Ylids reaction with

Due to the presence of these resonance forms in azomethine ylids, reaction with alkenes often leads to mixtures of regioisomeric cycloadducts. Resonance stabilizing substituents are usually employed to enhance the regioselectivity. Intramolecular reactions usually favor only one mode of addition. An example of an intermolecular reaction is taken from Williams synthesis of spirotryprostatin B,372 in which 5,6-diphenylmor-pholin-2-one (473) reacted with the aldehyde shown to give a mixture of ( )- and (Z)-azomethine ylids (474). This product was generated in situ with oxindole 475, and [3-i-2]-cycloaddition product 476 was obtained in 82% yield. 

Phase transfer catalysis, which proved extremely useful in classical ylid reactions with both phosphonium and sulfonium salts (Ref, 8, 42-45), was first used with a polymer by Farrall, Durst and Frechet in 1978 (Ref, 15) according to scheme 4. In this reaction, the polymeric sulfonium salt (IX), which is suspended in a dichloromethane solution of the carbonyl compound, is treated with aqueous sodium hydroxide in the presence of tetrabutyl ammonium hydroxide to give over 95% yield of the desired epoxide together with a polymeric by-product (X) which can be recycled and reused repeatedly without any loss of activity. In contrast, the same polymeric reagent (IX) used under classical conditions affords lower yields of epoxides and loses its activity rapidly on repeated recycling. This last observation shows clearly that phase transfer catalysis may contribute significantly to the prevention of side reactions in some modifications of polymers. 

Adducts from various quaternary salts have been isolated, in reactions with aldehydes, a-ketoaldehydes, dialkylacylphosphonates and dialkyl-phosphonates, isocyanates, isothiocyanates, and so forth (Scheme 15) (36). The ylid (11) resulting from removal of a Cj proton from 3.4-dimethyl-S-p-hydroxyethylthiazolium iodide by NEtj in DMF gives with phenylisothiocyanate the stable dipolar adduct (12) that has been identified by its NMR spectrum and reactional product, such as acid addition and thiazolidine obtention via NaBH4 reduction (Scheme 16) (35). It must be mentioned that the adduct issued from di-p-tolylcarbodiimide is separated in its halohydrogenated form. An alkaline treatment occasions an easy ring expansion into a 1,4-thiazine derivative (Scheme 17) (35). 

The only other reaction with an aromatic substance is the C-H insertion into ferrocene [85], giving 41,which illustrates the highly electrophilic character of the phosphinidene complex. Other aromatic C-H insertions have been observed, but these likely occur by means of intermediate P,0- and P,N-ylids,such as the reaction of (0C)5W=PR withbenzophenone and azobenzene that give 42 and 43,respectively [56a, 86]. 

C-H insertion also occurs in the reactions with acetone and acetophenone, presumably through the rearrangement of transient OH-substituted phosphi-ranes [87]. C-C insertions occur for diketones to give 45 and have been postulated to occur via initial 1,2-addition to the conjugated enol 44 [87]. Diimines 46 also undergo C-C insertions [88]. Based on a theoretical evaluation, the products 47 are considered to result from a 2,3-sigmatropic rearrangement of initial formed P,N-ylids. 

Disconnection (a2) leads to the industrial synthesis as the half aldehyde, hall ester (46) of fumarie acid (100% tpans) is available and the Wittig reaction with unstabilised ylid (45) gives 85% cis geometry in the new double bond. 

The adjustment of the oxidation level is most easily achieved by reducing the protected ester (56) to the alcohol and re-oxidising. The Wittig reaction with a stabilised ylid (55) gives mostly ff-(53). 

In the late 1960s, methods were developed for the synthesis of alkylated ketones, esters, and amides via the reaction of trialkyl-boranes with a-diazocarbonyl compounds (50,51), halogen-substituted enolates (52), and sulfur ylids (53) (eqs. [33]-[35]). Only one study has addressed the stereochemical aspects of these reactions in detail. Masamune (54) reported that diazoketones 56 (Ri = CH3, CH2Ph, Ph), upon reaction with tributylborane, afford almost exclusively the ( )-enolate, in qualitative agreement with an earlier report by Pasto (55). It was also found that E) - (Z)-enolate isomerization could be accomplished with a catalytic amount of lithium phenoxide (CgHg, 16 hr, 22°C) (54). 

Halo-lactonization of ketophosphoranes has been achieved via reaction with cyclic anhydrides and subsequent halogenation. " The products, halo enol lactones (75), are synthetically useful compounds, and an alternative synthesis via incorporation of the halogen at the ylid stage is also described. Mechanistic investigation of the Wittig reactions involved reveals subtle variations in pathway, allowing optimum experimental conditions to be selected to allow for the variation in reactivity of different anhydrides and halides. 

Heterocyclic carbanions stabilized by ylid formation, or by resonance that places the negative charge on a heteroatom, are specifically excluded. In addition, heterocyclic systems that do not depend on additional stabilization factors for their initial deprotonation, continued existence, or subsequent reaction with electrophilic substrates are discussed in less detail. 

The reaction scope was extended to a range of dipolarophiles (3,4). Ylid generation and cycloaddition with DMAD led to the formation of adduct 16, which can be reconciled by initial generation of the expected adduct followed by a 1,5-H shift. Reaction with either dimethyl furmarate or dimethyl maleate proceeded with complete stereospecihcity, furnishing 17 and 18, respectively (Fig. 3.1). 

On the other hand, its close relationship to the X -phosphorins as well as the extreme stability of a large series of compounds having hetero atoms at the phosphorus were more in line with a 67r-electron aromatic system. Indeed, many of these compounds fail to display typical ylid reactions. Current arguments support the aromatic nature of X-phosphorins 3 as we shall demonstrate. 

WITTIG, GEORGE (1897-1987). A University of Heidelberg professor who won the Nobel prize for chemistry in 1979 along with Herbert C. Brown of Purdue. Wittig s research showed that phosphorous ylids react with ketones and aldehydes to form alkenes. This reaction is used a great deal in the synthesis of pharmaceuticals and other complex organic substances. 

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