Aldehyde Wittig reaction

Synthesis We must be able to do a Wittig reaction on the aldehyde but not on the ketone, so we must protect the ketone therefore add the aldehyde as an ester (there are many other solutions). 

Enantiomerically pure tetroses, pentoses, and hexoses have been synthesized by the following reaction sequence (A.W.M. Lee, 1982 S.Y. Ko, 1983), which is useful as a repetitive two-carbon hotnologi-.ation in total syntheses of higher monosaccharides and other polyhydroxy compounds (1) Wittig reaction of a protected hydroxy aldehyde with (triphenylphosphor-... 

The synthesis of 11-oxaprostaglandlns from o-glucose uses the typical reactions of gl cofuranose diacetonide outlined on p. 267. Reduction of the hemiacetal group is achieved a thioacetal. The carbon chains are introduced by Wittig reactions on the aldehyde grou] which are liberated by periodate oxidation and laaone reduction (S. Hanessian, 1979 G Lourens, 1975). 

The methyl enol ether 37 is oxidized to the a,/3-unsaturated aldehyde 39 via hemiacetal 38. Unsaturated aldehyde 39, elongated one carbon from the aldehyde 36, is prepared by the Wittig reaction of 36 to give 37, and application of this reaction[ 88]. 

The Wittig reaction uses phosphorus ylides (called Wittig reagents) to convert aldehydes and ketones to alkenes... 

The most attractive feature of the Wittig reaction is its regiospecificity The location of the double bond is never m doubt The double bond connects the carbon of the ongi nal C=0 group of the aldehyde or ketone and the negatively charged carbon of the yhde... 

The Wittig reaction (Sections 17 12-17 13) Reaction of a phosphorus ylide with aldehydes and ketones leads to the formation of an alkene A versa tile method for the regiospecific prepa ration of alkenes... 

Wittig reaction (Section 17 12) Method for the synthesis of alkenes by the reaction of an aldehyde or a ketone with a phosphorus yhde... 

Another very important reaction initially involving nucleophilic attack on an aldehyde carbonyl is the Wittig reaction. An yUd adds to the carbonyl forming a betaine intermediate which then decomposes to produce an olefin and a tertiary phosphine oxide. 

The reaction has been extended to include carbanions generated from phosphonates. This is often referred to as the Horner-Wittig or Homer-Emmons reaction. The Horner-Emmons reaction has a number of advantages over the conventional Wittig reaction. It occurs with a wider variety of aldehydes and ketones under relatively mild conditions as a result of the higher nucleophilicity of the phosphonate carbanions. The separation of the olefinic product is easier due to the aqueous solubility of the phosphate by-product, and the phosphonates are readily available from the Arbusov reaction. Furthermore, although the reaction itself is not stereospecific, the majority favor the formation of the trans olefin and many produce the trans isomer as the sole product. 

Thiophene-2-carbaldehyde, 3-bromo-synthesis, 4, 81 Thiophenecarbaldehydes benzothiophene synthesis from, 4, 906 reactions, 4, 807 synthesis, 4, 148 Wittig reactions, 4, 807 Thiophene-2-carb aldehydes bromination, 4, 753 conformation, 4, 33 halogenation, 4, 753 reactions, 4, 72-73 reactivity, 4, 72-73 reduction, 4, 776 Thiophene-3-carb aldehydes conformation, 4, 33 reactivity, 4, 72... 

Cyanohydrin trimethylsilyl ethers are generally useful as precursors of ctir-bonyl anion equivalents and as protected forms of aldehydes. Direct conversion of p-anisaldehyde into 0-TRIMETHYLSILYL-4-METH0XYMANDEL0-NITRILE employs a convenient in situ generation of trimethylsilyl cyanide from chlorotnmethylsilane A general synthesis of allemc esters is a variant of the Wittig reaction. Ethyl (triphenylphosphoranylidene)acetate converts pro-pionyl chloride into ETHYL 2,3-PENTADlENOATE. 

