Cuprate transmetallations

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. 

Scheme 4.10 gives some examples of application of alkyne carboalumination in synthesis. The reaction in Entry 1 was carried out as part of a synthesis of the immunosuppressant drug FK-506. The vinyl alane was subsequently transmetallated to a cuprate reagent (see Chapter 8). In Entry 2, the vinyl alane was used as a nucleophile for opening an epoxide ring and extending the carbon chain by two atoms. In Entries 3 to 5, the vinyl alane adducts were converted to vinyl iodides. In Entry 6, the vinyl alane was converted to an ate reagent prior to reaction with formaldehyde. 

An alternative route to allenyl stannanes involves organocuprate displacements on propargylic chlorides bearing an alkynyl PhsSn substituent (equation 39)79. Interestingly, transmetallation by attack of the cuprate on the tin substituent is not observed in these systems. A parallel strategy can be employed for allenylgermanes (equation 39)79. The... 

A smoother transmetalation procedure should be ensured by the more electronegative character of aluminium, as first demonstrated by Wipf and Ireland [35]. Thus, hydroalumination of 1-hexyne with DIBAL-H, followed by addition of the cuprate 59, bearing non-transferable alkynyl groups, provides the copper intermediate 60. This adds smoothly to 2-cyclohexenone to produce the Michael adduct 61, in 72% yield (Scheme 2.18) [36],... 

Low chemical yields and a-selectivity on the allyl copper reagent are observed with the phenylthio analogues. These observations suggest that the pyridine nitrogen facilitates transmetalation and or cuprate reactivity and plays a role in the regio-selectivity of the reaction. 

Soon after the appearance of the series of papers from the Stryker labs [13, 15, 17, 19a], an alternative method for the presumed generation of stoichiometric hal-ohydrido cuprate XCu(H)Li (X = Cl or I) was reported (Scheme 5.2) [20]. It relies on a transmetalation between BusSnH and CuI/LiCl, the inorganic salts combining to form a mixed dihalocuprate (5) [21], which may then undergo a ligand exchange with the tin hydride to afford halohydrido species 6. 

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. 

The range of applications of lithiated vinyl ethers like 54 and 56 is distinctly enhanced by transmetalation. Thus, cuprate 178 derived of 1-ethoxy-1-lithioethene 54 undergoes... 

The small number of electrophiles that react well with Af-Boc-2-hthiopyrrolidine limits applications of the asymmetric deprotonation of Af-Boc-pyrrolidine. In a significant development. Dieter and coworkers have shown that transmetalation of the enantioen-riched 2-lithiopyrrolidine with CuCN-2LiCl forms a cuprate that reacts enantioselectively with vinyl and allenyl iodides (Scheme 34). Enantioselectivities in the 90-95% range were achieved, although the reaction is very sensitive to reagent purity. ... 

As indicated in Section ni.B, deprotonation of a carbamate affords a dipole-stabilized a-amino-organolithium that can be transmetalated with copper salts to form cuprates, thereby expanding the versatility of the organolithium. Suitable electrophiles include enones, alkenyl, alkynyl, allenyl and dienyl carboxylic acid derivatives, nitriles and sulfoxides. Dieter and coworkers have shown that the same process can be accomplished via transmetalation of a stannane (Scheme 36). The procedure is particularly... 

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