Cu-catalyzed direct hydroxylation of phosphonate compounds has been developed. This transformation provides a powerful method for the synthesis of quaternary α-hydroxy phosphonates in good yields.