Transition state theory cycloadditions

The Diels-Alder cycloaddition reaction of maleic anhydride with isoprene has been studied in supercritical-fluid CO2 under conditions near the critical point of CO2 [759]. The rate constants obtained for supercritical-fluid CO2 as solvent at 35 °C and high pressures (>200 bar) are similar to those obtained using normal liquid ethyl acetate as the solvent. However, at 35 °C and pressures approaching the critical pressure of CO2 (7.4 MPa), the effect of pressure on the rate constant becomes substantial. Obviously, AV takes on large negative values at temperatures and pressures near the critical point of CO2. Thus, pressure can be used to manipulate reaction rates in supercritical solvents under near-critical conditions. This effect of pressure on reacting systems in sc-fluids appears to be unique. A discussion of fundamental aspects of reaction kinetics under near-critical reaction conditions within the framework of transition-state theory can be found in reference [759],... 

The book comprises 8 chapters. The first provides background, introduces the topic of asymmetric synthesis, outlines principles of transition state theory as applied to stereoselective reactions, and includes the glossary. The second chapter details methods for analysis of mixtures of stereoisomers, including an important section on sample preparation. Then follow four chapters on carbon-carbon bond forming reactions, organized by reaction type and presented in order of increasing mechanistic complexity Chapter 3 is about enolate alkylations. Chapter 4 nucleophilic additions to carbonyls. Chapter 5 is on aldol and Michael additions (2 new stereocenters), while Chapter 6 covers rearrangements and cycloadditions. The last two chapters cover reductions and oxidations. 

One question that needs to be addressed is why are the activation volumes of pericyclic cycloadditions smaller (more negative) than those of the corresponding stepwise reactions involving diradical intermediates In the past it was assumed that the simultaneous formation of two new n bonds in a pericyclic [4 - - 2] cycloaddition leads to a larger contraction of volume than the formation of one bond in the stepwise process. The interpretation presented [28] is limited by the scope of Eyring transition state theory where the activation volume is related to the transition state volume, as mentioned above, and does not incorporate dynamic effects related to pressure-induced changes in viscosity [41]. An extensive discussion of reaction rates in highly viscous solvents can be found in Chapter 3. 

One of the main reasons is probably related to the small rate constant increase in the low pressure range (0-300 MPa) even for fairly pressure-dependent reactions such as pericyclic cycloadditions. The kinetic effect is derived from the relationship of Evans and Polanyi in the transition state theory as ... 

Another approach to analyzing concerted pericyclic reactions is based on the observation that the forbidden [2+2] cycloaddition involves a cyclic array of four electrons in the transition state, while the allowed [4+2] cycloaddition involves a cyclic array of six electrons. This is a familiar pattern that immediately calls to mind aromaticity, in which the ground states of molecules with four ir electrons in a cycle are destabilized and termed antiaromatic, while molecules with six tt electrons are stabilized and aromatic. Building off an earlier analysis by Evans, Zimmerman developed aromatic transition state theory. Simply put, reactions with a simple cyclic array of 4h + 2 electrons (commonly six) in a pericyclic transition state will be stabilized by aromaticity, making the reactions favorable. Note that the relevant electrons need not be exclusively in it orbitals a mixture of cr and it bonds in a cyclic array is acceptable. 

Occasionally, though, you will run across a more exotic pericyclic process, and will want to decide if it is allowed. In a complex case, a reaction that is not a simple electrocyclic ringopening or cycloaddition, often the basic orbital symmetry rules or FMO analyses are not easily applied. In contrast, aromatic transition state theory and the generalized orbital symmetry rule are easy to apply to any reaction. With aromatic transition state theory, we simply draw the cyclic array of orbitals, establish whether we have a Mobius or Hiickel topology, and then count electrons. Also, the generalized orbital symmetry rule is easy to apply. We simply break the reaction into two or more components and analyze the number of electrons and the ability of the components to react in a suprafacial or antarafacial manner. 

Ab initio Hartree-Fock and density functional theory calculations were performed to study the transition state geometry in intramolecular Diels-Alder cycloaddition of azoalkenes 55 to give 2-substituted 3,4,4u,5,6,7-hexahydro-8//-pyrido[l,2-ft]pyridazin-8-ones 56 (01MI7). 

The [3 + 2]-cycloaddition reactions of allenes with 1,3-dipoles are useful for the construction of a variety of five-membered heterocycles with a high degree of regio- and stereochemical control [67]. Generally, the dipolar cycloaddition reactions are concerted and synchronous processes with a relatively early transition state. The stereoselectivities and regiochemistries are accounted for by the FMO theory The reaction pathway is favored when maximal HOMO-LUMO overlap is achieved. 

Density functional theory and MC-SCF calculations have been applied to a number of pericyclic reactions including cycloadditions and electrocyclizations. It has been established that the transition states of thermally allowed electrocyclic reactions are aromatic. Apparently they not only have highly delocalized structures and large resonance stabilizations, but also strongly enhanced magnetic susceptibilities and show appreciable nucleus-independent chemical-shift values. 

When acrylamides are used as dipolarophUes, FMO theory predicts that the 4-amido isomer should be preferred, which is contrary to the results found with tertiary amides (129). Semiempirical, ab initio, and density functional theory (DFT) calculations were applied to the regioisomeric transition state stmctures of benzonitrile oxide cycloadditions (129-131). The results suggest that there is an unfavorable steric repulsion between the phenyl ring of the nitrile oxide and the methyl group of the ester (or amide) functionalities of the dipolarophile in the transition state leading to the 4-acyl regioisomer (Scheme 6.17). 

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