Stepwise and concerted pathways

The demonstration that formation of the nucleophile adduct R-Nu results in the same proportional decrease in the yields of the alkene and solvent adducts, so that the ratio of the yields of these reaction products is independent of [Nu-]. If the solvolysis and elimination reactions proceed by competing stepwise and concerted pathways, respectively, then the yield of R-OSolv will decrease with increasing trapping of the carbocation intermediate by added nucleophile, while the yield of alkene from elimination will remain constant, so that the ratio [R-OSolv]/[Alkene] will decrease as [Nu ] is increased. 

Another question of interest is that of the transition between stepwise and concerted pathways. A schematic representation of the problem is given in Fig. 6 this is schematic in the sense that the system is represented as depending on a single reaction coordinate, viz., the distance between the atoms forming the bond to be broken during the reaction. This is obviously the main reaction coordinate as far as the concerted pathway (48) and the decomposition of RX- (47) are concerned. It is also an important reaction... 

The exact pathway of the Peterson reaction is still not clear despite the intensive research effort. Most of the mechanistic studies suggest that both the stepwise and concerted pathways are feasible under basic conditions. In the concerted pathway a pentacoordinate 1,2-oxasiletanide is formed. The stepwise pathway is expected when chelation control operates in the reaction. The driving force is the formation of a very strong Si-0 bond. Under acidic conditions the 3-hydroxysilane undergoes an E2 elimination to afford the other alkene isomer. 

A simple pinacol rearrangement promoted by a protic acid is displayed here, including both stepwise and concerted pathways, though the stepwise route is the primary pathway. 

It follows that a proper description of the stepwise and concerted reaction pathways requires a three-dimensional representation as illustrated by Figs 8a and 8b. 

Generally, only a single stepwise or concerted pathway for aliphatic nucleophihc substitution is detected by experiment because of the very different activation barriers for formation of the respective reaction transition states for these reactions. The description of the borderline between stepwise and concerted nucleophilic substitution reactions presented in this chapter has been obtained through a search for those rare substrates that show comparable barriers to these two reactions and through the characterization of the barrier for nucleophile addition to the putative carbocation intermediate of the stepwise reaction in the region of this change in mechanism. 

The steric bulk of the diphosphine ligand hardly affects the barriers for methanolysis via the stepwise and concerted reductive elimination pathways. Based on these observations, it was postulated that the high activity and chemoselectivity in the methoxycarbonylation of ethene observed for t-butyl substituted wide bite angle diphosphine ligands are determined by a combination of electronic and steric effects induced by the diphosphine ligand. The high electron density at the metal center... 

FIGURE 6.10. Comparing the energetics of the EVB configurations in solution and in the active site of lysozyme. The calculations were done by using the PDLD and related models (Refs. 6 and 7) and they represent a study of a stepwise mechanism. The energetics of a more concerted pathway (e.g., that of Fig. 6.9) is almost identical to that of the stepwise mechanism and correlated in a similar way with the electrostatic effect of the protein. 

Ogliaro F, Harris N, Cohen S, et al. A model rebound mechanism of hydroxylation by cytochrome P450 stepwise and effectively concerted pathways, and their reactivity patterns. J Am Chem Soc 2000 122(37) 8977-8989. 

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). 

Mechanistic and theoretical studies of the Diels-Alder reaction have resulted in the characterization of this reaction as a concerted, although not necessarily synchronous, single-step process28-31 45. The parent reaction, the addition of 1,3-butadiene to ethylene yielding cyclohexene, has been the subject of an ongoing mechanistic debate. Experimental results supported a concerted mechanism, whereas results from calculations seemed to be dependent on the method used. Semi-empirical calculations predicted a stepwise mechanism, whereas ab initio calculations were in favor of a concerted pathway. At the end of the 80s experimental and theoretical evidence converged on the synchronous mechanism29-31. 

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. 

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