Allyl electrophiles

Vinyloxirancs and vinyl acetals constitute a special subset of allylic electrophiles. The product of Sn2 displacement of vinyloxiranes is an allylic alcohol, while the SN2 product from vinyl acetals is a vinyl ether. 

Cu-catalysed additions of ZnEt2 to Baylis-Hillman-derived allylic electrophiles with BINOL-based thioether ligand. 

Nickel(O) catalysis has been utilized for a three-component coupling between an allylic electrophile, and alkyne, and AlMe3 or ZnMe2. This reaction takes place though the insertion of a 7r-nickel(ll) intermediate into the alkyne,... 

Stereoselective substitution reactions of chiral dienyl electrophiles have also been carried out. In analogy to the copper-promoted 8 2 reactions of simple allylic electrophiles [3], the corresponding 8 2 (1,3) substitutions of dienyl carbonates [43] have been reported to proceed with high anti selectivity. Interestingly, treatment of chiral dienyl acetal 63 with the Yamamoto reagent PhCu BFs gave rise to the formation of a 1 3 mixture of the anti-S l substitution product 64 and the syn-Sn2" (1,5) substitution product 65 (Eq. 4.28) [44]. A mechanistic explanation of this puzzling result has yet to be put forward, however. 

Calb et al. have thoroughly investigated the use of allylic electrophiles containing heterocyclic leaving groups in regioselective allylic substitution (Scheme 8.7) [22]. 

Compared to the intensive and successful development of copper catalysts for asymmetric 1,4-addition reactions, discussed in Chapt. 7, catalytic asymmetric al-lylic substitution reactions have been the subjects of only a few studies. Difficulties arise because, in the asymmetric y substitution of unsymmetrical allylic electrophiles, the catalyst has to be capable of controlling both regioselectivity and enan-tioselectivity. 

Woodward et al. have used the binaphthol-derived ligand 40 in asymmetric conjugate addition reactions of dialkylzinc to enones [46]. Compound 40 has also been studied as a ligand in allylic substitutions with diorganozinc reagents [47]. To allow better control over selectivity in y substitution of the allylic electrophiles studied, Woodward et al. investigated the influence of an additional ester substituent in the jS-position (Scheme 8.25). 

The scope of allylic electrophiles that react with amines was shown to encompass electron-neutral and electron-rich ciimamyl methyl carbonates, as well as furan-2-yl and alkyl-substituted allylic methyl carbonates. An ort/io-substituted cinnamyl carbonate was found to react with lower enantioselectivity, a trend that has been observed in later studies of reactions with other nucleophiles. The electron-poor p-nitrocinnamyl carbonate also reacted, but with reduced enantioselectivity. Allylic amination of dienyl carbonates also occur in some cases with high selectivity for formation of the product with the amino group at the y-position over the s-position of the pentadienyl unit [66]. Arylamines did not react with allylic carbonates under these conditions. However, they have been shown to react in the presence of the metalacyclic iridium-phosphoramidite catalysts that are discussed in Sect. 4. 

Reactions of allylic electrophiles with stabilized carbon nucleophiles were shown by Helmchen and coworkers to occur in the presence of iridium-phosphoramidite catalysts containing LI (Scheme 10) [66,69], but alkylations of linear allylic acetates with salts of dimethylmalonate occurred with variable yield, branched-to-linear selectivity, and enantioselectivity. Although selectivities were improved by the addition of lithium chloride, enantioselectivities still ranged from 82-94%, and branched selectivities from 55-91%. Reactions catalyzed by complexes of phosphoramidite ligands derived from primary amines resulted in the formation of alkylation products with higher branched-to-linear ratios but lower enantioselectivities. These selectivities were improved by the development of metalacyclic iridium catalysts discussed in the next section and salt-free reaction conditions described later in this chapter. 

