Nucleophilic Addition to the Ligand

37Transition metal-catalyzed insertion of C02 into M-H and M-C bonds could be an important pathway toward utilization of this abundant Q molecule in organic synthesis and for industrial-scale processes, potentially replacing the use of CO. For examples of C02 insertion, see R. Johansson and O. F. Wendt, Dalton Transactions, 2007, 488 A. R. Cutler, P. K. Hanna, and J. C. Vites, Chem. Rev., 1988, 88, 1363 and W. J. Evans, C. A. Seibel, J. W. Ziller and R. J. Doedens, Organometallics, 1998,17, 2103. For another review, which discusses (in part) the utilization of C02 by way of M-C insertion, see T. J. Marks, et al., Chem. Rev., 2001,101, 953. 

38The latter three groups are generally also known as n ligands. 

The overall transformation represents formally the attack of an electrophile at the carbon of a carbonyl group. Normally, only nucleophiles attack carbonyl carbon atoms (as indicated in the first step of equation 8.26) because these carbons represent electron-deficient sites. By converting the carbonyl to a hemithioacetal and pulling off the now relatively acidic proton with base, the carbonyl carbon becomes nucleophilic instead of electrophilic. 

Alkenes, polyenes, arenes, and CO normally do not react with nucleophiles because these species are already electron rich. When these n ligands complex with a metal, however, (especially if the metal is electron deficient due to the presence of other electron-withdrawing ligands or due to a relatively high oxidation state), they are forced to give up some of their electron density to the attached metal complex fragment. The complexed ligands are now electron deficient compared with 

The tendency for a nucleophile to attack an unsaturated ligand directly is a function of the electron density on the metal (i.e., complexes with a formal positive charge on the metal are more reactive than neutral ones), the degree of coordinative saturation of the metal (unsaturated metals have a higher probability of attack directly at the metal), and the presence of n-electron attracting ligands (such as CO) that can absorb some of the increased electron density on the metal after attack has occurred. 

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The generally accepted mechanism for Pd-catalyzed allylic substitution involves association of the palladium(0) catalyst to the substrate, and oxidative addition to provide a ir-aUyl complex. The equilibrium between the neutral 7r-allyl complex and the more reactive cationic 7r-allyl complex depends on the nature/concentration of phosphine Ugand. Nucleophilic addition to the ligand involves direct attack on the ligand when stabilized enolates are employed. After dissociation of the product, the palladium is able to continue in the next catalytic cycle (Scheme 2). In general, the reaction proceeds via a Pd(0)/Pd(II) shuttle, although a Pd(II)/Pd(IV) pathway is also possible. 

Exo addition is always observed. When the 6-exo substituent is very bulky, as in complex (132 equation 50), nucleophile addition to the dienyl ligand is completely suppressed. Instead, decomplexation is observed giving the dienone (133), possibly via attack of nucleophile at the metal (i.e. ligand exchange).42 Endo addition is not observed. 

The weakness of most metal-metal bonds compared with metal-ligand bonds makes cleavage of metal-metal bonds by nucleophiles a common process (15). In the case of metal-metal double bonds this corresponds to nucleophilic addition to the metal-metal bonded systems. Since unsaturated clusters exist which can be considered to contain metal - metal double bonds, this should be an important aspect of substrate activation by clusters. 

Nucleophilic addition to unsaturated ligands, such as olefins, acetylenes, and arenes, coordinated to various metal centers is a useful strategy in organic synthesis (98). The ion-pair interaction of organometallic cations and anions is facile and can successfully lead to the nucleophilic activation of ethylene, acetylene, and benzene (99), for example,... 

In Scheme 12, step (i) represents ion-pair annihilation by nucleophilic addition to the methylene terminus of the ligand to yield the initially observed intermediate A, which is transformed by a 1,2-shift of mo to the iron center in step (ii) to generate the fluxional species B and B (step iii)... 

Coordinated alkenes and alkynes undergo two kinds of reactions substitution reactions and nucleophilic additions to the coordinated ligand. While a relahvely few examples of nucleophihc attack exist for stable Pd -alkene complexes, a far larger number of examples can be inferred from the palladium-catalyzed reactions of alkenes. 

A stepwise sequence of nucleophilic addition to the complexed norbomadiene followed by intramolecular alkene insertion was first observed with dichloro(norbornadiene)palla-dium(II) which, upon addition of methanol, only forms the normal adduct 11. Subsequent conversion with l,2-bis(triphenylphosphanyl)ethane (dppe), however, gave the nortricyclene complex 12. Reductive displacement of the alkyl ligand with lithium aluminum hydride or oxidative cleavage with halogens gave noncomplexed nortricyclene derivatives. ... 

Nucleophilic addition to the more electron-rich cation XXIV leads as expected to a higher proportion of attack onto the olefin than for complex XXI. The cation XXVn reacts with nucleophiles such as D and [CN] on the olefin ligand as expected. Nucleophilic addition by [i-PrS]", however, occurs onto the Ji-allyl ligand ... 

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