Catalytic Wittig Reaction Research Articles

A systematic review on catalytic Wittig and Knoevenagel condensation reactions

This review is focused on various reports in recent years on catalytic Wittig reactions and Knoevenagel condensation reactions in the presence of heterogeneous catalyst. The one-pot, cost-effective stereoselective catalytic Wittig reaction, is the reaction countering components generated by oxidation of primary alcohols without addition of base. Some reactions were reportedly performed under mild conditions, green and efficient approach providing the corresponding products in good to excellent yields within short times. The catalytic behavior over various catalysts for the Tandem oxidation reactions (TORs) was also summarized in this review.

Base-Free Catalytic Wittig-/Cross-Coupling Reaction Sequence as Short Synthetic Strategy for the Preparation of Highly Functionalized Arylbenzoxepinones

AbstractThe facile synthesis of highly functionalized building blocks with potential biological activity is of great interest to medicinal chemistry. The benzoxepinone core structures commonly exhibit biological activity. Thus, a short and efficient synthetic route towards benzoxepine containing scaffold, which enables late stage modification was developed. Namely, base-free catalytic Wittig reactions enabled the synthesis of bromobenzoxepinones from readily available starting materials. Subsequent, Suzuki–Miyaura and Stille reactions proved to be suitable methods to access a variety of benzoxepinone diaryl derivatives by late stage modification in only three steps. This three-step reaction sequence is suitable for high throughput applications and gives facile access to highly complex molecular structures, which are suitable for further functionalization. The antiproliferative properties of selected arylbenzoxepinones­ were tested in vitro on monolayer tumor cell line A549. Notably, in this initial screening, these compounds were found to be active in the micromolar range.

Convergent Synthesis of Polysubstituted Furans via Catalytic Phosphine Mediated Multicomponent Reactions.

Tri- or tetrasubstituted furans have been prepared from terminal activated olefins and acyl chlorides or anhydrides by a multicomponental convergent synthesis mode. Instead of stoichiometric nBu3P, only catalytic nBu3P or nBu3P=O is needed to furnish the furans in modest to excellent yields with a good functional group tolerance under the aid of reducing agent silane. This synthetic method features a silane-driven catalytic intramolecular Wittig reaction as a key annulation step and represents the first successful application of catalytic Wittig reaction in multicomponent cascade reaction.

Utilization of a Phosphetane Oxide for Catalytic Wittig-Reactions

Key words Wittig reaction - phosphetane oxides - aldehydes - alkenes - P(III)/P(V)-redox catalysis

Phosphetane Oxides as Redox Cycling Catalysts in the Catalytic Wittig Reaction at Room Temperature

Recently, phosphorus redox cycling has gained significant importance for a number of transformations originally requiring the use of stoichiometric amounts of phosphorus reagents. While these metho...

The preparation and application of optically active organophosphorus compounds

Racemic acyclic phosphine oxides were separated into their enantiomers applying classical resolution methods based on complexation with chiral host molecules. The preparation of chloro-3-phospholenium chlorides was elaborated by the reaction of 3-phospholene oxides with oxalyl chloride. The cyclic chlorophosphonium salts were key intermediates, as they could be converted to the corresponding 3-phospholene boranes. Moreover, these reactive intermediates could be reacted with chiral alcohols, which enabled us to develop a dynamic resolution of 3-phospholene oxides based on the formation of covalent diastereomeric intermediates. P-Stereogenic phosphine oxide pre-catalysts showed promising enantioselectivity values in a catalytic Wittig-reaction.

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.

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.

Highly functionalized alkenes produced from base-free organocatalytic Wittig reactions: (E)-3-benzylidenepyrrolidine-2,5-dione, (E)-3-benzylidene-1-methylpyrrolidine-2,5-dione and (E)-3-benzylidene-1-tert-butylpyrrolidine-2,5-dione

The Wittig reaction is a fundamental transformation for the preparation of alkenes from carbonyl compounds and phosphonium ylides. The ylides are prepared prior to the olefination step from the respective phosphonium salts by deprotonation utilizing strong bases. A first free-base catalytic Wittig reaction for the preparation of highly functionalized alkenes was based on tributylphosphane as the catalyst. Subsequently we developed a system employing a phospholene oxide as a pre-catalyst and trimethoxysilane as reducing agent which operates under milder conditions. The title compounds, (E)-3-benzylidenepyrrolidine-2,5-dione, C11H9NO2, (I), the methylpyrrolidine derivative, C12H11NO2, (II), and the tert-butylpyrrolidine derivative, C15H17NO2, (III), have been synthesized by base-free catalytic Wittig reactions. In the crystal of (I), molecules are linked into centrosymmetric dimers via pairs of N-H...O hydrogen bonds. Furthermore, in the crystal structure of (III), there are two molecules in the asymmetric unit, whereas in (I) and (II), only one molecule is present.

ChemInform Abstract: Novel Base‐Free Catalytic Wittig Reaction for the Synthesis of Highly Functionalized Alkenes.

AbstractThis novel base‐free Wittig reaction uses a readily available phosphine oxide as precatalyst and trimethoxy silane as reducing agent.

Novel Base-Free Catalytic Wittig Reaction for the Synthesis of Highly Functionalized Alkenes.

