Hammett acidity function - Wikipedia
The Curtin–Hammett principle is a principle in chemical kinetics proposed by David Yarrow The relationship between the (apparent) rate constants and equilibrium constant is known as the Winstein-Holness equation. The Taft equation is a linear free energy relationship (LFER) used in physical organic chemistry in the study of reaction mechanisms and in the development of quantitative structure activity relationships for organic compounds. It was developed by Robert W. Taft in as a modification to the Hammett. The photochemical reaction dynamics of a set of photochromic compounds based on thioindigo and stilbene molecular parts (hemithioindigos.
June Learn how and when to remove this template message The plot of the Hammett equation is typically seen as being linear, with either a positive or negative slope correlating to the value of rho. However, nonlinearity emerges in the Hammett plot when a substituent affects the rate of reaction or changes the rate-determining step or reaction mechanism of the reaction. For the reason of the former case, new sigma constants have been introduced to accommodate the deviation from linearity otherwise seen resulting from the effect of the substituent.
Therefore, an electron donating group EDG will accelerate the rate of the reaction by resonance stabilization and will give the following sigma plot with a negative rho value.
The EWG withdraws electron density by resonance and effectively stabilizes the negative charge that is generated. The corresponding plot will show a positive rho value. In the case of a nucleophilic acyl substitution the effect of the substituent, X, of the non-leaving group can in fact accelerate the rate of the nucleophilic addition reaction when X is an EWG. This is attributed to the resonance contribution of the EWG to withdraw electron density thereby increasing the susceptibility for nucleophilic attack on the carbonyl carbon.
A certain electronic effect may accelerate a certain step so that it is no longer the rds. Typically, the model used for measuring the changes in rate in this instance is that of the SN2 reaction. The use of a chiral catalyst results in a higher-energy and a lower-energy transition state for hydrogenation of the two enantiomers.
The transformation occurs via the lower-energy transition state to form the product as a single enantiomer. The relative free energy profile of one example of the Noyori asymmetric hydrogenation is shown below: Enantioselective lithiation[ edit ] Dynamic kinetic resolution under Curtin—Hammett conditions has also been applied to enantioselective lithiation reactions.
In the reaction below, it was observed that product enantioselectivities were independent of the chirality of the starting material.
Curtin–Hammett principle - Wikipedia
Were the two reactant complexes not rapidly interconverting, enantioselectivity would erode over time as the faster-reacting conformer was depleted. Application to regioselective acylation[ edit ] The Curtin—Hammett principle has been invoked to explain regioselectivity in the acylation of 1,2-diols. Ordinarily, the less-hindered site of an asymmetric 1,2-diol would experience more rapid esterification due to reduced steric hindrance between the diol and the acylating reagent.
Developing a selective esterification of the most substituted hydroxyl group is a useful transformation in synthetic organic chemistry, particularly in the synthesis of carbohydrates and other polyhdyroxylated compounds.
- Hammett acidity function
- Hammett equation
- Curtin–Hammett principle
This compound is then treated with one equivalent of acyl chloride to produce the stannyl monoester. Two isomers of the stannyl ester are accessible, and can undergo rapid interconversion through a tetrahedral intermediate.
Initially, the less stable isomer predominates, as it is formed more quickly from the stannyl acetal. However, allowing the two isomers to equilibrate results in an excess of the more stable primary alkoxystannane in solution.
The reaction is then quenched irreversibly, with the less hindered primary alkoxystannane reacting more rapidly. This results in selective production of the more-substituted monoester. This is a Curtin—Hammett scenario in which the more stable isomer also reacts more rapidly. Application to asymmetric epoxidation[ edit ] The epoxidation of asymmetric alkenes has also been studied as an example of Curtin—Hammett kinetics.
In a computational study of the diastereoselective epoxidation of chiral allylic alcohols by titanium peroxy complexes, the computed difference in transition state energies between the two conformers was 1. This product ratio is consistent with the computed difference in transition state energies. This is an example in which the conformer favored in the ground state, which experiences reduced A 1,3 strain, reacts through a lower-energy transition state to form the major product.
Synthetic applications[ edit ] Synthesis of ATA1[ edit ] The Curtin—Hammett principle has been invoked to explain selectivity in a variety of synthetic pathways. One example is observed en route to the antitumor antibiotic ATA1, in which a Mannich-type cyclization proceeds with excellent regioselectivity.
Studies demonstrate that the cyclization step is irreversible in the solvent used to run the reaction, suggesting that Curtin—Hammett kinetics can explain the product selectivity. The structure of each of the two compounds contains a twisted membered macrocycle. However, because the amide-bond-forming step was irreversible and the barrier to isomerization was low, the major product was derived from the faster-reacting intermediate.
This is an example of a Curtin—Hammett scenario in which the less-stable intermediate is significantly more reactive than the more stable intermediate that predominates in solution.
Because substrate isomerization is fast, throughout the course of the reaction excess substrate of the more stable form can be converted into the less stable form, which then undergoes rapid and irreversible amide bond formation to produce the desired macrocycle. I think there's an error in the Scheme. A key step in the synthesis is the rhodium-catalyzed formation of an oxonium ylide, which then undergoes a [2,3] sigmatropic rearrangement en route to the desired product.
Obtaining high selectivity for the desired product was possible, however, due to differences in the activation barriers for the step following ylide formation. If the ortho-methoxy group undergoes oxonium ylide formation, a 1,4-methyl shift can then generate an undesired product.