phospha-Michael Addition Research Articles

Recent advances in studying the mechanism of phospha-Michael addition of tertiary phosphines to electron-deficient alkenes on the basis of kinetic isotope effects

The previously proposed mechanism for phospha-Michael addition of tertiary phosphines to electron-deficient alkenes has been amended according to the secondary kinetic isotope effects provided by α-deuterated activated alkenes. The data obtained have shown that rate-determining protonation of intermediate phosphonium zwitterion proceeds not directly at its carbanionic center but first at a heteroatom of the attached electron-withdrawing group, with subsequent isomerization of the enolic/eniminic intermediate to stable keto-/cyanophosphonium product.

Magnesium Perchlorate Catalyzed Phospha-Michael Addition of Dialkyl Phosphite to Chalcone

Aim and Objective: Phosphonate possesses a broad range of applications ranging from agrochemistry to medicines. Because of the synthetic and biological importance of phosphonate, their chemistry has stimulated an increasing interest. Hence we developed an efficient and eco-friendly Mg(ClO4)2 catalyzed one pot, solvent free synthesis of phosphonate derivatives of chalcones. Materials and Methods: Magnesium perchlorate phosphonate derivatives of chalcones were synthesized. The reactions were executed at room temperature in the presence of Anhydrous Magnesium perchlorate Anhy. Mg(ClO4)2 under solvent free condition, affording high yield of the product. The cardinal significance of the method lies in its uncomplicated and eco- friendly experimental conditions. Results: The PMA method for P-C bond formation, using dialkyl phosphite with chalcone, was performed in the presence of Anhydrous Magnesium perchlorate under solvent free condition. Despite the solvent free condition, the methodology is efficient since it is required only in catalytic amount of Anhy. Mg(ClO4)2 in one pot reaction. Results demonstrated that the catalytic PMA of dimethyl phosphite, diethyl phosphite, diisopropyl phosphite and dibutyl phosphite with chalcone generates desired products with a percentage yield of 60-80%. Conclusion: We have developed a new efficient PMA method for P-C bond formation, using dialkyl phosphite with α,β-unsaturated ketone i.e. chalcone. To the best of our knowledge, Anhy. Mg(ClO4)2 catalyzed phosphamicheal addition of dialkyl phosphite with chalcones was found to be a new and efficient method for various biological applications.

Organocatalytic asymmetric cascade cyclization reaction of o-hydroxy cinnamaldehydes with diphenylphosphine oxide

A highly stereoselective asymmetric cascade cyclization reaction between o-hydroxycinnamaldehydes and diphenylphosphine oxide has been achieved with 84%–99% ee and 7:1-20:1 dr under the catalysis of l-diarylprolinol silyl ether. This reaction provides a facile access to highly enantioenriched 4-diphenylphosphinyl chroman-2-ols. It also represents a novel organocatalytic asymmetric phospha-Michael addition of α,β-unsaturated aldehydes with pentavalent P-nucleophiles.

Organocatalytic Phosphonylation of in Situ Formed o-Quinone Methides.

A new class of Brønsted acid catalysts based on N-heterocyclic phosphorodiamidic acids (NHPAs) has been developed. The NHPA catalyst promotes phospha-Michael addition reaction of trialkylphosphites to in situ generated ortho-quinone methides (o-QMs) for the construction of diaryl phosphonates in moderate to excellent yields with 1.5 mol % catalyst. Diastereoselective synthesis of P-chiral phosphinate esters is achieved with the use of dialkyl phenylphosphonites.

Azetidine-derived dinuclear zinc catalyzed asymmetric phospha-Michael addition of dialkyl phosphite to α,β-unsaturated carbonyl compounds.

