Optically active phosphine oxides. 5. P-chiral 2-aminoethyl phosphine oxides

Homochiral 2-aminoethyl phosphine oxides are expeditiously prepared by thermal addition of primary and secondary amines to (−)-(S)-methylphenylvinylphosphine oxide. Their transformation into optically active 2-aminoethyl phosphines and 2-aminoethyl phosphine sulphides is exemplified.     

Enantioselective reactions catalyzed by phosphine oxides

The development of chiral small organic molecules that serve as Lewis base catalysts promoting highly stereoselective transformations has been the subject of intense research over the past decades. As a matter of fact, among the plethora of molecules used as Lewis bases, chiral phosphine oxides have thoroughly been overlooked by the organic synthetic community. Thus, this review focuses exclusively on Lewis base catalysis mediated by chiral phosphine oxides with emphasis on mechanistic aspects, covering most of the publications related to this field since their first use as organocatalyst in 2005 until the end of March 2019.     

Thermal rearrangement of bis(hydroxymethyl)phosphines as a way to P-chiral phosphine oxides

Bis(hydroxymethyl)(2-pyridyl)- and bis(hydroxymethyl)-[(2-pyridyl)ethyl]phosphines on heating to 180 °C undergorearrangement leading to racemic P-chiral tertiary P-methyl-P-(hydroxymethyl)-containing phosphine oxides. The spontaneous self-resolution of these enantiomer mixtures during the crystallization was demonstrated.     

Enantioselective preparation of N-chirogenic tertiary amine oxides

We found that PLE can be used as an efficient catalyst for desymmetrization of prochiral tertiary amine N-oxides and demonstrated that they were hydrolyzed by PLE efficiently to afford N-chirogenic tertiary amine oxides up to 99% ee in moderate to good yields.     

Microemulsions with alkyldimethyl phosphine oxides and alkyldiethyl phosphine oxides

Alkyldimethyl phosphine oxides (C n DMPO) as well as alkyldiethyl phosphine oxides (C n DEPO) with chain lengths of n = 10 (decyl), 12 (dodecyl), and 14 (tetradecyl) were synthesized and purified to study how the formation of microemulsions depends on the size of the headgroup and on the length of the alkyl chain. For that purpose, equal amounts of water and n-octane were taken and surfactant was added to solubilize the two solvents. The resulting fish-shaped phase diagrams for C 10DEPO, C 12DEPO, and C 14DEPO show that the longer the hydrophobic chain the more efficient the surfactant. Simultaneously, the extension of the lamellar phase (L alpha) shifts toward lower total mass fractions gamma of the surfactant, i.e., the tendency to form lyotropic liquid crystals (LCs) increases. These trends are well-known for nonionic alkyl ethylene oxides and can thus be interpreted accordingly. What is astonishing, however, is the significant influence the size of the short side chains has. Replacing two methyl groups by two ethyl groups leads to a drastic drop of the three-phase region toward lower temperatures, while the efficiency remains nearly unchanged. Moreover, the tendency to form LCs decreases significantly.     

Nickel-catalyzed kinetic resolution to achieve P-chiral phosphine oxides and sec-phosphine oxides

P-Chiral phosphines and sec-phosphine oxides(SPO) are found in a diverse range of compounds that play crucial roles in various fields, including asymmetric catalysis, materials, agrochemistry, and pharmaceutical chemistry. Herein, we describe an enantioselective Ni-catalyzed kinetic resolution of racemic sec-phosphine oxides to obtain the corresponding optically pure Pchiral phosphine oxides and sec-phosphine oxides, respectively. These products are versatile chiral phosphine building blocks tha...     

An air-stable P-chiral phosphine ligand for highly enantioselective transition-metal-catalyzed reactions

A new P-chiral phosphine ligand, (R,R)-2,3-bis(tert-butylmethylphosphino)quinoxaline, has been prepared by the reaction of enantiomerically pure tert-butylmethylphosphine-borane with 2,3-dichloroquinoxaline. This ligand, in contrast to most of the previously reported P-chiral ligands, is an air-stable solid and exhibits excellent enantioselectivities in both Rh-catalyzed asymmetric hydrogenations and Rh- or Pd-catalyzed carbon-carbon bond-forming reactions.     

