Stepwise pathway

Isotope effect between the HH, HD, DH, and DD isotopomers was used as an important tool to determine the mechanism of the double-proton transfer. For concerted degenerate double-proton transfers in the absence of tunneling, the rule of the geometrical mean (RGM) should hold in good approximation, which states that /chh/ hd = /cdh/ dd-Tunneling may lead to a breakdown of this rule but the relation /chh > hd = dh > dd should remain valid. In the absence of secondary isotope effects the relation /chh HD = DH = 2 /cdd sliould liold for a stepwise pathway, even if tunneling is involved. 

The major developments of catalytic enantioselective cycloaddition reactions of carbonyl compounds with conjugated dienes have been presented. A variety of chiral catalysts is available for the different types of carbonyl compound. For unactivated aldehydes chiral catalysts such as BINOL-aluminum(III), BINOL-tita-nium(IV), acyloxylborane(III), and tridentate Schiff base chromium(III) complexes can catalyze highly diastereo- and enantioselective cycloaddition reactions. The mechanism of these reactions can be a stepwise pathway via a Mukaiyama aldol intermediate or a concerted mechanism. For a-dicarbonyl compounds, which can coordinate to the chiral catalyst in a bidentate fashion, the chiral BOX-copper(II)... 

The orbital interaction depicted in Scheme 1.15 shows that the two cr-bonds form at the same time but do not develop to the same extent. The Diels-Alder cycloaddition of unsymmetrical starting materials is therefore concerted but asynchronous. A highly unsymmetrical diene and/or dienophile give rise to a highly unsymmetrical transition state and a stepwise pathway can be followed. 

According to the calculations at high levels of theory, the [4+2] cycloaddition reactions of dienes with the singlet ( A oxygen follow stepwise pathways [37, 38], These results, which were unexpected from the Woodward-Hoffmann rule and the frontier orbital theory, suggest that the [4+2] cycloadditions of the singlet ( A oxygen could be the reactions in the pseudoexcitation band. 

Direct support for a stepwise pathway is, however, provided by comparison of the rates of reaction of a series of substrates, having different leaving groups, with the same nucleophile, e.g. 2,4-dinitro-halogenobenzenes (86) with piperidine (87) ... 

The cycloadditions in entries 1-3 are still believed to occur via a diradical stepwise pathway, as confirmed by obtaining a thermodynamic 78 22 trans/cis mixture of dispirooctanes 536 from frans-dicyanoethylene (533) (entry 3) [13b, 143], The cycloaddition to tetracyanoethylene (131) in the absence of oxygen gives only low yields of the [2 + 2] adduct, due to the simultaneous formation of products 542 and 543 (Scheme 74) [13b]. Still, the formation of the cyclobutanes 537 and 542 is noteworthy, since the reactions of TCNE with phenyl substituted MCPs exclusively afford methylenecyclopentane derivatives [37,144], The reaction is thought to occur via dipolar intermediates 539-541 formed after an initial SET process (Scheme 74) [13b]. The occurrence of intermediates 540 and 541 has been confirmed by trapping experiments [13b]. 

Cycloadditions give rise to four-membered rings. Thermal concerted [2+2] cycloadditions have to be antarafacial on one component and the geometrical and orbital constraints thus imposed ensure that this process is encountered only in special circumstances. Most thermal [2+2] cycloadditions of alkenes take place by a stepwise pathway involving diradical or zwitterionic intermediates [la]. Considerably fewer studies have been performed regarding the application of microwave irradiation in [2+2] cydoadditions than for other kinds of cydoaddition (vide supra). Such reactions have been commonly used to obtain /1-lactam derivatives by cycloaddition of ketenes with imines [18-20,117,118],... 

Song and Beak found intramolecular and intermolecular hydrogen-deuterium kinetic isotope effects of 1.1 0.2 and 1.2 0.1, respectively, for the tin tetrachloride catalysed ene reaction. Since significant intramolecular and intermolecular primary deuterium kinetic isotope effects of between two and three have been found for other concerted ene addition reactions161, the tin-catalysed reaction must proceed by the stepwise pathway with the k rate determining step (equation 107). 

Modes of cycloaddition of alkylideneallyl cation are also controlled by the reaction conditions. [4 + 3] Cycloaddition occurs in the reaction with furan. The [4 + 3] cycloaddition with furan was observed for the siloxy-substituted allyl cation 5S, but not for the methoxy-substituted allyl cation 5M. The lower electrophilicity of 5S may prefer the concerted pathway of [4 + 3] cycloaddition in competition with the stepwise pathway to yield a [3 + 2] cycloadduct and an electrophilic substitution product. 

FIGURE 3.1 8. Competition between a stepwise pathway, involving successively a n radical and a a radical (upper pathway), and a concerted pathway involving a a radical (lower pathway). 

