A more recent and inexpensive version of the reaction is the wittighorner reaction 1. Jan 24, 2012 p,pdichlorophosphines 2ac rpcl2, r ph a, tbu b, 2,4,6me3ph c and p,pdibromophosphines 4d,e rpbr2, r ipr3sic. Reaction b is a well known wittighorner reaction, and a is the kno evenagel reactio n. This reaction is a very common method used in the organic synthesis of alkenes. Novel onepot threecomponent coupling reaction with trimethylsilylmethylphosphonate, acyl fluoride, and aldehyde through the hornerwadsworthemmons reaction. Wittig reaction scope and limitations scope limitations. In the hornerwadsworthemmons modification, formation of the ylide from a phosphonate ester allows much easier isolation of the product alkene, since the sodium phosphate salt byproduct is watersoluble. Wittig reaction a property of carbonyl compounds involves the conversion of aldehydesand ketones to alkenes with the help ofphosphorous ylides 2.
The reaction mechanism is similar to the mechanism of the wittig reaction. P,pdichlorophosphines 2ac rpcl2, r ph a, tbu b, 2,4,6me3ph c and p,pdibromophosphines 4d,e rpbr2, r ipr3sic. Mechanism of the wittig reaction the ez selectivity of the wittig reaction depends upon the structure of the ylide that is used. Sep 28, 2012 the wittighorner reaction is a classic method to get alkenes by reaction phosphonates with carbonyl compounds. The wittighorner reaction of protected 3formylindazoles 323 with.
However, the yield of 7 slightly increased to 53% when the reaction was repeated with dmsod 6 in an nmr tube table 1, entry 3. A recent example of the wittig reaction is shown in figure 1. The wittig reaction synthetic method for preparing alkenes. Horner reaction with substituted triethyl phosphonoacetates shahak, i almog, j bergmann, e. The reaction between a phosphorane and an aldehyde or a ketone to form a phosphine oxide and an alkene is known as the wittig reaction fig. Likewise, phosphonatestabilized carbanions can be alkylated. Synthesis of stilbene by the wittig and hornerwadsworthemmons reactions. The wittig reaction is an important method for the formation of alkenes. A mixture of two stilbene isomers were prepared from benzyltriphenylphosphonium chloride and benzaldehyde by a phasetransfer wittig reaction. The first observation of this possi bility was the formation of an 82% yield of stilbenes, consisting of 20% cis isomer and 62% trans isomer i. One major milestone in this regard is the horner wadsworthemmons hwe reaction, a slightly di erent approach to the wittig reaction that is based on a modi ed wittig 1. Emmons further defined the reaction in contrast to phosphonium ylides used in the wittig reaction, phosphonatestabilized carbanions are more nucleophilic but less basic.
Synthesis of stilbene by the wittig and horner wadsworthemmons reactions. Pdf wittig and wittighorner reactions under phase transfer. Samantha adkison chem 2122 l1 experiment 1 061617 joshua albus 1 out of abstract. Wittig reaction plural wittig reactions a chemical reaction of an aldehyde or ketone with a triphenyl phosphonium ylide to give an alkene and triphenylphosphine oxide. Synthesis of stilbene by the wittig and hornerwadsworth. Organic chemistry portal, wittighornerreaction rsc ontology id, rxno. The wittig reaction in the carbohydrate series generally results in the insertion of an unsaturated fragment in various positions of the sugar molecule. Here, an overview is given on wittig and hornerwadsworthemmons hwe reactions run in combination with other. The wittighorner reaction is a classic method to get alkenes by reaction phosphonates with carbonyl compounds.
This process is experimental and the keywords may be updated as the learning algorithm improves. The horner wadsworthemmons hwe olefination is the synthesis of olefins from the condensation between carbonyl compounds both aldehydes and ketones and carboanions derived from alkyl phosphine oxides horner s condition, phosphonates wadsworth and emmonss condition, phosphonamides corey, and their thiono counterparts corey. The wittig reaction or wittig olefination is a chemical reaction of an aldehyde or ketone with a triphenyl phosphonium ylide often called a wittig reagent to give an alkene and triphenylphosphine oxide. In this method, ethyl diethoxyphosphinylacetate and dimethylaminoacetaldehyde diethylacetal, replacing e4dimethylaminobut2enoyl acid hydrochloride and oxalyl chloride, were used to synthesize the. Revisiting the phosphawittighorner reaction organometallics. The reaction is easy to carry out and proceeds under mild conditions. In contrast to phosphonium ylides used in the wittig reaction, phosphonatestabilized carbanions are more nucleophilic but less basic. Unlike elimination reactions such as dehydrohalogenation of alkyl halides, which produce mixtures of alkene regioisomers determined by saytzeffs rule, the wittig reaction forms the double bond in one position with no ambiguity. Stereochemistry of the wittig reaction the wittig reaction of phosphonium ylids with aldehydes or ketones can give rise to cis or fransolefins. Industrial applications of the wittig reaction springerlink. The wittig reaction in carbohydrate chemistry pdf free. Horneremmons aka wittighorner aka hornerwadsworthemmons.
