Wittig-type Reaction Research Articles

Synthesis of gem‑bromofluoroolefins using singlet bromofluorocarbene generated from ethyl dibromofluoroacetate via a Wittig-type reaction

A halon-free method for the synthesis of gem‑bromofluoroolefins utilizing ethyldibromofluoro-acetate is disclosed via a Wittig type reaction. The reaction system takes advantage of inexpensive and readily available reagents. The method was applied to a wide variety of aryl aldehydes. Both electron donating and electron withdrawing moieties on the aryl ring were tolerated and the desired olefin products were obtained in good to excellent yields.

1,2-Thiaphosphetanes: The Quest for Wittig-Type Ring Cleavage, Rearrangement, and Sulfur Atom Transfer

The potential energy surface for opening and ring-enlargement reactions of 1,2-thiaphosphetane with different oxidation states and coordination at phosphorus has been computationally explored. The most favored [2 + 2] cycloreversions are the so-called normal Wittig-type reactions furnishing an alkene and a P═S-containing component. Somewhat unfavored are reactions involving the P-S bond cleavage and a C-to-P hydrogen shift as well as a ring enlargement to a 1,3,2-dithiaphospholane in the case of high coordinate derivatives. Apart from a two-step P-to-S oxygen transfer in 1,2σ4λ5-thiaphosphetane P-oxide, an interesting reaction is the P-S bond cleavage leading to a thiabetaine which, alternatively, can be formed by the C-attack of a phosphinidene oxide on a thiirane. A similar route, energetically more favored, was found for 1,2σ5λ5-thiaphosphetane starting from thiirane and the corresponding phosphane. For a wide set of P(III) reagents including HPR2 (R = Me, Ph), PR3 (R = Me, Ph, NMe2, OMe, F, Cl), and HP═O, the competitive direct S-attack was found to be the preferred pathway for the desulfurization of thiiranes, and the relative tendency for these P(III) reagents to act as an S-atom acceptor, the thermodynamic S-transfer potential (TSP) scale, was defined using the S8/S7 couple as a point of reference.

Recent advances in catalytic Wittig-type reactions based on P(III)/P(V) redox cycling

Abstract Numerous organic transformations are based on the use of stoichiometric amounts of phosphorus reagents. The formation of phosphane oxides from phosphanes is usually the thermodynamic driving force for these reactions. The stoichiometric amounts of phosphane oxide which are formed as by-products often significantly hamper the product purification. Organophosphorus catalysis based on P(III)/P(V) redox cycling aims to address these problems. Herein we present our recent advances in developing catalytic Wittig-type reactions. More specifically, we reported our results on catalytic Wittig reactions based on readily available Bu3P=O as pre-catalyst as well as the first microwave-assisted version of this reaction and the first enantioselective catalytic Wittig reaction utilizing chiral phosphane catalysts. Further developments led to the implementation of catalytic base-free Wittig reactions yielding highly functionalized alkylidene and arylidene succinates.

Synthesis, Characterization and Theoretical Study of the Chemical Reactivity of New Cyclic Sulfamides Linked to Tetrathiafulvalene

The synthesis of the title compounds has been carried out by condensation via a Wittig-type reaction of a pyridinium hexafluorophosphate with a phosphonate ester to give the desired (4-nitrophenyl)tetrathiafulvalene the nitro group of which was reduced to an amino group. Reaction of the amine with chlorosulfonyl isocyanate and subsequently with tert-butyl alcohol gave the corresponding open-chain sulfamide. Cyclization under basic conditions and de-protection led to 2-[4-(4′,5′-dipropyltetrathiafulvalen-4-yl)]phenyl-1,2,6-thiadiazinane 1,1-dioxide. Finally, N-alkylated and N-acylated cyclic sulfamides linked to tetrathiafulvalene were obtained. Their electron donor ability was measured by cyclic voltammetry. A detailed DFT study based on B3LYP/6–31G (d,p) of electronic properties is also presented. The calculated molecular electrostatic potential shows that, the negative charge covers the nitro and sulfamide function, while positive charge is located at the hydrogen atoms of the amine and sulfamide rings. The calculated HOMO and LUMO energy reveals that charge transfer occurs within the molecule. The chemical reactivity parameters reveal that tetrathiafulvalene 1 is highly reactive, which facilitates the desired formation of the cyclic sulfamide. The first hyperpolarizability βtot shows that compounds 1 and 5 are good candidates as a NLO material.

Catalytic Wittig and aza-Wittig reactions.

This review surveys the literature regarding the development of catalytic versions of the Wittig and aza-Wittig reactions. The first section summarizes how arsenic and tellurium-based catalytic Wittig-type reaction systems were developed first due to the relatively easy reduction of the oxides involved. This is followed by a presentation of the current state of the art regarding phosphine-catalyzed Wittig reactions. The second section covers the field of related catalytic aza-Wittig reactions that are catalyzed by both phosphine oxides and phosphines.

