Synchronous concerted mechanism

The second step of the arylation process involves a coupling reaction between two of the ligands linked to the bismuth atom. Various mechanistic pathways were considered to be possible. Study of the relative migratory aptitudes of aryl groups indicated that the C-phenylation reaction with either a phenol or a p-dicarbonyl does not follow an ionic pathway. Although these migratory aptitudes were of the same order as a free-radical type, the relative ratios are more consistent with a non-synchronous concerted mechanism.26... 

In addition to the cationic, radical, and non-synchronous concerted mechanisms outlined above, many other proposals have been offered [9, 56], In a recent provocative paper, an organometallic mechanism was postulated for the activation of alkanes by a ferryl porphyrin model species [79]. Less reactive substrates such as H2, D2 and CH4 were observed to inhibit the reaction between the synthetic catalyst and cyclohexane. In the proposed mechanism, a 2 -t- 2 C-H addition across the Fe-O bond is preceded by coordination of the alkane to the metal center to form an intermolecular <7-adduct. Inhibition arises from preferential binding of the smaller substrates to the congested metal site. Attempts to identify a similar effect with sMMO have been unsuccessful the presence of H2 had no effect on the rate of reaction between methane and Q (A. M. Valentine, S. S. Stahl, S. J. Lippard, unpublished results). 

The introduction of an atom other than carbon to either dienes or dienophiles will result in the hetero-Diels-Alder reaction. Owing to the nature (steric effect, electronic effect, etc.) of substituents on dienes and dienophiles, the Diels-Alder reaction might occur through a synchronous concerted, an asynchronous concerted, or a stepwise reaction mechanism. The stepwise and asynchronous concerted Diels-Alder reactions proceed via diradical intermediates, whereas the synchronous concerted mechanisms does not. It should be pointed out that most of the Diels-Alder reactions are concerted as a result, both the rate constants and the stereoselectivities of Diels-Alder reaction are only moderately sensitive to the changes in the nature of organic sol vents. However, it has been clearly shown that the applications of water to the reaction system can greatly accelerate such reactions. Other modifications on this reactions include the application of high pressure, Lewis acid, and ultrasound radiation.More information about this reaction can be easily attained from reviews and relevant books. 

Provided here is a simple illustration for the Diels-Alder reaction proceeding through a synchronous concerted mechanism. 

A review of recent developments in 1,3-dipolar cycloaddition of nitrones with sila-, thia-, phospha-, and halo-substituted alkenes has been reported. A DFT study of solvent effects on the intermolecular 3-l-2-cycloaddition reaction of norbornadiene with 3,4-dihydroisoquinoline A(-oxide at 398.15 K indicated that the reaction proceeds via a synchronous concerted mechanism. Chiral imidazolidinone salts, in the absence of water, promote the 1,3-dipolar cycloaddition reaction of alanine-derived ketonitrones... 

Most Diels-Alder reactions, particularly the thermal ones and those involving apolar dienes and dienophiles, are described by a concerted mechanism [17]. The reaction between 1,3-butadiene and ethene is a prototype of concerted synchronous reactions that have been investigated both experimentally and theoretically [18]. A concerted unsymmetrical transition state has been invoked to justify the stereochemistry of AICI3-catalyzed cycloadditions of alkylcyclohexenones with methyl-butadienes [12]. The high syn stereospecificity of the reaction, the low solvent effect on the reaction rate, and the large negative values of both activation entropy and activation volume comprise the chemical evidence usually given in favor of a pericyclic Diels-Alder reaction. 

The well-known Diels-Alder reaction [95,104-106] is a standard method for forming substituted cyclohexenes through the thermally allowed 4s + 2s cycloaddition of alkenes and dienes. In particular, the reaction between ethene and 1,3-butadiene to yield cyclohexene is the prototype of a Diels-Alder reaction (Scheme 28.4). It is now well recognized that this reaction takes place via a synchronous and concerted mechanism through an aromatic boatlike TS [105]. 

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. 

Fig. 10.11 The stepwise and concerted mechanisms for the Diels-Alder reaction between butadiene and ethylene. The reactants (lower left) proceed to the product, cyclohexene (lower right) either through a two step, two transition state mechanism involving the formation of a diradical intermediate (top center), or more directly through the symmetric synchronous transition state (bottom center) (Storer, J. W., Raimondi, L., and Houk, K. N., J. Am. Chem. Soc. 116, 9675 (1994))...

The experimentally observed substituent effect on the triplet and singlet quantum yields in the complete series of methyl-substituted dioxetanes, as well as the predicted C—C and 0—0 bond strength for the four-membered peroxidic rings , have led to the hypothesis that a more concerted, almost synchronized, decomposition mechanism should lead to high excitation quantum yields (as in the case of tetramethyl-l,2-dioxetane), whereas the biradical pathway presumably leads to low quantum yields (as in the case of the unsubstituted 1,2-dioxetane)" . However, it appears that this criterion of concertedness is difficult to apply generally to structurally dissimilar dioxetane derivatives. 

A third possible type of catalysis requires that a base and an acid act synchronously to effect the breaking and formation of bonds in a single step. Thus, tetramethyl-glucose mutarotates very slowly in benzene containing either pyridine (a base) or phenol (an acid). However, when both pyridine and phenol are present, mutarota-tion is rapid. This suggested to Swain and Brown132 a concerted mechanism (Eq. 9-92) in which both an acid and a base participate. 

Evaluate intermediates for stability and valence. If they fit normal chemical expectations, then the mechanism is potentially correct. There may be other mechanisms operating or the timing of individual steps (synchronous, concerted, etc.) may be different, but the above process can be used to generate diem as well. 

Therefore, in the case of an effective concerted mechanism, the decrease of the synchronization probability (asyn) with increasing n must be compensated for by an appreciable decrease in the activation energy. 

Enzymatic reactions, despite the obvious energy preference of certain concerted mechanisms, may be inefficient because of a too low synchronization factor. In such cases, the sequential transformation of the system through a number of steps is favorable. Here, the role of a multi-functional catalyst, in reaching a pretransition state is to provide favorable energy and synchronization factors through the optical use of the corresponding functional groups at each step of the process. 

S-adenosyl-L methionine (ADO-Met) dependent DNA methyl transferase catalyzed the transfer of a methyl group from AdoMet to a specific nucleotide within the DNA helix (Cheng et al., 1993). In a concerted reaction in the enzyme active site (Fig X) with a simultaneous addition of methyl residue of AdoMet to the cytosine ring and with an elimination of the ring proton by a water molecule requires involving seven heavy nuclei (two ofCys 81, four of AdoMet and one of water. An estimation with aid of Eq. 2.44 leads to value of the reaction synchronization factor asyn 10 4, that does not rule out the concerted mechanism, if the activation energy is less than 10 kcal/mole Nevertheless, a... 

Other phosphoryl transfer mechanisms are an associative, two-step mechanism (An + Dn) and a concerted mechanism (ANDN) with no intermediate. The AN+DN mechanism is an addition-elimination pathway in which a stable pentacoordinate intermediate, called a phosphorane, is formed. This mechanism occurs in some reactions of phosphate triesters and diesters, and has been speculated to occur in enzymatic reactions of monoesters. In the concerted ANDN mechanism, bond formation to the nucleophile and bond fission to the leaving group both occur in the transition state. This transition state could be loose or tight, depending upon the synchronicity between nucleophilic attack and leaving group departure. The concerted mechanism of Fig. 2 is drawn to indicate a loose transition state, typical of phosphate monoester reactions. 

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