Dimethyl sulfoxide Wittig reaction

Reactions with sodium hydride in dimethyl sulfoxide Wittig synthesis Ethylene derivatives... 

Wittig reactions may be carried out m a number of different solvents normally tetrahydrofuran (THF) or dimethyl sulfoxide (DMSO) is used... 

Quebrachitol was converted into iL-c/j/roinositol (105). Exhaustive O-isopropylidenation of 105 with 2,2-dimethoxypropane, selective removal of the 3,4-0-protective group, and preferential 3-0-benzylation gave compound 106. Oxidation of 106 with dimethyl sulfoxide-oxalyl chloride provided the inosose 107. Wittig reaction of 107 with methyl(triphenyl)phos-phonium bromide and butyllithium, and subsequent hydroboration and oxidation furnished compound 108. A series of reactions, namely, protection of the primary hydroxyl group, 0-debenzylation, formation of A-methyl dithiocarbonate, deoxygenation with tributyltin hydride, and removal of the protective groups, converted 108 into 7. 

After the first attempts of a Russian school to prepare 6 [1], Ball and Landor [4] also did not arrive at a conclusive result when they treated 1-chlorocyclohexene (32a) with sodium amide. Wittig and Fritze [50] were the first to demonstrate clearly the existence of 6. After the reaction of 1-bromocyclohexene (32b) (Scheme 6.9) with potassium iert-butoxidc (KOtBu) in dimethyl sulfoxide (DMSO), they isolated the dimer 38 (Scheme 6.10) of 6 in 7% yield and, when the elimination was performed... 

The alkyl halide must be one that is reactive toward SN2 displacement. Alkyltriphenylphosphonium halides are only weakly acidic, and strong bases must be used for deprotonation. These include organolithium reagents, the sodium salt of dimethyl sulfoxide, amide ion, or substituted amide anions such as hexamethyldisilylamide (HMDS). The ylides are not normally isolated so the reaction is carried out either with the carbonyl compound present or it may be added immediately after ylide formation. Ylides with nonpolar substituents, for example, H, alkyl, or aryl, are quite reactive toward both ketones and aldehydes. Scheme 2.16 gives some examples of Wittig reactions. 

Involvement of 625 in a Wittig reaction with 4-carboxybutyl(triphenyl)phosphorane dissolved in dimethyl sulfoxide generates a mixture of double bond isomers rich in 623. 

R. The use of butyllithium in tetrahydrofuran or ether-hexane affords the triene 1n only 50-60% yield. When the ylide was generated with sodium hydride or potassium tert-butoxide in dimethyl sulfoxide by the submitter, the Wittig reaction gave triene containing 10-20% of the Z isomer. Part C illustrates the selective hydroboration of a diene with disiamylborane.1 The reaction is best carried out by adding preformed disiamylborane to the triene. Lower yields of homogeraniol were obtained by the submitter when the triene was added to the borane reagent. 

Reaction of 3-formyl-4//-pyrido[l,2-a]pyrimidin-4-ones 409 with [(ethoxycarbonyl)methylene]triphenylphosphorane in a Wittig reaction in dimethylformamide at ambient temperature for 10 hours gave 3-trans-acrylates 410 (92JHC559). The 3-formyl group of 3,9-diformyl-l,6,7,8,-tetrahydro and 3-formyl-9-phenylhydrazono-6,7,8,9-tetrahydro-4//-pyr-ido[l,2-a]pyrimidines was transformed to a trans-acrylate side chain in a Wittig reaction with [(ethoxycarbonyl)methylene]triphenylphosphorane in dimethyl sulfoxide at room temperature for 24 hours (84JMC1253). 

The effects of the solvent and finite temperature (entropy) on the Wittig reaction are studied by using density functional theory in combination with molecular dynamics and a continuum solvation model.21 The introduction of the solvent dimethyl sulfoxide causes a change in the structure of the intermediate from the oxaphosphetane structure to the dipolar betaine structure. 

Among insect pheromones a great number of mono- and polyolefinic compounds are found a lot of them can be obtained by the Wittig reaction. Especially the syntheses of sex attractants of female butterflies and moths, which are mostly mono- and bisunsaturated alcohols, acetates or aldehydes 168), offer a broad field for the application of the Wittig reaction and have stimulated the development of many new stereoselective variants. Thus, the methods of salt-free Wittig reactions (Chapter 2) like the sodium amide method11 31 32, the silazide technique33, potassium in HMPA 34,35 or the use of dipolar aprotic solvents like dimethyl formamide 169>, dimethyl sulfoxide 51,170) or hexamethylphosphoric triamide 51 170) were often used. 

The Wittig reaction proceeds more rapidly in dimethyl sulfoxide than in other customary solvents due to the enhanced deprotonation of the phosphonium salts to alkylidenephosphoranes [327]. Even camphor, a rather unreactive ketone, undergoes the Wittig reaction easily in base/CH3SOCH3 systems [327]. 

Corey and co-workers " found that when powdered sodium hydride is stirred into excess dimethyl sulfoxide under nitrogen at 65-70° hydrogen is evolved with formation of a solution of the highly reactive sodium methylsulfinyl methylide (1). This salt reacts with ethyltriphenylphosphonium bromide at room temperature to form the Wittig reagent (2), as shown by its rapid reaction with benzophenone to form 1,1-diphenylpropene-l (3). The strongly basic character of methylsulfinyl... 

