New chiral phosphine-phosphonites derived from (2R,3R)-dimethyl tartrate, (S)-binaphthol and (1R,2S)-ephedrine

The reaction of 2-lithiophenyldiphenylphosphine with phosphorus trichloride afforded the new unsymmetric phosphine, dichloro(2-diphenylphosphinophenyl)phosphine (4). Condensation of 4 with (a) (2R,3R)-dimethyl tartrate or (b) (S)-binaphthol in the presence of triethylamine gave new chiral phosphine-phosphonite ligands, (2R,3R)-[2-(2′-(diphenylphosphino)phenyl)-4,5-bis(carbomethoxy)-1,3,2-dioxaphospholane] ((2R,3R)-5) and (S)-[2-(diphenylphosphino)benzene][1,1′-binaphthalen-2,2′-diyl]phosphonite] ((S)-6). The analogous reaction of 4 with (1R,2S)-ephedrine using N-methylmorpholine as the base, gave [2-(2′-(diphenylphosphino)phenyl)-3,4-dimethyl-5-phenyl-1,3,2-oxazaphospholidine] (7) as a 95:5 mixture of diastereoisomers.     

Stereoelectronic control in the base catalyzed hydrolysis of five-membered ring cyclic phosphonamidates

The base catalyzed hydrolysis of 2-phenyl-2-oxo-3-(2,6-dimethylphenyl)-1,3,2-oxazaphospholidine, $\text{6}$, and 2-phenyl-2-oxo-3-(2,6-diisopropylphenyl)-1,3,2-oxazaphospholidine, $\text{7}$, yields ring opened products involving 95% and 100% P-O cleavage, respectively.     

Chiral bicyclic spirophosphoranes in an arbuzov-type reaction

The reaction of 2-hydroxy-5-nitro-benzyl halides with three chiral five-or six-membered oxaphosphacycloalkanes has been studied. In each case, a ³¹P NMR analysis shows the formation of resonance signals in the phosphorane region but these phosphoranes are usually unstable. However both enantiomers of the 2-phenyl-1,3,2-oxazaphospholidine give chiral bicyclic spirophosphoranes which have been characterized by ³¹P and ¹H NMR and high resolution mass speetroscopies.     

Reaction of 5-oxo-2-phenyl-4,4-bis(trifluoromethyl)-4,5-dihydro-1,3,2-benzodioxaphosphepine with chloral. The synthesis and spatial structure of 5-carbaphosphatrane containing a four-membered ring

Phosphorylation of 2-hydroxyphenyl 2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl ketone with dichloro(phenyl)phosphine gave 5-oxo-2-phenyl-4,4-bis(trifluoromethyl)-4,5-di-hydro-1,3,2-benzodioxaphosphepine. Heating of the latter initiated an intramolecular interaction of the P atom with the carbonyl group. Hydrolysis of the intermediate product yielded 3-hydroxy-2-oxo-2-phenyl-3-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]-2,3-di-hydro-1,2λ⁵-benzo[d]oxaphosphole. The reaction was highly stereoselective (P_RC_S/P_SC_R). The reaction of the starting phosphepine with chloral proceeded highly stereoselectively (P_RC_SC_S/P_SC_RC_R) to give a 5-carbaphosphatrane derivative containing a four-membered ring, namely, 1-phenyl-3-trichloromethyl-10,10-bis(trifluoromethyl)-6,7-benzo-2,4,8,9-tetraoxa-1λ⁵-phosphatricyclo[3.3.2.0¹,⁵]decene. The trigonal bipyramid of the 5-carbaphosphatrane derivative is made up of the equatorial O atoms and the apical C atoms.     

