Zirconacycles

Copper-catalyzed or mediated carbon-carbon bond formation reactions of zirconacycles and alkenylzirconocenes 97YGK958. 

Whitby and Kasatkin have extended this idea to insertion of stabilized metalated epoxides into zirconacycles (Scheme 5.30) [50]. 

A general method for the synthesis of highly substituted styrenes as 6/4-91, vinyl-cyclohexadienes and related compounds was developed by Xi, Takahashi and coworkers [301] by reacting an intermediately formed five-membered zirconacycle 6/4-89 with propargyl derivatives 6/4-90 or allyl bishalides in the presence of CuCl (Scheme 6/4.21). 

Formation and characterization of zirconacyclopropanes and zirconacyclopropenes In addition to / -H abstraction of dialkylzirconocenes discussed earlier (Schemes 5 and 6), several other methods are also available for the preparation of three-membered zirconacycles as summarized in Scheme 35. From the viewpoint of cyclic carbozirconation reactions, especially those under Zr-catalyzed conditions, /3-H abstraction, 7t-ligand substitution, and decarbometallative ring contraction are particularly important. As such, these three-membered zirconacycles are generally unstable, but they can be stabilized with phosphines, for example, PMe3, and other bases, and are fully identified. Some of the well-identified examples are shown in Scheme 36.206-209... 

Scheme 36 Preparation of three-membered zirconacycles via (1 -butenejzirconocene.

The Zr-catalyzed ethylalumination of alkynes under certain conditions1,9 (Scheme 4) and ethylmagnesation of alkenes10 11 (Scheme 5) represent some of the earliest examples of the catalytic carbozirconation proceeding via zirconacycles. In Scheme 5, the carbometallative ring expansion of (ethylene)zirconocene to produce a... 

Zirconacyclopentanes can readily undergo skeletal rearrangements, exemplified by those shown in Scheme 41. Although the process involving Zr reveals only the final zirconacycle, examination by NMR spectroscopy of the corresponding Hf reaction shows the formation and decay of the 2,5- and 2,4-dimethylhafnacyclopentanes. All of the three hafnacycles as well as the zirconacyclic product are >98% dl.229... 

Scheme 48 Skeletal rearrangement of zirconacycles via dipolar zirconates.

The zirconacyclopropene 1, which was prepared by treatment of Cp2ZrCl2 with magnesium metal in the presence of bis(trimethylsilyl)acetylene, reacted with one molecule of C02 under atmospheric pressure at room temperature to give the dimeric zirconacycle 2 in good yield (Scheme iy6>6a>6b Further insertion of C02 did not occur, although 2 has... 

Scheme 1.15. Synthesis of other three-membered zirconacycles.

Another major protocol for the generation of three-membered zirconacycles was initially devised by Erker [47—49] and was extensively developed by Buchwald [36—44] (Erker—Buchwald protocol) (Scheme 1.14). No alkenes or alkynes are used as temporary ligands in this protocol. Unless hydrozirconation is used to generate the initial organyl-zirconocene derivatives, even final alkene or alkyne ligands are not usually derived from the corresponding ji-compounds. Thus, the synthetic values of the two representative protocols are quite different and often complementary to each other. 

In addition to the methods discussed above, transmetallation and migratory insertion also provide useful routes to three-membered zirconacycles (Scheme 1.15). 

Although 16-electron three-membered zirconacycles are generally unsuitable for X-ray analysis, their complexes with phosphines, such as PMe3, or some ethers, such as THF, have often yielded crystalline compounds suitable for X-ray analysis. Thus, their existence and identity have been firmly established. 

The synthetic utility of the carbonylation of zirconacycles was further enhanced by the development of a pair of selective procedures producing either ketones or alcohols [30] and has been extensively applied to the synthesis of cyclic ketones and alcohols, most extensively by Negishi [22—27,29—33,65,87,131—134], as detailed below in Section I.4.3.3.4. The preparation of unsaturated aldehydes by carbonylation with CO is not very satisfactory. The use of isonitriles in place of CO, however, has provided a useful alternative [135], and this has been applied to the synthesis of curacin A [125]. Another interesting variation is the cyanation of alkenes [136]. Further developments and a critical comparison with carbonylation using CO will be necessary before the isonitrile reaction can become widely useful. The relevant results are shown in Scheme 1.35. 

It has recently been established that carbozirconation with organylzirconocene derivatives evidently requires dipolar (and mostly bimetallic) activation and/or small-ring zirconacycles, especially three-membered ones, that can undergo cyclic carbozirconation (Generalization 6 ) [149]. One of the recent examples has been shown to involve both bimetallic and cyclic organo-zirconium species [150], These reactions can be either stoichiometric or catalytic in Zr. 

Stoichiometric intermolecular cyclic carbozirconation of three-membered zirconacycles... 

As mentioned earlier, a random and statistical cyclization with two different and regio-defined Ti-compounds would produce a synthetically unattractive mixture of ten different zirconacycles. In reality, however, there are a few factors that can be exploited to produce a single desired zirconacycle. A systematic investigation has revealed that there are several discrete types offive-membered zirconacycle formation, as shown in Scheme 1.53 [88,89] (Generalization 20). In the Type I reaction, the cross-selective cyclization is kinetically favored. Presumably, little ethylene is displaced during the reaction. Type I reactions cannot be readily observed with ZrCp2 complexes with 1-butene. In contrast, Type II cyclization must be thermodynamically controlled, as 1-butene is readily displaced by a number of better Ti-ligands. It is predicted, however, that the cross-combination of the two Ti-com-... 

A few other interesting and potentially important consequences of the reversible formation of five-membered zirconacycles include stereo- and regioselective skeletal rearrangement, as exemplified by Scheme 1.57 [197], and 1,3-C=C bond and Zr migration (Scheme 1.58) [191,192], supporting the associative mechanism for alkene displacement (Generalization 22 ). 

Until recently, the structures of the five-membered zirconacycles had been proposed on the basis of NMR data and identification of the final organic compounds, especially the products of deuterolysis, iodinolysis, and carbonylation. Determination of their structures by X-ray analysis proved to be more difficult than that of three-membered zirconacycles, largely because attempts to obtain their stable 18-electron derivatives led to ring-contraction to give three-membered zirconacycles, as in the last example in Scheme 1.56. This difficulty was overcome by the use of bulky Cp derivatives that permitted the formation of stable, crystalline, 16-electron, five-membered zirconacycles such as 5 [198] and (tBujQHj Z Ch (6) [199] (Scheme 1.59). 

In some of the preceding sections, the significance of interactions between three-mem-bered zirconacycles with 7T-bonds (Pattern 7 in Scheme 1.3 and Scheme 1.51) has been amply demonstrated. More recently, their c-bond analogues (Pattern 13) and variants involving five-membered zirconacycles, as shown in Scheme 1.65, have been recognized as important fundamental processes in organozirconium chemistry. 

In these early studies, however, the concept of c-bond metathesis most probably did not exist, and the results were presented just as observed facts. Mainly in the 1990s, a wide variety of c-bond metathesis reactions of both three- and five-membered zirconacycles were reported. In Scheme 1.4, the reaction of the five-membered zirconacycle with EtMgBr via c-bond metathesis followed by another c-bond metathesis (p-H abstraction) produces the ethylmagnesation product along with ethylene-zirconocene [51], Some representative examples of c-bond metathesis reactions of three-membered zirconacycles are shown in Scheme 1.69. These are examples of stoichiometric c-bond metathesis reactions from which the products have been identified. 

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