Umpolung allylation, aldehyd

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. 

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. 

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. 

RCHO to a ketone RCOR (for other methods, see 10-71, 16-82, and 18-9). In this procedure the normal mode of reaction of a carbonyl carbon is reversed. The C atom of an aldehyde molecule is normally electrophilic and is attacked by nucleophiles (Chapter 16), but by conversion to the protected cyanohydrin this carbon atom has been induced to perform as a nucleophile. The German word Umpolung is used to describe this kind of reversal (another example is found in 10-71). Since the ion 166 serves as a substitute for the unavailable R— C=0 anion, it is often called a masked R( C=0) ion. This method fads for formaldehyde (R = H), but other masked formaldehydes have proved successful. In an interesting variation of nitrile alkylation, a quaternary bromide [PhC(Br)(Me)CN] reacted with allyl bromide, in the presence of a Grignard reagent, to give the alkylated product [PhC(CN)(Me)CH2CH=CH2]. ... 

Allylation of aldehydes with allyl alcohols. Umpolung of allylic alcohols (e.g., isoprenol) and the direct nucleophilic attack on aldehydes is realized in the presence of (PhCN)2PdCl2 and SnCh. 

Tamaru discovered that 2-methylenepropane-l,3-diol (260) showed a different type of bifunctionality under slightly different conditions in the reaction with the aldehyde 259. In the presence of Et3B, Et3N, and LiCl, electrophilic a-allylation of the aldehyde took place to afford 261 in 93 % yield. Then nucleophilic allylation of the aldehyde 261 in the absence of Et3N and LiCl occurred to give the homoallylic alcohol 262. EtsB plays interesting dual roles first, it promotes a-allylation of the aldehyde enolate in the presence of amine, and second, umpolung of an allyl alcohol exhibits nucleophilic attack to aldehyde (Chapter 4.3.3) [96]. 

In 2006, Tamaru and coworkers have reported that vinyloxirane 118 is capable of undergoing amphiphilic allylation of aldehydes 117 where, under Pd(0) catalysis, the allylic ether moiety serves as an allyl cation and reacts with aldehydes in the a-position, giving 6-hydroxy-4-hexenals 119 in good yields (Scheme 12.57). In the second step, the allyl alcohol moiety in turn serves as an allyl anion under umpolung catalysis with Pd(0)-EtjB and furnishes 2-vinylcyclobutanols 120 in good to modest yields [138]. 

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