Nonstabilized ylide

Retrosynthetic cleavage of the trans A8,9 disubstituted double bond in intermediate 11, the projected precursor of diketone 10, provides phosphorus ylide 12 and aldehyde 13 as potential precursors. In the forward sense, a Wittig reaction could conceivably achieve a convergent coupling of intermediates 12 and 13 with concomitant formation of the requisite trans C8-C9 olefin. Ordinarily, the union of a nonstabilized ylide, such as 12, with an aldehyde would be expected to afford an alkene with a cis geometry.8 Fortunately, however, the Schlosser modification of the Wittig reaction permits the construction of trans olefins from aldehydes and nonstabilized phosphorus ylides.9... 

Activated alcohols can be converted into olefins with Mn02 and nonstabilized ylides, see Blackburn, L. Pei, C., Taylor,... 

Syntheses of (l )-frans-isomers were reported by Crombie [24] and Elliott [25] starting from (1 /t Wran.v-chrysanthemic acid by means of the Wittig reaction. Their method were convenient to obtain (Z)-isomer (Scheme 10, step a) but not appropriate for the synthesis of ( )-isomer because of the (Z)-selective nature of the Wittig reaction in the case of nonstabilized ylides. It was very difficult to separate the pure ( )-isomer out of the (E)- and (Z)-mixture. This problem was overcome by use of the Takai s method (Scheme 10, step b) [26]. The ( )-selectivity of the double bond was fairly high (E Z = 89 11) (Scheme 10). 

The normal Wittig reaction of nonstabilized ylides with aldehydes gives Z-olefms. The Schlosser modification of the Wittig reaction of nonstabilized ylides furnishes f-olefins instead. 

Some particular aspects of the chemistry of ylides as ligands have been reviewed throughout the years [15-27]. The topics are quite specific in most cases, and are mainly treated comprehensively nonstabilized ylides [15, 16], S-ylides [17], Au ylides and methanides [18], Li derivatives [19], Pd and Pt complexes [20-23], zwitterionic metallates [24], stabilized ylides [25], and applications [26, 27] have been reported upon. We will try in the following sections to give a basic complementary point of view about the chemistry of ylides as ligands. 

A different approach to synthesize nonstabilized ylide complexes is the reaction of halomethyl-metallic precursors with the corresponding nucleophile EZ . This method is quite general and usually occurs in very mild reaction conditions. Platinum, rhodium, iron, and palladium complexes (21)-(25) (Scheme 8) have been prepared, using phosphines [79-83], amines [84], or sulfides [85] as nucleophiles. Some of the most representative examples are shown in Scheme 8. 

Scheme 10 Carbene complexes obtained from nonstabilized ylides as CTR...

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). 

Hosami and co-workers (12,173,174) prepared alternative forms of nonstabilized ylides (Scheme 4.87). They generated tailor-made carbonyl ylides from substituted 1,3-dichloroethers through a 1,3-elimination pathway mediated with a samarium reagent. These simple carbonyl ylide intermediates are valuable for preparing tetrahydro- and dihydrofurans. To a mixture of bis(chloromethyl) ethers and... 

Alkylthieno[2,3-4furans 414 and 4-alkylfuro[3,4-, ]furans 416 were obtained as unexpected side products from the reaction of 2-acetyl-5-bromothiophene and 2-acetyl-5-methylfuran with stabilized and nonstabilized ylides, along with the corresponding phosphoranes 415, pyrans 417, and dimeric products 418, respectively (Scheme 45) <2000T7573>. 

Current results indicate that stabilized arsonium ylides such as phenacylide, carbomethoxymethylide, cyanomethylide, fluorenylide, and cyclopentadienylide afford only olefinic products upon reaction with carbonyl compounds. Nonstabilized ylides such as ethylide afford almost exclusively epoxides or rearranged products thereof. However, semi-stabilized arsonium ylides, such as the benzylides, afford approximately equimolar amounts of olefin and epoxide. Obviously, the nature of the carbanion moiety of the arsonium ylide greatly affects the course of the reaction. It is reasonable to suppose that a two-step mechanism is involved in the reaction of heteronium (P, S, and As) ylides with carbonyl compounds (56). 

Nonstabilized ylides react with the aldehyde as soon as they form on the surface of the base, therefore kaolinite does not influence the course of the reaction. 

Under salt-free conditions, the cw-oxaphosphetanes formed from nonstabilized ylides can be kept from participating in the stereochemical drift and left intact until they decompose to give the alkene in the terminating step. This alkene is then a pure ci.s-isomer. In other words, salt-free Wittig reactions of nonstabilized ylides represent a stereoselective synthesis of cis-alkenes. 

Fig. 11.4. Optimum cis-selec-tivities of Wittig olefinations of different aldehydes with nonstabilized ylides under "salt-free" conditions.

Fig. 11.5. Chemosetective and stereoselective Wittig ole-fination with a nonstabilized ylide.

A different reaction mode of lithiobetaines is used in the Schlosser variant of the Wittig reaction. Here, too, one starts from a nonstabilized ylide and works under non-salt-free conditions. However, the Schlosser variant is an olefination which gives a pure frans-alkene rather than a trans.cis mixture. The experimental procedure looks like magic at first ... 

Ylide type nonstabilized ylide semi-stabilized ylide stabilized ylide... 

Stereogenic Wittig reactions of nonstabilized ylides of the structure Ph3P+—CH —R2 have been studied in-depth in many instances. They give the cis-configured oxaphosphetane rapidly, with the rate constant kcis, and reversibly (Figure 9.7). On the other hand, the same nonstabilized ylide produces the /ran.v-oxaphosphetane slowly, with the rate constant ktrans, and irreversibly. The primary product of the [2+2]-cycloaddition of a nonstabilized P ylide to a substituted aldehyde is therefore a cis-oxaphosphetane. Why this is so has not been ascertained despite the numerous suggestions about details of the mechanism which have been made. 

Fig. 9.9. Chemoselective and stereoselective Wittig olefination with a nonstabilized ylide.

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