Hydrometallation, pathway

Mechanistic hypotheses play an important role in developing new catalytic and selective heterofunctionalizations of alkenes. Two basic reaction cycles for metal-catalyzed hydroalkoxylation (and hydration, for R = H) of alkenes can be postulated (Scheme 2). One pathway leads to Markovnikov products via activation of the nucleophile, oxy-metallation, and protonolysis (hydro-de-metallation) (Scheme 2a). Alternatively to the inner sphere syn-oxymetallation depicted in Scheme 2a, external anti-attack of the nucleophUe to coordinated olefin is plausible. The oxidation state of the metal remains constant in this cycle. The alternative hydrometallation pathway (Scheme 2b) proceeds via oxidative addition of the H-OR bond, hydrometallation of the olefin, and reductive elimination to the anti-Markovnikov addition product [3,4]. 

Scheme 2 Projected catalytic hydroaUcoxylation cycles (a) Oxymetallation pathway giving Markovnikov products, (b) Hydrometallation pathway leading to anti-Markovnikov products...

The (postulated) hydrometallation pathway of hydroalkoxylation (or hydration) of olefins (Scheme 2b) relies on O-H bond activation by oxidative addition of RO-H to metal centers, a process that is studied eagerly in the organometallic chemistry community [3, 24]. However, the insertion of olefins into the M-H bonds of metal... 

In addition to the metallacycle-based mechanism depicted above, stepwise insertion pathways such as alkyne hydrometallation followed by aldehyde... 

Diastereoselective reductive coupling of MVK and p-nitrobenzaldehyde performed under an atmosphere of elemental deuterium provides an aldol adduct incorporating a single deuterium atom at the former enone f>-pos-ition [69]. Deuterium incorporation at the a-carbon is not observed, excluding Morita-Baylis-Hillman pathways en route to product. Incorporation of a single deuterium atom suggests irreversible enone hydrometallation (Scheme 5). 

Similar intramolecular hydroarylations of alkynes and alkenes, which obviate the need for a halide or triflate group on the aryl ring, are now well established. Sames group screened over 60 potential catalysts and over 200 reaction conditions, and found that Ru(m) complexes and a silver salt were optimal. This process appears to tolerate steric hindrance and halogen substrates on the arene (Equations (175)—(177)). The reaction is thought to involve alkene-Ru coordination and an electrophilic pathway rather than a formal C-H activation of the arene followed by alkene hydrometallation, and advocates the necessary cautious approach to labeling this reaction as a C-H functionalization... 

It is postulated that the mechanism of the silane-mediated reaction involves silane oxidative addition to nickel(O) followed by diene hydrometallation to afford the nickel -jr-allyl complex A-16. Insertion of the appendant aldehyde provides the nickel alkoxide B-12, which upon oxygen-silicon reductive elimination affords the silyl protected product 71c along with nickel(O). Silane oxidative addition to nickel(O) closes the catalytic cycle. In contrast, the Bu 2Al(acac)-mediated reaction is believed to involve a pathway initiated by oxidative coupling of the diene and... 

Reductive coupling of 1,1-dimethylallene and 5-nitro-2-furancarboxaldehyde under a deuterium atmosphere provides the product of ferf-prenylation incorporating deuterium at the interior vinylic position (80% H). This result is consistent with a mechanism involving allene-aldehyde oxidative coupling. However, alternate pathways involving allene hydrometallation to furnish allyliridium species cannot be excluded on the basis of these data (Scheme 10). 

The mechanism of the intramolecular hydrosilylation catalyzed by Rh and Pt complexes was investigated by using deuterated silanes, which indicated the operation of both the traditional Chalk-Harrod hydrometallation and silylmetallation pathways accompanied by rapid P-hydride elimination [65]. This intramolecular reaction was applied to the syntheses of natural products [66],... 

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). 

Besides enyne metathesis [66] (see also the chapter Recent Advances in Alkenes Metathesis in this volume), which generally produces 1-vinylcyclo-alkenes, ruthenium-catalyzed enyne cycloisomerization can proceed by two major pathways via hydrometallation or a ruthenacycle intermediate. The RuClH(CO)(PPh3)3 complex catalyzed the cyclization of 1,5- and 1,6-enynes with an electron-withdrawing group on the alkene to give cyclized 1,3-dienes, dialkylidenecyclopentanes (for n=2), or alkylidenecyclopentenes (for n= 1) [69,70] (Eq. 51). Hydroruthenation of the alkyne can give two vinylruthenium complexes which can undergo intramolecular alkene insertion into the Ru-C bond. 

