Butyllithium reaction with vinyl bromides

Arylation and vinylation of lithium ester enolates. Addition of -butyllithium lo suspensions of nickeKlI) bromide in THF produces a species that catalyzes substitution of lithium e.ster enolates (prepared with LDA in THF at -78°) by aryl and vinyl halides with retention of configuration. Lithium enolates of a./j-unsaturated esters undergo substitution in this reaction at the y-position (last example). The mechanism of this reaction is not certain. ... 

A general methodology for the construction of quaternary carbon atoms at the carbonyl carbon of ketones has been successfully exploited for the facile synthesis of ( )-lycoramine (299) (Scheme 30) (165). Thus, the O-allylated o-vanillin 322 was allowed to react with vinyl magnesium bromide followed by Jones oxidation, and the acid-catalyzed addition of benzyl IV-methylcarbamate to the intermediate a,(3-unsaturated ketone furnished 323. Wadsworth-Emmons olefination of 323 with the anion derived from diethyl[(benzylideneami-no)methyl]phosphonate (BAMP) provided the 2-azadiene 324. The subsequent regioselective addition of n-butyllithium to 324 delivered a metalloenamine that suffered alkylation with 2-(2-bromoethyl)-2-methyl-l,3-dioxolane to give, after acid-catalyzed hydrolysis of the imine and ketal moieties, the 8-keto aldehyde 325. Base-catalyzed cycloaldolization and dehydration of 325 then provided the 4,4-disubstituted cyclohexenone 326. The entire sequence of reactions involved in the conversion of 323 to 326 proceeded in very good overall yield and in one pot. 

A more concise route to ( )-cherylline was also devised and commenced with the reductive animation of isovanillin with methylamine followed by reaction of the intermediate benzylamine with vinyl triphenylphosphonium bromide to provide the aminophosphonium salt 619. Sequential treatment of 619 with n-butyllithium and the quinone ketal 615 followed by reaction of the resulting crude allylic amine 620 with boron trifluoride etherate gave the phenolic amine 618 in good overall yield (225). 

Although /-butyllithium has been successfully applied to metallate methyl vinyl ether, one might prefer to use the cheaper and less dangerous combination of ra-BuLi and r-BuOK for the metallation of simple vinyl ethers. If an excess of ethyl vinyl ether is used, quantitative metallation can be obtained. Some derivatization reactions give much better results with the lithium compounds. The requisite transformation into the lithiovinyl ethers can be carried out by addition of a solution of anhydrous lithium bromide in THF. 

Metalation of phenyl vinyl seleiUde (1). The reaction of this selenide and n-butyllithium follows mainly two courses Se—C cleavage and addition to the double bond. The most satisfactory reagent for metalation is LDA however, depending on the solvent, elimination can occur as well. For example, reaction of 1 with 1.5 equiv. of LDA at —78° in THF-HMPT (20 1) and then with decyl bromide gives 2-phenylseleno l-dodecene (2) in 70% yield. Elimination to 3 predominates in THF-HMPT (3 1). ... 

Vinylfithium derivatires. Terminal alkenyllithiums (2) are not generally available by Br/Li exchange of vinyl bromides (1) with alkyllithiums because of dehydrobromination to alkynes. However, they are accessible by reaction of (1) with 2 equiv. of r-butyllithium at -20° in THF-ether-pentane. Subsequent... 

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