Phosphonate Carbanions Research Articles

Efficient Synthesis of Long‐wavelength Absorbing Cyanochlorophyll a Derivatives via Stereoselective Horner–Wadsworth–Emmons Reaction

In this article, we report the stereoselective Horner–Wadsworth–Emmons reaction of reactive carbonyl‐substituted chlorophyll a derivatives with diethyl cyanomethylphosphonate. We found that the formyl or keto group at the chlorin periphery can react stereoselectively with phosphonate carbanions to produce a series of cyanomethylene‐substituted chlorins with predominantly E geometry. Considering that no consistent records are available in the literature on the results of the allomerization of methyl pyropheophorbide a, we propose a reliable process for the transformation of this chlorophyll derivative. Our methodology represents a simple and efficient way for the preparation of novel, differently functionalized long‐wavelength absorbing chlorins, those can be applied for photodynamic therapy, solar cells, and other relevant purposes.

Hydrophosphonylation of chiral hexahydroquinoxalin-2(1H)-one derivatives as an effective route to new bicyclic compounds: Aminophosphonates, enamines and imines

A series of new aminophosphonate and phosphonic acid derivatives of hexahydroquinoxalin-2(1H)-ones and tetrahydroquinoxalin-2(1H)-ones were synthesised via hydrophosphonylation of the corresponding bicyclic imines with various dialkyl or diaryl H-phosphonates, H-phosphinates or H-phosphine oxides as phosphorus nucleophiles. The utility of the obtained compounds was demonstrated by their application as a source of phosphonate carbanion in the Horner-Wadsworth-Emmons (HWE) reaction leading to new bicyclic amines with an exocyclic, and unexpectedly, also endocyclic double bond depending on the structure of the aldehyde used.

Stereoselective syntheses of sanshool derivatives

Accessible methods for the syntheses of some representatives of tetradecapentaenoic acid derivatives using organophosphorus reagents and highly stereoselective properties of phosphonate carbanions were developed.

Olefination of N‐Sulfinylimines under Mild Conditions

A very simple and efficient diastereoselective synthesis of 1,2‐disubstituted alkenes has been achieved under mild conditions. Sulfoxide stabilised N‐sulfinylimines reacted with in‐situ‐generated phosphonate carbanions to give 1,2‐disubtituted alkenes in good to excellent yields. Different aryl phosphonates reacted with a range of electronically diverse N‐sulfinylimines to give alkenes with >99:1 E selectivity. The most important feature of this protocol is that the reaction can be carried out at room temperature with inexpensive sodium hydride as the most effective base to generate the reactive phosphonate carbanions, and producing the alkenes with E selectivity in up to 85 % isolated yield.

Tandem Chemoselective 1,2‐/1,4‐Migration of the Thio Group in Keto Thioesters: An Efficient Approach to Substituted Butenolides

AbstractWe report herein an efficient and mechanistically unique tandem chemoselective 1,2‐/1,4‐migration of the thio group in keto thioesters that provides substituted butenolides in moderate to excellent yields. Thus, α‐keto thioesters in the presence of stabilized phosphonate carbanions undergo tandem 1,2‐sulfur migration; whereas 1,4‐migration of the thio group has been achieved with the same thioesters after the treatment with Wittig reagents followed by BF3⋅OEt2‐catalyzed tandem reaction. The crossover experiments and the isolation of intermediates reveal a stepwise mechanism for both of these transformations.magnified image

Oxy-Wittig reactions of 1-naphthyl(aryl)methylphosphonates: a new approach to naphthylarylketones

Valuable compounds, naphthylarylketones are synthesized via oxy-Wittig (oxygenation of phosphonate carbanions) type reactions of diverse 1-naphthyl(aryl)methylphosphonates at room temperature by producing water soluble by-product. Commercially known but synthetically unexposed and expensive naphthylarylketones are easily synthesized using this transition metal-free, operationally simple strategy. As precursors, a range of new naphthyl(aryl)methylphosphonates are obtained in excellent yield and regioselectivity by direct and clean synthetic protocol that involves FeCl3 or triflic acid (TfOH) mediated arylation reactions of easily accessible (hydroxy)-1-naphthylmethylphosphonate with activated as well as unactivated arenes including halogenated anisoles, biphenyl, naphthalene and pyrene (extended π-systems) at room temperature.

有機化学反応からみた化学発光：過シュウ酸エステル化学発光を中心とした基礎的研究および応用展開

Chemiluminescence is a phenomenon in which an electronically excited fluorescent molecule is generated during the chemical reaction and emits light as a visual output. Although there have been numerous investigations of chemiluminescence so far, a lot of problems unsettled are remaining, for example, a question of what is the high-energy intermediates that interact with fluorophores. In this review, our investigations on chemiluminescence from the viewpoint of organic chemistry are described, emphasizing the mechanistic studies and the application of peroxyoxalate chemiluminescence. Employing various reactive oxalate derivatives, the kinetic studies allowed us to suggest the structures of the high-energy intermediates in the peroxyoxalate chemiluminescence. The chemiluminescence of the suitable phosphonate carbanions during the oxy-Wittig type reaction was also mentioned, in which the phospha-1,2-dioxetane is the most likely high-energy intermediate. Some chemiluminescence reactions were connected with ligand-metal ion host-guest chemistry to get a useful hint for further application of chemiluminescence to chemical detection.

