Wittig reaction examples

Out first example is 2-hydroxy-2-methyl-3-octanone. 3-Octanone can be purchased, but it would be difficult to differentiate the two activated methylene groups in alkylation and oxidation reactions. Usual syntheses of acyloins are based upon addition of terminal alkynes to ketones (disconnection 1 see p. 52). For syntheses of unsymmetrical 1,2-difunctional compounds it is often advisable to look also for reactive starting materials, which do already contain the right substitution pattern. In the present case it turns out that 3-hydroxy-3-methyl-2-butanone is an inexpensive commercial product. This molecule dictates disconnection 3. Another practical synthesis starts with acetone cyanohydrin and pentylmagnesium bromide (disconnection 2). Many 1,2-difunctional compounds are accessible via oxidation of C—C multiple bonds. In this case the target molecule may be obtained by simple permanganate oxidation of 2-methyl-2-octene, which may be synthesized by Wittig reaction (disconnection 1). 

The phosphonates obtained by the Arbuzov reaction are starting materials for the Wittig-Homer reaction (Wittig reaction), for example, appropriate phosphonates have been used for the synthesis of vitamin A and its derivatives/... 

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. 

In addition to its other properties, interest in the potential use of the vasodilative properties of prostaglandin El, alprostadil ( ), has led to several conceptually different syntheses.For this purpose, the classic Corey process has to be modified by reversing the order of addition of the side chains to allow for convenient removal of the unwanted double bond in the upper side chain. For example, Corey lactone is protected with dihydropyran (acid catalysis), reduced to the lactol with diisobutyaluminum hydride, and then subjected to the usual Wittig reaction to give intermediate This is... 

Treatment of dimethylsulfoxide (DMSO) with sodium hydride generates methylsulfinyl carbanion (dimsyl ion), which acts as an efficient base in the production of ylides. The Wittig reaction appears to proceed more readily in the DMSO solvent, and yields are generally improved over the reaction with -butyl lithium (i). Examples of this modification are given. 

The teal value of the Wittig reaction is that it yields a pure alkene of defined structure. The C=C bond in the product is always exactly where the OO group was in the reactant, and no alkene isomers (except E,Z isomers) are formed. For example, Wittig reaction of cyclohexanone with methylenetriphenyl-phosphorane yields only the single alkene product methylenecyclohexane. By contrast, addition of methylmagnesium bromide to cyclohexanone, followed by dehydration with POCI3, yields a roughly 9 1 mixture of two alkenes. 

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,... 

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. 

The present preparation illustrates a general and convenient method for the fnms-iodopropenylation of an alkyl halide.4 The iodopropenyl-ated material is not usually stable but is a useful synthetic intermediate. For example, it forms a stable crystalline triphenylphosphonium salt for use in the Wittig reaction, and under Kornblum reaction conditions (DMS0-NaHC03, 130°, 3 minutes) it gives an (E)-a,/9-unsaturated aldehyde.4 In addition to the phosphonium salt described in Note 15, the following have been prepared (4-p-methoxyphenyl-2-butenyl)-triphenylphosphonium iodide [Phosphonium, [4-(4-methoxyphenyl)-2-butenyl]triphenyl-, iodide], m.p. 123-127° (2-octenyl)triphenyl-phosphonium iodide [Phosphonium, 2-octenyltriphenyl-, iodide], m.p. 98° and (2-octadecenyl)triphenylphosphonium iodide [Phosphonium, 2-octadecenyltriphenyl-, iodide], m.p. 50°. 

This result is similar to that obtained in the Reformatsky reaction (16-31), but this is more general since no ester or other group is required to be a to the halogen. Another important advantage of the Wittig reaction is that the position of the new double bond is always certain, in contrast to the result in the Reformatsky reaction and in most of the base-catalyzed condensations (16-38-16-46). Examples of this are given below. 

The Wittig reaction has proved very useful in the synthesis of natural products, some of which are quite difficult to prepare in other ways. One example out of many is the synthesis of P-carotene ... 

Triphenylphosphine gives Michael additions to the activated triple bond of acetylene dicarboxylic esters in presence of acidic compounds HY (Scheme 1). The reactions take place easily at room temperature, even at -10°C [1], through formation of intermediate activated vinylic phosphonium salts, which undergo a subsequent Michael addition of HY. The reactions afford various stabilized ylides which can be isolated in high yields or undergo possibly evolution, for example by intramolecular Wittig reaction [2]. 

With a-monosubstituted ylides the oxidation results in the formation of alkenes (by subsequent Wittig reaction on the intermediate aldehyde). A recent example of such synthesis is found in the preparation of all-(Z)-cyclododecate-traene by oxidation of the appropriate bis-ylide [33]. It must be pointed out that an approach of the same macrocycle based on ring closing metathesis was found ineffective. 

Examples of name reactions can be found by first considering the nature of the starting material and product. The Wittig reaction, for instance, is in Section 199 (Alkenes from Aldehydes) and Section 207 (Alkenes frorm Ketones). The aldol condensation can be found in the chapters on difunctional compounds in Section 324 (Alcohol, Thiol-Aldehyde) and in Section 330 (Alcohol, Thiol-Ketone). 

An example of such an impact is the Wittig reaction. For the formation of double bonds from 2-nitrobenzyltriphenylphosphonium bromide and methyl 4-formyl-benzoate, it was determined that the ratio of cis and trans products (Z/F ratio) can be changed by simply adjusting the voltages in an electroosmotic-flow driven chip... 

C) [9, 10]. It is said to be the first example of a heated organic reaction performed in a glass chip reactor imder electroosmohc flow (EOF) control [10] (for EOF see [14]). The performance of this reactor for room-temperatare reactions such as the Wittig reaction and Suzuki coupling was demonstrated before. 

Both neutral and anionic phosphorus compounds are good nucleophiles toward alkyl halides. We encountered examples of these reactions in Chapter 2 in connection with the preparation of the valuable phosphorane and phosphonate intermediates used for Wittig reactions. 

Wittig reactions have also been employed in domino processes. For example, Schobert and coworkers developed an effective addition/Wittig reaction protocol which provides access to a, 3-disubstituted tetronic acids, tetronates, as well as to five-, six- and seven-membered O-, N-, and S-heterocycles [149]. 

The following example completes the section of threefold anionic domino processes initiated by a SN-type reaction. As discussed earlier in Section 2.2, the reaction of a five-membered cyclic phosphonium ylide with enones, a, 3-unsaturated esters, and a, 3-unsaturated thioesters provides cycloheptene or hydroazulene derivatives in a domino Michael/intramolecular Wittig reaction. This sequence... 

Only one example of the potentially diatropic [19]annulenones is known. Wittig reaction of 5-(/3-formylvinyl)-2-furaldehyde 135 with the bisphosphonium salt 120... 

Unsaturated derivatives of saccharides in which fluorine is attached to sp2-hybridized carbon atoms have been synthesized by application of the Wittig reaction to sugars bearing a carbonyl group. For example,... 

There is not just one predominating method for the generation of alienes with at least one electron-withdrawing group, but a number of important routes. Even for the synthesis of alienes with a given acceptor function, for example allenic esters, different routes are often used such as the Wittig reaction, prototropic isomerization or alkoxycarbonylation. 

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