Wittig reaction Sodium amide

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... 

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. 

Wittig reaction (see also Methylenation) General considerations, 14 Reactions to form Z olefins (3-Dimethylaminopropyl)triphenyl-phosphorane, 119 Sodium amide, 278 Other reactions... 

By Wittig and related reactions (3-Dimethylaminopropyl)-triphenylphosphorane, 119 Sodium amide, 278 Vinyl(triphenyl)phosphonium bromide, 343 (E)-Alkenes By elimination reactions Arylselenocarboxamides, 22 Dichlorobis(cyclopentadienyl)-titanium, 102 Hydrogen peroxide, 145 From three-membered heterocycles Tributyltinlithium-Trimethylalu-minum, 320 Trisubstituted alkenes Chloromethyldiphenylsilane, 74 Organocopper reagents, 207 Alkenes (Methods to form alkenes)... 

From carbonyl groups using Wittig or Wittig-Horner reaction Alumina, 14 Sodium amide, 278... 

In the first step a Wittig reaction" is used to transform the aldehyde into a terminal olefin. This requires initial preparation of a quaternary phosphonium salt. The latter is then deprotonated with sodium amide to give phosphorus ylide 46, which after nucleophilic attack on aldehyde 12 leads to the oxaphosphetane intermediate 47. This intermediate in turn decomposes into olefin 48 and triphenylphosphine oxide. 

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 (S)-lactone acid 1, obtained from L-glutamic acid by nitrous acid deamination, was converted to the acid chloride, then treated with excess diazomethane followed by hydrogen iodide to yield the keto-lactone 2. Amidation occurred quantitatively to give the partially racemized amide 3, which was purified by repeated recrystallizations. The vicinal diol resulting from reaction with excess methylmagnesium iodide was protected as the acetonide 4. An isomeric mixture of olefins (Z , 26 74) was obtained from the subsequent Wittig reaction. Reduction followed by separation on silver nitrate coated silica gel gave the (Z)-and ( )-alcohols in 20% (6) and 61% (5) yield, respectively. Conversion of the (S)-( )-alcohol (5) to the chloride then afforded the thioether (7) on reaction with sodium phenylsulfide. The thio ether anion was formed by treatment with n-butyllithium. Alkylation with the allylic chloride" (8), followed by removal of sulfur, then yielded the diene 9, which was converted in several steps to (/ ) (-t-)-10,11 -epoxy famesol. 

Reactive ylides, in apolar solvents under salt-free conditions, preferentially form olefins with the (Z)-configuration (see Section C.l). To optimize this effect, various techniques have been developed for preparing salt-free ylide solutions [21-25]. The phosphonium salt is deprotonated, for example with sodium amide in THF or liquid ammonia [23], with sodium hexamethyldisilazane in an ether solvent such as THF [21], or with potassium r-butoxide in THF or toluene [22], with the addition of crown ether if appropriate [24]. A particularly elegant application of the salt-free Wittig reaction is the instant-ylide technique [25]. 

The intramolecular aza-Wittig reaction of functionalized phosphazenes containing an amide moiety has been used as the key-step for the preparation of the natural product deoxyvasicinone. Azide 149 (R = H) was obtained from 148 and pyrrolidone 147 (R = H) in the presence of sodium hydride as a base at room tanperature (Scheme 15.34). Then azide 149 (R = H) was treated with tributylphosphine and the natural product deoxy vasicinone (150) was successfully obtained in 99% yield even at room temperature for 2 h. More recently, fused [2,l-b]quinazolinones, namely vasicinone, deoxyvacisinone and related heterocycles have been prepared by solid-phase methods using the intramolecular aza-Wittig reaction of a phosphazene with an amide moiety.Similarly, this... 

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