Wittig reaction n suzuki reaction mechanism authorstream. For the wittig reaction follow the procedure in the book. The hornerwadsworthemmons hwe reaction is a chemical reaction used in organic. Georg wittig was a german chemist and nobel prize winner in 1979 for the wittig reaction 1. Wittig reaction the wittig reaction is an organic reaction used to convert a primary or secondary alkyl halide and an aldehyde or ketone to an olefin using triphenylphosphine and base. Transfer of substituent r from boron to the palladium center, thus generating a palladiumii species that contains both the substituent r and r1 that are to be coupled. The procedure in the wittig reaction can be divided. Both the cis and trans stilbenes will result from the reaction although the cis formation will act as a biproduct making the major product the trans.
In this study, it was used for the synthesis of the anticancer drug neratinib. Ylide a molecule with adjacent opposite charges prepared from alkyl halides with triphenylphosphene 4. Jun 11, 2005 retinoic acid phosphonium salt carotenoid synthesis wittig reaction triphenylphosphine oxide these keywords were added by machine and not by the authors. Get data from wadsworthemmons and include in your report e. Experiment 27 a solvent free wittig reaction page 2 of 5 figure 3. Hornerwadsworthemmons reaction an overview sciencedirect. When k 2 co 3 was used, although the conversion rate was lower at room temperature, a good. On the other hand, the cyclic phosphonate adduct 9a was isolated from the reaction of 1 with wittig horner reagent 6a using alcoholic sodium alkoxide. Because of environmental concerns, safety consideration, reduction of the costs, and simplicity of the. Phosphaalkenes are prominent ligands in homogenous catalysis due to their.
This file is licensed under the creative commons attributionshare alike 3. In the horner wadsworthemmons modification, formation of the ylide from a phosphonate ester allows much easier isolation of the product alkene, since the sodium phosphate salt byproduct is watersoluble. Wittighorner reaction hornerwadsworthemmons reaction. Jun 17, 20 phosphaalkenes are prominent ligands in homogenous catalysis due to their. After complexation to wco5 and treatment with ch3ona, phosphawittighorner reagents 9a,b are obtained on. An example of the wittig reaction is provided below. When the r group of the ylide is a simple alkyl, the species is called an unstabilized ylide and the z double bond isomer predominates in the products. He was born in berlin, on june 16, 1897, and died august. The reactions of wittighorner reagents and dialkyl. The phosphawittighorner reaction proceeds through stepwise pp cleavage of an oxadiphosphetane intermediate, followed. Mechanism of the wittighorner reaction organic chemistry portal. In this particular reaction a mixture of stilbenes is synthesized by a phasetransfer wittig reaction. The basic wittig reaction for the formation of an alkene is shown in figure 1. The phosphawittighorner reaction proceeds through stepwise pp cleavage of an oxadiphosphetane intermediate, followed by a 2,3sigmatropic rearrangement that paves.
The reaction of aldehydes or ketones with stabilized phosphorus ylides phosphonate. Wittig reaction mechanism with reagent preparation detailed. Further hydrolysis of this mixture and methanolysis provided triol. The wittig reaction is a well known method within the art for the synthetic preparation of olefins georg wittig, ulrich sch. The alkene product 4 that you make today is the one that was used a few weeks ago as the colorizer for the chemiluminscence experiment it gave the green solution. Background the ability to prepare alkenes is an extremely valuable reaction in organic synthesis. Application of the wittig horner reaction to steroid ketones. The reactions of wittighorner reagents and dialkyl phosphonate. The general mechanism of the wittig reaction is shown above. Modifications of this procedure include use of a hornerwadsworthemmons reagent or inclusion in a multistep synthesis ie. Wittig reaction n suzuki reaction mechanism authorstream presentation. The wittighorner reaction for the synthesis of neratinib. The wittig reaction hasproved to be quite versatile in the preparationof different substituted.
Students are reintroduced to dry glassware techniques, recrystallization, and stereochemical determination by nmr. Wittig reactions are more general in that the product carbonyl does not need to have an attached carbonyl. C d and h2cch e react with triethylphosphite under michaelisarbuzov conditions to give phosphinodiphosphonates 3ae in quantitative yields. Modifications of this procedure include use of a horner wadsworthemmons reagent or inclusion in a multistep synthesis ie. Mechanism the general mechanism of the wittig reaction is shown above. The hornerwadsworthemmons reaction begins with the deprotonation of the phosphonate to give. Wittighorner reaction proceeds through stepwise p p cleavage of an oxadiphosphetane intermediate, followed by a 2,3. Solventfree hornerwadsworthemmons reaction using dbu. The mechanism is thus greatly different to that of its carbon analogue, that is, the. Mar 01, 2007 when the reaction was performed with nbuli or nah in thf, the wittig reactions did not completely generate 7 due to the poor solubility of 4 in thf table 1, entries 1 and 2. A highly efficient catalyst system for basefree catalytic wittig reactions has been developed and optimized. Wittig reaction mechanism with reagent preparation. Reaction b is a well known wittig horner reaction, and a is the kno evenagel reactio n.
