Reaction of Vinylpyridines with Active Modifications of Elemental Phosphorus in KOH/DMSO

The phosphorylation of 2-vinyl- and 4-vinylpyridines by white phosphorus and active modifications of red phosphorus (obtained by thermal polymerization of white phosphorus in the presence of graphite or the action of ionizing radiation in benzene) in the KOH/DMSO superbase system at room temperature leads to the formation of tris[2-(2-pyridyl)ethyl]- and tris[2-(4-pyridyl)ethyl]phosphine oxides in 58-72% yield. These oxides are promising ligands for design of metal complex catalysts. These vinylpyridines react less efficiently with ordinary red phosphorus and the yield of the corresponding tris(2-pyridylethyl)phosphine oxides does not exceed 10%.     

Hexadecyl esters of certain inoganic acids

Summary Trihexadecyl phosphite and tetrahexadecylorhosilicate have been prepared by transesterification of the ethyl esters of the corresponding acids by means of 1-hexadecarol, Trihexadecyl borate has been prepared by the action of 1-hexadecanol on boric acid. All the esters obtained may be distilled in a high vacuum without decomposition.     

Synthesis of oligonucleotides containing thiazole and thiazole N-oxide nucleobases

[reaction: see text] The thiazole C-nucleoside analogue was synthesized by the Hantzsch cyclization method to form the thiazole ring and was then converted to the thiazole N-oxide C-nucleoside analogue by peracid oxidation of the heterocycle nitrogen. Incorporation of the thiazole and thiazole N-oxide phosphoramidites into DNA was successful though significant deoxygenation of the N-oxide occurred during DNA assembly. The mechanism proposed for the reduction of the thiazole N-oxide to thiazole involves the formation of an N-oxide phosphite ester.     

Studies on reactions of the N-phosphonium salts of pyridines—VII : Preparation of peptides and active esters of amino acids by means of diphenyl and triphenyl phosphites in the presence of tertiary amines

Peptides and active esters of amino acids were produced in high yields from carboxyl and amino or hydroxyl components in pyridine with an equivalent amount of diphenyl phosphite or half an equivalent amount of triphenyl phosphite and tertiary amines. Condensation reactions competed with the reaction with a phenoxy group of the phosphite to produce the phenyl ester and were governed by the tertiary amine employed in the reaction. The reactions are assumed to proceed via the N- phosphonium salts of pyridines, similar to those obtained by the oxidation of phosphorus compounds with mercuric salts in pyridine.     

Sodium in liquid ammonia—a versatile tool in modifications of arylphosphine oxides

A simple and practical method for modifications of tertiary arylphosphine oxides based on their reaction with sodium in liquid ammonia is presented. Depending on the structure of the starting compounds, either dearomatisation of the phenyl substituent or cleavage of a P-aryl bond from phosphorus atom can be selectively performed and the corresponding (1,4-cyclohexadien-3-yl)phosphine oxides or secondary phosphine oxides were obtained in good to excellent yields.     

Über eine Reaktion von o-Hydroxybenzylalkoholen mit Estern von Säuren des Phosphors mit der Koordinationszahl 3

Abstract

o-Hydroxybenzyl alcohol reacts with trimethyl phosphite under smooth conditions to o-hydroxyphenylmethane phosphonic acid dimethyl ester. This unusual reaction is of widest applicability. Derivatives of o-hydroxybenzyl alcohol independent of type, number or position of substituents in the ring, react with alkyl esters of phosphorous, phosphonous or phosphinous acids in an analogous process, forming the corresponding o-hydroxyphenylmethane phosphonic or phosphinic esters or phosphine oxides.     

Mild Reduction of Phosphine Oxides with Phosphites To Access Phosphines

A new method for the iodine‐catalyzed reduction of phosphine oxides with phosphites at room temperature is reported. The mild reaction conditions, scalability, and simple purification requirements render it a method of choice for the large‐scale production and facile regeneration of a variety of phosphines. Mechanistic studies, supported by DFT calculations of the oxygen transfer between the starting phosphine oxide and the phosphite reagent, are also presented. Such transmutations of phosphorus species were previously unknown.     