Additional mechanistic insights were gained when Hartwig and coworkers isolated and characterized the first 7t-allyl complexes that are chemically and kinetically competent to be intermediates in iridium-catalyzed allylic substitution [46]. These complexes were prepared independently from allylic electrophiles that are more reactive than allylic carbonates. The isolation and structural characterization of these species provided a detailed view into the origins of enantioselectivity. 

The alkyl substituent meta to the methoxy substituent was easily introduced into the symmetrical diamide 72 by yet another ortholithiation. Allyl electrophiles react poorly with aryllithiums, so the ortholithiated amide 73 was first transmetallated to the Grignard reagent before allylation with allyl bromide to give 74. 

The scope of reaction has been further extended to allylic electrophiles. An extensive investigation of the intramolecular acylpalladation has been performed in a series of < -iodoalkenylbenzenes with both terminal and internal double bonds and 1-iodo-substituted 1,4-, 1,5-, or 1,6-dienes. ... 

SCHEME 22. Proposed mechanisms for oxidative addition of Pd to alkenyl and allyl electrophiles... 

Although not discussed in this chapter, the Tsuji-Trost reaction159 is undoubtedly the most extensively investigated Pd-catalyzed allylation with allyl electrophiles. There have also been some uncatalyzed and Cu-catalyzed reactions of allyl electrophiles with alkyl metals and metal cyanides. On the other hand, the Pd- or Ni-catalyzed reactions of allyl electrophiles with organometals containing allyl-, benzyl-, propargyl- and other alkylmetals do not appear to have been extensively investigated. 

The copper-catalysed asymmetric conjugate addition of dialkylzinc leads to homo-chiral zinc enolates.28 These intermediates have been trapped in situ with activated allylic electrophiles, without the need for additional palladium catalysis (Scheme 3). 

Allyl electrophiles, addition to zirconacycles, 10, 281 Allyl ethers, isomerization, 10, 85... 

Allylic electrophiles can react with nucleophiles either with or without allylic rearrangement [213], The outcome of such reactions will depend on whether or not an allylic carbocation is formed as intermediate, and on the steric requirement and hardness of the two electrophilic centers and the nucleophile. Bimolecular substitutions at allylic electrophiles which occur with rearrangement are called Sn2 reactions. 

Allylic electrophiles react readily with Pd(0) complexes to yield rf-allyl Pd(II) complexes, which retain electrophilic character and react with nucleophiles to yield the product of allylic substitution and Pd(0). Thus, catalytic amounts of Pd(0) provide an additional mechanism (in addition to SnI, Sn2, and Sn2 ) by which an allylic substitution can proceed. Because the metal generally attacks the allylic electrophile... 

Scheme4.56. Nucleophilic substitutions at allylic electrophiles with organocopper reagents [230, 234—237],...

For Pd-catalyzed cross-coupling reactions the organopalladium complex is generated from an organic electrophile RX and a Pd(0) complex in the presence of a carbon nucleophile. Not only organic halides but also sulfonium salts [38], iodonium salts [39], diazonium salts [40], or thiol esters (to yield acylpalladium complexes) [41] can be used as electrophiles. With allylic electrophiles (allyl halides, esters, or carbonates, or strained allylic ethers and related compounds) Pd-i73-jt-allyl complexes are formed these react as soft, electrophilic allylating reagents. 

Metals other than palladium and molybdenum can be used for allylic substitution reactions. For example, nickel in the presence of the oxazolinylferrocenylphosphine 9 provides good asymmetric induction for the reaction of a Grignard reagent with allylic electrophilic systems such as acetates.151... 

An example for the use of the boron-zinc exchange reaction for copper-mediated SN2 -substitutions of allylic electrophiles is the hydroboration of nitroolefin 130 with diethylborane, followed by successive transmetallation of the borane 131 with diethylzinc and CuCN-2LiCl, and final trapping with allyl bromide to give the product 133 with 83% yield over four steps (Scheme 34).34,34a This transformation again demonstrates the tolerance of the method towards functional groups and acidic hydrogen atoms. 

---