The Reductive Elimination Step

The transmetallation reaction involves the transfer of the organic group from an organometallic species to a Pd(II) species and produces a trails Pd(II) species. Isomerization from the trans arrangement to a cis one is necessary prior to the reductive elimination step. Reductive elimination yields the coupled product and regenerates the transition metal catalyst. Because the reductive elimination is very fast, competing reactions leading to by-products are usually not observed. 

Procedures for the synthesis of ketones based on coupling of organostannanes with acyl halides have also been developed.211 The catalytic cycle is similar to that involved in coupling with aryl halides. The scope of compounds to which the reaction is applicable includes tetra-u-butylstannane. This example indicates that the reductive elimination step competes successfully with (3-elimination. 

Similar models explain the 1,8-, 1,10- and 1,12-addition reactions to the extended Michael acceptors 91, 93 and 95, respectively (Schemes 2.32 and 2.33). Again, these transformations start with the formation of a cuprate Jt-complex at the double bond neighbouring the acceptor group [61a]. Subsequently, an equilibrating mixture of a-copper(III) intermediates is presumably formed and the regioselectivity of the reaction may then be governed by the different relative rates of the reductive elimination step of these intermediates. Consequently, the exclusive formation of allenic prod-... 

Two catalytic cycles having the rr-aryl-nickel intermediate in common should be taken into account for the nickel-bpy system, as illustrated in Scheme 2. In the first cycle (left-hand side), similar to the previous one with dppe as ligand, Ni X which is formed in the reductive elimination step disproportion-ates into Ni° and Ni followed by a further reduction of Ni" [35]. An alternative mechanism has also been proposed in which the product results from the... 

The reductive elimination step has undergone much less examination, with the majority of authors considering that the acyl species produces CH3COI and regenerates the active anionic [Irl2(CO)2] species. When a DFT study was carried out by Kinnunen and Laasonen [39], the Jac,cis-[Ir(COCH3)l3(CO)2] isomer was seen to be the dominant intermediate for the anionic route, whereas for the neutral pathway the mer,ds-[lr(COCHi)l2(CO)i] isomer allowed a faster reductive elimination reaction. 

Knochel and co-workers developed the Ni(acac)3-catalyzed cross-coupling reaction between polyfunctional primary iodoalkanes and a variety of primary diorganozinc compounds in the presence of w-trifluoromethylstyrene as a promoter. " The addition of this unsaturated promoter is required in order to coordinate to the nickel center and remove electron density from the metal atom, to facilitate the reductive elimination step. " " The scope of the reaction is extended, when Ni(acac)2 is used in the presence of BU4NI and fluorostyrene (Scheme With these... 

Figure 8.5 Catalytic cycle for the metal-catalyzed carbonylation of methanol, with the reductive elimination step highlighted. In the case of iridium, the diiodotricarbonyl species has also been suggested as a possible precursor to reductive elimination. What aie the issues of stereochemistry associated with the intermediates What special basis-set requirements will be involved in modeling this system ...

In this generic example, the oxidation state of the metal is reduced by two, while the product is released in the reductive elimination step. In many reactions the oxidative addition does not provide the proper stereochemistry for elimination an isomerization must occur. 

Attack by nucleophiles on the electrophilic ir-allylpalladium complex can take place by two distinct mechanisms, which have opposite stereochemical consequences. Stereochemical inversion is achieved by attack of the nucleophile directly on the allyl ligand on the face opposite the palladium (equation 148). Retention is achieved by attack of the nucleophile at the metal center, followed by reductive elimination (equation 149). The reductive elimination step could proceed through an V-allylpalladium-Nuc species or directly from an i)3-allylpalladium-Nuc complex. Recent evidence strongly suggests the latter pathway.384... 

Similar to the tin- and zinc-based methodologies, electron deficient alkenes were found to strongly catalyze the reductive elimination step.155 156-395 Organomercury reagents are also believed to add via metal addition.385... 

The palladium-catalyzed cross-coupling of an aryl, alkenyl, or benzylzinc bromide 11 with aryl iodide 12 succeeds with 0.15 mol-% [Pd P(C6H4C6Fi3)3 4] in toluene/1-bromoperfluorooctane, taking advantage of variable miscibility through thermoregulation [20], In this case the electron-deficiency of the phosphanes, due to the perfluorinated side chains, appears to influence the reductive elimination step in the cross-coupling reactions. 

Accordingly, it seems plausible that the reductive elimination step in the catalytic cycle with bidentate ligands (F to E in Figure 5) follows an associative mechanism in which first an alkene or nitrile (displayed as S) coordinates to the nickel,... 

