Carbometallation, reviews

The currently known carbometallation chemistry of the group 6 metals is dominated by the reactions of metal-carbene and metal-carbyne complexes with alkenes and alkynes leading to the formation of four-membered metallacycles, shown in Scheme 1. Many different fates of such species have been reported, and the readers are referred to reviews discussing these reactions.253 An especially noteworthy reaction of this class is the Dotz reaction,254 which is stoichiometric in Cr in essentially all cases. Beyond the formation of the four-membered metallacycles via carbometallation, metathesis and other processes that may not involve carbometallation appear to dominate. It is, however, of interest to note that metallacyclobutadienes containing group 6 metals can undergo the second carbometallation with alkynes to produce metallabenzenes, as shown in Scheme 53.255 As the observed conversion of metallacyclobutadienes to metallabenzenes can also proceed via a Diels-Alder-like... 

The ruthenium-, rhodium-, and palladium-catalyzed C-C bond formations involving C-H activation have been reviewed from the reaction types and mechanistic point of view.135-138 The activation of aromatic carbonyl compounds by transition metal catalyst undergoes ortho-alkylation through the carbometallation of unsaturated partner. This method offers an elegant way to activate C-H bond as a nucleophilic partner. The rhodium catalyst 112 has been used for the alkylation of benzophenone by vinyltrimethylsilane, affording the monoalkylated product 110 in 88% yield (Scheme 34). The formation of the dialkylated product is also observed in some cases. The ruthenium catalyst 113 has shown efficiency for such alkylation reactions, and n-methylacetophenone is transformed to the ortho-disubstituted acetophenone 111 in 97% yield without over-alkylation at the methyl substituent. 

For a review of enantioselec-tive carbometallation of unactivated alkenes (both catalytic and non-catalytic), see I. 

Despite its inherent difficulties, carbometallation has, in fact, played important roles in catalytic asymmetric carbon-carbonal bond formation. Isotactic and syndiotactic alkene polymerization involving both heterogeneous and homogeneous Ti and Zr catalysts must involve a series of face-selective carbometallation processes, although the main stereochemical concern in poly(alkene) formation is diastereoselectivity rather than enantioselectivity. This fascinating topic, however, is outside the scope of this chapter, and the readers are referred to Chapter 11 and other previous reviews [6]. 

To be synthetically useful, the new organometallic 3 must have a reactivity different from that of 1 in order to avoid the polymerization of the carbometallated substrate [2]. So, the carbometallation ability of 1 must be higher than that of 3, except for an intramolecular carbometallation reaction, in which case the entropy factors favor the mono-addition even if the starting organometallic and the product have similar reactivities. Since an outstanding number of additions of organometallics to carbon-carbon multiple bond have been reported and reviewed [3-5], we will focus this chapter on the more recent advances in this field (from 1991 until the present time), both from our own and from other research groups. 

The addition of an organometallic to an unactivated olefin is generally difficult to control since such an addition may lead to polymerization of the olefin unless the final organometallic adduct is stabilized, or has a structural modification. Thus, no general reaction for the intermolecular carbometallation of alkenes is known, although since the last review concerning this topic [3], many relevant papers have appeared. 

Thus, for a synthetically useful reaction, both regioselectivity and diastereoselectivity of the carbometallation process must be controlled, where spatial arrangement and reactivity of the sp organometallic species determine the diastereoselection. Since the earlier editions of this book [3], an increasing number of reports have appeared in the literature that have been summarized in excellent reviews and book chapters. In this chapter, the focus will be on the most important and recent advances in this field since the preceding edition of this book. 

An intramolecular carbometallation of a carbon-carbon triple bond generally leads to a five-membered carbo- or heterocycle possessing an exocyclic carbon-carbon double bond. The selectivity of this transformation has been reviewed thoroughly in the previous edition of this book and in several comprehensive reviews [3b, 59,122). In the past decade, intramolecular carbolithiation reactions have been studied both experimentally and computationally. For example, Maddaluno et al. [123] examined... 

The application of ynamides in various organic transformations, including carbometallation processes has recently been summarized in an excellent review Evano, G., Coste, A., and Jouvin, K. (2010) Angew. Chem. Int. Ed., 49, 2840-2859. 

Normant has reviewed the carbometallation of alkynes to give stereospecific syntheses of alkenyl-metal derivatives, and their addition to aldehydes and ketones to afford allylic alcohols. Specific titanium-catalysed 5yn-hydromag-nesiation of 2-propynylic alcohols (Scheme 16), and the related zirconium-catalysed 5yn-carboalumination of propargylic alcohol itself (also Scheme 16) or its t-butyldimethylsilyl ether (c/. 3, 139 4,160) can both lead to allylic alcohols. 

Other Unsaturated Alcohols. The review mentioned above of carbometallation of alkynes, includes a survey of additions of alkenyl-metal derivatives to epoxides to give homoallylic alcohols. The zirconium-catalysed carboalumination of propargylic systems (Scheme 16) is also applicable to the homopropargylic to homoallylic alcohol transformation. ... 

An elementary step to cleave C-C bonds is a reverse process of a C-C bond forming process. Oxidative addition of a C-C bond to a low-valent transition metal complex is a reverse process of reductive elimination, which occurs with a high-valent diorganometal, forming a C-C bond. P-Carbon elimination is a reverse process of insertion of an unsaturated bond into a carbon-metal bond, that is, carbometallation, or 1,2-addition of an organometal across a double bond. Such fundamental reactions are described along with typical examples. Besides this chapter, there are some excellent reviews on C-C bond cleavage available [1]. 

For two representative reviews see Negishi, E. Bimetalhc Catalytic Systems Containing Titanium, Zirconium, Nickel and Palladium. Their Apphcations to Selective Organic Syntheses Pure Appl. Chem. 1981, 53,2333-2356. Fallis, A. G. Forgione, P. Metal Mediated Carbometallation of Alkynes and Alkenes Containing Adjacent Heteroatoms Tetrahedron 2001, 57, 5899-5913. 

The carbometalation reaction has been reviewed recently [28-30]. Negishi has demonstrated that zirconium(TV) complexes catalyze the carboalumination of MesAl to various alkynes and enynes [31]. Also the Zr-catalyzed asymmetric carboalumination of aUcenes (ZACA reaction) [32-34] has found important applications in the synthesis of natural products [35-37]. Especially efficient was the asymmetric synthesis of insect pheromones such as (S. / ./ ,S. / ,S)-4,6,8,10,16,18-hexamethyl-docosane (88) (Scheme 8) [38]. 

As important as the bimetallic activation of C-Zr or C-Ti bonds is, this only represents part of the mechanistic diversity displayed by Zr or Ti. Only within the last decade or so have the mechanisms of some of the Zr-catalyzed car-boalumination proceeding via cyclic carbozirconation been adequately clarified [13,14,17], following the unexpected clarification of the cyclic mechanism of the Zr-catalyzed ethylmagnesation of alkenes [18,19]. For a review, see [19]. Some mechanistic details of these various carbometallation reactions vis-a-vis metal countercations will be presented later. 

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