Cyclic transition states in reactions

Another such effect is the intervention of cyclic transition states in reactions of organometallic compounds (Section II, B, 5) with azines or in intramolecular nucleophilic substitutions (Section II, F). 

Enby 6 is an example of a stereospecific elimination reaction of an alkyl halide in which the transition state requires die proton and bromide ion that are lost to be in an anti orientation with respect to each odier. The diastereomeric threo- and e/ytAra-l-bromo-1,2-diphenyl-propanes undergo )3-elimination to produce stereoisomeric products. Enby 7 is an example of a pyrolytic elimination requiring a syn orientation of die proton that is removed and the nitrogen atom of the amine oxide group. The elimination proceeds through a cyclic transition state in which the proton is transferred to die oxygen of die amine oxide group. 

Substitution, addition, and group transfer reactions can occur intramolecularly. Intramolecular substitution reactions that involve hydrogen abstraction have some important synthetic applications, since they permit functionalization of carbon atoms relatively remote from the initial reaction site. ° The preference for a six-membered cyclic transition state in the hydrogen abstraction step imparts position selectivity to the process ... 

The mechanism of the Diels-Alder cycloaddition is different from that of other reactions we ve studied because it is neither polar nor radical. Rather, the Diels-Alder reaction is a pericyclic process. Pericyclic reactions, which we ll discuss in more detail in Chapter 30, take place in a single step by a cyclic redistribution of bonding electrons. The two reactants simply join together through a cyclic transition state in which the two new carbon-carbon bonds form at the same time. 

Figure 14.7 Mechanism of the Diels-Alder cycloaddition reaction. The reaction occurs in a single step through a cyclic transition state in which the two new carbon-carbon bonds form simultaneously.

The diene must adopt what is called an s-cis conformation, meaning "cis-like" about the single bond, to undergo a Diels-Alder reaction. Only in the s-cis conformation are carbons 1 and 4 of the diene close enough to react through a cyclic transition state. In the alternative s-trans conformation, the ends of the diene partner are too far apart to overlap with the dienophile p orbitals. 

Evidence for a cyclic transition state in iododesilylation of phenyltrimethyl-silane by iodine monochloride (reaction (311), X2 = IC1 giving Phi and SiMe3Cl) has been obtained by comparing rates of chlorodesilylation and iododesilylation in acetic acid at 25 °C743. Good second-order kinetics for the latter reaction were obtained by application of equation (312)... 

The chemical reactions through cyclic transition states are controlled by the symmetry of the frontier orbitals [11]. At the symmetrical (Cs) six-membered ring transition state of Diels-Alder reaction between butadiene and ethylene, the HOMO of butadiene and the LUMO of ethylene (Scheme 18) are antisymmetric with respect to the reflection in the mirror plane (Scheme 24). The symmetry allows the frontier orbitals to have the same signs of the overlap integrals between the p-or-bital components at both reaction sites. The simultaneous interactions at the both sites promotes the frontier orbital interaction more than the interaction at one site of an acyclic transition state. This is also the case with interaction between the HOMO of ethylene and the LUMO of butadiene. The Diels-Alder reactions occur through the cyclic transition states in a concerted and stereospecific manner with retention of configuration of the reactants. 

The second mechanism, due to the permutational properties of the electronic wave function is referred to as the permutational mechanism. It was introduced in Section I for the H4 system, and above for pericyclic reactions and is closely related to the aromaticity of the reaction. Following Evans principle, an aromatic transition state is defined in analogy with the hybrid of the two Kekule structures of benzene. A cyclic transition state in pericyclic reactions is defined as aromatic or antiaromatic according to whether it is more stable or less stable than the open chain analogue, respectively. In [32], it was assumed that the in-phase combination in Eq. (14) lies always the on the ground state potential. As discussed above, it can be shown that the ground state of aromatic systems is always represented by the in-phase combination of Eq. (14), and antiaromatic ones—by the out-of-phase combination. 

There is also a group of reactions in which hydride is transferred from carbon. The carbon-hydrogen bond has little intrinsic tendency to act as a hydride donor so especially favorable circumstances are required to observe this reactivity. Frequently, these reactions proceed through a cyclic transition state in which a new C—H bond is formed simultaneously with the C—H cleavage. Hydride transfer is facilitated by high electron density at the carbon atom. Aluminum alkoxides catalyze transfer of hydride from an alcohol to a ketone. This is generally an equlibrium process, and the reaction can be driven to completion if the ketone is removed from the system by distillation, for example. This process is called the Meerwein-Pondorff-Verley reduction.122... 