The asymmetric phospha-Michael addition of dialkyl phosphite to α,β-unsaturated carbonyl compounds by using an azetidine-derived dinuclear zinc catalyst was described. The catalyst was proved to be general and efficient for a broad spectrum of enones and α,β-unsaturated N-acylpyrroles. A series of phosphonate-containing compounds were generated with excellent enantioselectivities (up to 99% ee) and chemical yields (up to 99%) under mild conditions without using additives. The products were obtained with more than 95% ee for 23 examples of α,β-unsaturated carbonyl compounds. A positive nonlinear effect was observed and the possible mechanism was proposed.

A Reagent-Controlled Phospha-Michael Addition Reaction of Nitroalkenes with Bifunctional N-Heterocyclic Phosphine (NHP)-Thioureas.

Bifunctional N-heterocyclic phosphine (NHP)-thioureas have been successfully applied for phospha-Michael addition reaction of nitroalkenes to afford diversely substituted β-nitrodiazaphosphonates. This transformation takes place at room temperature under catalyst-free conditions and exhibits broad functional group tolerance. The key to success in catalyst, additive-free reaction conditions is the suitable hydrogen-bond activation of the nitro group by a Brønsted acid (thiourea), which artfully combined with the highly nucleophilic NHP motif for a synergetic effect. Importantly, this transformation enables a two-step synthesis of pharmaceutically, biologically significant β-amino phosphonic acids.

Amine-Catalyzed Phospha-Michael Reaction of α,β-Unsaturated Aldehydes and Ketones with Multifunctional N-Heterocyclic Phosphine-Thioureas as Phosphonylation Reagent.

An efficient amine-catalyzed phospha-Michael addition reaction of α,β-unsaturated aldehydes/ketones with N-heterocyclic phosphines for the synthesis of γ-ketodiazaphosphonates has been developed. With freedom from nucleophile additives, this mild process affords a range of structurally diverse γ-ketodiazaphosphonates in moderate to excellent yields. Importantly, various α,β-unsaturated ketones were also tolerated in this process and gave moderate yields.

Mechanistic insights into phospha–Michael reaction of tertiary phosphines with electron-deficient alkenes

ABSTRACTThe Michael-type addition of tertiary phosphines to electron-deficient alkenes is a convenient way to generate reactive phosphonium zwitterionic intermediates, which participate readily in many synthetically useful transformations. Although the synthetic usefulness of the phospha–Michael addition has been largely demonstrated, knowledge on the kinetics and mechanism of this reaction is sparse. This paper briefly summarizes the contribution of our research group to find out the mechanism of this reaction.

A Polymer-Supported Phosphazene Catalyst for Phospha-Michael Additions

Key words heterogeneous catalysis - phospha-Michael addition - alkenes - phosphazenes - phosphonates

Phospha-Michael Addition as a New Click Reaction for Protein Functionalization.

A new type of click reaction between an alkyl phosphine and acrylamide was developed and applied for site-specific protein labeling in vitro and in live cells. Acrylamide is a small electrophilic olefin that readily undergoes phospha-Michael addition with an alkyl phosphine. Our kinetic study indicated a second-order rate constant of 0.07 m(-1) s(-1) for the reaction between tris(2-carboxyethyl)phosphine and acrylamide at pH 7.4. To demonstrate its application in protein functionalization, we used a dansyl-phosphine conjugate to successfully label proteins that were site-specifically installed with N(ɛ) -acryloyl-l-lysine and employed a biotin-phosphine conjugate to selectively probe human proteins that were metabolically labeled with N-acryloyl-galactosamine.

Palladium-Catalyzed Asymmetric Phospha-Michael Reaction

Key words hydrophosphination - chiral phospines - phospha-Michael addition

Phospha-Michael addition reaction of maleimides employing N-heterocyclic phosphine-thiourea as a phosphonylation reagent: synthesis of 1-aryl-2,5-dioxopyrrolidine-3-yl-phosphonate derivatives.