Chiral bisphosphinite metalloligands derived from a P-chiral secondary phosphine oxide

Interaction of PdCl(2)(MeCN)(2) with 2 equiv of (S(P))-(t)BuPhP(O)H (1H) followed by treatment with Et(3)N gave [Pd((1)(2)H)](2)(micro-Cl)(2) (2). Reaction of 2 with Na[S(2)CNEt(2)] or K[N(PPh(2)S)(2)] afforded Pd[(1)(2)H](S(2)CNEt(2)) (3) or Pd[(1)(2)H)[N(PPh(2)S)(2)] (4), respectively. Treatment of 3 with V(O)(acac)(2) (acac = acetylacetonate) and CuSO(4) in the presence of Et(3)N afforded bimetallic complexes V(O)[Pd(1)(2)(S(2)CNEt(2))](2) (5) or Cu[Pd(1)(2)(S(2)CNEt(2))](2) (6), respectively. X-ray crystallography established the S(P) configuration for the phosphinous acid ligands in 3 and 6, indicating that 1H binds to Pd(II) with retention of configuration at phosphorus. The geometry around Cu in 6 is approximately square planar with the average Cu-O distance of 1.915(3) A. Treatment of 2 with HBF(4) gave the BF(2)-capped compound [Pd((1)(2)BF(2))](2)(micro-Cl)(2) (7). The solid-state structure of 7 containing a PdP(2)O(2)B metallacycle has been determined. Chloride abstraction of 7 with AgBF(4) in acetone/water afforded the aqua compound [Pd((1)(2)BF(2))(H(2)O)(2)][BF(4)] (8) that reacted with [NH(4)](2)[WS(4)] to give [Pd((1)(2)BF(2))(2)](2)[micro-WS(4)] (9). The average Pd-S and W-S distances in 9 are 2.385(3) and 2.189(3) A, respectively. Treatment of [(eta(6)-p-cymene)RuCl(2)](2) with 1H afforded the phosphinous acid adduct (eta(6)-p-cymene)RuCl(2)(1H) (10). Reduction of [CpRuCl(2)](x)() (Cp = eta(5)-C(5)Me(5)) with Zn followed by treatment with 1H resulted in the formation of the Zn(II) phosphinate complex [(CpRu(eta(6)-C(6)H(5)))(t)BuPO(2))](2)(ZnCl(2))(2) (11) that contains a Zn(2)O(4)P(2) eight-membered ring.     

Unprecedented base effect on the synthesis of chiral phosphinate esters: A new route to P-chiral phosphine oxides of high enantiomeric purity

The stereochemical outcome of the reaction of chiral secondary alcohols with a phosphinyl chloride was found to be highly dependent on the achiral base used. Thus, the reaction of the readily available sugar derived carbinols, 1 and 2, with methylphenylphosphinyl chloride in the presence of triethylamine yields stereoselectively the corresponding Snp-phosphinates 3Sp and 5Sp in 94 and 92% diastereomeric excess (de). Simply changing the base from triethylamine to pyridine affords Rp-phosphinates 4Rp and 6Rp epimers to 3Sp and 5Sp at the phosphinyl phosphorus in 50 and 40% de respectively. These phosphinate esters were found to be good P-chiral transferring intermediates, they react with Grignard reagents under very mild conditions to give the corresponding phosphine oxides. Both enantiomers Sp- and Rp-o-anisylmethylphenylphosphine oxide (PAMPO) as well Sp- and Rp- methylphenylpropyl phosphine oxide were obained enantiomerically pure in high yields     

Michael-type addition of secondary phosphine oxides to (1,4-cyclohexadien-3-yl)phosphine oxides

Base-induced reaction between (1,4-cyclohexadien-3-yl)phosphine oxides and secondary phosphine oxides gives 3,4-bis(phosphinoyl)cyclohexenes and 2,3-bis(phosphinoyl)cyclohexenes through an in situ isomerization of one of the cyclohexadienyl double bonds and a subsequent Michael-type addition of the secondary phosphine oxide.     