Atom-Economic Synthesis of Tris[2-(organylthio)ethyl]phosphine Oxides from Phosphine and Vinyl Sulfides

Abstract

Phosphine, generated from elemental phosphorus in the system KOH-toluene-H₂O, reacts with vinyl sulfides under free radical conditions (AIBN, dioxane, 65–70°C, atmospheric pressure) to form regiospecifically tris[2-(organylthio)ethyl]phosphines, which are readily oxidized in air to corresponding tris[2-(organylthio)ethyl]phosphine oxides.     

Synthesis of new thiazole-2, -4, and -5-yl-(amino)methylphosphonates and phosphinates: unprecedented cleavage of thiazole-2 derivatives under acidic conditions

An efficient and reliable synthesis of new thiazole-(amino)methylphosphonic, phosphinic acids, and phosphine oxides is reported. The synthetic protocol is based on nucleophilic addition of phosphorous species to thiazole derived imines. Unexpectedly, it was discovered that heating of thiazole-2-yl-(amino)methylphosphonates and phosphinates with aqueous HCl leads to their decomposition resulting in a rupture of the C-P bond, rejecting of the phosphorus containing fragment and formation of the corresponding secondary N-(thiazole-2-yl-methyl)-alkylamines. Two alternative mechanisms for this cleavage are postulated.     

Reactions of Elemental Phosphorus and Phosphine with Electrophiles in Superbasic Systems: XIV.1 Phosphorylation of 2-Vinylnaphthalene with Elemental Phosphorus and Phosphines in the KOH-DMSO System

Elemental phosphorus (red or white) reacts with 2-vinylnaphthalene while heating at 90-96°C in the superbasic KOH-DMSO system to form 2-(2-naphthyl)ethylphosphine, 2-(2-naphthyl)ethylphosphinic acid, bis[2-(2-naphthyl)ethyl]phosphine, bis[2-(2-naphthyl)ethyl]phosphine oxide, and tris[2-(2-naphthyl)ethyl]phosphine oxide in a total yield of up to 40%. Selective conditions for preparing the tertiary phosphine oxide from white phosphorus and 2-vinylnaphthalene in 58% yield were found. Phosphine and (2-phenylpropyl)phosphine add to 2-vinylnaphthalene in the KOH-DMSO system to form, under certain conditions, corresponding secondary phosphines in high yields.     

Intermediate carbene formation in the reaction of thioamides with phosphorus (III) derivatives: Quantum chemical investigation

The reactions of perfluoroalkyl thioamides with trimethyl phosphine, trimethyl phosphite, and tris(dimethylamino)phosphine have been analyzed by means of quantum chemical (DFT and MP2) calculations. The reaction seems to proceed via the nucleophilic attack of the electrophilic carbon atom by the phosphorus lone pair with the formation of cyclic or acyclic adducts. The latter releases the thiophosphate molecule forming perfluoroalkylaminocarbene as the short‐lived intermediate. The reaction of the carbene with the second molecule of trialkyl phosphite yields phosphorus ylide. The ylide undergoes a migration of fluorine from carbon to phosphorus. The reactions of perfluoroalkyl thioamides with phosphines and tris(dimethylamino)phosphine probably proceeds differently. Using alkyl thioamides or amides instead of perfluoroalkyl thioamides also makes the reaction less favorable. The only combination of perfluoroalkyl thioamides with trialkyl phosphite fulfills both the kinetic requirements (moderate activation energies and relative energies for intermediates) and the thermodynamic aspects (higher stabilities of the reaction products compared with the starting materials). © 2013 Wiley Periodicals, Inc.     

Aza-Baylis-Hillman reactions of N-tosylated aldimines with activated allenes and alkynes in the presence of various Lewis base promoters

[reaction: see text] The attempted aza-Baylis-Hillman reactions of N-tosylated aldimines with ethyl 2,3-butadienoate, ethyl penta-2,3-dienoate, penta-3,4-dien-2-one, methyl propiolate, and but-3-yn-2-one have been systematically investigated in the presence of various nitrogen or phosphine Lewis base promoters. We found that a series of nitrogen-containing heterocyclic compounds, as "abnormal" aza-Baylis-Hillman reaction products, can be formed in the presence of an appropriate Lewis base promoter. The Lewis base and solvent effects in these reactions have been discussed along with the corresponding plausible mechanism.     

