Transmetalation-isomerization

In his review of 1986, Stille proposed a mechanism based primarily on data obtained from the coupling of benzoyl chloride with tri-n-butyl(phenyl)tin. This proposal already clearly stated four main steps of the catalytic cycle oxidative addition, transmetalation, isomerization, and reductive elimination. 

In 1994, Aliprantis and coworkers studied the catalytic intermediates in the Suzuki reaction by ESI-MS [1]. The currently accepted catalytic cycle involves oxidative addition, transmetalation, isomerization, and reductive elimination (Scheme 4.1). In order to form the protonated intermediates detectable by ESI-MS, pyridyl bromide and three phenylboronic acids were chosen for the reaction. Intermediate ions of [(pyrH)Pd(PPh3)2Br], diaryl Pd(II) species, and some other derivative palladium species were detected in the reaction mixture. 

The most commonly proposed mechanism is shown in Figure 9. This mechanism involves the same basic steps (oxidative addition, transmetallation, isomerization, and reductive elimination) as discussed previously. It is important to note that the mechanism shown in Figure 6 is more consistent with the recent developments of the Stille reaction. The exact mechanism followed may vary depending on the exact substrates and reaction conditions. 

The same method was employed for the synthesis of benzo[<2]phenotellurazine 42 and proven to be more efficient. The heterocycle 42 was obtained in 55% yield (89H1007). A possible explanation for the higher yield of 42 is that the transmetallation reaction in this particular case dominates the side formation of nonreactive complex of the amine with tellurium tetrachloride. There is no need for an additional step of the isomerization of the formed aryltellurim trichloride. 

In the direct coupling reaction (Scheme 30), it is presumed that a coordinatively unsaturated 14-electron palladium(o) complex such as bis(triphenylphosphine)palladium(o) serves as the catalytically active species. An oxidative addition of the organic electrophile, RX, to the palladium catalyst generates a 16-electron palladium(n) complex A, which then participates in a transmetalation with the organotin reagent (see A—>B). After facile trans- cis isomerization (see B— C), a reductive elimination releases the primary organic product D and regenerates the catalytically active palladium ) complex. 

Although analogous to the direct coupling reaction, the catalytic cycle for the carbonylative coupling reaction is distinguished by an insertion of carbon monoxide into the C-Pd bond of complex A (see A—>B, Scheme 31). The transmetalation step-then gives trans complex C which isomerizes to the cis complex D. The ketone product E is revealed after reductive elimination. 

Both allylstannane transmetalation and thermolysis of homoallyl stannoxanes have been used to prepare 2-butenyltin halides as (E)j(Z) mixtures44-45. The reaction between 2-butenyl-(tributyl)stannane and dibutyltin dichloride initially provides dibutyl(l-methyl-2-propenyl)tin chloride as the kinetic product by an SE2 process, but this isomerizes under the reaction conditions to give a mixture containing the (Z)- and (E)-2-butenyl isomers46. 

Transmetalation to give l-methyl-2-propenylaluminum followed by isomerization to 2-butenyl isomers may be involved in reactions between aldehydes and 2-butenyl(tributyl)-stannane induced by aluminum(III) chloride in the presence of one mole equivalent of 2-propanol. Benzaldehyde and reactive, unhindered, aliphatic aldehydes give rise to the formation of linear homoallyl alcohols, whereas branched products are obtained with less reactive, more hindered, aldehydes66,79. 

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. 

The anti stereochemistry is consistent with a cyclic TS, but the reaction is stereocon-vergent for the E- and Z-2-butenylstannanes, indicating that isomerization must occur at the transmetallation stage. The adducts are equilibrated at 82 °C and under these conditions the anti product is isolated on workup. 

BINAP-AgF gives good enantioselectivity, especially for the major anti product in the addition of 2-butenylstannanes to benzaldehyde.188 This system appears to be stereoconvergent, suggesting that isomerization of the 2-butenyl system occurs, perhaps by transmetallation. 

Hayashi et al. proposed a catalytic cycle for the rhodium-catalyzed 1,4-addition of phenylboronic acid to 2-cyclo-hexenone (Scheme 28), which was confirmed by NMR spectroscopic studies.96 The reaction presumably involved three intermediates, phenylrhodium a, oxa-7r-allylrhodium b, and hydroxorhodium c complexes. Complex a reacted with 2-cyclohexenone to give b by insertion of the carbon-carbon double bond of enone into the phenyl-rhodium bond followed by isomerization into the thermodynamically more stable complex. Complex b was converted to c upon addition of water, liberating the phenylation product. Transmetallation of the phenyl group from phenylboronic acid to rhodium took place in the presence of triphenylphosphine to regenerate a. 

