Wittig reactions of moderate ylides with heteroaryl substituents at the phosphorus atom

The influence of various heteroaryl substituents at the phosphorus atom to the stereoselectivity of Wittig reactions of allylic and benzylic ylides has been studied. In the case of nitrogen bearing heteroaromatic ligands at the phosphorous atom of benzylidenephosphoranes high E-alkene selectivity's of up to 90:10 could be observed. NMR spectroscopic investigations revealed that substituents at the phosphorus have influences on the reactivity of ylides as well as the stability of reaction intermediates. Indications for chelation of lithium ions with ylides could also be detected and will be discussed in this article.     

A convergent synthesis of the immunosuppressant FTY720 employing aqueous Wittig chemistry

A short, convergent synthesis of the immunosuppressant FTY720 is described involving the use of 4-hydroxymethylbenzaldehyde as a pivotal intermediate. A double Wittig strategy was developed to connect this dual-functional aldehyde with an alkyl-tether and to a readily available TRIS-derivative leading to an efficient synthesis of the target molecule.     

Wittig reaction of formyl-substituted organotrifluoroborates and stabilized phosphonium ylides in an aqueous medium

The synthesis of unsaturated organotrifluoroborates using the Wittig alkenation is described. These transformations to disubstituted alkenes were achieved by using formyl-substituted organotrifluoroborates and stabilized ylides using water as a solvent. The products were isolated in moderate to excellent yields and the reaction gave preferentially the E-isomer.     

(E)-Selective Wittig reactions of Garner's aldehyde with nonstabilized ylides

In the Wittig olefination reactions of Garner's aldehyde with certain nonstabilized ylides, the (E)-alkenes could be produced as a major product by simply quenching the reactions with a large excess of MeOH at −78 °C. Even under the salt-free conditions, more than a 10:1 ratio of the (E)- to (Z)-alkene was resulted consistently from the ylides of a linear alkyl chain. Without addition of MeOH, usual selectivity for the (Z)-alkene was obtained in a ratio of 94:6.     

An efficient synthesis of 2-(guaiazulen-1-yl)furan derivatives via intramolecular Wittig reactions

An efficient and mild synthesis of 2-(guaiazulen-1-yl)furans,starting from easily accessible 1-(3-aryl-2-cyanopropenoyl) guaiazulenes,tributylphosphine and acyl chlorides,is described.The strategy employs the intramolecular Wittig protocol as a key step to append the crticial furan ring,leading to the highly functional furans in good yields.     

Reactions of novel mono- and difluoroacetyltrialkylsilanes with sulfur and phosphorus ylides

The reactions of difluoroacetyltrialkylsilanes with methylidene triphenylphosphorane and benzylidene triphenylphosphorane are affected by the nature of the silyl substituents giving either the enol silyl ether or normal Wittig product exclusively, or mixture of both. Reactions with Horner-Emmons type ylide gave only the alkene products. Reactions of mono- and difluoroacetyltrialkylsilanes with dimethylsulfoxonium methylide gave the enol silyl ether products exclusively. Conversion of an enol silyl ether to an epoxide was effected with m-CPBA.     

Wittig approach to carbohydrate-derived vinyl sulfides, new substrates for regiocontrolled ring-closure reactions

Reaction of methyl- and phenylthiomethylidene phosphoranes 1 and 2 with a variety of reducing sugars has been explored. Furano-type carbohydrates afforded with good yields the corresponding open-chain vinyl sulfides, whereas pyrano derivatives produced elimination compounds together with the expected vinyl sulfides, depending on the nature of the protective groups.     

Wittig reactions in water media employing stabilized ylides with aldehydes. Synthesis of alpha,beta-unsaturated esters from mixing aldehydes, alpha-bromoesters, and Ph3P in aqueous NaHCO3