Scheme 6.2). In the previous mechanism, B was formed in concert with electron transfer, whereas the present mechanism follows the stepwise pathway. (The stepwise vs. concerted dichotomy is discussed in detail in Chapter 3 for the cased where the B —> B step is a bond-breaking reaction.) Although equation (6.51) still applies, equation (6.58) is replaced by... 

The same relationships apply, in principle, to the concerted pathway (60). However, the intrinsic barrier is now so high, because of the contribution of bond breaking, that the possibility of observing a region that is counterdiffusion controlled is quite unlikely since the rate constant of the forward reaction would then be immeasurably small in most cases. At any rate, even if one conceives that such a situation might occur, and AGq then determined would be so different from that of the outer sphere electron transfer (59) in the stepwise pathway that the confusion would hardly be possible. 

From the rate data thus obtained it is difficult to conclude whether the reaction goes through the intermediacy of the polyhalogenoalkane anion radical or rather follows a concerted pathway. The fact that the anion radicals have been detected under quite different medium and driving force conditions (Brickenstein and Khairutdinov, 1985 Mishra and Symons, 1973) does not provide unequivocal evidence for the stepwise pathway, as discussed earlier. Some evidence in favour of the latter mechanism was. 

For the reduction of CCI4 by electrochemically generated aromatic anion radicals in DMF (Eberson et al., 1989), the kinetics were treated according to a reaction scheme in which CCl, " appears as an intermediate, but no strong evidence was offered that they would not fit a concerted pathway as well. As discussed on pp. 32, 33, it is indeed not possible to distinguish between the two pathways in such types of experiment when, in the stepwise pathway, the cleavage reaction is so fast that the electron-transfer step would be rate determining, a situation likely to be met in the present case. 

SO that there is some formal resemblance to S 2. The above pathway must, however, differ in that attack by Y cannot take place from the back of the carbon atom carrying the leaving group (cf. Sf 2, p. 78), but must occur from the side it is thus often referred to as Sff2(aromatic). Further, on the basis of the above rate law the reaction could be concerted (like Sf 2)—in which case (81) is a transition state—or it could proceed by a stepwise pathway with either step (1) or step (2) as the slow, rate-limiting one—in which case (81) is an intermediate. 

Scheme 6.13 A stepwise pathway via five-membered cyclic intermediate radical 66 in the 1,2 migration of an acyloxy group...

Thus, if the concerted pathway has a stronger driving force than that of the first step of the stepwise pathway, the cleavage of anion-radical is thermodynamically favorable. Stepwise mechanisms are considered viable when the intermediate (anion-radical in the preceding schemes) has a lifetime that is longer than the time for a bond vibration (ca. 10 s). Concerted mechanisms occur under... 

Campos, Sampedro and Rodriguez studied theoretically in 1998 the competition of the concerted and stepwise mechanism of hydrogen migration and lithium iodide a-eUmination in the trihydrate 1-iodo-l-lithioethene 28. Since the lithiated derivative of 1-iodoethane readily decomposes to ethylene, experimental techniques are found to be of less use. Their ab initio theoretical calculations indicate that the preferred mechanism is the concerted rather than stepwise pathway as illustrated in Eigure 33. Their studies also suggest that 1-iodo-l-thioethene prefers to be a monomer in THE and the activation barriers for the cis and trans hydrogen migration are nearly the same. 

Other mechanistic possibilities also exist for the [5-1-2] cycloaddition reaction and cannot be mled out at this point In addition to the stepwise pathways depicted in Scheme 13.8, it is also possible that coordination of the 27r-component to 42 could lead directly to 48 through simultaneous insertion and cleavage. Variations on these events, such as direct insertion into the cyclopropane to form a metaUacyclobutane, are also possible. 

In 2003, Gimeno, Bassetti and coworkers reported an unusual diastereoselective [2 + 2] cycloaddition of two C=C bonds under mild thermal conditions (Scheme 4.18) [128]. Heating the vinylidene complexes Rul leads to the bicyclic alkylidene complexes Ru2. In 2004, Sordo and coworkers investigated the mechanism of this [2 + 2] cycloaddition theoretically [25]. With model complexes in which the indenyl ligand was modeled with a Cp ligand, two different pathways (paths a and b) were studied, shown in Scheme 4.19. Path a considers a concerted process. In the stepwise pathway (path b), the vinylidene-to-alkyne tautomerization of R1 followed by... 

The standard potentials for the formation of the radical anion, °ab/ab -i are too scattered to provide useful information and indeed some work in this direction is currently underway. However, it is interesting to observe that these °ab/ab - values are often close to those estimated for the concerted process, E°ab/A, b This would suggest that, at least on thermodynamic grounds, the two ET mechanisms can compete. On the other hand, the stepwise pathway is kinetically favored over the concerted reaction, even... 

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