Stereochemical Selection in Phosphoranyl Radical Formation Using Ionizing Radiation

Abstract

Recent electron spin resonance (ESR) experiments on phosphorus-centered radicals generated by ionizing radiation demonstrate that stereochemical aspects act strongly on the rate of radical formation and can be decisive in the selection between the possible resulting radical structures. This phenomenon was first established in a single crystal ESR study on radiogenic electron-capture phosphorus-centered radicals of the racemic and meso stereoisomers of 1.2-dimethyl-1,2-diphenyldiphosphine disulfide (1). The radiation process of the racemic form involves the formation of a symmetric species with a threeelectron bond in an overall low yield. The meso isomer, on the other hand, yields exclusively asymmetric radical configurations in which the unpaired electmn resides on one of the two phosphorus nuclei. The high intensity of the ESR spectra for the meso compound indicate a more efficient electron-capture process. A similar pronounced difference in radiosensitivity was observed for the R_p (1 and S_p (2) isomers of (4S,5R)-2-chloro-3,4-dimethyl-5-phenyl-1,3,2-Oxazaphospholidine 2-sulfide. Upon X irradiation, 1 readily results in an electron-capture phosphorus centered radical, whereas the concurrent process in 2 is almost completely absent. Since the geometric parameters of the atoms directly linked to phosphorus are very much alike for 1 and 2 il can be concluded that the efficiency of electron-capture at phosphorus strongly depends on the relative configuration of the distant chiral centers at C₄ and C₅.     

A convenient method for the preparation of chiral phosphonoacetamides and their Horner–Wadsworth–Emmons reaction

Chiral phosphonoacetamides bearing (S)-(α-methylbenzyl)benzylamine, (S,S)-bis(α-methylbenzyl)amine, l-phenylglycine methyl ester and l-phenylglycinol were easily prepared in good yield by means of the Michaelis–Arbuzov reaction of chiral bromoacetamides obtained in quantitative yield, with trimethyl phosphite, which under Horner–Wadsworth–Emmons conditions with several aryl and alkyl aldehydes under Masamune–Roush procedure using LiCl and DBU in THF or toluene gave the corresponding chiral α,β-unsaturated amides. The present procedure is a convenient and efficient methodology for the preparation of phosphonoacetamides and chiral α,β-unsaturated amides in high E-selectivity.     

Synthesis,Crystal Structure,and Diastereomeric Transfer of Pentacoordinated Phosphoranes Containing Valine or Iso-Leucine Residue

Pentacoordinated phosphoranes containing valine or iso-leucine residue (2-phenyl-2,7⁵-spiro[1,3,2-phenanthrodioxaphosphole-2,2′-1,3,2-oxazaphospholan]-5′-one) were synthesized through sequential two-step reactions, whereby the reaction products of phenyldichlorophosphine with N,O-bis(trimethylsilyl)valine or iso-leucine were followed by the addition of phenanthrenequione, and the crystals of 4a and 4b were obtained from benzene and hexane mixed solution. The x-ray structure of the crystals 4a and 4b revealed that they are distorted TBP, exhibiting R_P absolute configuration. The ³¹P NMR spectra showed that the S_P diastereomer could transfer into the other one R_P that came out from the solution during crystallization. Correspondingly, when it was dissolved in solvents the R_P diastereomer transferred into the other one S_P, and the pair of diastereomers changed each other in solution at room temperature through a phosphonium carboxylate zwitterions intermediate.

     

Turning Regioselectivity into Stereoselectivity: Efficient Dual Resolution of P‐Stereogenic Phosphine Oxides through Bifurcation of the Reaction Pathway of a Common Intermediate

Synthetic routes that provide facile access to either enantiomeric form of a target compound are particularly valuable. The crystallization‐free dual resolution of phosphine oxides that gives highly enantioenriched materials (up to 94 % ee) in excellent yields is reported. Both enantiomeric oxides have been prepared from a single intermediate, (R_P)‐alkoxyphosphonium chloride, which is formed in the course of a selective dynamic kinetic resolution using a single enantiomer of menthol as the chiral auxiliary. The origin of the dual stereoselectivity lies in bifurcation of the reaction pathway of this intermediate, which works as a stereochemical railroad switch. Under controlled conditions, Arbuzov‐type collapse of this intermediate proceeds through C O bond fission with retention of the configuration at the phosphorus center. Conversely, alkaline hydrolysis of the P O bond leads to the opposite S_P enantiomer.     

