Reduction Of Phosphine Oxides Research Articles

Catalytic Enantioselective Synthesis of Axially Chiral Imidazoles by Cation-Directed Desymmetrization.

Axially chiral five-membered heterobiaryls synthesized by enantioselective catalysis typically feature large ortho-substituents or a heteroatom in the chiral axis to maintain a stable configuration. Herein we report a cation-directed catalytic enantioselective desymmetrization method that enables rapid access to axially chiral imidazoles with the basic nitrogen at the ortho position and efficiently integrates π-stacking moieties to ensure a stable axial configuration for further applications. The process is operationally simple, is highly enantioselective, and can be performed on the gram scale. The majority of the products are obtained in >90% ee, but interestingly even those with only moderate ee can readily be enriched to near optical purity by selective racemate crystallization. Together with a mild phosphine oxide reduction method, axially chiral imidazoles such as StackPhos and its derivatives are readily prepared in high yield and excellent enantioselectivity on the gram scale. The method also enables the preparation of new chiral non-phosphine-bearing imidazoles.

Tertiary Amine-Mediated Reductions of Phosphine Oxides to Phosphines.

The reduction of phosphine oxides without the use of highly reactive reductants represents a safer and more sustainable solution for recycling of organophosphorus compounds. Herein, we disclose an N,N,N',N'-tetramethylethylenediamine (TMEDA)-mediated reduction via an unusual intermolecular hydride transfer. Mechanistic studies suggest that TMEDA serves as a hydride donor, while the P(V) halophosphonium salt acts as the hydride acceptor. This methodology provides a scalable and efficient protocol to reduce phosphine oxides under mild conditions.

Highly Chemoselective Reduction of Phosphine Oxides through Electrophilic Activation of the P=O Bond with Anhydride

AbstractA highly chemoselective reduction of phosphine oxides was demonstrated under transition‐metal‐free and alkaline reaction conditions. During the reaction, P=O bond was firstly electrophilically activated by an anhydride and subsequently reduced by the versatile and cheap NaH, which was strengthened by 15‐crown‐5. By this strategy, a variety of phosphine oxides including those bearing functional groups such as methyl, methoxyl, phenyl, fluorine, chlorine, bromine, iodine, trifluoromethyl, nitrile, ester, alkenyl, alkynyl and heterocycles were transformed readily into the corresponding phosphines in good to high yields. This work represents an efficient method for reducing phosphine oxides forming phosphines.

Fluorinated 2-Azetines: Synthesis, Applications, Biological Tests, and Development of a Catalytic Process.

An efficient and straightforward phosphine-promoted tandem aza-Michael addition/intramolecular Wittig reaction was developed for the synthesis of polyfunctionalized 2-azetines. After demonstrating that this transformation could be made catalytic in phosphine through in situ reduction of phosphine oxide with phenylsilane, different post-transformation steps have been demonstrated, including an original [2 + 2] photodimerization. Preliminary biological tests highlighted that these fluorinated 1,2-dihydroazete-2,3-dicarboxylates exhibited significant cytotoxicity against the human tumor cell line.

Reduction of Triphenylphosphine Oxide to Triphenylphosphine by Phosphonic Acid.

A novel method for the iodine-mediated reduction of phosphine oxides (sulfides) to phosphines using phosphonic acid under solvent-free conditions is described. By using a combination of H3PO3 and I2, both tertiary monophosphine oxides and bis-phosphine oxides were reduced under this system, readily producing monodentate and bidentate phosphines, respectively, in good yields. Notably, chiral (R)-(+)-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl dioxide could be also tolerated without racemization. This new approach is inexpensive and features simple conditions and a wide substrate scope.