Water is demonstrated to be an effective medium for the Wittig reaction over a wide range of stabilized ylides and aldehydes. Despite sometimes poor solubility of the reactants, good chemical yields normally ranging from 80 to 98% and high E-selectivities (up to 99%) are achieved, and the rate of the reactions in water is unexpectedly accelerated. The efficiency of water as a medium in the Wittig reaction is compared to conventional organic solvents ranging from carbon tetrachloride to methanol. The aqueous Wittig reaction works best when large hydrophobic entities are present, such as aromatic, heterocyclic aromatic carboxaldehydes, and long-chain aliphatic aldehydes with triphenylphosphoranes. The E/Z-isomeric ratio of the Wittig products appears dependent on the electron-accepting/donating capacity and the location of the substituents present in the aromatic ring. The effect of additives, such as benzoic acid, LiCl, and sodium dodecyl sulfate (SDS), on the Wittig reaction has been explored. The Wittig reaction can also be conducted in the presence of acidic entities, such as phenols and carboxylic acids. In addition, large alpha-substituents in the aliphatic aldehydes do not jeopardize the reaction. It is also demonstrated that hydrates of aldehydes can be used directly in the aqueous Wittig reaction as substrates. The scope of the aqueous Wittig reaction is extended to 24 examples of one-pot mixtures of Ph3P, alpha-bromoesters, and aldehydes in sodium bicarbonate solution (at 20 degrees C for 40 min to 3 h) to provide Wittig products of up to 99% yield and up to 98% E-selectivity. Since water is inexpensive, extremely easy to handle, and represents no environmental concerns, it should be considered a possible medium for new organic reactions.     

A scalable process for the synthesis of (E)-pterostilbene involving aqueous Wittig olefination chemistry

A synthetic approach toward the pharmacologically active (E)-stilbene pterostilbene is described using a Wittig reaction conducted under mildly basic, aqueous conditions. A surprising, non-intuitive difference in (E)/(Z) stereoselectivity was observed comparing the two possible isomeric Wittig routes, allowing for the development of a highly efficient process to access the title stilbene derivative through a one-pot olefination deprotection sequence.     

Water as an efficient medium for the synthesis of tetrahydro-β-carbolines via Pictet-Spengler reactions

A mild and efficient protocol for the Pictet-Spengler reaction in water using an acid catalyst has been described. The condensation of tryptophan, tryptamine, and N_b-benzyl tryptophan with different aldehydes having both electron-withdrawing and -donating substituents in the presence of a catalytic amount of TFA in water furnished tetrahydro-β-carbolines in good isolated yields. A salient feature of the water mediated Pictet-Spengler reaction was the general trend observed during the condensation of Trp-OMe and aryl/aliphatic aldehydes furnishing diastereomeric mixtures with a preference for the cis-isomer.     

One-pot combination of the Wittig olefination with oxidation, hydrogenation, bromination, and photocyclization reactions

Co-polycondensation of tetramethoxysilane, 2-diphenyl(phosphino)ethyltri(ethoxy)silane, and N-2-(aminoethyl)-3-aminopropyltri(methoxy)silane forms a heterogenized tertiary phosphine reagent (HPR) that reacts with benzyl chlorides and aldehydes to give alkenes. This Wittig condensation can be coupled, as a one-pot process, with hydrogenation, oxidation, bromination or photocyclization.     

A concise and efficient synthesis of tetrahydroquinoline alkaloids using the phase transfer mediated Wittig olefination reaction

The present study describes the total synthesis of 1,2,3,4-tetrahydroquinoline alkaloids (±)-galipinine, (±)-cuspareine, (±)-galipeine and (±)-angustureine, in three steps and high yields (78%, 76%, 74%, and 66%, respectively) from common aldehyde and the ylide respectives. The key step of this approach is based on an unusual Wittig reaction by using the phase transfer medium (aq. NaOH/CH₂Cl₂ 1:1 or t-BuOK/t-BuOH/CH₂Cl₂ 1:1), affording olefinic intermediates in high yields.     

Water as efficient medium for mild decarbonylation of tertiary aldehydes

Decarbonylation of the tertiary aldehydes 4-ethyl-4-formyl-hexanenitrile (2) and 2-methyl-2-phenylpropanal (4) promoted by dioxygen occurs at room temperature only if suspended in water probably via the sequential acyl radical-CO liberation-tertiary radical that is promoted by an ‘on water’ process originating preferentially from the corresponding tertiary hydroperoxide.     

One-Pot Wittig and Knoevenagel Reactions in Ionic Liquid as Convenient Methods for the Synthesis of Coumarin Derivatives

Efficient synthesis of a variety of 3-substituted coumarins via NaOMe-catalyzed Knoevenagel condensation and one-pot preparation of 3,4-unsubstituted coumarins in the presence of NaOMe via Wittig reaction in room-temperature ionic liquids are described. Knoevenagel condensation of 2-hydroxybenzaldehyde with dimethyl- and diethylmalonate was performed with excellent yields in room-temperature ionic liquids. Although diethyl- and dimethylchloromalonates were mostly recovered unchanged in Knoevenagel condensation, higher conversions were observed via Wittig reaction of these compounds with 2-hydroxybenzaldehyde derivatives and triphenylphosphine. Other 2-hydroxybenzaldehyde derivatives, methyl- and ethylchloroacetates, were reacted in ionic liquids to afford simple coumarins in good yields. These reactions widen the applicability of ionic liquid in organic synthesis.     