Reduction—complexation des thiophosphinates par le nickelocene

2-Phenyl-1,3,2-dioxaphosphorinane rearranges at 250°C to afford 2-phenyl-2-oxo-l,2-oxaphospholane which is, in turn, converted into the 2-thio derivative by P₄S₁₀. This cyclic thiophosphinate reacts with nickelocene and allyl iodide to yield

(L = 2-phenyl-1,2-oxaphospholane) by reduction—complexation. The same scheme is successfully applied to the 1-oxa-2-phosphacyclohepta-4,6-diene nucleus. Thus, the P^IV=S reduction—complexation process works with POC compounds. This is not the case with PSC compounds (for example, with dithiophosphinates). Some chemistry of 2-phenyl-l,3,2-dithiaphosphorinane is also described: Arbuzov reaction with PhCH₂Br, thermal rearrangement and complexation with nickelocene and allyl iodide.     

[NiCl2(dppp)]‐Catalyzed Cross‐Coupling of Aryl Halides with Dialkyl Phosphite,Diphenylphosphine Oxide,and Diphenylphosphine

We present a general approach to C? P bond formation through the cross‐coupling of aryl halides with a dialkyl phosphite, diphenylphosphine oxide, and diphenylphosphane by using [NiCl₂(dppp)] as catalyst (dppp=1,3‐bis(diphenylphosphino)propane). This catalyst system displays a broad applicability that is capable of catalyzing the cross‐coupling of aryl bromides, particularly a range of unreactive aryl chlorides, with various types of phosphorus substrates, such as a dialkyl phosphite, diphenylphosphine oxide, and diphenylphosphane. Consequently, the synthesis of valuable phosphonates, phosphine oxides, and phosphanes can be achieved with one catalyst system. Moreover, the reaction proceeds not only at a much lower temperature (100–120 °C) relative to the classic Arbuzov reaction (ca. 160–220 °C), but also without the need of external reductants and supporting ligands. In addition, owing to the relatively mild reaction conditions, a range of labile groups, such as ether, ester, ketone, and cyano groups, are tolerated. Finally, a brief mechanistic study revealed that by using [NiCl₂(dppp)] as a catalyst, the Ni^II center could be readily reduced in situ to Ni⁰ by the phosphorus substrates due to the influence of the dppp ligand, thereby facilitating the oxidative addition of aryl halides to a Ni⁰ center. This step is the key to bringing the reaction into the catalytic cycle.     

A study on the stereoselectivity of C,O bond formation in esterification of cyclic thiohydroxamic acids

Esterification of cyclic thiohydroxamic acids, for example, N-hydroxypyridine-2(1H)-thione, N-hydroxy-4-methylthiazole-2(3H)-thione, and N-hydroxy-4-(p-chlorophenyl)-thiazole-2(3H)-thione, occurred with inversion of configuration at the attacked stereocenter, as evident from the use of chiral alcohols, alkyl p-toluene sulfonates, and cyclic sulfates. Stereochemical analysis of enantiomerically pure O-alkyl thiohydroxamates was performed on the basis of CD-spectroscopy and chemical derivatization. The assignment of the relative configuration in cyclic O-esters was feasible via NMR spectroscopy, whereas chiral aliphatic glycolato monoesters required hydroxyl group derivatization with chloro-(4R,5R)-bis[(1R,2S,5R)-menth-1-yloxycarbonyl)]-1,3,2-dioxaphospholane for this purpose.     

Dichlorido[(S,RS)‐1‐diphenylphosphino‐2‐(ethylsulfanylmethyl)ferrocene]palladium(II)

The reaction of enantiomerically pure planar chiral ferrocene phosphine thioether with bis(acetonitrile)dichloridopalladium yields the title square‐planar mononuclear palladium complex as an enantiomerically pure single diastereoisomer, [PdFe(C₅H₅)(C₂₀H₂₀PS)Cl₂]. The planar chirality of the ligand is retained in the complex and fully controls the central chirality on the S atom. The absolute configuration, viz. S for the planar chirality and R for the S atom, is unequivocally determined by refinement of the Flack parameter.     