Stereospecific nucleophilic substitution of optically pure H-phosphinates: a general way for the preparation of chiral P-stereogenic phosphine oxides

Contrary to the generally held view, it is found that the rapid epimerization of (-)-menthyl (RP)-phenylphosphinate under basic conditions is not due to the so far believed inherent stereolability of its corresponding anion but due to a reaction of the hydrogen phosphinate ester with a metal alkoxide. This finding successfully leads to a discovery that, by adding an H-phosphinate to organolithiums or Grignard reagents at a low temperature, the nucleophilic substitution of the alkoxy group of the H-phosphinate with organolithiums or Grignard reagents proceeds stereospecifically with inversion of configurations at phosphorus to give a wide range of P-stereogenic secondary phosphine oxides and tertiary phosphine oxides, by quenching the reaction mixture with water and alkyl halides, respectively. This finding establishes a general protocol for the preparation of optically active secondary phosphine oxides and tertiary phosphine oxides from the easily accessible optically pure H-phosphinates. Mechanistic studies show that the substitution reactions of H-phosphinates with organolithiums and Grignard reagents proceed via two competing reaction paths, that is, a two-step reaction path involving first a deprotonation of H-phosphinates followed by a substitution of the corresponding anion with inversion of configuration at phosphorus and a direct substitution of RM with H-phosphinates generating the SPO directly.     

A three-component coupling process based on vicarious nucleophilic substitution (VNS(AR))-alkylation reactions: an approach to indoprofen and derivatives.

The intermediate anion derived from the vicarious nucleophilic substitution (VNS) of hydrogen reacts with a series of alkyl halides to generate the corresponding alpha-alkylated conventional VNS product in a one-pot process. This one-pot VNS-alkylation reaction offers a convenient route to a range alpha-substituted nitrobenzyl phosphine oxides, sulfones, and esters via a three-component coupling reaction. Reactions of alpha-chloroethyl phenyl sulfone (14) and ethyl 2-chloropropionate (16) with nitrobenzene followed by subsequent addition of an alkylating agent give a series of sulfones and esters bearing an alpha-aryl quaternary center. The VNS-alkylation protocol has been applied to the synthesis of derivatives of Indoprofen from nitrobenzene using readily available inexpensive starting materials. Indoprofen itself was prepared using the conventional VNS reaction in four steps and 24% overall yield from nitrobenzene.     

Reactions of a 4-(trifluoromethyl)thiazole dianion

Treatment of 2-trifluoroacetamido-4-(trifluoromethyl)thiazole with two equivalents of n-butyllithium at -78° produced the thiazole dianion 5 in situ, which reacted preferentially at the 5-position with a variety of electrophiles. These electrophiles include: an aldehyde, ketone, chloroformate, acid chloride, phosphorus oxychloride, silicon chloride, and disulfide. Dianion 5 also combined with dibromodifluoromethane at -98° to give the corresponding 5-(bromodifluoromethyl)thiazole 7 , which is an unusual reaction for an aromatic or heteroaromatic system. Compound 7 was converted to a 4,5-bis-(trifluoromethyl)thiazole 8 using tetrabutylammonium fluoride.     

Regioselective synthesis of fluoroalkylated beta-aminophosphorus derivatives and aziridines from phosphorylated oximes and nucleophilic reagents

A simple and efficient stereoselective synthesis of fluoroalkyl substituted aziridine-2-phosphine oxides and -phosphonates by diastereoselective addition of methoxide, imidazole, benzenethiol, and Grignard reagents to functionalized ketoxime-phosphine oxides and -phosphonates is described. Aziridines are used as intermediates for the regioselective synthesis of fluorine containing beta-amino phosphine oxides and beta-amino phosphonates. Amino phosphorus derivatives can also be obtained from ketoximes derived from phosphine oxides and phosphonates with sodium borohydride.     

