Allyl metal compounds reactions with electrophiles

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. 

Both stoichiometric and catalytic reactions of allylic compounds via 7r-allyl complexes are known. Reactions of nucleophilic 71-allyl complexes with electrophiles involve oxidation of metals and hence constitutes stoichiometric reactions. 7i-Allyl complexes of Ni, Fe, Mo, Co and others are nucleophilic and undergo the stoichiometric reaction with electrophiles. However, electrophilic 71-allyl complexes react with nucleophiles, accompanying reduction of metals. For example, 71-allylnickel chloride (2) reacts with electrophiles such as aldehydes, generating Ni(II), and hence the reaction is stoichiometric. In contrast, electrophilic 7i-allylpalladium chloride (3) reacts with nucleophiles such as malonate and Pd(0) is generated. Thus repeated oxidative addition of allylic compounds to Pd(0) constitutes a catalytic reaction. 

There are two main synthetic applications where the reaction of an allyl system with electrophiles is accompanied by an allylic rearrangement. One consists of the use of heteroatom-substituted allylic anions as homoenolate anion equivalents and the other represents a synthetically valuable alternative to the aldol reaction by addition of allyl metal compounds to aldehydes. 

The potential of homoenolate anions on reaction with different electrophiles (Scheme 77) is evident and explains why a great deal of effort has been expended to get high y-selectivity in reactions of such allyl metal compounds. 

A number of highly enantioselective chiral allyl organometallic reagents have been described in the literature. These are of considerable interest both for the asymmetric synthesis of homoallyl alcohols as well as in double asymmetric reactions with chiral C=X electrophiles. - Two distinct groups of chiral allyl metal reagents can be identified those with conventional, easily introduced chiral auxiliaries and ones in which the center of chirality is a structural component of the reagent (e.g. allyl metal compounds with substituents at C-1). These are discussed separately in the sections that follow. 

We have seen in Section 1.1.3 that reactions of many allyl organometallics and chiral C=X electrophiles proceed with only modest levels of relative diastereoselection. Significant improvement in dia-stereoselectivity is possible, however, by using double asymmetric synthesis, that is, by using the highly enantioselective allyl metal reagents described in Section 1.1.4 rather than the less diastereoface-selec-tive achiral allyl metal compounds discussed in Section 1.1.3. Double asymmetric synthesis is also... 

Significantly, this discovery showed that 7r-allylpalladium is an electrophilic allyl complex, and Pd(0) is generated after the reaction with nucleophiles, indicating the possibility of a catalytic reaction. In contrast, allylic compounds of some other transition metals and main group metals, such as allyl Grignard reagent, are nucleophilic, and their reactions with electrophiles involve oxidation of the metals, and hence the reaction is stoichiometric, because in situ reduction of the oxidized metals is practically impossible (Scheme 2). 

When the metallic additive to the intermediate 374 was zinc dihalide (or another Lewis acid, such as aluminum trichloride, iron trichloride or boron trifluoride), a conjugate addition to electrophilic olefins affords 381 . In the case of the lithium-zinc transmetallation, a palladium-catalyzed Negishi cross-coupling reaction with aryl bromides or iodides allowed the preparation of arylated componnds 384 ° in 26-77% yield. In addition, a Sn2 allylation of the mentioned zinc intermediates with reagents of type R CH=CHCH(R )X (X = chlorine, bromine) gave the corresponding compounds 385 in 52-68% yield. ... 

Benzyl methyl ether or allyl methyl ethers can be selectively metalated at the benzylic/allylic position by treatment with BuLi or sBuLi in THF at -40 °C to -80 C, and the resulting organolithium compounds react with primary and secondary alkyl halides, epoxides, aldehydes, or other electrophiles to yield the expected products [187, 252, 253]. With allyl ethers mixtures of a- and y-alkylated products can result [254], but transmetalation of the lithiated allyl ethers with indium yields y-metalated enol ethers, which are attacked by electrophiles at the a position (Scheme 5.29). Ethers with ft hydrogen usually undergo rapid elimination when treated with strong bases, and cannot be readily C-alkylated (last reaction, Scheme 5.29). Metalation of benzyl ethers at room temperature can also lead to metalation of the arene [255] (Section 5.3.11) or to Wittig rearrangement [256]. Epoxides have been lithiated and silylated by treatment with sBuLi at -90 °C in the presence of a diamine and a silyl chloride [257]. 

Mixed bimetallic reagents possess two carbon-metal bonds of different reactivity, and a selective and sequential reaction with two different electrophiles should be possible. Thus, the treatment of the l,l-bimetailic compound 15 with iodine, at — 78"C, affords an intermediate zinc carbenoid 16 that, after hydrolysis, furnishes an unsaturated alkyl iodide in 61% yield [Eq. (15) 8]. The reverse addition sequence [AcOH (1 equiv), —80 to — 40 C iodine (1 equiv)] leads to the desired product, with equally high yield [8]. A range of electrophile couples can be added, and the stannylation of 15 is an especially efficient process [Eq. (16) 8]. A smooth oxidation of the bimetallic functionality by using methyl disulfide, followed by an acidic hydrolysis, produces the aldehyde 17 (53%), whereas the treatment with methyl disulfide, followed by the addition of allyl bromide, furnishes a dienic thioether in 76% yield [Eq. (17) 8]. The addition of allylzinc bromide to 1-octenyllithium produces the lithium-zinc bimetallic reagent 18, which can be treated with an excess of methyl iodide, leading to only the monomethylated product 19. The carbon zinc bond is unreactive toward methyl iodide and, after hydrolysis, the alkene 19... 

Catalytic reactions of allylic electrophiles with carbon or heteroatom nucleophiles to form the products of formal S 2 or S 2 substitutions (Equation 20.1) are called "catalytic allylic substitution reactions." Tliese reactions have become classic processes catalyzed by transition metal complexes and are often conducted in an asymmetric fashion. The aUylic electrophile is typically an allylic chloride, acetate, carbonate, or other t)q e of ester derived from an allylic alcohol. The nucleophile is most commonly a so-called soft nucleophile, such as the anion of a p-dicarbonyl compound, or it is a heteroatom nucleophile, such as an amine or the anion of an imide. The reactions with carbon nucleophiles are often called allylic alkylations. 

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