Carbozirconation

As already indicated, the carbometallation reactions of zirconacyclopropanes and zirconacyclopropenes with alkenes and alkynes are in many ways similar to the corresponding reactions of titanacycles developed more recently. At the same time, however, there are a number of significant differences, as detailed in Section 10.06.2.2. At the present time, synthetically useful carbotitanation reactions are predominantly cyclic and stoichiometric in Ti and more so than the corresponding chemistry of Zr. It seems reasonable to state that Ti and Zr are complementary to each other more often than not. The cyclic carbozirconation may be either stoichiometric or catalytic. Frequently, the difference between the two is that the stoichiometric reactions lack one or more microsteps for completing catalytic cycles. Otherwise, they often share same stoichiometric microsteps. With this general notion in mind, many stoichiometric carbozirconation reactions have indeed been developed into Zr-catalyzed reactions, as discussed later. 

Since the topic of cyclic carbozirconation is so diverse and extensive, it cannot be discussed in detail in this chapter. So, the readers are referred to a number of recent reviews and chapters on this topic 13>13b,l3d-l3g,204,204a,205 jn section, a very brief summary with emphasis on some previously unknown and unexpected reactions, which nevertheless promise to significantly broaden the scope of cyclic carbozirconation, is presented. 

The topics of the cyclic carbozirconation may be divided as follows, and these topics will be discussed very briefly in the order indicated below ... 

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... 

It is much more difficult to control the pair-selectivity and regioselectivity of the intermolecular cyclic carbozirconation. The fundamentally dynamic and reversible nature of most of the microsteps in these reactions is primarily responsible for the often capricious nature of these reactions. Nevertheless, considerable progress has been made recently. In particular, the use of (ethylene)zirconocene in place of (l-butene)zirconocene has been shown to provide convenient and selective procedures, as shown in Scheme 39 13,13c,212,226,227 q [lcsc procedures, however, are still not fully satisfactory, especially in terms of regioselectivity, and additional developmental works are desirable. 

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... 

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. 

Virtually all known acyclic carbozirconation reactions involve activation through dynamic polarization or ate complexation as shown in Scheme 1.7. Some of the representative examples are shown in Scheme 1.43. The reaction of allylzirconocene derivatives [151] shares similar regiochemical features with the Zr-catalyzed allylalumination [22,152] and appears to be mechanistically closely related. 

Scheme 1.43. Examples of stoichiometric carbozirconation. Rl/ rCp2CI R2— 5% Ph3CB(C6F5)4 [153] / ZrCp2CI - Rt V=< R2 H...

Although the application of carboalumination to the synthesis of natural products is still in its infancy, a few preliminary results shown in Scheme 1.50 [167,168,171,172] suggest that it promises to become a major asymmetric synthetic reaction, provided that (i) the singularly important case of methylalumination can be made to proceed with S90% ee, and (ii) satisfactory and convenient methods for enantiomeric and diastereo-meric separation/purification can be developed. In this context, significant increases in ee in the synthesis of methyl-substituted alkanols from around 75 % to 90—93 % achieved through some strategic modifications are noteworthy (Scheme 1.50) [168]. Shortly before the discovery of the Zr-catalyzed enantioselective carboalumination, a fundamentally discrete Zr-catalyzed asymmetric reaction of allylically heterosubstituted alkenes proceeding via cyclic carbozirconation was reported, as discussed later in this section. 

Stoichiometric bicydization of enynes, diynes, and dienes by cyclic carbozirconation... 

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

Zr-catalyzed C C bond formation by cyclic carbozirconation and o-bond metathesis of zirconacydes... 

Most probably, Zr-catalyzed C—C bond formation by cyclic carbozirconation was first observed in 1978, when the Zr-catalyzed reaction of alkynes with Et3Al was reported [13,56]. An acyclic carbozirconation mechanism similar to that of methylalumination was initially... 

A recent study has, however, unraveled a most intricate four-step catalytic cycle involving a bimetallic cyclic carbozirconation (Scheme 1.60) [150]. The stoichiometric conversion of EtZrCp2Cl and Et3Al into the five-membered bimetallic complex and its subsequent stoichiometric reaction with an alkyne to give an aluminacydopentene and EtZrCp2Cl were the two key experimental findings. 

Mg Monometallic cyclic carbozirconation occurs cf. Monometallic cyclic carbozirconation mechanism in Scheme 1.4. 

Zn Monometallic cyclic carbozirconation occurs EtMgBr needed as catalyst Et2Zn is capable of sustaining the catalytic cycle shown in Scheme 1.61 but incapable of generating Et2ZrCp2... 

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