A more recent and inexpensive version of the reaction is the wittig horner reaction 1. The mechanism is thus greatly different to that of its carbon analogue, that is, the hornerwadsworthemmons reaction. The double bond forms specifically at the location of the original aldehyde or ketone. Wittig reaction major reference works wiley online. However, the yield of 7 slightly increased to 53% when the reaction was repeated with dmso d 6 in an nmr tube table 1, entry 3. Abstract2phenylmethylene 1,3diphenylpropanedione 1 reacts with wittig horner reagent 6a in the presence of sodium hydride as a base to give the novel phosphonate product 8a. The wittig reaction is known to proceed at a slow reaction rate when nonpolar solvents are employed. In fact, the discoverer of this reaction, george wittig, was awarded the 1979.
Mechanism of the phosphawittighorner reaction arkhypchuk. The wittig reaction chem 115 fan liu stabilized ylides are proposed to have a later and more productlike transition state with 1e thermodynamically favored over 1z. Preparation and wittig reactions of organotrifluoroborato. The mechanism beings with attack of the pph 3 on the alkyl halide which releases the halide anion and forms a. The wittig reaction allows the chemist to synthesize phosphoranes in the lab with relative ease. Leopold horner 1911 2005 born in kehl am rhein germany.
The phosphawittighorner reaction proceeds through stepwise p p cleavage of an oxadiphosphetane intermediate, followed by a 2,3sigmatropic rearrangement that paves the way for the final e2 elimination to form 1phosphaallenes. Horner reaction with substituted triethyl phosphonoacetates the wittig. The wittig reaction in carbohydrate chemistry pdf free download. Wittig reagents also called phosphorus ylids or phosphoranes are typically formed in situ by the treatment of a phosphonium salt with strong base ex. In 1958, leopold horner published a modified wittig reaction using phosphonatestabilized carbanions. The wittig reaction is named after georg wittig 18971987 and was so useful as a cc bond formation reaction that he won the nobel prize in 1979. Phosphorus ylides r is usually c 6 h 5 phenyl key point is that carbon is negatively polarized and nucleophilic c 6 h 5 3. George wittig, the german chemist, has first showed the value of this procedure in the synthesis of alkenes. Retinoic acid phosphonium salt carotenoid synthesis wittig reaction triphenylphosphine oxide these keywords were added by machine and not by the authors.
When the reaction was performed with nbuli or nah in thf, the wittig reactions did not completely generate 7 due to the poor solubility of 4 in thf table 1, entries 1 and 2. In order to elucidate the mechanism of the wittig reaction, it is necessary to under stand formation of the two intermediates. There are a number of reactions that can be used to prepare alkenes, but one of the most important is the wittig reaction. The mechanism of the wittig olefination has been the subject of intense debate 1. A mechanism for the degradation of 3 involving formation of 314 prior to cleavage of the cobalt complex has been proposed. Download hires image download to mspowerpoint cite this. Here you will find a brief introduction to the wittig reaction. One of the prime advantages of alkene synthesis is that the site of a double bond is precisely fixed in comparison to the mixtures of differently located double bonds formed by alcohol dehydration. The wittig reaction has become a popular method for alkene synthesis precisely because of its wide applicability. Wittig reagent in situwittig reagents also called phosphorus ylids or phosphoranes are typically formed in situ by the treatment of a phosphonium salt with strong base ex. One major milestone in this regard is the hornerwadsworthemmons hwe reaction, a slightly di erent approach to the wittig reaction that is based on a modi ed wittig 1. The mechanism beings with attack of the pph 3 on the alkyl halide which releases the halide anion and forms a phosphonium ion. The stere oselectiv ity for reactio ns using k f depos ited on al 2 o 3 is given in table. The hornerwadsworthemmons modification of the wittig reaction is a widely used method for the preparation of.
Uber triphenylphosphin methylene ah olefinbildende reagenzien i. After complexation to wco5 and treatment with ch3ona, phosphawittighorner reagents 9a,b are. The melting point of the product resulted in a range from 120124. The extension of this reaction by the application of a phosphine oxide carbanion, instead of a phosphonium ylide is known as the horner reaction or wittig horner reaction, while the preparation of olefin from a phosphonate carbanion is commonly referred to as the horner wadsworthemmons olefination.
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