Olefination Reactions of Stabilized Carbon Nucleophiles

This section deals with reactions that correspond to Pathway C, defined earlier (p. 64), that lead to formation of alkenes. The reactions discussed include those of phosphorus-stabilized nucleophiles (Wittig and related reactions), a a-silyl (Peterson reaction) and a-sulfonyl (Julia olefination) with aldehydes and ketones. These important rections can be used to convert a carbonyl group to an alkene by reaction with a carbon nucleophile. In each case, the addition step is followed by an elimination. 

A crucial issue for these reactions is the stereoselectivity for formation of E- or Z-alkene. This is determined by the mechanisms of the reactions and, as we will see, can be controlled in some cases by the choice of particular reagents and reaction conditions. 

The Wittig and Related Reactions of Phosphorus-Stabilized Carbon Nucleophiles 

Reactions of Carbon Nucleophiles with Carbonyl Compounds 

NMR spectroscopic studies f111,13C, and 31P) are consistent with the dipolar ylide structure and suggest only a minor contribution from the ylene structure.234 Theoretical calculations support this view.235 The phosphonium ylides react with carbonyl compounds to give olefins and the phosphine oxide. 

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The nucleophilic 1,4-addition of stabilized carbon nucleophiles to electron-poor olefins, generally a,fS-unsaturated carbonyl compounds, is known as Michael addition, although it was first reported by Komnenos [14] in 1883. Michael-type reactions can be considered as one of the most powerful and reliable tools for the stereo-controlled formation of carbon-carbon and carbon-heteroatom bonds [15], as has been demonstrated by the huge number of examples in which it has been applied as a key strategic transformation in total synthesis. As a consequence, in recent years, many different organocatalytic versions of this important transformation... 

Nucleophilic attack of stabilized carbon nucleophiles on coordinated olefins is also known. Hegedus developed the alkylation of olefins shown in Equation 11.31. The (olefin)palladium(II) chloride complexes did not react with malonate nucleophiles, but the triethylamine adduct does react with this carbon nucleophile to provide the alkylation product. This reaction has recently been incorporated into a catalytic alkylation of olefins by Widenhoefer. - Intramolecular reaction of the 1,3-dicarbonyl compounds with pendant olefins in the presence of (GHjCNl PdCl occurs to generate cyclic products containing a new C-C bond (Equation 11.32). Some intermolecular reactions with ethylene and propylene have also been developed by this group. Deuterium labeling studies (Equation 11.32) have shown that the addition occurs by external attack on the coordinated olefin. ... 

Carbopalladation Reactions. The transition metal-induced addition of carbon nucleophiles to unactivated alkenes is an attractive area of research. Although the addition of stabilized carbon nucleophiles or an alkoxycarbonyl group across the C=C bond of an unactivated olefin was initially achieved in the presence of stoichiometric amount of Pd salts, such as Pd(OAc)2 or PdCl2(CH3CN)2, more recently this reaction has been achieved catalytically. 

Palladium(0)-catalysed coupling of non-conjugated dienes, aryl iodides and stabilized carbon nucleophiles has been developed468. An incredibly high yield (86%) of pentacycle 343 has been obtained from a Pd(0)-catalysed zipper reaction of acetylenic pentaene 342. The reaction is triggered off by a Pd-catalysed cyclization of acetylenic bond and the first olefinic bond469. 

Recent advances in the stereoselective olefination of phosphorus-stabilized carbon nucleophiles have been reviewed. Recent applications of the Horner-Wadsworth-Emmons reaction to the synthesis of natural products have been highlighted. ... 

Recent advances in the stereoselective olefination of phosphorus-stabilized carbon nucleophiles have been reviewed. Applications of the Horner-Wadsworth-Emmons reaction to the synthesis of natural products have been highligted. A highly Z-selective synthesis of a, -unsaturated nitriles using the Homer-Wadsworth-Emmons reaction has been reported this involves a new nitrile reagent, (o-t-BuC6H40)2P(0)CH2CN, which reacts with various types of aldehydes with 86 to >99% Z selectivity. 

Stereodefined alkenes are ubiquitous structural motifs in many natural products and pharmaceutics, and, moreover, they serve as a foundation for a broad range of chemical transformations. Nowadays, carbonyl olefination, elimination, alkyne addition, alkenylation, and alkene metathesis constitute the most widely used methods for the stereoselective synthesis of various alkenes [1-3]. Whereas no single method provides a universal solution to stereoselective alkene synthesis, the olefination reactions of aldehydes and ketones with phosphorus-stabilized carbon nucleophiles have enjoyed widespread prominence and recognition owing to their simplicity, convenience, complete positional selectivity, and generally high levels of geometrical control [4-9]. 

Each of these transformations has its own advantages and limitations, and the selection of an appropriate method is essential for a desired stereoselective alkene synthesis. In this chapter we would like to discuss briefly the general stereochemical trends and focus on recent developments in the field of olefination reactions based on these phosphoms-stabilized carbon nucleophiles. 

Scheme 1 Olefination reactions of phosphorus-stabilized carbon nucleophiles...

In contrast to many other methods commonly employed for stereoselective alkene synthesis such as elimination, alkenylation, alkene metathesis, alkyne addition, the JuUa olefination, and the Peterson olefination [1-3], the olefination reactions of phosphorus-stabilized carbon nucleophiles remain very powerful for modem stereoselective alkene synthesis owing to their convenience, complete positional selectivity, and generally high levels of geometrical control. However, further modifications of these olefination reactions are definitely needed to broaden substrate scope, enhance stereoselectivity, and improve environmental impacts. 

Pampus and co-workers (65) established the relative reactivity of a series of olefins to be 1-butene > 2-butene > isobutylene. This order of reactivity has been confirmed by others, and exactly parallels the reported order of stability of transition metal (Rh) complexes with these olefins (66), thus clearly implicating precomplexation of the olefin with the transition metal prior to metathesis. On a limited scale, Schrock observed a similar order of reactivity for olefins in reactions with (175-C5H5 )TaCl2[=CH(CH3 )3 ], which is known to possess a nucleophilic car-bene carbon (64). This complex also provides the requisite empty coordination site needed for precomplexation. In that study, cyclopropanes or metathesis olefins were not observed as products. 

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