Another important family of elimination reactions has as the common mechanistic feature cyclic transition states in which an intramolecular proton transfer accompanies elimination to form a new carbon-carbon double bond. Scheme 6.16 depicts examples of the most important of these reaction types. These reactions are thermally activated unimolecular reactions that normally do not involve acidic or basic catalysts. There is, however, a wide variation in the temperature at which elimination proceeds at a convenient rate. The cyclic transition states dictate that elimination occurs with syn stereochemistry. At least in a formal sense, all the reactions can proceed by a concerted mechanism. The reactions, as a group, are referred to as thermal syn eliminations. 

Aldol reactions of magnesium enolates are frequently more diastereoselective than the corresponding reactions of lithium enolates. The aldol condensation proceeds via a cyclic transition state in agreement with the Zimmerman-Traxler chelated model . 

A number of mechanistic studies of the reaction have been made and a cyclic transition state in which hydrogen transfer occurs from the / -C—H bond of an alkoxide to a coordinated ketone or aldehyde has been postulated.245 However, kinetic measurements are complicated by the oligomeric nature of the aluminum reagent (see 3).24[Pg.354]

For reaction (42) in solvent dioxan, the evidence for mechanism SE2(open) rests on the interpretation of sequence (29), and for reaction (42) in solvents acetone and dimethylformamide there is no available evidence for or against mechanism SE2(open). It seems to the author that some substantial evidence is required in order to support the hypothesis that a bimolecular reaction between two neutral molecules in a solvent of as low a dielectric constant as dioxan (e = 2.1) proceeds through a transition state with a degree of charge separation, when an alternative pathway is available for the reaction to proceed through an SE2(cyclic) transition state in which little or no charge separation occurs. 

Mechanisms have been suggested for the N-bromosuccinimide (NBS) oxidation of cyclopentanol and cyclohexanol, catalysed by iridium(III) chloride,120 of ethanolamine, diethanolamine, and triethanolamine in alkaline medium,121 and for ruthenium(III)-catalysed and uncatalysed oxidation of ethylamine and benzylamine.122 A suitable mechanism has been suggested to explain the break in the Hammett plot observed in the oxidation of substituted acetophenone oximes by NBS in acidic solution.123 Oxidation of substituted benhydrols with NBS showed a C-H/C-D primary kinetic isotope effect and a linear correlation with er+ values with p = —0.69. A cyclic transition state in the absence of mineral acid and a non-cyclic transition state in the presence of the acid are proposed.124 Sulfides are selectively oxidized to sulfoxides with NBS, catalysed by ft-cyclodextrin, in water. This reaction proceeds without over-oxidation to sulfones under mild conditions.125... 

The intramolecular methylation of the substrate of Figure 2.6, which was not observed, would have had to take place through a six-membered cyclic transition state. In other cases, cyclic, six-membered transition states of intramolecular reactions are so favored that intermolecular reactions usually do not occur. Why then is a cyclic transition state not able to compete in the SN reactions in Figure 2.6 ... 

Pericyclic reaction (Section 22.1) A concerted reaction that proceeds through a cyclic transition state in which two or more bonds are made and/or broken. 

Diastereoselectivily in compounds without rings is different it is less well controlled, because there are many more conformations available to the molecule. But even in acyclic compounds, rings can still be important, and some of the best dia stereoselectivities arise when there is a ring formed temporarily in the transition state of the reaction. With or without cyclic transition states, in some cases we have good prospects of predicting which diastereoisomer will be the major reaction product, or explaining the diastereoselectivity if we already know this. That is the subject of the next chapter. 

The unhomogeneous composition of the products generated by the photochemical reaction is due to another mechanism. While the thermal isomerization of 1,5-dienes proceeds via a cyclic transition state in a synchronous sense, the photochemically induced transformation causes a reorientation of the allyl radicals generated from the educts. Warming up the reaction mixture to 100°C activates a complete transfer from 4c to 5c) of all isomers. This step may be explained by a radical CC bond split of the 1,2-diphenylethylene unit. Since the isomerization of the diastereomeric compound 4c to 5c is activated at much lower temperatures than for the Cope rearrangement (from 3c to 4c), it is clear that the thermal transfer exclusively forms the twofold changed product. 

A similar ploy has been used for the addition of cinnamyl tributyltin to isobutyral-dehyde [23], In that reaction InCls serves as the catalyst and TMSCl is used as the catalyst liberating reagent (Eq. 15). The diastereoselectivity of the addition is solvent-dependent, ranging from 88 12 anttsyn in acetonitrile at 25 °C, to 12 88 antisyn in dichloromethane at -30 °C. The former addition proceeds by transmetalation to the cinnamyl dichloroindium species, which adds to the aldehyde by way of a cyclic transition state. In the latter addition InCb serves as a Lewis acid and the reaction proceeds by the usual acyclic transition state to give the syn adduct in predominance. 

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