Allylation umpolung

Pd-catalyzed umpolung allylation reactions of aldehydes, ketones, and imines... 

Compared with well-established electrophilic it-allylpalladium chemisty, the catalytic asymmetric reaction via umpolung of jt-allylpalladium has received very limited exploration [93]. Zhou and co-workers investigated the Pd-catalyzed asymmetric umpolung allylation reactions of aldehydes [22a, 94], activated ketones [95], and imines [96] by using chiral spiro ligands (5)-18e, (S)-17c, and (5)-17a, respectively. One representative example is that of the Pd/(5)-18e-catalyzed umpolung allylation of aldehydes with allylic alcohols and their derivatives, which provided synthetically useful homoallylic alcohols from readily available allylic alcohols, with high yields and excellent enantioselectivities (Scheme 33). 

In direct contrast to what is observed for Tj -allyl complexes, the allyl ligand in ri compounds is nucleophilic. This was exploited in the asymmetric Pd-catalysed nucleophilic addition of allylic reagents to aldehydes (also known as umpolung allylation of aldehydes). There are only three recent studies with NHC-Pd catalysts, by Shi, and Jarvo, but activities and/or enantioselectivities were only modest. 

Allylic metal compounds useful for further transformations can be prepared by Pd-catalyzed reactions of allylic compounds with bimetallic reagents. By this transformation, umpolung of nucleophilic 7r-allylpalladium complexes to electrophilic allylmetal species can be accomplished. Transfer of an allyl moiety from Pd to Sn is a typical umpolung. 

Notice that the final result is a 1,3 charge affinity inversion Umpolung) of an allylic derivative via a FGI of a functional group of type E by a group of type A, followed by a [2,3]-sigmatropic rearrangement. If the intermediate allyl anion reacts with a carbonyl compound as the electrophile the result is then a 1,4-D system, such as ... 

For selected reviews on carbonyl allylation via umpolung of 7C-allyls, see [242-247]. 

Hetero-substituted allyl compounds obtained by electrophilic attack in the 1-position can be reduced to give the heteroalkyl compounds carrying the new substituent on the a-carbon atom ( ). In this case, the double bond was used as an activating substituent only, to achieve easier deprotonation and higher nucleophilicity. In both cases the synthetically important umpolung of reactivity was achieved20. 

The reversal in mode of reactivity or umpolung of ir-allylpalladium complexes can be accomplished by two strategies. The first involves conversion of the ir-allyl species to an allyl-M species, where M is a... 

Both of these methods could be included as examples of umpolung of ir-allyl species, as the electrophilic allylpalladium has now been transformed into a nucleophilic allyl moiety. Finally, Bn can also be added to ir-allylpalladium complexes (equation 134).342... 

Scheme 8.6 Umpolung of allyl acetate for the formation of homoallylic alcohols and reaction of aldehydes with ethyl diazoacetate.

A three-component reaction based on the umpolung of re-allylpalladium (II) complexes indium metal was reported by Grigg and co-workers (Scheme 8.31) [74]. In this reaction, the electrophilic nature of the n-allyl palladium species generated from aryl halides and allenes is reversed by transmetallation with indium metal. The resultant nucleophilic allylindium reagent subsequently adds to the third component - aldehyde [75] or imine [76] - to give the corresponding homo-allylic alcohol 64 or amine 65 respectively. 

Allylstannane 176 is formed by the reaction of allyl acetate with distannanes [97,98], In this reaction, umpolung of the electrophilic 7r-ally] palladium to the nucleophilic allylstannane occurs. Allylation of bromoindole 198 to give allylindole 199 involves the oxidative addition of 198 to Pd, transmetallation with the allylstannane 176, and final reductive elimination [99],... 

The side chain R in these enals contained functionalities such as a double bond, or an acetoxy group, which were unaffected. The reaction proceeds again through a vinyl iodonium intermediate which serves as a reactive allyl cation. In this way the umpolung of allylsilanes is achieved and, indirectly, the reactivity of allyl halides is considerably increased. 

The reductive lithiation of dioxolanes requires the formation of an allylic or benzylic organolithium, and represents a valuable umpolung method for the functionalisation of carbonyl compounds. 

Metal rf-inline complexes with various transition metals [1-10] and lanthanides [11,12] are well known in the literature. Early transition metal if-imine complexes have attracted attention as a-amino carbanion equivalents. Zirconium rf-imine complexes, or zirconaaziridines (the names describe different resonance structures), are readily accessible and have been applied in organic synthesis in view of the umpolung [13] of their carbons whereas imines readily react with nucleophiles, zirconaaziridines undergo the insertion of electrophilic reagents. Accessible compounds include heterocycles and nitrogen-containing products such as allylic amines, diamines, amino alcohols, amino amides, amino am-idines, and amino acid esters. Asymmetric syntheses of allylic amines and a-amino acid esters have even been carried out. The mechanism of such transformations has implications not only for imine complexes, but also for the related aldehyde and ketone complexes [14-16]. The synthesis and properties of zirconaaziridines and their applications toward organic transformations will be discussed in this chapter. 

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