Via Carbometallation

The addition of 1-alkynes to a,/3-unsaturated ketones in water is catalyzed by a palladium(n)/phosphine combination. Deuteration studies suggest that this reaction proceeds via carbometallation of the olefinic moiety by an alkynylpalladium intermediate (Equation (193)).1... 

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... 

Cationic zirconocene species efficiently activate alkenes toward carbon—carbon bond formation via carbometalation, as has been demonstrated in studies of alkene polymerization. Today, some zirconocene catalysts are available that allow single additions of metal-alkyls (mainly aluminum-alkyls) to alkenes or alkynes, thereby forming stable alkyl- or alkenyl-metals that do not undergo any further oligomerization. On the other hand, carbozirconation with Cp2ZrRCl in the presence of stoichiometric or catalytic amounts of activators has also been realized. 

When alkynic esters are used as substrates in the reaction sequence, activated alkenes of good isomeric purity can be prepared. Initiation of the difunctionalization usually is by means of organocopper-medi-ated 1,4-addition, which proceeds via carbometallation of the alkynyl moiety of the ester to give a vi-nylcopper intermediate, (14). Trapping by an electrophile affords cis-difunctionalized alkenoates... 

Considering the mechanistic rationales of the transition metal-catalyzed enyne cycloisomerization, different catalytic pathways have been proposed, depending on the reaction conditions and the choice of metal catalyst [3-5, 45], Complexation of the transition metal to alkene or alkyne moieties can activate one or both of them. Depending on the manner of formation of the intermediates, three major mechanisms have been proposed. The simultaneous coordination of both unsaturated bonds to the transition metal led to the formation of metallacydes, which is the most common pathway in transition metal-catalyzed cycloisomerization reactions. Hydrometalation of the alkyne led to the corresponding vinylmetal species, which reacts in turn with olefins via carbometalation. The last possible pathway involves the formation of a Jt-allyl complex which could further react with the alkyne moiety. The Jt-allyl complex could be formed either with a functional group at the allylic position or via direct C-H activation. Here the three major pathways will be discussed in a generalized form to illustrate the mechanisms (Scheme 8). 

Abstraction of chloride from a vinylpalladium complex by silver acetate has been reported,45 as well as halide abstraction by silver triflate from arylpalladium halides.46 More interestingly in the context of creating C-C bonds, silver perchlorate was able to promote the reaction of (r -aryl)palladium bromide with dienes. Silver-promoted bromide abstraction led to the formation of (r 1-r 2-enyl)palladium complexes, which evolved further through the regioselective formation of a C-C bond between the aryl group and the former diene. Reactions with nonconjugated dienes suggested that the reaction proceeds via carbometallation of the less crowded double bond. Isomerization and (3 elimination led to a (ri3-allyl)palladium complex (Scheme 10.26).47... 

Some alkyl or alkenylmagnesium compounds were obtained via carbometallation or ring-opening reactions with other Grignard reagents. These methods are described in the sections dedicated to the addition to multiple bonds or... 

In this area, Krische and co-workers have developed a family of catalytic transformations based on the use of enones as latent enolates. Nucleophilic activation of the enone is induced via carbometallation, nucleophilic organocatalysis or hydrometallation. The following examples illustrate some aspects of these new catalytic conjugate addition/electrophilic trapping reactions. 

Until recently, most of the organic compounds prepared via carbometallation had been relatively simple and highly symmetrical cyclic or polymeric compounds. More recently, however, intensive efforts have been made to utilize c ometallation reactions in the synthesis of complex molecules. In particular, the fact that two new bonds, i.e. one carbon-carbon and one carbon-metal, are formed in carbometallation has led to the development of a number of cyclization methodologies. Furthermore,... 

Similar cia-exo carbocarbonylations of norbornene and norbornadiene can be accomplished in stoichiometric conversions via carbometalation with vinyl- and allylpalladium systems followed by carbonylation10,11. 

Carbohalogenation of double and triple bonds can be achieved in various ways one method is a two-step version via carbometalation, followed by oxidative cleavage of the newly formed metal carbon bond (see Section 1.5.8.4.4.). Several examples using this methodology in stereoselective organic synthesis have employed catalytic (see Section I.5.8.4.4.) or stoichiometric use of transition metals. An example of the latter case is the zirconium-mediated cyclization of 1,6-hep-tadienes which leads to tram- or (is-1,2-bis(haIomethyI)cydopentane (1), depending on the metal reagent1. 

Several other examples of intramolecular ruthenium-, copper-, rhodium- and iron-catalyzed cyclizations via carbometalation with polyhalocarbons are known, with a range of stereoselectivities25 4 49. Similarly, palladium-catalyzed intramolecular ene-halogenocyclization" of unsaturated a-iodo carbonyl compounds, using Pd(dppe)2, has been applied to heterocyclic synthesis26 29. 

Carbometalation reactions play an important role in Ziegler-Aufbaureaktionen (growth reactions) of ethene to form oligomers when a stoichiometric amount of an organoaluminum compound is used. They are also crucial steps in transition metal catalyzed oligomerization and polymerization of unsaturated compounds, as well as in many cyclization. cycloaddition and cyclooligomcrization reactions. Ketone-forming carbonylative addition reactions also proceed via carbometalation steps. 

Several coupling reactions of 2-substituted cycloalkenyhnetal reagents have been re-ported. " " For example, cyclobutenylmetals, generated in situ via carbometallation of 4-halo-1-metaUo-l-alkynes, are reacted with iodobenzene to give 1,2-disubstituted cyclobutenes, as shown in Scheme 35. 

For successful application of this strategy, ready access to vinyl halides with defined configuration of the carbon-carbon double bond is required. Such building blocks can be obtained via carbometallation of terminal alkynes [26] or by hydrometallation of internal alkynes, often with appropriate re-gioselectivity [27] (Scheme 3.16). 

A new Ni-catalysed carbocyanative cyclization of allene-ynes and bis-allenes has been reported. The reaction starts with the regioselective hydronickelation of the allene moiety, which is followed by cyclization via carbometalation. ... 

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