Application of Silicon-based Methodologies for the Synthesis of Functionalized Mono- and Bisphosphonic Acids

The aim of this article is to present an overview of new and useful silicon-based methodologies valuable for the selective construction of highly functionalized mono- and bisphosphonic acids of high synthetic and biological importance. The reactions of trimethylsilyl phosphites with alkyl halides, carbonyl compounds and imines are presented as a platform for developing new approaches to biologically active hydroxy-, amino-, fluoro-substituted mono- and bisphosphonates. The second part of the review consists of a presentation of methodology involving the fluoride-induced formation of α-phosphonylated carbanions from 1-trimethylsilyl methylphosphonates. The third part of the review describes the methodology employing silylated phosphonate carbanions. Application of trimethylsilyl as protecting group is discussed in separate section. Keywords: Silicon, phosphonic acids, bisphosphonic acids, organosilicon-mediated synthesis, phosphites, herbicides, pesticides, antibiotics, antiviral, antitumor agents, enzyme inhibitors, calcium metabolism, osteolysis, hexamethyldisilazane (HMDS), phosphocarnitine

ChemInform Abstract: Reactions of Phosphonate Carbanions with Selenium or Sulfur in the Presence of Amines. Synthesis of Seleno- and Thioamides.

The reaction of phosphonate carbanions with elemental selenium in the presence of amines afforded the corresponding selenoamides in moderate yields. The reaction of these anions with sulfur also gave thioamides. These reactions might proceed through thio- or selenoaldehyde intermediates

A facile access to condensed and spirosubstituted pyrimidine phosphor esters

Treatment of alloxan-5-oximes with different types of phosphonate carbanions gave moderate to high yields of condensed and spiro bis-heterocyclic systems bearing a phosphonate substituent. Mechanisms for the formation of the five- and six-membered rings were provided. A marked resemblance between alloxan-5-oxime and 1,3-dimethyl derivative is observed through the studied reactions. The bioassay indicated that some of the products have good selective anti- tumor activity and the structure-activity relationship (SAR) of new phosphonates has also been studied.

Easy and Stereoselective Synthesis of Cyclopropyl-Substituted Phosphonates via α-Chlorophosphonates

A facile stereoselective synthesis of cyclopropylphosphonates from the reaction of inexpensive α-chlorophosphonates with alkyl acrylates in the presence of sodium hydride is reported. Reaction with dimethyl maleate or fumarate also leads to cyclopropyl-substituted phosphonates. These reactions take place via Michael addition of acrylate, dimethyl maleate, or fumarate to the phosphonate carbanion, followed by expulsion of the chloride ion.

Diastereoselective Synthesis of 2-Amino-4-phosphonobutanoic Acids by Electrophilic Substitution and Tin−Peterson Olefination of Bis-lactim Ethers Derived fromcyclo-[l-AP4-d-Val

Electrophilic substitutions on lithiated Schöllkopf's bis-lactim ethers derived from cyclo-[L-AP4-D-Val] take place regio- and stereoselectively at the alpha-position of the phosphonate ester. Subsequent olefination of alpha-silyl-, alpha-phosphoryl-, and alpha-stannyl-stabilized phosphonate carbanions give rise exclusively to vinylphosphonates. Both processes allow a direct and stereoselective access to a variety of 4-substituted and 3,4-disubstituted 2-amino-4-phosphonobutanoic acids (AP4 derivatives) in enantiomerically pure form that may be useful tools for characterizing the molecular pharmacology of metabotropic glutamate receptors (mGluRs) of group III. The relative stereochemistry was assigned from X-ray diffraction analyses or NMR studies of 1,2-oxaphosphorinane and other cyclic derivatives. In accordance to density functional theory (DFT) calculations, the syn-selectivity in the electrophilic substitutions may originate from the intervention of seven- and eight-membered chelate structures in which the bis-lactim ether moiety shields one of the faces of the phosphonate carbanion. DFT calculations for the tin-Peterson olefination of alpha-stannyl stabilized phosphonate carbanions indicate that rate and selectivity are determined in the initial carbon-carbon bond formation step where the unlike transition structures leading to (Z)-vinylphosphonates are favored both in the gas phase and in THF solution.

