Alkenylzirconium complex

The synthetic potential of alkenylzirconium complexes is partially due to the fact that the hydrozirconation of alkynes can be carried out in the presence of some synthetically useful functional groups such as halide [80,153, 211, 212], acetals, amides, imides, carbamates, sulfides [186], ester, cyano [95, 213] and chiral propargyl amino functionalities [214]. 

Coupling of n- allylic)paUadium complexes with an alkenylzirconium(IV) complex l,4-< enes.2 A recent stereospecific synthesis of natural (20R)-cholestanone-3 (4) involves coupling of the alkenylzirconium complex 2 with the jr-(allylic)palladium chloride dimer (1) of a (Z)-17(2U)-pregnene. The major product is a 1,4-diene (3), formed by regioselective attack of 2 at C20, the less hindered terminus of the allylic unit, and with inversion at C20. Coupling of 2 with the 7i-(allylic)palladium chloride dimer of the (E)-isomer of 1 results in a 1,4-diene epimeric at C20 with 3. Hydrogenation of the diene completes the synthesis of the desired natural cholestanone-3 (4). 

Alkenylzirconium complexes can also undergo transmetalation from Zr to Cu to form alkcnylcoppcr(l) complexes, which are useful as synthetic intermediates. Since alkenylcopper(l) complexes are thermally unstable, dienes are oblainerl when the reaction is carried out at 0 20, with formation of a copper... 

A catalyst prepared from [Ni(acac)2] and di-isobutylaluminium hydride catalyses the conjugate addition of alkenylzirconium complexes to a,/8-enones the same catalyst also promotes 1,4-addition of alanes to cyclic a,j8-unsaturated enones. ... 

Hard carbon nucleophiles of organometallic compounds react with 7r-allyl-palladium complexes. A steroidal side-chain is introduced regio- and stereo-selectively by the reaction of the steroidal 7T-allylpalladium complex 319 with the alkenylzirconium compound 320[283]. 

During the last ten years, the chemistry of 1,1-boriozirconocene complexes has been studied. Both hydrozirconation and hydroboration reactions are well established, and are widely applicable to a wide variety of vinyl and acetylene derivatives [1], Alkenylboranes and alkenylzirconium compounds can also be readily prepared. Therefore, hydrometalla-tion of the corresponding alkenyl metals should offer a convenient method for preparing gem-boriozirconocenes [24]. 

The coupling of alkenylzirconiums with ir-allyl complexes derived from the D-ring of steroids has been demonstrated to be regiospecific and to yield products which possess the natural configuration at C-20 (equation 39).155... 

Alkenylzirconiums react with either preformed allylpalladium complexes155 or allyl acetates and Pd° catalysts156-395 via addition directly to the palladium, followed by reductive elimination. In the reaction with steroidal iT-allylpalladium complexes (equation 174) the natural configuration at C-20 is now obtained, in contrast with the addition of malonates (ligand attack) which yielded the unnatural configuration.74... 

Some additional examples of regioselectivity of Grignard reagents have been reported. In contrast to the addition of alkenylzirconiums to the identical steroidal rr-allyl complexes which selectively coupled to C-20, the Grignard reagent in the presence of maleic anhydride shows complete selectivity for addition to C-16 (equation 251).396,397... 

The total synthesis of apoptolidin was accomplished in the laboratory of K.C. Nicolaou. The key C12-C28 vinyl iodide fragment was prepared using the Schwartz hydrozirconation of an internal alkyne followed by trapping of the alkenylzirconium intermediate with iodine (I2). The vinyl iodide was formed as a 6 1 mixture of regioisomers. Under the reaction conditions, the methyl orthoester was converted to the methyl glycoside moiety at C21, which was presumably facilitated by the complexation of Zr with the pyranoside oxygen atom. 

The reaction of alkenyManes and alkenylzirconium derivatives with 1-iodoalkynes doubly catalyzed with a Pd-phosphine complex and ZnCl2 appears to be the first example of this protocol. A related alkenylboron reaction was published shortly thereafter. Some additional examples involving Cu, Zn, and Sn are also known. These results are shown in Scheme 11. 

According to the proposed mechanism, the electrophilic arylpaUadium iodide 326, formed by an oxidative addition of Ar-1 to a Pd(0) species, was proposed to activate the central carbon-carbon double bond in the cyclic cumulene intermediate 317b to form the complex 327. A subsequent attack by the Zr-C(sp ) nucleophilic center produces the aUcenylpalladium intermediate 325, which upon reductive elimination furnishes the corresponding alkenylzirconium species 324. Hydrolysis of the latter finally produces the 3-methylenecyclopentene 319. To support the mechanistic hypothesis, deuterolysis was carried out to provide the deuterated compound 319-D in 60% yield with a high level of deuterium incorporation [87]. 

Alkenylzirconium compounds, prepared from acetylenes and normally inert to a,/3-unsaturated ketones, have been activated towards conjugate addition by [Ni(acac)2], or by [Ni(acac)2] pre-reduced by di-isobutylaluminium hydride. Alkylzirconium reagents were not activated by the nickel complexes. 1-Alkynyltrialkylborates require the presence of a Lewis acid, preferably titanium tetrachloride, to add to methyl vinyl ketone (Scheme 60). The product isolated after oxidation is the 1,5-diketone. 

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