New polydentate amino-substituted phosphine oxides

Conclusions We have synthesized new diamino-substituted bis(phosphine oxides) in which the coordination centers are separated by fragments with different rigidities.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 9, pp. 2114–2117, September, 1978.     

Reduction of phosphine oxides to phosphines

The digest is devoted to the most widespread reducing agents which are used for the reduction of tertiary and secondary phosphine oxides, phospholene oxides, phospholane oxides, phosphonates, phosphinates, α- and β-hydroxy and thiomethyl phosphine oxides, α-aminophosphine oxides. Stereoselectivity of reactions is described. Methods of stabilization of phosphines which are prone to re-oxidation by the formation of borane-adduct or metal complexes are considered.     

Selective reduction of allenyl(diphenyl)phosphine oxides to allyl(diphenyl)phosphine oxides

The reduction of allenyl(diphenyl)phosphine oxides with HSiCl₃ or LiAlH₄ selectively afforded the corresponding allyl(diphenyl)phosphine oxides. 3-Methylbut-2-en-1-yl(diphenyl)phosphine oxide reacted with AlCl₃ to give a mixture of 4,4-dimethyl-1-phenyl-1,2,3,4-tetrahydro-λ⁵-phosphinoline 1-oxide and 4,4-dimethyl-1-phenyl-1,4-dihydro-λ⁵-phosphinoline 1-oxide.     

Highly stereoselective,thermodynamically controlled and reversible formation of a new P-chiral phosphine

The highly stereoselective formation of a chiral alpha-hydroxyphospholane under very mild condition is reported, taking place on a camphor skeleton by an intramolecular thermodynamically controlled and reversible addition of an epimeric secondary phosphine group to a carbonyl group.     

(Perfluoroalkyl-ethyl) dimethyl phosphine oxides

Phosphine oxidesC_nF_2n+1-C₂H₄-P(O)Me₂, as well as mixtures of the same with C_nF_2n+1-CH Me-P(O)Me₂ are synthesized in two ways. Some of them display outstanding surface activity.     

Reduction of tertiary phosphine oxides with DIBAL-H

The reduction of tertiary phosphine oxides (TPOs) and sulfides with diisobutylaluminum hydride (DIBAL-H) has been studied in detail. An extensive solvent screen has revealed that hindered aliphatic ethers, such as MTBE, are optimum for this reaction at ambient temperature. Many TPOs undergo considerable reduction at ambient temperature and then stall due to inhibition. 31P and 13C NMR studies using isotopically labeled substrates as well as competition studies have revealed that the source of this inhibition is tetraisobutyldialuminoxane (TIBAO), which builds up as the reaction proceeds. TIBAO selectively coordinates the TPO starting material, preventing further reduction. Several strategies have been found to circumvent this inhibition and obtain full conversion with this extremely inexpensive reducing agent for the first time. Practical reduction protocols for these critical targets have been developed.     

Reaction of secondary phosphine oxides with acylacetylenes

Secondary phosphine oxides reacted with 1-alkanoyl-2-phenylacetylenes in chemoselective fashion under mild conditions (20°C, THF) in the absence of a catalyst (diphenylphosphine oxide) or in the presence of potassium hydroxide [bis(2-phenylethyl)phosphine oxide] to give 1-alkyl-1-diphenyl(or 2-phenylethyl)-phosphoryl-3-phenylprop-2-yn-1-ols in up to 96% yield. The reaction of diphenylphosphine oxide with 1-alkanoyl-2-phenylacetylenes in the system KOH-THF (20°C) afforded not only adducts at the carbonyl group but also products of double α,β-addition at the triple bond, 2,3-bis(diphenylphosphoryl)-3-phenylpropan-1-ones.     

A simple resolution procedure using the Staudinger reaction for the preparation of P-stereogenic phosphine oxides.

The resolution of a variety of (+/-)-P-stereogenic phosphines is achieved by exploiting the Staudinger reaction of a (+/-)-phosphine with enantiopure (1S,2R)-O-(tert-butyldimethylsilyl)isobornyl-10-sulfonyl azide. The resulting mixtures of diastereomeric phosphinimines are generally separable by fractional crystallization or flash chromatography. Subsequent acid-catalyzed hydrolysis provides the corresponding optically pure phosphine oxides in high yields.