Facile reduction of phosphine oxides andH-phosphonates by ditetrelenes

The addition of secondary phosphine oxides to tetramesityldisilene and tetramesityldigermene results in the mild, partial reduction of the P(V) centre of the organophosphorus oxide to P(III) to yield disilyl and digermyl phosphinite derivatives and illustrates the potential of ditetrelenes to serve as mild reducing agents under ambient conditions. An analogous reaction happens with H-phosphonates. Mechanistic experiments, including deuterium labelling, kinetic isotope effect, and variable time normalization analysis experiments, reveal that the 1,3-PH addition likely proceeds through a stepwise reaction pathway with the organophosphorus oxide acting as the nucleophile toward the ditetrelene. Furthermore, a facile exchange between the R2PO moiety of the digermylphosphinite and the R2PO moiety of phosphine oxides was discovered and likely proceeds through a direct substitution mechanism.

Inherently Chiral 6,7-Diphenyldibenzo[ e,g ][1,4]diazocine: Enantioselective Synthesis and Application as a Ligand Platform

Inherently Chiral 6,7-Diphenyldibenzo[ <i>e,g</i> ][1,4]diazocine: Enantioselective Synthesis and Application as a Ligand Platform

Phosphine-Mediated Morita-Baylis-Hillman-Type/Wittig Cascade: Access to E-Configured 3-Styryl- and 3-(Benzopyrrole/furan-2-yl) Quinolinones.

A phosphine-mediated, well-designed Morita-Baylis-Hillman-type/Wittig cascade for the rapid assembly of a quinolinone framework from benzaldehyde derivatives is developed for the first time. By rationally combining I2/NIS-mediated cyclization, biologically relevant 3-(benzopyrrole/furan-2-yl) quinolinones were facilely synthesized in a one-pot process by starting from 3-styryl-quinolinones bearing an o-hydroxy/amino group, significantly expanding the chemical space of this privileged skeleton. Further utility of this protocol is illustrated by successfully performing this transformation in a catalytic manner through in situ reduction of phosphine oxide by phenylsilane.

Synthesis of Functionalized Cyclobutenes and Spirocycles via Asymmetric P(III)/P(V) Redox Catalysis

AbstractAn enantioselective phosphine‐catalyzed transformation has been developed for the synthesis of chiral cyclobutene triesters and fluorinated spirocyclic compounds. The strategy involved a P(III)/P(V) redox cycling process, via in situ reduction of phosphine oxide with phenylsilane. This catalytic methodology has enabled the enantioselective synthesis of functionalized cyclobutenes (24 examples, up to 94% ee). On the occasion of the extension of this study to α‐ketoester indenone substrates, a surprising reactivity has been discovered for the synthesis of spiro‐indenone products.magnified image

Phosphine‐Catalyzed Synthesis of Chiral N‐Heterocycles through (Asymmetric) P(III)/P(V) Redox Cycling

AbstractPhosphine‐catalyzed tandem Michael addition/intramolecular Wittig reactions have been developed for the synthesis of chiral 2,5‐dihydro‐1H‐pyrrole and tetrahydropyridine derivatives. These processes have been rendered catalytic in phosphine, thanks to the in situ reduction of phosphine oxide by phenylsilane. Furthermore, catalytic and asymmetric P(III)/P(V) processes were implemented using enantiopure chiral phosphines.

Phosphine-Catalyzed Chemoselective Reduction/Elimination/Wittig Sequence for Synthesis of Functionalized 3-Alkenyl Benzofurans.

An efficient protocol for the construction of functionalized 3-alkenyl benzofurans is demonstrated under metal-free conditions using catalytic amount of phosphine proceeding an intramolecular Wittig reaction. This one-pot reaction initiated by the phospha-Michael addition of phosphine to O-acylated nitrostyrene, in which phosphine was in-situ-generated from the chemoselective reduction of phosphine oxide with PhSiH3, would provide the phosphorus ylide to result in the aforementioned multifunctionalized benzofuran via O-acylation/nitrous acid elimination/Wittig reaction.

Microwaves as "Co-Catalysts" or as Substitute for Catalysts in Organophosphorus Chemistry.