Synthesis and selective carbocupration reaction of fluorine-containing enynic esters, enynylphosphine oxides, and enynylphosphates

Some new fluorine-containing enynic esters, enynylphosphine oxides, and enynylphosphates were synthesized stereoselectively in good yields by the dehydrohalogenation reaction of fluoroalkylated 3-iodoacrylates, 2-iodovinylphosphonates, and 2-iodovinylphosphine oxides under basic conditions. These fluorine-containing enynic compounds could undergo carbocupration reaction with organocopper reagents and the vinylcopper intermediates formed in situ could further react with some electrophiles such as allyl bromide, phenylselenyl bromide, and iodine to give the corresponding polysubstituted fluorine-containing dienoic esters, phosphates, and phosphine oxides with high regio- and stereoselectivity.     

Lipase-mediated stereoselective transformations of chiral organophosphorus P-boranes revisited: revision of the absolute configuration of alkoxy(hydroxymethyl)phenylphosphine P-boranes

The lipase-promoted kinetic resolution of a series of alkoxy(hydroxymethyl)phenylphosphine P-boranes proceeded with moderate stereoselectivity to give both the unreacted substrates and their O-acetyl derivatives. The absolute configurations of the products, which were earlier ascribed on the basis of the stereoselective reduction of the corresponding phosphine oxides with borane and comparison with the literature data concerning bicyclic phosphine oxides, were disputed by theoretical calculation. Some additional studies were carried out, including theoretical calculations and more accurate chemical correlation, which proved that the borane reduction of acyclic phosphine oxides proceeded with inversion of configuration at the phosphorus center and, therefore, the former assignment of the absolute configurations was incorrect. On this basis, the stereochemistry of the enzymatic reaction was ultimately determined. A mechanism of the borane reduction of acyclic phosphine oxides explaining inversion of configuration at phosphorus is proposed.     

Theoretical investigation of the mechanisms and stereoselectivities of reductions of acyclic phosphine oxides and sulfides by chlorosilanes

Computational studies were performed to explain the highly varied stereoselectivities obtained in the reductions of acyclic phosphine oxides and sulfides by different chlorosilanes. The reductions of phosphine oxides by HSiCl(3), HSiCl(3)/Et(3)N, and Si(2)Cl(6) and the reductions of phosphine sulfides by Si(2)Cl(6) (all in benzene) were explored by means of B3LYP, B3LYP-D, and SCS-MP2 calculations. For the reductions of phosphine oxides by HSiCl(3), the calculations support the mechanism proposed by Horner in which a hydride is transferred from silicon to phosphorus through a four-centered, frontside transition state. This mechanism leads to retention of stereochemistry at phosphorus. For the other three reductions, two classes of mechanisms were explored. Phosphorane-based mechanisms that were previously proposed by Mislow and involve SiCl(3)(-) were compared with novel alternative mechanisms that involve nonionic rearrangement processes. In one of these, donor-stabilized SiCl(2) is formed as an intermediate. The calculations support a phosphorane-based mechanism for the reductions of phosphine oxides by HSiCl(3)/Et(3)N and Si(2)Cl(6) (which proceed with inversion) but favor the rearrangement pathways for the reductions of phosphine sulfides by Si(2)Cl(6) (which proceed with retention).     

Preparation of new imidazol-2-yl-(amino)methylphosphonates,phosphinates and phosphine oxides and their unexpected cleavage under acidic conditions

The efficient synthesis of new imidazol-2-yl-(amino)methylphosphonic acids, phosphonates phosphinate esters and phosphine oxides is described. The synthetic methodology is based on nucleophilic addition of phosphorus species to imidazole-2 derived imines. Additionally, it was discovered that heating the imidazol-2-yl-(amino)methylphosphonates with aqueous HCl or H₂SO₄ leads to their decomposition resulting in a rupture of the C–P bond, elimination of the phosphorous-containing fragment and formation of the corresponding secondary imidazole-2 alkylamines. A mechanistic pathway for the cleavage is postulated.