The Wittig reaction, for which George Wittig received the 1979 Nobel Prize in Chemistry, is an important synthetic procedure for converting aldehydes and ketones into alkenes. The active reagent is a phosphorous ylide which undergoes nucleophilic addition to the carbonyl carbon, e.g., for addition of triphenylphosphinemethylidene to acetone. 

The Peterson olefination can be viewed as a silicon variant of the Wittig reaction, the well-known method for the formation of carbon-carbon double bonds. A ketone or aldehyde 1 can react with an a-silyl organometallic compound 2—e.g. with M = Li or Mg—to yield an alkene 3. 

The reaction of an alkylidene phosphorane 1 (i.e. a phosphorus ylide) with an aldehyde or ketone 2 to yield an alkene 3 (i.e. an olefin) and a phosphine oxide 4, is called the Wittig reaction or Wittig olefination reaction. ... 

With respect to the carbonyl substrate, a variety of additional functional groups is tolerated, e.g. ester, ether, halogen. With compounds that contain an ester as well as a keto or aldehyde function, the latter usually reacts preferentially. Due to its mild reaction conditions the Wittig reaction is an important method for the synthesis of sensitive alkenes, as for example highly unsaturated compounds like the carotinoid 17 shown above. 

Aldehydes and ketones are converted into alkenes by means of a nucleophilic addition called the Wittig reaction. The reaction has no direct biological counterpart but is important both because of its wide use in the laboratory and drug manufacture and because of its mechanistic similarity to reactions of the coenzyme thiamin diphosphate, which well see in Section 29.6. 

In the Wittig reaction, a phosphorus ylide, R2C—P(C6H03, also called a phosphoreme and sometimes written in the resonance form R2C=P(C6H5)3, adds to an aldehyde or ketone to yield a dipolar intermediate called a betaine. (An ylide—pronounced ill-id—is a neutral, dipolar compound with adjacent plus and minus charges. A betaine—pronounced bay-ta-een—is a neutral, dipolar compound with nonadjacent charges.)... 

Active Figure 19.13 MECHANISM The mechanism of the Wittig reaction between a phosphorus ylide and an aldehyde or ketone to yield an alkene. Sign in at www.thomsonedu.com fo see a simulation based on this figure and to take a short Quiz. 

Wittig reactions are used commercially in tire synthesis of numerous pharmaceutical agents. For example, the German chemical company BASF prepares vitamin A by Wittig reaction between a 15-carbon ylide and a 5-carbon aldehyde. 

Aldehydes can be prepared by the Wittig reaction using (methoxymethylene)-triphenylphosphorane as the Wittig reagent and then hydrolyzing the product with acid. For example,... 

Wittig reaction (Section 19.11) The reaction of a phosphorus ylide with a ketone or aldehyde to yield an alkene. 

Retrosynthetic cleavage of the trans A8,9 disubstituted double bond in intermediate 11, the projected precursor of diketone 10, provides phosphorus ylide 12 and aldehyde 13 as potential precursors. In the forward sense, a Wittig reaction could conceivably achieve a convergent coupling of intermediates 12 and 13 with concomitant formation of the requisite trans C8-C9 olefin. Ordinarily, the union of a nonstabilized ylide, such as 12, with an aldehyde would be expected to afford an alkene with a cis geometry.8 Fortunately, however, the Schlosser modification of the Wittig reaction permits the construction of trans olefins from aldehydes and nonstabilized phosphorus ylides.9... 

Intermediates 18 and 19 are comparable in complexity and complementary in reactivity. Treatment of a solution of phosphonium iodide 19 in DMSO at 25 °C with several equivalents of sodium hydride produces a deep red phosphorous ylide which couples smoothly with aldehyde 18 to give cis alkene 17 accompanied by 20 % of the undesired trans olefin (see Scheme 6a). This reaction is an example of the familiar Wittig reaction,17 a most powerful carbon-carbon bond forming process in organic synthesis. 

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