The purpose of this review is to summarize the importance of microwave (MW) irradiation as a kind of catalyst in organophosphorus chemistry. Slow or reluctant reactions, such as the Diels-Alder cycloaddition or an inverse-Wittig type reaction, may be performed efficiently under MW irradiation. The direct esterification of phosphinic and phosphonic acids, which is practically impossible on conventional heating, may be realized under MW conditions. Ionic liquid additives may promote further esterifications. The opposite reaction, the hydrolysis of P-esters, has also relevance among the MW-assisted transformations. A typical case is when the catalysts are substituted by MWs, which is exemplified by the reduction of phosphine oxides, and by the Kabachnik–Fields condensation affording α-aminophosphonic derivatives. Finally, the Hirao P–C coupling reaction may serve as an example, when the catalyst may be simplified under MW conditions. All of the examples discussed fulfill the expectations of green chemistry.

On the Borate-Catalyzed Electrochemical Reduction of Phosphine Oxide: A Computational Study.

Recently, Nocera and co-workers (J. Am. Chem. Soc. 2018, 140, 13711) demonstrated that triaryl borate Lewis acids facilitate the direct electrochemical reduction of triphenylphosphine oxide (TPPO) to triphenylphosphine (TPP). In the present contribution, we report a quantum chemical study unravelling details of the reaction, which also supports the proposed ECrECi mechanism. Alternative electrochemical routes to TPPO reduction facilitated by other Lewis acids (CH3+), or by photocatalysis at semiconductor surfaces, are also briefly discussed.

Enantioselective Protonation: Hydrophosphinylation of 1,1-Vinyl Azaheterocycle N-Oxides Catalyzed by Chiral Bis(guanidino)iminophosphorane Organosuperbase.

Enantioselective protonation by hydrophosphinylation of diarylphosphine oxides with 2-vinyl azaheterocycle N-oxide derivatives was demonstrated using chiral bis(guanidino)iminophosphorane as the higher-order organosuperbase catalyst. It was confirmed by several control experiments that a chiral weak conjugate acid of the chiral bis(guanidino)iminophosphorane, instead of achiral diarylphosphine oxides, directly functioned as the proton source to afford the corresponding product in a highly enantioselective manner in most cases. Enantioselective protonation by a weak conjugate acid generated from the higher-order organosuperbase would broaden the scope of enantioselective reaction systems because of utilization of a range of less acidic pronucleophiles. This method is highlighted by the valuable synthesis of a series of chiral P,N-ligands for chiral metal complexes through the reduction of phosphine oxide and N-oxide units of the corresponding product without loss of enantiomeric purity.

Enantioselective Protonation: Hydrophosphinylation of 1,1‐Vinyl Azaheterocycle N‐Oxides Catalyzed by Chiral Bis(guanidino)iminophosphorane Organosuperbase

AbstractEnantioselective protonation by hydrophosphinylation of diarylphosphine oxides with 2‐vinyl azaheterocycle N‐oxide derivatives was demonstrated using chiral bis(guanidino)iminophosphorane as the higher‐order organosuperbase catalyst. It was confirmed by several control experiments that a chiral weak conjugate acid of the chiral bis(guanidino)iminophosphorane, instead of achiral diarylphosphine oxides, directly functioned as the proton source to afford the corresponding product in a highly enantioselective manner in most cases. Enantioselective protonation by a weak conjugate acid generated from the higher‐order organosuperbase would broaden the scope of enantioselective reaction systems because of utilization of a range of less acidic pronucleophiles. This method is highlighted by the valuable synthesis of a series of chiral P,N‐ligands for chiral metal complexes through the reduction of phosphine oxide and N‐oxide units of the corresponding product without loss of enantiomeric purity.