Chiral Phosphinophenyloxazolines Bearing Alkoxymethyl Substituents: Synthesis and Application in the Palladium Catalyzed Allylic Substitution Reactions

The chiral phosphine‐oxazoline ligands 3 and 4 bearing 4‐alkoxymethyl substituents on the oxazoline ring with (R)‐configuration were prepared from L‐serine methyl ester in 66% and 33% yields, respectively. Along this synthetic pathway, the β‐hydroxylamides derived from L‐serine methyl ester and 2‐halobenzoyl chlorides were expediently converted to the corresponding oxazolines by using diethylaminosulfur trifluoride as the activation agent. Potassium diphenylphosphide was the reagent of choice for replacing the bromine atom on the phenyl ring, giving the desired oxazoline‐phosphine ligands 3 and 4 . Together with [Pd(η³‐allyl)Cl]₂, ligands 3 and 4 induced an enantioselective allylic substitution reaction of 1,3‐diphenyl‐2‐pro‐penyl acetate by dimethyl malonate. Although ligands 3 and 4 exhibit the (R)‐configuration, differing from the (S)‐configuration of Pfaltz‐Helmchen‐Williams phosphine‐oxazoline ligands, all these ligands led to the same enantiotopic preference in the allylic substitution reaction. To facilitate the recovery and reuse of the phosphine‐oxazoline ligand, immobilization on Merrifield resin was attempted, albeit in low loading.     

Structural and electronic trends in ortho-metalated dirhodium(II) complexes

Properties of chiral dirhodium catalysts with ortho-metalated aryl phosphine ligands have been studied by a computational quantum chemical density functional theory method. The main aim in the current work was to systematically modify the ligand core of the Rh₂(O₂C R)₂(PC)₂ catalysts (PC is ortho-metalated aryl phosphine) in order to find structural and electronic trends involved with the modifications. The strongest impact on the properties of the active rhodium site was found when electron-withdrawing groups were introduced in the ligand core. The computational approach offers a possibility for a stepwise study of the properties of the catalysts and therefore a tool for further design of the most effective structures.     

Dediazoniation of arenediazonium salts with trivalent-phosphorus compounds. Tool for examination of the reactivity of phosphorus-centered radicals

Trialkyl phosphites ( 1 ), dialkyl phenylphosphinites ( 2 ), and alkyl diphenylphosphonites ( 3 ) as well as 2-phenyl-1,3,2-dioxaphospholan ( 4b ) and 2-phenyl-1,3,2-dioxaphosphorinan ( 4b ) give rise to dediazoniation of arenediazonium salt ( 5 ) in an alcoholic solvent under an argon atmosphere at 20°C. The reaction proceeds via a radical-chain mechanism initiated by single-electron transfer (SET) from the trivalent-phosphorus compounds to 5 , as a result of which, an aryl radical Ar⋅ and a cation radical 15 are generated from the former and the latter, respectively. The aryl radical Ar⋅ participates in this chain process abstracting a hydrogen from the solvent alcohol, yielding the corresponding arene ArH. The cation radical 15 undergoes both an ionic reaction with the solvent alcohol and a radical coupling with Ar⋅, giving the phosphoranyl radical 16 and the phosphonium ion 17 , respectively, as intermediates. The phosphoranyl intermediate 16 decomposes through either the SET process to 5 or by β-scission, yielding the oxidation product (phosphate, phosphonate, or phosphinate from 1 , 2 , or 3 , respectively, or phosphonates from 4 ). The phosphonium intermediate 17 affords the arylated product (phosphonate, phosphinate, or phosphine oxide from 1 , 2 , 3 , respectively, or the phosphinate from 4 ). Among the trivalent-phosphorus compounds tested, 1 gives the arylated product in the highest yield. This observation, together with the literature data of ESR for structurally related phosphoranyl radicals, indicates that the radical coupling of 15 with Ar⋅ is facilitated by the high spin density on its central phosphorus atom.     