Several reactions in organometaUic chemistry also appear to contravene the rule, but which can be explained in a somewhat similar way. Hydrometallation [5.45, see (Section 5.1.3.4) page 162], carbometallation, metallo-metallation, and olefin metathesis reactions are all stereospecifically suprafacial [2 + 2] additions to an alkene or alkyne, for which the all-suprafacial pathway is forbidden. Hydroboration, for example, begins with electrophilic attack by the boron atom, but it is not fully stepwise, because electron-donating substituents on the alkene do not speed up the reaction as much as they do when alkenes are attacked by electrophiles. Nevertheless, the reaction is stereospecifically syn—there must be some hydride delivery more or less concerted with the electrophilic attack. The empty p orbital on the boron is the electrophilic site and the s orbital of the hydrogen atom is the nucleophilic site. These orbitals are orthogonal, and so the addition 6.126 is not pericyclic. 

A general picture for the mechanism is shown in Scheme 4, which is based upon a theoretical analysis by Thom and Hoffmann. Here distinction between (2) and (2a) reflects the general assumption, supported by calculations, that the insertion step requires the M—H and C==C groups to be cis and coplanar, which need not be the case for the first-formed and/or thermodynamically most stable alkene complex (2). Thom and Hoffmann conclude that most or all metal hydrides will have some pathway that leads to hydrometallation without a large kinetic barrier, so long as none of the key intermediates along the way is too stable. The same inference was drawn for the bent metallocene systems discussed earlier (Figure 1) a kinetic barrier to insertion, found only for the cP-cases, is a consequence of the thermodynamic stabilization of alkene complex (2). ... 

The two reaction pathways are not unique to the corresponding molybdenum or tungsten centers. For example, both metal hydrides effect hydrogenation of maleic anhydride [58]. Thus, the hydrogenation path may involve prior hydrometallation followed by reductive elimination of the hydridoalkyltungsten adduct (Eqs 61, 62). 

Deprotonation of CP2WH2" " and Cp2MoH2" clearly occurs upon electrochemical generation of the cation radicals, and subsequent dimerization of the resulting hydridometallocene radicals has been observed [59]. Finally, the charge-transfer hydrogenation and hydrometallation of olefins closely parallels the thermal pathways in that the same type of u-adducts are found [185]. 

Apart from the formation of vinylmetals and metallacycles and all the possible pathways deriving from them, jt-aUyl metal pathway (n -metal pathway Scheme 7.10) are quite rare in the cycloisomerization of enynes. On the other hand, cycloisomerizations of dienes are common to be performed either through the generation jt-allyl complexes or through hydrometallation of alkenes [26a]. 

SCHEME 7.35 (a) Hydrometalation of dienes and (b) x-allyl metal pathways. 

Catalytic hydrofunctionalization of the multiple bonds involves oxidative addition of H-Het to low valent metal complex and intermediate formation of H-MLn-Het complex. As a next step, either heterometallation (insertion into M-Het) or hydrometallation (insertion into M-H) may take place (Scheme 13). Involvement of both pathways was proposed in practical hydrofunctionalization reactions with various substrates and different metal complexes [20-28]. 

Scheme 13 Alkyne insertion through the hydrometallation vs. heterometallation pathways [39, 52, 53]...

For producing ri -coordinated allyl metal species, two pathways are proposed as shown in Scheme 4, and in either case an acid is involved, often added as a cocatalyst or in situ generated path (a) formation of metal hydride species followed by coordination of C-C double bond and subsequent migratory insertion into M-H bond [hydrometallation], and path (b) coordination of C-C double bond followed by protonation of the coordinated alkene [41]. To the terminal carbon of the rj -allyl system, an amine attacks from external side. This type of hydroamination has different characteristics in that the formation of C-H bond precedes by the formation of C-N bond, by contrast to the reactions of other mechanisms which have the opposite bond-forming order, that is, the formation of C-N bond occurs first. 

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