Facile Reduction of Phosphine Oxides by O-Silylated Hydrazide Supported Hydrosilanes

The present work describes the investigations on a metal-free reduction of pentavalent tetracoordinate phosphine oxides to the corresponding trivalent phosphines using inexpensive hydrosilanes (Ph3SiH, Ph2SiH2, Et2SiH2, and Cl2SiMeH) in the presence of various activators including O-silylated hydrazide derivative. The presence of hydrazide precursor with CH3SiHCl2 leading to a hypercoordinate silicon(IV) complex has proved more effective in the reduction of phosphine oxides. Various phosphine oxides with substituents like alkyl, aryl, or N-alkyl on central phosphorus atom were reduced with notable features of chemoselectivity in the presence of other active reducible groups. They exhibited good to excellent yields under the safe reaction conditions. A generalized reduction mechanism has been proposed involving the formation of hypercoordinate silicon(IV) species as the key intermediates. According to the DFT calculations, the reactivity of silanes as reducing agents is influenced by the oxophilic/electrophilic nature of silicon atom present therein. On comparison, the order of reactivity calculated on the basis of NPA charge distribution appears as: pentacoordinate silicon(IV) complex > Ph3SiH > Cl2SiMeH > Ph2SiH2 ~ Et2SiH2 > PhSiH3 > SiH4.

1,3-Diphenyldisiloxane Enables Additive-Free Redox Recycling Reactions and Catalysis with Triphenylphosphine

The recently reported chemoselective reduction of phosphine oxides with 1,3-diphenyldisiloxane (DPDS) has opened up the possibility of additive-free phosphine oxide reductions in catalytic systems. Herein we disclose the use of this new reducing agent as an enabler of phosphorus redox recycling in Wittig, Staudinger, and alcohol substitution reactions. DPDS was successfully utilized in ambient-temperature additive-free redox recycling variants of the Wittig olefination, Appel halogenation, and Staudinger reduction. Triphenylphosphine-promoted catalytic recycling reactions were also facilitated by DPDS. Additive-free triphenylphosphine-promoted catalytic Staudinger reductions could even be performed at ambient temperature due to the rapid nature of phosphinimine reduction, for which we characterized kinetic and thermodynamic parameters. These results demonstrate the utility of DPDS as an excellent reducing agent for the development of phosphorus redox recycling reactions.

Catalytic and Asymmetric Process via PIII/PV═O Redox Cycling: Access to (Trifluoromethyl)cyclobutenes via a Michael Addition/Wittig Olefination Reaction.

In the present study, we report the first enantioselective and highly efficient phosphine-catalyzed process via a chemoselective in situ phosphine oxide reduction. Starting with 4,4,4-trifluorobutane-1,3-dione and dialkyl acetylenedicarboxylate substrates, highly functionalized fluorinated cyclobutenes were obtained in excellent yields and enantioselectivities. Using the same methodology, CF3-spirocyclobutene derivatives were also synthesized (34 examples, up to 95% ee).

Reduction of Phosphine Oxide by Using Chlorination Reagents and Dihydrogen: DFT Mechanistic Insights.

Extensive DFT calculations provide detailed mechanistic insights into the metal-free reduction of phosphine oxide Ph3 P=O by using chlorination reagents O=CClX (X=COCl, Cl, OCCl3 and Ph) and H2 . Fast electrophilic attack to the P=O group oxygen atom is favored by exergonic CO2 release to form phosphonium Ph3 PCl+ and chloride Cl- , which may slowly cleave H2 by an unstable HPh3 PCl complex yielding Ph3 PH+ and Cl- ions in solution. Moderate heating is required to accelerate the slow H2 -activation step and to eliminate HCl to form phosphine Ph3 P instead of Ph3 PH+ Cl- salt as the desired product. Though partially quenched by Ph3 P (and reactant Ph3 P=O if present), borane B(2,6-F2 C6 H3 )3 can be still combined with Cl- and Ph3 P as reactive frustrated Lewis pair (FLP) catalysts.

Mechanistic Insight into the Catalytic Staudinger Ligation.

Organophosphorus-catalyzed Staudinger ligation between carboxylic acids and azides in the presence of phenylsilane reductant produces amides. NMR-based mechanistic investigations revealed that the catalytic Staudinger ligation does not proceed via reduction of phosphine oxide but rather via reduction of iminophosphorane, which can subsequently undergo several transformations to produce the amide product.