N-Heterocyclic phosphine (NHP)-thiourea as a novel phosphonylation reagent has been successfully applied for the phospha-Michael reaction of maleimides under catalyst and additive free reaction conditions. This methodology enables desymmetrization of a variety of maleimide derivatives to provide 1-aryl-2,5-dioxopyrrolidine-3-yl-phosphonates in up to 92% yield. Synthetic manipulation of this Michael adduct afforded an ethylphosphonate and a phosphino lactam. Furthermore, a scale-up experiment for its practical usage as a versatile precursor in organic synthesis was readily demonstrated.

PS-BEMP as a basic catalyst for the phospha-Michael addition to electron-poor alkenes.

PS-BEMP was used as a heterogeneous catalyst for the phospha-Michael addition of phosphorus nucleophiles to a variety of electron-poor alkenes. The addition reactions were generally performed with equimolar amounts of reagents under solvent free conditions. The protocol proved to be very efficient for the addition to aromatic, non-aromatic and cyclic ketones, giving good yields (78-85%) in all cases. The protocol was also extended with good results to α,β-unsaturated esters and nitriles. This demonstrates that PS-BEMP is a good catalyst for the phospha-Michael addition to electron-poor alkenes.

The Pudovik Reaction Catalyzed by Tertiary Phosphines

Conjugate addition of dialkyl phosphites and ethyl phenylphosphinate to electron-deficient alkenes containing ester, nitrile or amide group under PBu3 catalysis afforded corresponding phosphonates and phosphinates in high yields within short reaction times. Under the optimized conditions developed, the chemistry was free from side reactions involving competitive phosphine-catalyzed dimerization of the activated alkene. Long chain alkyl groups in the phosphite were well tolerated in this transformation. The catalytic activity of PBu3 was far superior to that of tertiary amines. High efficiency, mild reaction conditions, and ease of the catalyst recovery make the proposed procedure competitive with the classical base-promoted reaction. Keywords: Alkyl H-phosphinates, dialkyl phosphites, phospha-Michael addition, phosphine-catalyzed reactions, phosphonium zwitterions, X-ray analysis.

Ionic Liquid–Promoted Phospha-Michael Reaction: Convenient Access to β-Nitrophosphonates

A convenient and mild procedure is developed for β-nitrophosphonates via phospha-Michael addition of phosphites to nitrostyrene at room temperature in the presence of 1,8-diazabicyclo-[5.4.0]undec-7-ene (DBU)–based ionic liquid [DBUH][OAc]. The operational simplicity, convenient workup, and reusability of the ionic liquid make this method attractive.

Zeolitic imidazolate frameworks as heterogeneous catalysts for a one-pot P–C bond formation reaction via Knoevenagel condensation and phospha-Michael addition

ZIF-8 promotes a sequential one-pot reaction efficiently to produce organophosphorus compounds via Knoevenagel condensation and phospha-Michael addition.

Pyridine-grafted graphene oxide: a reusable acid–base bifunctional catalyst for the one-pot synthesis of β-phosphonomalonates via a cascade Knoevenagel–phospha Michael addition reaction in water

Py–GO as a new acid–base bifunctional catalyst was synthesized and employed for the one-pot synthesis of β-phosphonomalonates in water.

ChemInform Abstract: Enantioselective Phospha‐Michael Addition of Diarylphosphines to β,γ‐Unsaturated α‐Ketoesters and Amides.

AbstractThe first protocol involving the catalytic enantioselective phospha‐Michael addition of β,γ‐unsaturated α‐ketoesters and amides is presented.

ChemInform Abstract: Chiral Ytterbium Silylamide Catalyzed Enantioselective Phospha‐Michael Addition of Diethyl Phosphite to Chalcones.

An efficient and enantioselective phospha-Michael addition of diethyl phosphite to chalcones has been established. In the presence of a catalytic amount of chiral lanthanide silylamide generated from [(Me3Si)2N]3Yb(μ-Cl)Li(THF)3 and salen, the reaction produced the target γ-oxophosphonates with high yields and enantioselectivity.

ChemInform Abstract: Microwave‐Assisted Synthesis of P‐Heterocycles

AbstractReview: 73 refs.