Alkenylmetals

H. 1,1-Dimetal Species from Zincated Hydrazone and Alkenylmetal. 675... 

Type zinc-ene reactions seem to be more difficult to achieve compared to type I cyclizations even though successful examples of six- or seven-membered ring formations have been reported. Nevertheless, type I reactions constitute a particularly attractive strategy for the formation of five-membered rings that proceed smoothly compared to intermolecular additions to monosubstituted alkenes. However, allylic organozincs are able to add to substituted alkenylmetals under extremely mild conditions. 

Preliminary studies demonstrated that, under the above conditions, the more substituted the alkenylmetal, the less reactive it was towards addition of allylzinc bromide. Disubstitution at the /J position significantly retarded the addition127. The reaction still occurred efficiently in THF at 35 °C if silyl or aryl groups were present at the a-position... 

The stereochemical outcome was in agreement with the formation of a chelated allyl alkenylzinc compound that underwent a metalla-Claisen rearrangement with delivery of the allyl moiety anti to the homoallylic substituent. Although the stereocenter was more remote from the alkenylmetal, excellent induction was still observed152,153. 

For alkenylmetals bearing two stereocenters at both the allylic and homoallylic positions, two situations have to be distinguished depending on their relative influence (matched or mismatched) with respect to the stereochemical outcome of the allylzincation. Not surprisingly, in the matched case, as illustrated for substrate 232, the diastereoselectivity was excellent and 233 was obtained as a single diastereomer. The allyl moiety was delivered anti to both the allylic and homoallylic substituents in the chelated allyl alkenylzinc species (equation 113). 

Although substrate-induced diastereoselection can be conveniently achieved when the alkenylmetal was coordinated by an oxygen atom, other heteroatoms such as sulfur and nitrogen resulted in high inductions as illustrated by the crotylzincation of the organolithium reagents derived from the allylic sulfide 238 or the tertiary amine 239 (equation 117)154. 

Substrate-induced diastereoselective allylzincations essentially rely on coordination of the alkenylmetal by an appropriately located heteroatom, but a zinc-alkene -interaction23 27 can also exert a remarkable stereodirecting effect. Indeed, the alkenyllithium derived from 248, bearing an appropriately located carbon—carbon double bond, underwent highly diastereoselective allyl- and crotylzincations which led after hydrolysis to the corresponding 1,6-dienes 249 and 250. The stereochemical outcome... 

Thus, the weak interaction between the zinc and a double bond was remarkably efficient at promoting the differentiation of the two pro-stereogenic faces of the alkenylmetal during the allylzincation process. Nevertheless, recent results have demonstrated that n-interactions with arenes or alkenes are less powerful in magnitude than the coordination by an alkoxy group such as a MOM ether, when both can exert a role on the stereochemical outcome158. 

As mutual face selectivity between an alkenylmetal and a substituted ally lie organozinc reagent, combined with the alkenylmetal-induced diastereoselection, enabled the creation of two stereocenters, turning the sp3 dimetallated carbon into an additional asymmetric carbon has also been examined. 

Allylzincation of alkenylmetals provides a useful entry to the diastereoselective synthesis of sp3 yem-dirnclallic species that can react with two different electrophiles in a one-pot protocol, leading to elaborated acyclic structures with control of the configuration of up to three adjacent stereocenters, as well as to cyclopropanes bearing various substitution patterns126,163. 

When the first electrophile was not a ketone or an aldehyde, as illustrated for the reaction of 276 with crotonyl chloride, the intermediate chelated alkenylmetal 278 could also be subjected to iodinolysis or palladium-catalyzed cross-coupling reactions with aryl and alkenyl iodides in the presence of a stoichiometric amount of CuBr as a promotor as well as a polar cosolvent such as IV, IV-di methyl acetamide (DMA) (equation 131)165 166. 

By contrast, when the first electrophile was an aldehyde as illustrated for the reaction of 276 with benzaldehyde, the resulting alkenylmetal presumably became part of a six-membered ring alkoxide 279 and hence so poorly reactive that it did not even react with iodine. However, treatment with Me3SiCl resulted in the silylation of the secondary zinc alkoxide and allowed iodinolysis to subsequently proceed, affording the (Z)-alkenyl iodide 280 (equation 132)165. Unfortunately, this protocol was not efficient for tertiary alkoxides generated by initial reaction of 276 with ketones. 

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