Practical Stereoselective Synthesis of (2E)‐ and (2Z)‐4‐Cycloalkylidenebut‐2‐enoic Acids

Stereoselective synthesis of α,β‐unsaturated esters 7 and 8 was achieved through Horner–Wadsworth–Emmons reaction of β,β‐disubstituted α,β‐unsaturated aldehydes. Thus, aldehydes 6 undergo olefination with phosphonate carbanion generated from triethyl phosphonoacetate 3 and lithium hydroxide or butyl lithium/DMPU to give (E)‐α,β‐unsaturated esters 7 with excellent selectivity. The treatment of 6 with the new Horner–Emmons reagents, ethyl(diphenylphosphono)acetate 4a and ethyl (di‐o‐tolyl‐phosphono) acetate 4b in the presence of benzyltrimethyl ammonium hydroxide (Triton B) afforded (Z)‐α,β‐unsaturated esters 8 with 73–89% selectivity. The esters 7 and 8 were converted to (2E)‐ and (2Z)‐4‐cycloalkylidenebut‐2‐enoic acids 9 and 10, respectively.

Practical Stereoselective Synthesis of (2E)‐ and (2Z)‐4‐Cycloalkylidenebut‐2‐enoic Acids.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Chemiluminescence in autoxidation of phosphonate carbanions. Phospha-1,2-dioxetanes as the most likely high-energy intermediates.

Autoxidation of the phosphonate carbanions derived from 9-phosphono-10-hydroacridanes provided chemiluminescence ascribed to the excited acridone anion. The intramolecular CIEEL (chemically initiated electron exchange luminescence) mechanism can be applied to this chemiluminescence because of the much higher emission efficiency compared to that of 9-phosphono-10-methylacridanes. The effect of the phosphonate substituents on the emission efficiency and especially on the rates of the chemiluminescence decay can be interpreted to originate from the valence deviation of the phosphorus atoms, which is connected with the substituent effect on the geometrical selectivity in the olefination reaction of the phosphonate carbanions. The enhanced chemiluminescence in the presence of the fluorophores was also detected in autoxidation of the carbanions of diethyl diphenylmethylphosphonate and fluorenylphosphonate. Although the evidence is circumstantial, these results strongly support the belief that phospha-1,2-dioxetane is the most likely high-energy intermediate generating the excited molecules.

A Comparison of Phosphonium and Phosphonate Carbanion Reagents in Reactions with 1,3‐Diphenyl‐2‐(hydroxyimino)‐1,3‐propanedione.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Diastereoselective Synthesis of 4‐Alkylidene‐2‐amino‐4‐phosphonobutanoic Acids.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Gas chromatographic analysis of the thermally unstable dimethyl methylphosphonate carbanion via trimethylsilyl derivatization.

A sensitive gas chromatographic method was developed to monitor the reaction of lithium diisopropylamide (LDA) with dimethyl methylphosphonate (DMMP) to generate the phosphonate carbanion (DMMPA). Analysis of the DMMPA was complicated due to its thermal instability and lack of a chromophore. To overcome these problems, samples were derivatized with trimethylsilylchloride (TMSCI) to form DMMPA-TMS which was sufficiently volatile and thermally stable for GC analysis. Work-up of the derivatized solution with 10 vol.% 2-propanol in hexanes was necessary to quench residual TMSCI prior to GC analysis. The presence of DMMPA-TMS and other sample components was confirmed by GC-MS analysis. This method was utilized to profile the synthesis of DMMPA as DMMP was added to LDA and then aged at -78 degrees C. Method precision for DMMPA-TMS of less than 0.2% RSD was achieved for repeat injections after normalization of the response with n-dodecane contained in the sample. Due to the thermal instability of the DMMPA, subambient derivatization temperatures were essential to the stability, and consequently, accurate quantification. Under optimized conditions, this derivatization was successfully utilized as a process monitoring tool.

Diastereoselective synthesis of 4-alkylidene-2-amino-4-phosphonobutanoic acids

Olefination of α-silyl-, α-phosphoryl- and α-stannyl-stabilised phosphonate carbanions derived from cyclo-[ l-AP4- d-Val] Li + 4b– d − allow a ( Z)-selective access to the α,β-substituted vinylphosphonates 7A– E that have been transformed into enantiomerically pure 4-alkylidene AP4 derivatives 12A, B and 13A, C . According to semi-empirical (PM3) calculations, the preference for like topologies in the intermediate adducts of the phosphonate addition step accounts for the highly ( Z)-selective course of the ‘tin-Peterson-like’ olefination.

A Comparison of Phosphonium and Phosphonate Carbanion Reagents inReactions with 1,3-Diphenyl-2-(hydroxyimino)-1,3-propanedione

1,3-Diphenyl-2-(hydroxyimino)-1,3-propanedione 1 reacted with phosphonium ylides 2a,b to give mainly the substituted 1-hydroxy-2,3-dihydropyrroles 6a,b along with the novel ylides 10a,b whereas the phosphono substituted-N-heterocycles lla,b and 14a,b were obtained from the reaction of I with α-phosphoryl carbanion counterparts 3a,b. Reaction of 1 with cyanomethylene(tri-phenyl)phosphorane 2c afforded the Wittig product 17 and the oxazole derivative 18 while the phosphono 2,2-disubstituted dihydrooxazole 20 and the diolefin 19 were produced in the reaction with the phosphonate ylide 3c. Application of the unsaturated carbanions 2d and 3d on 1 yielded the pyrrole 23 and the phosphono substituted 2H-1,4-oxazine 25, respectively.