Nucleophilic protic/halide additives

Alternatively, the rhodium dimer 30 may be cleaved by an amine nucleophile to give 34. Since amine-rhodium complexes are known to be stable, this interaction may sequester the catalyst from the productive catalytic cycle. Amine-rhodium complexes are also known to undergo a-oxidation to give hydridorhodium imine complexes 35, which may also be a source of catalyst poisoning. However, in the presence of protic and halide additives, the amine-rhodium complex 34 could react to give the dihalorhodate complex 36. This could occur by associative nucleophilic displacement of the amine by a halide anion. Dihalorhodate 36 could then reform the dimeric complex 30 by reaction with another rhodium monomer, or go on to react directly with another substrate molecule with loss of one of the halide ligands. It is important to note that the dihalorhodate 36 may become a new resting state for the catalyst under these conditions, in addition to or in place of the dimeric complex. 

Finally, in the presence of halide salts (bromide or chloride, which in low polarity non-protic solvents bind to Br2 to give a stable trihalide species), the addition reaction proceeds through a rate- and product-determining nucleophilic attack of Br anion on the 1 1 it complex, Scheme 2 path c. No intermediate is formed in this latter reaction the nucleophilic attack of halide (X ) and the Br-Br bond breaking are indeed concerted, although not necessarily synchronous. 

Enolate ions, which are usually strong nucleophiles, are more important in preparative applications than are the enols. In additions to carbonyl groups, the carbon end, rather than the oxygen end, attacks but in SA,2 substitutions on alkyl halides, significant amounts of O-alkylation occur. The more acidic compounds, such as those with the j3-dicarbonyl structure, yield enolates with the greater tendency toward O-alkylation. Protic solvents and small cations favor C-alkylation, because the harder oxygen base of the enolate coordinates more strongly than does the carbon with these hard Lewis acids.147... 

Similar information is available for other bases. Lithium phenoxide (LiOPh) is a tetramer in THF. Lithium 3,5-dimethylphenoxide is a tetramer in ether, but addition of HMPA leads to dissociation to a monomer. Enolate anions are nucleophiles in reactions with alkyl halides (reaction 10-68), with aldehydes and ketones (reactions 16-34, 16-36) and with acid derivatives (reaction 16-85). Enolate anions are also bases, reacting with water, alcohols and other protic solvents, and even the carbonyl precursor to the enolate anion. Enolate anions exist as aggregates, and the effect of solvent on aggregation and reactivity of lithium enolate anions has been studied. The influence of alkyl substitution on the energetics of enolate anions has been studied. ... 

The critical difference between addition of halogen (X2) and the many HX additions we saw in Chapter 9 is the presence of the intermediate halonium (bromo-nium or chloronium) ion. This intermediate is demanded by the observed preference for anti addition. However, occasionally the cyclic halonium ion is less stable than the corresponding open ion and the open ion will be favored. One way to stabilize the open ion is through resonance. If the open ion is the intermediate, the products of both cis and trans addition will be observed. When a protic nucleophilic solvent is used in the reaction, the solvent as well as the halide will add to the intermediate. In such cases halohydrins or halogenated ethers are formed along with dihalides. 

In addition to the striking difference in absolute rates in different media, there are differences and reversals in relative rates. For instance, the halogen nucleophilic order is changed from F > Cl > Br" > I" in the gas phase and polar aprotic solvents such as acetone and DMF, to I > Br" > Cl" > F" in protic solvents such as methanol and water [23]. This difference can also be understood in terms of differential solvation of the TS and the reactants. The enthalpies of transfer from dimethylsulphoxide (polar aprotic solvent) to methanol are, at 298 K in kJ/mol, Cl" (—10.4), Br" (—0.4), and I" (11.3). The increase in the relative solvation of the smaller halides in methanol is enough to reverse their order of reactivity, since the solvation of the TSs is not as sensitive to solvent changes as the solvation of the reactant anions [23]. 

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