Ylides reaction with double

In the alternative approach.the 1,3-dipolar system can be constructed in several ways. Treatment of a-chloroacylhydrazones of diaryl ketones and certain aralkyl and dialkyl ketones (382) with NaH in anhydrous THF gives l-(disubstituted methylene)-3-oxo-l,2-diazetidinium inner salts (383). Reaction of (383) with DMAD in methylene chloride gave (384), a 2 1 adduct with loss of CO. Double bond migration in (384) occurred on heating to give (385). The intermediate in the cycloaddition was found to be (386), which on heating lost CO to form a new ylide system which in turn underwent reaction with more DMAD <81JA7743). 

Wittig reactions are versatile and useful for preparing alkenes, under mild conditions, where the position of the double bond is known unambiguously. The reaction involves the facile formation of a phosphonium salt from an alkyl halide and a phosphine. In the presence of base this loses HX to form an ylide (Scheme 1.15). This highly polar ylide reacts with a carbonyl compound to give an alkene and a stoichiometric amount of a phosphine oxide, usually triphenylphosphine oxide. 

Ketophosphonium salts are considerably more acidic than alkylphosphonium salts and can be converted to ylides by relatively weak bases. The resulting ylides, which are stabilized by the carbonyl group, are substantially less reactive than unfunctionalized ylides. More vigorous conditions are required to bring about reactions with ketones. Stabilized ylides such as (carboethoxymethylidene)triphenylphosphorane (Entries 8 and 9) react with aldehydes to give exclusively trans double bonds. 

Spirophosphonium ylide 17 undergoes a two-step addition process with diols first the P-N bond is cleaved, followed by addition of the OH bond across the P=N double bond. Reaction with binaphthol stops after the first step to give 137, whereas catechol adds across the double bond to give 138 (Scheme 3) <2004JOC1880>. 

The 5,6-double bond in activated pyrimidines can participate in thermal [4-1-2] cyclization reactions as demonstrated by the 1,3-dipolar cycloaddition reactions of O-protected thymidine derivatives 483 with the nonstabilized azo-methine ylide 484, which is generated from trimethylamine AT-oxide by reaction with EDA <2002SC1977>. 

Dodd and co-workers (5) reported the first known synthesis of 11//-indolizino[8,7-h]indoles by the cycloaddition reaction of a nonstabilized ylide 21 and diethylacetylene dicarboxylate (DEAD). The azomethine ylide, formed by the alkylation of the 3,4-dihydro-p-carboline (22) with trimethylsilyl methyl triflate to the triflate salt, followed by in situ desilyation with cesium fluoride, underwent cycloaddition with DEAD at low temperature. The expected major cycloadduct 23 was isolated, along with quantities of a minor product 24, presumed to have been formed by initial reaction of the ylide with 1 equiv of DEAD and the intermediate undergoing reaction with a further equivalent of DEAD before cyclization. Dodd offers no explanation for the unexpected position of the double bond in the newly generated five-membered ring, although it is most likely due to post-reaction isomerization to the thermodynamically more stable p-amino acrylate system (Scheme 3.5). 

CHMe, cyclopropylidene, and CMe2 to activated double bonds.1075 Similar reactions have been performed with phosphorus ylides, 076 with pyridinium ylides,1077 and with the compounds (PhS)3CLi and Me3Si(PhS)2CLi.1078 The reactions with ylides are of course nucleophilic addition. 

Ylide (364) has been obtained by heating (363) in pyridine. Isoquinoline yields a stable ylide upon reaction with ethoxycarbonylcarbene (70TL941) and the relative rates of reaction of ethoxy-carbonylcarbene with pyridine, quinoline, and acridine have been studied (88JOC4374). However, the isoquinolone (365) undergoes attack at the isoquinoline double bond to give (366). 

Reaction of triazolopyrimidinium ylides (256) with active acetylenes gave the 1 2 adducts 260. The formation of 260 may occur in two ways the shortest pathway consists of the double 1,3-dipolar cycloaddition of the diylide 256A with two molecules of the acetylene at two different sites to form the tetracyclic adduct 257, followed by ring opening under basic conditions to give 260. The second pathway consists of cycloaddition between the ylide carbanion of 256 and the bridged carbon C-4 to form the 1 1 adduct 258, which isomerizes to the more stable compound 259, which may be formed directly by the cycloaddition at the ylide carbanion and C-2. The second cycloaddition afforded the 1 2 adduct 257 [87JCS(P1)2531] (Scheme 49). 

The required chiral sulfur ylide of type 59 is formed in a reaction with a diazo compound in the presence of an achiral metal catalyst. Subsequently, asymmetric reaction of the chiral ylide 59 with the C=N double bond of the imine proceeds diastereoselectively and enantioselectively, giving the optically active aziridine 57. The chiral sulfide catalyst released is then used for the next catalytic cycle. The cat-alytically active species in the asymmetric process is the sulfide, so this concept can also be regarded as an organocatalytic reaction. 

The generation of nonstabilized azomethine ylide 256 via PET-initiated sequential double desilylation and [3 + 2]-cycloaddition reaction with various dipolarophiles to generate five-membered heterocycles 257, has also been established by Pandey et al., as shown in Table 8.5 [110]. 

Oxaspiropentanes have been obtained from the cyclopropylide 103, prepared by treatment of cyclopropyldiphenylsulfonium tetrafluoroborate 102 either with sodium methylsulfmyl carbanion in dimethoxyethane at —45 °C or with potassium hydroxide in dimethylsulfoxide at 25 °C. While the reaction of the ylide 103 with a,p-unsaturated carbonyl compounds has resulted in selective cyclopropylidene transfer to the a, 3-carbon-carbon double bond leading to spiropentanes, condensation of 103 with non-conjugated aldehydes and ketones led to oxaspiropentanes such as 104, which have been isolated in 59-100% yields, Eq. (30) 57). 

The phosphonium salt is more acidic than usual because its conjugate base, the ylide, is stabilized by resonance involving the double bonds. Therefore, methoxide ion, a weaker base than usual, can be used lo form the ylide. Reaction of the ylide with the aldehyde that has its hydroxy group protected as an ester produces vitamin A acetate. The acetate group can readily be removed to complete the synthesis of vitamin A (see Section 10.2). 

The formation and intramolecular dipolar cycloaddition of azomethine ylides formed by carbenoid reaction with C-N double bonds has recently been studied by the author s group [66]. Treatment of 2-(diazoacetyl)benzaldehyde O-methyl oxime (118) with rhodium (II) octanoate in the presence of dimethyl acetylenedicarboxylate or iV-phenylmaleimide produced cycloadducts 120 and... 

The lability of the carbon-tellurium double bond has frequently thwarted attempts to study both telluraldehydes and telluroketones. Tel-lurocarbonyl compounds stabilized by coordination to transition metals have been known since 1980 [80CC635 83AG(E)314 88JOM161]. However, free telluraldehydes were unknown until 1989 when two different synthetic routes were reported. Erker and Hock trapped tellurobenzalde-hyde (92, R = Ph) generated by reaction of ylide (91) with tellurium powder adduct 93 was obtained in low yield [89AG(E)179]. 

The presence of the triphenylphosphonium substituent makes 351 (Scheme 2.122) an active dienophile. Resulting cycloadducts such as 352 are immediately recognized as precursors for the formation of ylides. Products with an exocyclic double bond such as 353 are easily synthesized via a tandem sequence of Diels-Alder and Wittig reactions. The formation of adduct 353 could have been achieved via the Diels-Alder reaction with the allene CH2 = C = CHR, but this direct route is generally unapplicable owing to the low activity of allenes as dienophiles. 

---