Hydrozirconation/transmetallation from

AICI3 is a moisture-sensitive and strong Lewis acid. It is a first choice for Friedel-Crafts-type reactions, which provide numerous important transformations in laboratory and industry. It can also be applied to the transformation of alkenes to ketones via alkylaluminum halides.303 Hydrozirconation of an olefin and subsequent transmetalation from zirconium to aluminum gives the corresponding alkylaluminum dichloride, and the subsequent acetylation by acetyl chloride affords the corresponding ketone in high yield (Scheme 66). 

The structurally novel antimitotic agent curacin A (1) was prepared with an overall yield of 2.5 % for the longest linear synthesis. Three of the four stereogenic centers were built up using asymmetric transformations one was derived from a chiral pool substrate. Key steps of the total synthesis are a hydrozirconation - transmetalation protocol, the stereoselective formation of the acyclic triene segment via enol triflate chemistry and another hydrozirconation followed by an isocyanide insertion. For the preparation of the heterocyclic moiety of curacin A (1) the oxazoline - thiazoline conversion provides efficient access to the sensitive marine natural product. 

Ganem, B. Hydrozirconation-transmetalation a mild, direct route to higher-order vinylic cuprates from monosubstituted alkenes. One-pot synthesis of protected prostaglandins from alkynes and cyclopentenones in situ generation of higher-order cyanocuprates from alkenylzirconium intermediates. Chemtracts Org. Chem. 1991, 4, 44-47. 

As Scheme 16 shows, vinyl(methyl)zinc compounds 17 were obtained from the hydrozirconation of terminal alkynes with Cp2ZrHGl, followed by treatment with dimethylzinc. The initially formed vinyl zirconium complex undergoes rapid transmetallation with ZnMe2 to yield the product.44... 

Transmetallations starting from alkenylzirconium species, which are obtained by hydrozirconation using H(Cl)ZrCp2, are readily accomplished.98,99 "3 Ichikawa, Minami, and co-workers have elegantly shown that diflurovinylzinc iodide is obtained by the addition of ZrCp2 to the corresponding alkenyl tosylate (Equation (36)). In situ transmetallation reactions have also been reported. 

Transmetalation. Carr and Schwartz have found that an organic group bound to zirconium can be transferred to aluminum. Thus reaction of 1, obtained by hydrozirconation of alkenes or alkynes, with AlCln results in a color change from bright yellow to orange as an organoaluminum dichloride is formed. On addition of an acid chloride, a ketone (2) is formed rapidly. This new ketone synthesis proceeds in high yield from alkyl- and alkenylaluminum dichlorides. 

Vinylzirconium species arising from hydrozirconation reactions can be readily transmetallated [60] to the corresponding organozincs by the addition of zinc halides [61] or Me2Zn [62] (Scheme 4.9). 

Wipf and coworkers have used the Zr-Zn transmetalation, aldehyde addition methodology for the rapid, stereocontrolled preparation of a//-(E)-poly-enes [82] in the total syntheses of (+)-curacin A [83] and ( )-nisamycin [84]. Synthesis of the eastern side chain of ( )-nisamycin was accomplished in two steps from alkyne 79 (Scheme 17). Hydrozirconation of 79 followed by addition to cyclohexylcarboxaldehyde in the presence of dimethylzinc afforded the allylic alcohol 80. Elimination of the newly formed hydroxyl group was accomplished via the corresponding trifluoroacetate. Addition of alkenylzirconocenes... 

Hydrozirconation of functionalized alkyne 8 in CH2C32 with the Schwartz reagent followed by in situ transmetallation to Me2Zn and addition of N-diphenyl-phosphinoylimine 15 provides the functionalized trans-aminocydopropane 16 in 60% yield [15]. The cydopropane formation can be rationalized by the formation of a transient zinc-carbenoid species from CH2CI2, which subjected the intermediate allylic amine derivative to an efficient Simmons-Smith-type cydopropanation. 

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