A highly efficient catalyst system for base-free catalytic Wittig reactions has been developed and optimized. Initially, several potential (pre)catalysts as well as different silanes as reducing agents were screened. A system based on a readily available phosphine oxide as precatalyst and trimethoxy silane as reducing agent proved to be optimal. The effect of various Brønsted acidic additives was studied. Subsequently, the reaction conditions were optimized and standard reaction conditions were determined. Under these conditions the scope of this new protocol was evaluated. Nine activated olefins and 33 aldehydes were converted into 42 highly functionalized alkenes. Notably, aromatic, aliphatic as well as heteroaromatic aldehydes could be converted, giving the desired products in isolated yields up to 99 % and with good to excellent E/Z selectivities. These results underline the remarkable efficiency of this protocol considering the complexity of the reaction mixture and the four reaction steps that proceed in parallel in one pot.

ChemInform Abstract: Scope and Limitation of the Microwave‐Assisted Catalytic Wittig Reaction.

AbstractThe effect of various reaction parameters, silanes as reducing agents, masked bases as well as the substrate scope of the title reaction are studied in detail.

Crystal structure of diethyl (E)-2-[(benzo-furan-2-yl)methyl-idene]succinate.

The title compound, C17H18O5, was synthesized by a base-free catalytic Wittig reaction. The mol­ecule consists of a diethyl itaconate unit, which is connected via the C=C double bond to a benzo­furan moiety. The benzo­furan ring system (r.m.s. deviation = 0.007 Å) forms dihedral angles of 79.58 (4) and 12.12 (10)° with the mean planes through the cis and trans eth­oxy­carbonyl groups, respectively. An intra­molecular C—H⋯O hydrogen bond involving the O atom of the benzo­furan moiety is observed. In the crystal, mol­ecules are linked into ribbons running parallel to the b axis by C—H⋯O hydrogen bonds.

Scope and Limitation of the Microwave‐Assisted Catalytic Wittig Reaction

AbstractWe have developed a microwave‐assisted catalytic Wittig reaction. In this paper, we give full account of the scope and limitations of this reaction. A screening of various commercially available phosphine oxides as precatalysts revealed Bu3P=O to be the most promising candidate. We tested 10 silanes for the in situ reduction of the phosphine oxide to generate Bu3P as the actual catalyst. Different epoxides were tested as masked bases. In this context, cyclohexene oxide as well as butylene oxide proved to be suitable. The reaction could be carried out at 125 °C, but higher yields and E/Z selectivities were obtained at 150 °C. Under the optimised reaction conditions, more than 40 examples for the conversion of various aldehydes into the corresponding alkenes are reported. The products were obtained in yields of up to 88 % with high E selectivities. Moreover, we also describe the further screening of several chiral phosphines as catalysts for the microwave‐assisted enantioselective catalytic Wittig reaction.

First Base-Free Catalytic Wittig Reaction.

The first base-free catalytic Wittig reaction utilizing readily available Bu3P (5 mol %) as an organocatalyst is reported. The initial Michael addition of the phosphine to a suitable acceptor substituted alkene ultimately results in the formation of an ylide which is subsequently converted with an aldehyde. The presented (1)H NMR studies actually reveal evidence for the Michael addition and proposed ylide formation. Under the optimized reaction conditions various maleates and fumarates were converted with aromatic, heteroaromatic, and aliphatic aldehydes to evaluate the scope and limitations of this unprecedented reaction. Notably, maleates and fumarates react in a stereoconvergent fashion. The corresponding products were obtained in up to 95% isolated yield and E/Z-selectivities up to 99:1.

Phospholane‐Catalyzed Wittig Reaction

AbstractWe identified 2‐phenylisophosphindoline 2‐oxide as a suitable and potentially tunable catalyst for the catalytic Wittig reaction of aldehydes with activated organohalides. This catalyst was obtained by a straightforward two‐step synthesis. Trimethoxysilane proved to be an efficient reducing agent for the in situ generation and regeneration of the catalyst from the corresponding phosphane oxide. Sodium carbonate was identified as a suitable base for the transformation. It is noteworthy that the particle size of the sodium carbonate had a tremendous effect on the outcome of the reaction. Under the optimized reaction conditions, 23 aldehydes were converted into the corresponding alkenes in high isolated yields of up to 88 %. Moreover, an asymmetric catalytic Wittig reaction was performed for the desymmetrization of a prochiral diketone.

ChemInform Abstract: Catalytic Wittig Reactions of Semi‐ and Nonstabilized Ylides Enabled by Ylide Tuning.

AbstractDifferent phosphinoxide catalysts are employed in the Wittig reaction between aromatic aldehydes, benzyl halogenides, and alkyl halogenides.

ChemInform Abstract: First Microwave‐Assisted Catalytic Wittig Reaction.

AbstractThe tributylphosphane‐catalyzed reaction delivers aryl, hetaryl, and alkyl substituted alkenes with high E/Z‐selectivity in favor for the E‐isomer.

ChemInform Abstract: First Enantioselective Catalytic Wittig Reaction.

AbstractThis first example of an enantioselective catalytic Wittig reaction gives product (II) in low yields but with 90% enantiomeric excess.

First Microwave‐Assisted Catalytic Wittig Reaction

AbstractWe introduce a novel catalytic Wittig reaction based on an inexpensive and readily available phosphane oxide as a precatalyst. The performance of the reaction under microwave irradiation led to significantly improved yields and reaction rates relative to those obtained under conventional heating. Moreover, herein we enclose the first example of the asymmetric catalytic Wittig reaction based on a chiral phosphane as the catalyst.