It is advisable to use l,5-diazabicyclo[4.3.0]non-5-ene1008 in dimethyl sulfoxide for Wittig reactions with alkali-sensitive aldehydes. 

Stereoselective Wittig reaction. A stereoselective synthesis has been reported of the sex pheromone of the Egyptian cotton leafworm, (Z)-9,(E)-11-tetradecadien-l-yl acetate (3), by the Wittig reaction of (E)-2-pentenal (1) with (2) in dry dimethyl sulfoxide with dimsylsodium as base followed by deprotection and acetylation. The 9Z,11E- and 9E, 11 E-isomers were obtained in a... 

The key intermediate in the Joule syntheses (251) in this series is the pyridyl keto indole 604, which was prepared by Scheme 37. Standard reactions gave the y-amino enone, 605. Reaction of 605 with the salt of dimethyl sulfoxide and acetic acid-catalyzed rearrangement of the tetracyclic intermediate 606 gave dasycarpidone (607) and 3-epidasycarpidone (608) via the iminium 609. Dasycarpidone was converted to uleine (610) by the Wittig reaction, but 3-epidasycarpidone required somewhat different conditions for conversion to 3-epiuleine (611 Scheme 37). 

NaH stirred ca. 45 min. at 65-70° under Ng in excess dimethyl sulfoxide until Hg-evolution is complete, allowed to react with 1 equivalent of ethyl triphenyl-phosphonium bromide, then with 0.85 equivalent of benzophenone 1,1-di-phenyl-l-propene. Y 97.5%.—The reactivity of the methylsulfinyl carbanion (formed by reaction of NaH with dimethyl sulfoxide), which is even more basic than the trityl anion, is sufficient to convert phosphonium salts into ylides thereby permitting a simple and convenient modification of the Wittig reaction. E. J. Gorey and M. Ghaykowsky, Am. Soc. 8A, 866 (1962) / -diketones from carboxylic acid esters and ketones (s. Synth. Meth. 6, 737), sym. ) -diketones, s. J. J. Bloomfield, J. Org. Chem. 27, 2742 (1962). 

Dilithium tetrachlorocuprate is recommended as an additive for cross coupling of Grignard compounds with tosylates even allylic and benzylic acetates give good yields . a-Methylene-ketones, -carboxylic acids and -lactones have been prepared via sulfides and sulfoxides. A convenient and general synthesis of acetylene derivatives from boranes via the reaction of iodine with lithium 1-alkynyltriorganoborates has been published ar-Nitrostyrenes can be easily obtained by a Wittig synthesis with formaldehyde in an aqueous medium . A new synthesis of unsym. ketones by reaction of dialkyldiloroboranes with lithium aldimines has recently been published . Metallo aldimines have also served for the synthesis of a variety of other compound classes such as a-hydroxyketones, a-keto acids, nitriles, and for the asym. synthesis of a-amino acids . Polycondensations of malononitriles with benzylic chlorides have been carried out quantitatively under mild conditions in dimethyl sulfoxide with triethylamine as acid acceptor . Carbonyl compounds can react with dibromoacetonitrile to yield a-bromo esters with additional carbon atom . ... 

The Wittig reaction is regiospecific. The double bond forms between the carbonyl carbon atom and the carbon atom bonded to the phosphorus atom of the ylide. However, the reaction is not stereospecific. Thus, if geometric isomers are possible, both isomers form. The Wittig reaction is carried out in polar aprotic solvents such as diethyl ether, tetrahydrofuran, or dimethyl sulfoxide. The Wittig reaction can be carried out in the presence of alkene, alkyne, halogen, ether, or ester functional groups. 

In general, nonstabilized and semistabilized phosphonium ylides are prepared by deprotonation of the corresponding phosphonium salts with strong bases that are incompatible with aldehydes or ketones. However, some studies have shown that these phosphonium ylides can be generated in the presence of aldehydes by treatment of the corresponding phosphonium salts with a weaker base such as l,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) [100], NaOH, LiOH [101, 102], KOH [103], or K2CO3 [49, 104, 105] (Scheme 20). In addition, these bases promote the one-pot Wittig reaction of phosphonium salts with aldehydes in a number of solvents such as toluene, tetrahydrofuran, dimethyl sulfoxide, isopropanol, and water. 

Asymmetric synthesis of a chroman. Solladie and Moine have effected an en-antiospecific synthesis of the chroman-2-carboxaldehyde 7, a key intermediate in the synthesis of a-tocopherol, from (R)-( +)-l. The phosphonate 2, derived from 1, undergoes a Wittig-Horner reaction with the dimethyl ketal of pyruvaldehyde to afford the optically active vinyl sulfoxide 3. Condensation of the aldehyde 4 with the lithio derivative of 3 affords, after silyl deprotection, the allylic alcohol 5 as the only diastereoisomer. This... 

Chiral vinyl sulfoxides have been prepared by a Wittig Horner reaction of chiral (R)- or (.Si-dimethyl (4-tolylsulfinyl)methanephosphonate with carbonyl compounds3-66,67. For acyclic systems reprotonation of the anions from vinyl sulfoxides gave a mixture of E- and Z-isomers3, whereas isomerization of an exocyclic double bond in a ring system provided access to chiral aryl 1-cycloalkenylmethyl sulfoxides66-67. 

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