The reaction of CO2 with 1,3-butadienes in the presence of Ni catalysts usually gave an isomeric mixture of carboxylic acids 89 and 90 after hydrolysis (Scheme 32).47,48 The oxa-7r-allylnickel complexes 87 and 88 might be the reaction intermediates, which could be formed through oxidative cyclization of Ni(0) with C02 and the dienes. When Me2Zn was used as a transmetallation agent to react with the oxa-7r-allylnickel intermediates under a C02 atmosphere, further carboxylation took place at the 7r-allylnickel unit. Thus, the 1,4-diesters 95 were obtained after acidic hydrolysis and treatment with diazomethane as shown in Scheme 32.47... 

Two isomeric l,l-bis(zirconium) complexes, 143a and 143b, were obtained in a 3 1 ratio by transmetallation of gem-aluminiozirconium complexes 3 (Schemes 7.1 and 7.43) [15]. Indeed, when gem-aluminiozirconium complex 3 [24] was treated with 1 equivalent of hexamethylphosphoramide, red-brown crystals (31 % yield) were isolated. 

The propargylic trichlorotin intermediate isomerizes to the more stable allenyltri-chlorotin species on standing or being warmed to 0 °C. The isomerization, which is highly stereoselective, takes place with retention. A possible transmetallation and isomerization pathway is illustrated in Scheme 9.21. 

Under basic conditions, obviously only one isomerization step takes place and thus a terminal alkyne will deliver 1,2-dienes selectively. With internal alkynes, on the other hand, selectivity can only be achieved when the alkyne is either symmetrical as in 14 [34] (Scheme 1.6) or has a tertiary center on one side as in 16 [35, 36] (Scheme 1.7). So, unlike potassium 3-aminopropylamide in 1,3-diaminopropane, where the Jt-bonds can migrate over a long distance by a sequence of deprotonations and reprotonations, here the stoichiometric deprotonation delivers one specific anion which is then reprotonated (in 16 after transmetalation). 

Hydrolysis of the diethylacetal function employing p-toluenesulphonic acid in acetone, pyridinium p-toluene-sulphonate in EtOH, and a suspension of Si02 in hexane. In all cases the corresponding aldehyde is obtained in high yield as a Z E isomeric mixture. Transmetallation of acetal with Me2Cu(CN)Li2 followed by treatment with c-hexenones giving the 1,4-addition product. Alternatively, transmetallation with n-BuLi and reaction with benzaldehyde giving the expected alcohol. 

In the presence of additional olefin, an exchange of metal for allylic proton or transmetallation may take place, resulting in the isomerized olefin and more of the basic intermediate. 

To elucidate the reaction pathway, deuterium-labeled allenyl pinacol boronate 10 was prepared, and the addition reaction with hydrazonoester 6 was conducted in the presence of Bi(OH)3 and Cu(OH)2 (Scheme 4). In both Bi- and Cu-catalyzed cases, the reactions proceeded smoothly (in quantitative yields in both cases). In the Bi(OH)3-catalyzed reaction, a major product was allenyl compound 11, in which the internal position was deuterized. It was assumed that a propargyl bismuth was formed via transmetalation from boron to bismuth, followed by addition to hydrazonoester via y-addition to afford allenyl compound 11. Thus, two y-additions could selectively provide a-addition products [75, 76, 105, 106]. It was confirmed that isomerization of 10 did not occur. Recently, we reported Ag20-catalyzed anti-selective a-addition of a-substituted allyltributyltin with aldehydes in aqueous media [107], On the other hand, in the Cu(OH)2-catalyzed reaction, a major product was propargyl compound 12, in which the terminal position was deuterized. A possible mechanism is that Cu(OH)2 worked as a Lewis acid catalyst to activate hydrazonoester 6 and that allenyl boronate 10 [83-85] reacted with activated 6 via y-addition to afford 12. 

Furthermore, isomerization of the heptadentate XXXI, coordinated to Ni(II) via transmetallation (91), occurs again aimed at its adaptation to a octahedral coordination sphere around ions with d8 configuration. In the case of the more flexible pentadentate ligands, XXXII and its analogue with three methylene groups (L2) (92), formation of monomeric (with XXXII) and dimeric (with L2), but also of polymeric (with L2) Ni(II) complexes with an octahedral environment around the metal is possible (94). 

The experimental observations presented can be explained by a carbanionic mechanism with prototropic rearrangement. On heterogeneous catalysts this involves the formation of an ally lie carbanion by proton abstraction112,125 [Eq. (4.24)]. The carbanion then participates in transmetalation to yield a new anion and the isomerized product [Eq. (4.25)] ... 

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