Addition Wittig reaction

Scheme 2.48. Results of the chiral auxiliary supported domino Michael addition/ 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]. 

Cycloalkenes by tandem addition-Wittig reactions of vinylphosphonium salts... 

Several other stereoselective transformations have been presented that afford ehiral eyelohexenones, ° ° cyclohexadienones, or cyclopenta-nones. °° For instanee, tandem Michael addition/Wittig reaction of (3-carbo q -2-oxopropylidene) triphenylphosphorane and a,p-unsaturated aldehydes has been developed by employing catalysis by newly designed bullq chiral secondary amine C10. ° The multifunctional 6-carbo3gr-cyclohex-2-en-l-ones were generally obtained in excellent diastereo- and enantioselectivities (Seheme 8.23). 

There are many different ways to increase the carbon skeleton by more than one carbon. Acetylide ions, epoxides, Grignard reagents, aldol additions, Wittig reactions, and coupling reactions are just some of the methods that can be used. Common methods used to form new C—C bonds are summarized in Appendix IV. 

Literature in molecular chemistry has shown that TBD can be employed as a strong base for a variety of reactions, including Michael additions, Wittig reactions, enantioselective... 

The importance of sulfonyloxy—or sulfonate ester—linkers results from their stability under several conditions including compatibihty with Grignard additions, Wittig reactions, NaBH4-reduction, reductive aminations, acylations, Suzuki couplings and treatment with various other electrophiles. Some linkers of the sulfonate ester type are shown in Fig. 15. 

The Julia-Lythgoc olefination operates by addition of alkyl sulfone anions to carbonyl compounds and subsequent reductive deoxysulfonation (P. Kocienski, 1985). In comparison with the Wittig reaction, it has several advantages sulfones are often more readily available than phosphorus ylides, and it was often successful when the Wittig olefination failed. The elimination step yields exclusively or predominantly the more stable trans olefin stereoisomer. 

Some straightforward, efficient cyclopentanellation procedures were developed recently. Addition of a malonic ester anion to a cyclopropane-1,1-dicarboxylic ester followed by a Dieckmann condensation (S. Danishefsky, 1974) or addition of iJ-ketoester anions to a (l-phenylthiocyclopropyl)phosphonium cation followed by intramolecular Wittig reaction (J.P, Marino. 1975) produced cyclopentanones. Another procedure starts with a (2 + 21-cycloaddition of dichloroketene to alkenes followed by regioselective ring expansion with diazomethane. The resulting 2,2-dichlorocyclopentanones can be converted to a large variety of cyclopentane derivatives (A.E. Greene. 1979 J.-P. Deprds, 1980). 

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 use of a vinylphosphonium salt as the source of the QQ fragment instead of the more commonly employed 1,2-dicarbonyl substrate is illustrated by the pyrrole synthesis in Scheme 79b (8UOC2570). A particularly interesting feature is the intramolecular Wittig reaction with an amide carbonyl group. A very useful synthesis of pyrroles depends upon the addition of the anion of p-toluenesulfonylmethyl isocyanide (TOSMIC) to a,/3-unsatur-... 

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. 

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... 

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. 

Nucleophilic Addition of Phosphorus Ylides The Wittig Reaction 721... 

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. 

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°. 

A new approach to indoloquinohne alkaloids from Cryptolepis sanguino-lenta has been reported based on the cyclization of an o-substituted vinyl isocyanate 244 imder microwave irradiation and further additional cyclization based on an Aza-Wittig reaction carried out in the presence of microwaves [159]. The apphcation of this synthetic scheme to the synthesis of Cryptotackienine 247 is reported in Scheme 91. 

The overall sequence of three steps may be called the Wittig reaction, or only the final step. Phosphonium salts are also prepared by addition of phosphines to Michael alkenes (hke 15-8) and in other ways. The phosphonium salts are most often converted to the ylids by treatment with a strong base such as butyllithium, sodium amide, sodium hydride, or a sodium alkoxide, though weaker bases can be used if... 

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]. 

The unique feature of the Horner-Wittig reaction is that the addition intermediate can be isolated and purified, which provides a means for control of the reaction s stereochemistry. It is possible to separate the two diastereomeric adducts in order to prepare the pure alkenes. The elimination process is syn, so the stereochemistry of the alkene that is formed depends on the stereochemistry of the adduct. Usually the anti adduct is the major product, so it is the Z-alkene that is favored. The syn adduct is most easily obtained by reduction of (3-ketophosphine oxides.269... 

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