Copper vinyl cuprates

The stannylcupration of alkynes has been widely studied. Reaction of alkynes with lithium bis(tributylstannyl) cuprate leads to r -2-(tri butyl stannyl) vinyl cuprates, which are synthetically equivalent to cis- 1,2-ethylene dianions. Addition of the tin-copper reagent across the triple bond occurs i>7/-stereospecifically, thus providing Z-vinylstannanes. Phenylacetylene reacts with the tin cuprate with a regiochemistry opposite to that of 1-decyne.294 The intermediate cuprates react well with the various electrophiles.295 For example, the reaction with ethylene oxide gives primary alcohols, and further treatment of their />-toluenesulfonates with butyllithium gives 1-substituted cyclobutenes (Equation (120)) 294... 

An excellent illustration of both these types of vinyl anion equivalent appears in Corey and Wollenberg s synthesis40 of the antibiotic brefeldin A 163. This interesting molecule has two E-alkenes, one attached to a hydroxyl group as an allylic alcohol, and so accessible by direct addition of a vinyl lithium 165 to an aldehyde, and one in a 1,3-relationship with an alcohol and so accessible in theory by conjugate addition of a vinyl copper (or cuprate) 166 to the simple double electrophile 164. Each OH group must be protected. 

Lithium dimethyl copper reacted with (186) to introduce a methyl group stereo-selectively trans to the 5-isopropyl group. The enolate anion (187) so formed underwent intramolecular alkylation to give the cis-decalone(188), which was reduced to d/-valerane (189). Conjugate addition of lithium methyl vinyl cuprate to cyclopent-2-... 

Cyclohexenones and Related Derivatives. House and Wilkins have now demonstrated that addition of lithium dimethylcuprate to 3-methylcyclohex-3-enone in 1 1 molar equivalents results in a solution of the lithium enolate and a precipitate of (MeCu). Even when soluble cuprous species occur, there is no evidence to suggest that reaction with lithium enolates to give copper(i) enolates occurs. In a 1,4-addition reaction phenylithio[(a-diethoxymethyl)vinyl] cuprate with cyclohexenone at 233 K in Et20 gave ultimately 88% of the 3-allylcyclohexanone (38) (a-diethoxymethyl)-vinylcopper gave the 1,2-addition product. 

Reaction with Alkynes. The silyl cuprate reacts with alkynes by syn stereospecific metallo-metallation (eq 3). Provided that the cuprate is derived from copper cyanide, the regioselectivity with terminal alkynes is highly in favor of the isomer with the sUyl group on the terminus. The intermediate vinyl cuprate (3) reacts with many substrates, familiar in carbon-based cuprate chemistry, to give overall syn addition of a silyl group and an electrophile to the alkyne. A curious feature of this reaction is that the intermediate (3), although uncharacterized, has the stoichiometry of a mixed silicon-carbon cuprate, and yet it transfers the carbon-based group to most substrates, in contrast to the behavior of mixed silyl alkyl cuprates. 

A key step in the reaction mechanism appears to be nucleophilic attack on the alkyl halide by the negatively charged copper atom but the details of the mechanism are not well understood Indeed there is probably more than one mechanism by which cuprates react with organic halogen compounds Vinyl halides and aryl halides are known to be very unreactive toward nucleophilic attack yet react with lithium dialkylcuprates... 

A further improvement in the cuprate-based methodology for producing PGs utilizes a one-pot procedure (203). The CO-chain precursor (67) was first functionalized with zirconocene chloride hydride ia THF. The vinyl zirconium iatermediate was transmetalated direcdy by treatment with two equivalents of / -butyUithium or methyUithium at —30 to —70° C. Sequential addition of copper cyanide and methyUithium eUcited the /V situ generation of the higher order cyanocuprate which was then reacted with the protected enone to give the PG. 

Although the resulting vinylallenes 48 were usually obtained as mixtures of the E and Z isomers, complete stereoselection with regard to the vinylic double bond was achieved in some cases. In addition to enyne acetates, the corresponding oxiranes (e.g. 49) also participate in the 1,5-substitution (Scheme 2.18) and are transformed into synthetically interesting hydroxy-substituted vinylallenes (e.g. 50) [42], Moreover, these transformations can also be conducted under copper catalysis by simultaneous addition of the organolithium compound and the substrate to catalytic amounts of the cuprate (see Section 3.2.3). 

A preliminary investigation directed to determine the influence of the substituents in both the telluride and the starting cuprate, employing cyclohexenone as substrate, showed that phenylvinyl tellurides are not appropriate as the source of the vinyl copper reagent, since both the vinyl and phenyl groups are transmetallated and add to the enone. This result could be anticipated since both the formed carbanions are sp hybridized. Otherwise, butyl vinyl tellurides undergo exclusive Te/vinyl transmetallation followed by the desired vinyl transfer. 

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