Syntheses and properties of a new series of tetrathiafulvalene derivatives incorporating fused ethyleneoxymethylene and ethylenethiomethylene units, and their charge–transfer complexes

Nine tetrathiafulvalene (TTF) derivatives incorporating fused ethyleneoxymethylene (EOM) and ethylenethiomethylene (ETM) units were newly synthesized by self-coupling or cross-coupling reactions. Unsymmetrical ETMEDT-TTF (4) was also synthesized by a Wittig-type reaction. Crystal structural analysis of these neutral donors revealed specific intermolecular interactions between donors, and many S⋯S, O⋯H, and S⋯H short contacts. Electrochemical properties of these donors were investigated by cyclic voltammetry under two different measurement conditions. Electronic spectra of neutral donors in chloroform and some cation radicals in methanol and on KBr pellets were measured and discussed. A distribution of the highest occupied molecular orbital (HOMO) around the EOM and ETM moieties of these donors was not found. The introduction of EOM and ETM groups to the TTF skeleton only slightly modulated the HOMO energy. Some charge–transfer (CT) complexes of these donors with tetracyanoquinodimethane (TCNQ) derivatives were prepared. A needle crystal of the CT complex of EOMMDT-TTF (5) with TCNQ was metallic down to 102K with a high σRT value of 169Scm−1. TTF derivatives incorporating fused EOM groups were more effective in conductivity than those incorporating fused ETM groups.

Wittig Reactions of Trialkylphosphine-derived Ylides: New Directions and Applications in Organic Synthesis

GRAPHICAL ABSTRACT

Mechanistic Insights into the Methylenation of Ketone by a Trinuclear Rare-Earth-Metal Methylidene Complex

Trinuclear rare-earth-metal methylidene (CH22–) complexes are an emerging class of compounds that serve as methylidene transfer agents for methylenation of carbonyl compounds. Herein, the reaction of a trinuclear scandium methylidene complex with acetophenone was used as a model reaction of the multimetallic-cooperating methylidene transfer case, and its detailed mechanism has been investigated by the DFT approach. The analyses of Wiberg bond index, electron occupation, the frontier molecular orbital, and natural charge provide us a clear and comprehensive understanding of the CH22–/O2– group interchange process assisted by cooperating multimetal sites. The mechanism presented here is markedly different from conventional Wittig and transition-metal-mediated Wittig-type reactions. In addition, the behavior of μ3-CH2 in a multinuclear complex system is also demonstrated. This study not only enriches the chemistry of metal Wittig-type reactions but also sheds light on the intermetallic cooperation for methyl...

ChemInform Abstract: Microwave‐Assisted Synthesis of P‐Heterocycles

AbstractReview: 73 refs.

Microwave-Assisted Synthesis of P-Heterocycles*

The direct esterification, thioesterification and amidation of cyclic phosphinic acids, such as 1-hydroxy-3-phospholene 1-oxides, 1-hydroxy-phospholane 1-oxides and a 1-hydroxy-1,2,3,4,5,6-hexahydrophosphinine 1-oxide, which do not take place on conventional heating, were carried out under MW conditions in excess of the alcohol, thioalcohol and amine, respectively. The cyclic phosphinates were also prepared by MW-assisted alkylating esterification of the corresponding phosphinic acids in solid–liquid phase. Using alkyl halides of normal reactivity, the application of a phase transfer catalyst was also beneficial. In addition, MW-assisted Diels–Alder reactions, so-called inverse Wittig-type reactions furnishing β-oxophosphoranes, a few kinds of phospha-Michael additions leading to precursors of bidentate P-ligands, and a few Kabachnik–Fields condensations affording α-aminophosphonates and α-aminophosphine oxides are discussed.

Stereoselective Enzyme Cascades: An Efficient Synthesis of Chiral γ-Butyrolactones

A one-pot consecutive two-enzyme sequential cascade toward chiral γ-butyrolactones using an enoate reductase as well as alcohol dehydrogenases in combination with a glucose dehydrogenase is reported. In this scalable process, the products were obtained in high yield (up to 90%) and with perfect enantioselectivity (98→99% ee). The starting materials, ethyl 4-oxo-pent-2-enoates, are readily accessible via Wittig-type reactions. Furthermore, the stereoselectivity of the enoate reductase catalyzed reaction has been studied in detail, leading to deeper insights into the mechanism of this enzyme.

The use of methyl 2,2-difluoro-2-(fluorosulfonyl)acetate as the difluorocarbene source to generate an in situ source of difluoromethylene triphenylphosphonium ylide

Under moderate conditions in the presence of a demethylating reagent, such as iodide, methyl 2,2,-difluoro-2-(fluorosulfonyl)acetate (MDFA) releases difluorocarbene, which in the presence of triphenylphosphine forms difluoromethylene triphenylphosphonium ylide. When the process is carried out also in the presence of aldehydes or activated ketones, the ensuing in situ Wittig-type reaction of the ylide with the carbonyl reactants produces 1,1-difluoroalkenes in good yield. Density Functional Theory calculations were used to provide new estimates of the energies and structures of singlet and triplet states of CH2:, CHF:, and CF2: carbenes, as well as those of their respective triphenylphosphonium ylides.