Ionic liquid-supported TEMPO as catalyst in the oxidation of alcohols to aldehydes and ketones

We describe an efficient synthesis of an ionic liquid-supported TEMPO which was used for the oxidation of alcohols to aldehydes and ketones. The predictable solubility of ionic liquids allows an easy separation of the oxidation products from reagents. Furthermore, the oxidation can be carried out using an ionic liquid as the solvent instead of dichloromethane; and the IL-supported TEMPO can be recycled and used several times without the loss of efficiency.     

Use of Wittig reaction for the synthesis of conjugated Aza-BODIPYs and their spectral and electrochemical properties

The 2-formyl 1,3,5,7-tetraaryl aza-BODIPY and 2-formyl-6-bromo 1,3,5,7-tetraaryl aza-BODIPY were subjected to Wittig reaction with three different ylides under simple reaction conditions and afforded the conjugated aza-BODIPYs in high yields. The aza-BODIPYconjugates resulted from 2-formyl-6-bromo aza-BODIPYs were reacted further with 4-anisyl boronic acid under mild Pd(0) coupling conditions and afforded 1,2,3,5,7-pentaaryl aza-BODIPYconjugates. The method works efficiently and allows to introduce different substituents at the aza-BODIPY core. All compounds were characterized by HRMS, 1D, 2D NMR, absorption, fluorescence and electrochemical techniques. The spectral and electrochemical studies indicated that the introduction of conjugated substituents at the aza-BODIPY core alter the electronic properties significantly.     

A convenient method for the preparation of α-vinylfurans by phosphine-initiated reactions of various substituted enynes bearing a carbonyl group with aldehydes

α-Vinylfurans were obtained by phosphine-initiated cyclization of various enynes bearing a carbonyl group at the ene end in the presence of various aldehydes, in moderate to high yields. The reaction may consist of 1,6-addition of phosphine to the enynes, ring closure, and Wittig reaction between the ylid resulting from cyclization and an aldehyde. Thus, various aldehydes were able to be used in the reaction. The reaction was influenced greatly by the substituents at the acetylene position (R¹) and the α-position of the carbonyl group (R³).     

Computational Study of the Substitution Effect on the Mechanism for the Aza‐ and Arsa‐Wittig Reactions

The aza‐ and arsa‐Wittig reactions HM=PH₃ + O=CHX → HM=CHX + O=PH₃ (M = N, As; X = H, F, Cl, Me, OMe, NMe₂, CMe₃) were examined using the density functional theory calculations. All of the structures were completely optimized at the B3LYP/6‐311++G** level of theory. The main finding of this work is that the difference between singlet‐triplet splitting of O=CHX and HM=PH₃ play an important role in determining the kinetic and thermodynamic stability of the aza‐ and arsa‐Wittig reactions. When HM=PH₃ with more ylidic character is utilized, the reaction has a smaller activation energy and a larger exothermicity.     

p-TSA-catalyzed facile and efficient one-pot eco-friendly synthesis of novel isoxazolyl amino furo[3,2-c]quinolinone derivatives in aqueous medium

A green and operationally simple approach for the synthesis of novel isoxazolyl amino furo[3,2-c]quinolinone derivatives by a one-pot three-component reaction of 4-amino-3-methyl-5 styrylisoxazoles, aryl glyoxal monohydrates and 4-hydroxy-1-methyl-2-quinolinone using p-TSA as the catalyst in aqueous medium was developed. The protocol proves to be an efficient and an environmentally benign in terms of high yields, operational simplicity, clean reaction profile, compatibility with wide range of substrates, water as a solvent and easy purification.     

Organic synthesis in solid media. Silica gel as an effective and reusable medium for the selective allylation of aldehydes with tetraallyltin

Wet silica gel promotes the chemoselective and almost complete allylation of aldehydes with 0.25-0.30 molar equivalents of tetraallyltin without an organic solvent, leaving no organotin compounds, requiring neither extraction nor chromatographic separation after the reaction, and enabling the repeated use of the silica gel.