Probing the steric limits of rhodium catalyzed hydrophosphinylation. P-H addition vs. dimerization/oligomerization/polymerization

The reactivity of secondary phosphine oxides containing bulky organic fragments in hydrophosphinylation reactions has been investigated using several rhodium based catalysts. Upon heating in a focused microwave reactor, HP(O)(2-C₆H₄Me)₂ adds to prototypical terminal alkynes affording a complex mixture containing 1,2 and 1,1-addition products. Addition of a second ortho-substituent (HP(O)Mes₂) completely suppresses the hydrophosphinylation reaction for alkyl and aryl substituted alkynes. Variations in the temperature, catalyst loading, solvent, and microwave power were unable to induce an addition reaction in the case of HP(O)Mes₂. While this secondary phosphine oxide did not participate in the hydrophosphinylation reaction, it promoted the polymerization of phenylacetylene. HP(O)R₂ substrates are not commonly thought of as innocent ligands for rhodium complexes in reactions involving alkynes due to facile hydrophosphinylation. While this is certainly true for diphenylphosphine oxide, the chemistry presented herein suggests that HP(O)Mes₂ and related bulky secondary phosphine oxides have great potential as valuable ligands for rhodium catalyzed transformations involving alkynes due to their lack of reactivity towards the addition reaction.     

Air-stable P-stereogenic secondary phosphine oxides as chiral monodentate ligands for asymmetric catalytic carboncarbon bond formation

P-Stereogenic secondary phosphine oxides are configurationally stable in the presence of metal ions both in solution and in the solid state. They have the potential to serve as chiral monodentate phosphorus ligands for asymmetric catalysis. In the asymmetric allylic alkylation of 1,3-diphenylprop-2-enyl acetate, ca. 80% ee was achieved using (R_p)-tert-butylphenylphosphine oxide.     

Asymmetric hydroformylation of styrene using rhodium and platinum complexes of diphosphites containing chiral chelate backbones and chiral 1,3,2-dioxaphosphorinane moieties

Several chiral diphosphite ligands containing six stereogenic centres were synthesised and tested in order to study chiral cooperativity in the Rh- and Pt-catalysed asymmetric hydroformylation of styrene. The ligands were prepared either by the reaction of 2,4-pentanediol enantiomers with (4R,6R)-4,6-dimethyl-2-chloro-1,3,2-dioxaphosphorinane or that of (1S,3S)-1,3-diphenyl-1,3-propanediol with 4,6-dimethyl-2-chloro-1,3,2-dioxaphosphorinane enantiomers. Thus the chirality was varied both in the chelate backbone and in the terminal groups of the ligands. In case of Pt-catalysed hydroformylation, the stereogenic elements in the bridge have been found to be determinate for the product configuration with a cooperative effect from the terminal groups when the constellations are matched with 40% e.e. maximum enantioselectivity. Some coordination chemistry and the crystal structure determination of these ligands are also reported.     

Umpolung of Methylenephosphonium Ions in Their Manganese Half‐Sandwich Complexes and Application to the Synthesis of Chiral Phosphorus‐Containing Ligand Scaffolds

Half‐sandwich manganese methylenephosphonium complexes [Cp(CO)₂Mn(η²‐R₂P?C(H)Ph)]BF₄ were obtained in high yield through a straightforward reaction sequence involving a classical Fischer‐type manganese complex and a secondary phosphine as key starting materials. The addition of various nucleophiles (Nu) to these species took place regioselectively at the double‐bonded carbon center of the coordinated methylenephosphonium ligand R₂P⁺?C(H)Ph to produce the corresponding chiral phosphine complexes [Cp(CO)₂Mn(κ¹‐R₂P? C(H)(Ph)Nu)], from which the phosphines were ultimately recovered as free entities upon simple irradiation with visible light. The synthetic potential of this umpolung approach is illustrated herein by the preparation of novel chiral pincer‐type phosphine–NHC–phosphine ligand architectures.     

Triphenylethanediol-Derived 2-Chloro-1,3,2- dioxaphospholane: Synthesis,Structure, and Reaction with Chiral Alcohols

The reaction of (S)-1,1,2-triphenylethanediol (3) with phosphorus trichloride leads to the diastereoselective formation of (S _C,R _P)-2-chloro-1,3,2-dioxaphospholane (2). Its configuration has been determined by single crystal X-ray diffraction. When reacted with racemic secondary alcohols, diastereomeric phosphites are obtained, which display substantial shift differences in the ³¹P NMR spectra. Thus, chlorodioxaphospholane 2 can serve as derivatizing reagent for chiral secondary alcohols permitting to determine their enantiomeric excess.