The reductive elimination step (iv) is a three-centre mechanism, which creates the carbon-carbon bond, regenerates the catalyst and needs the R1 and R3 groups to be cis on the palladium. This may be the case when cis bidentate ligands are used188. On the other hand, a trans to cis isomerization may precede the reductive elimination, which operates through T-shaped Pd(II)189,190 or Pd(IV)191-193 intermediates. Finally, recent studies argued that a T-shaped three-coordinate species c -[PdR1R2L] may be formed directly by an associative transmetallation step. 

This diagram illustrates many important points. First of all, it shows the mechanistic complexity that may be anticipated for even an apparently simple reaction, reductive elimination of acetone from 2.5. Second, it shows that RhCl(PPh3)3 is thermodynamically more stable than complex 2.5 by about 40 kJ/mol. However, complex 2.5 does not undergo spontaneous conversion to RhCl(PPh3)3 because it has sufficient kinetic stability (>92 kJ/mol). Third, the high free energy of activation is associated with a ligand dissociation step that precedes the reductive elimination step. The five-coordinated intermediate, once... 

Ab initio quantum-mechanical calculations have also been carried out to estimate theoretically the relative energies of different transition states and intermediates. To keep the calculations at a manageable level the model catalytic cycle shown in Fig. 7.4 has been considered. According to this calculation, conversion of 7.14 to 7.15 is found to be the rate-determining step. This is consistent with the empirical kinetic results. Isomerization of 7.15 to 7.16 is found to be thermodynamically highly favorable. The reductive elimination step, that is, 7.16 to 7.7, is found to have a very low free energy of activation and be thermoneutral, that is, thermodynamically neither strongly favorable nor unfavorable. 

One role of the phosphite ligand (besides preventing catalyst deactivation) is to assist the reductive elimination step [17]. In fact, the olefin exists as an equilibrium mixture of isomers under the hydrocyanation conditions and, tlterefore, the regioselccUvity of the addition of HCN to a double bond is determined by the ulcfin insertion into the Ni—II bond and the relative rates... 

As shown in the proposed reaction scheme [Scheme 5-3] [42a], this protocol is based on the discovery of Cul-catalyzed transmetallation in amine [45] and is constructed by a combination of two catalytic cycles A and B. There is no evidence for the acceleration of the reductive elimination step (step iii, from 76 to 74 in Scheme 5-3), although a coordination of the copper ion to or alkynyl group is expected. 

A second application of the use of Lewis acid catalysis in the Julia coupling can be found in the synthesis of trans-Biiktnt isosteres of dipeptides (478 Scheme 62). Initially, attempts to couple aldehydes derived from amino acids (473) resulted in poor overall yield of the alkene. This difficulty was solved by reversing the substituents, and introducing the amino acid portion as the anion of sulfone (476) to the chiral aldehyde (477). The dianion of the sulfone was formed and to it were added 2 equiv. of aldehyde and 1 equiv. of diisobutylaluminum methoxide. The resulting p-hydroxy sulfone was t en on to the reductive elimination step to produce the desired ( )-alkene (478), in 74% overall yield. 

The reductive elimination step is effected by adding an excess of 5,65% Na(Hg) (2.5 mg atom of Na g" ) to an efficiently stirred solution of the sulfone in 3 1 THF-MeOH at -20 °C. A protic solvent is essential for the reaction and a detailed studyrevealed that MeOH was superior to EtOH or Pr OH at low... 

Quite stable catalytic reaction solutions were obtained in THF with the starting pressure for ethylene of 6-6.5 MPa at a reaction temperature of 120 °C. Under these conditions and with the ratios piperidine/rhodium of 100 1 and 1000 1 in 36 and 72 h, yields of 70 and 50 % ethylpiperidine were reached, which correspond to TONs of 2 and 7 mol amine/(mol Rh) per h, respectively. Total conversion is also possible if the reaction time is prolonged further. As a side reaction, ethylene dimerization to butene was observed. This indicates the formation of a hydrido rhodium(III) complex in the hydroamination reaction, as formulated in Scheme 3, route (b). Hydrido rhodium(III) complexes are known as catalysts for ethylene dimerization [19], and if the reductive elimination of ethylpiperidine from the hydrido-y9-aminoethyl rhodium(III) complex is the rate-limiting step in the catalytic cycle of hydroamination, a competitive catalysis of the ethylene dimerization seems possible. In the context of these mechanistic considerations, an increase of the catalytic activity for hydroamination requires as much facilitation of the reductive elimination step as possible. 

---