Electronic Properties and Reactivity of an Isolable Phosphagermaheterocyclic Carbene

A highly reactive phosphagermacarbene (PGeHC) was synthesized by [3+2] cycloaddition between phosphagermaallene Tip(tBu)GeCPMes* (Tip= 2,4,6-triisopropylphenyl; Mes*=2,4,6-tris-tert-butylphenyl) and diphenylketene. It forms complexes with [{Rh(CO)2Cl}2] and Me3P, and undergoes a Wittig-type reaction with diphenylketene (see scheme).

ChemInform Abstract: Microwave‐Assisted Synthesis of Medicinally Relevant Indoles

AbstractReview: 138 refs.

Microwave-Assisted Synthesis of Medicinally Relevant Indoles

Indoles represent an important structural class in medicinal chemistry with broad spectrum of biological activities. The synthesis of indoles, therefore, has attracted enormous attention from synthetic chemists. Microwave methods for the preparation of indole analogs have been developed to speed up the synthesis, therefore, microwave assisted organic synthesis (MAOS) in controlled conditions is an invaluable technique for medicinal chemistry. In this review, indole forming classical reactions such as Fischer, Madelung, Bischler-Mohlau, Batcho-Leimgruber, Hemetsberger-Knittel, Graebe-Ullmann, Diels-Alder and Wittig type reactions using microwave radiation has been summarized. In addition, metal mediated cyclizations along with solid phase synthesis of indoles have been discussed.

X-ray Crystal Structures of Ethoxycarbonyl-, Diethyl-2-Triphenyl-Λ5-Phosphoranylidene-N-Phenylimide Derivatives

Phenylisothiocyanate reacts with ethyltriphenylphosphanylideneacetate at room temperature to yield 2-(ethoxycar-bonyl)-2-(triphenyl-Λ5-phosphanylidene)-N’-phenylethane thioimidic acid and diethyl-2-(triphenyl-Λ5-phosphanylidene)-3-(phenylimino)pentanedioate. The formation of phosphoranes are explained according to mechanism of the Wittig type reaction. The X-ray analysis structures of phosphorane adducts were studied.

(E) Enol ethers from the stereoselective reduction of α-alkoxy-β-ketophosphonates and Wittig type reaction

When α-alkoxy-β-ketophosphonates, prepared by the Rh(II) mediated insertion reaction of α-diazo-β-ketophosphonates into the OH bond of primary alcohols, were reduced either by NaBH4 in the presence of CaCl2 or by DIBAL, they respectively gave the corresponding anti or syn stereomeric hydroxyphosphonates with pronounced to complete stereoselectivity. Submitted to the action of potassium tert-butoxyde, syn isomers led to the corresponding pure (E) enol ethers in moderate to good yields. Under the same conditions anti isomers led to a mixture of (Z) and (E) enol ethers in rather poor yields. The sequence was applied to the preparation of some allyl-vinyl ethers with a (E) configuration for the vinylic double bond.

ChemInform Abstract: Aza Wittig-Type Reaction Between the Iminophosphorane Derived from 3- Amino-4-phenylthiazole-2(3H)-thione and Iso(thio)cyanates: Preparation of Mesoionic Thiazolo(2,3-b)-1,3,4-thiadiazoles and N,N- Bisheteroarylamines.

Abstract Aza Wittig-type reaction of iminophosphorane 1 derived from 3-amino-4-phenylthiazole-2(3H)-thione with several types of iso(thio)cyanates has been studied. The reaction of 1 with aromatic iso(thio)cyanates leads to thiazolo[2,3-b]-1,3,4-thiadiazoles 2 which display mesoionic character, whereas that with aliphatic isothiocyanates affords the betaines 3 . N,N′-Bisheteroarylguanidines 5 are obtained from the reaction of 1 with aliphatic isocyanates; further treatment of compounds 5 with @Tetrafluoroboric acid leads to N,N-bisheteroarylamines 8 . The reaction of 1 with acyl chlorides affords thiazolo[2,3-b]-1,2,4-thiadiazolium salts 12 .

ChemInform Abstract: Preparation of Phosphonium Salt from (S)-Trifluoropropene Oxide and Wittig Type Reactions.

Abstract ( S )-3,3,3-Trifluoropropene oxide was reacted with triphenylphosphine in the presence of trifluoroacetic acid to afford the corresponding β-hydroxyalkyl phosphonium salt. Wittig type reaction of aldehydes with the salt under basic condition readily occurred to form optically active α-trifluoromethylated allylic alcohols. The trans -selectivity of these reactions were discussed.

ChemInform Abstract: An Efficient Method to Construct the A,B-Rings Component Toward Total Syntheses of Phycocyanobilin and Its Derivative as a Photoprobe.

Total syntheses of phycocyanobilin and its derivative bearing a photoreactive group at the D-ring were accomplished by developing a new and efficient method for the construction of A,B-rings component, which consists of the Wittig-type new coupling reaction of 4-(1-methoxyethyl or 1-tosylethyl)-3-methyl-5-tosyl-1,5-dihydro-2H-pyrrol-2-one and a 2-formyl pyrrole derivative in the presence of nBu3P and a base, followed by reduction with aluminum amalgam and a subsequent acid or base treatment.