Pericyclic reactions rearrangements

Apart from the thoroughly studied aqueous Diels-Alder reaction, a limited number of other transformations have been reported to benefit considerably from the use of water. These include the aldol condensation , the benzoin condensation , the Baylis-Hillman reaction (tertiary-amine catalysed coupling of aldehydes with acrylic acid derivatives) and pericyclic reactions like the 1,3-dipolar cycloaddition and the Qaisen rearrangement (see below). These reactions have one thing in common a negative volume of activation. This observation has tempted many authors to propose hydrophobic effects as primary cause of ftie observed rate enhancements. 

The best way to understand how orbital symmetry affects pericyclic reactions is to look at some examples. Let s look first at a group of polyene rearrangements called electrocyclic reactions. An electrocyclic reaction is a pericyclic process that involves the cycli/ation of a conjugated polyene. One 7r bond is broken, the other 7t bonds change position, a new cr bond is formed, and a cyclic compound results. For example, a conjugated triene can be converted into a cyclohexa-diene, and a conjugated diene can be converted into a cyclobutene. 

Two other important sigmatropic reactions are the Claisen rearrangement of an allyl aryl ether discussed in Section 18.4 and the Cope rearrangement of a 1,5-hexadiene. These two, along with the Diels-Alder reaction, are the most useful pericyclic reactions for organic synthesis many thousands of examples of all three are known. Note that the Claisen rearrangement occurs with both allylic aryl ethers and allylic vinylic ethers. 

Problem 30.9 When a 2,6-disubslituted allyl phenyl ether is heated in an attempted Claisen rearrangement, migration occurs to give the />-allyl product as the result of two sequential pericyclic reactions. Explain. 

A pericyclic reaction is one that takes place in a single step through a cyclic transition state without intermediates. There are three major classes of peri-cyclic processes electrocyclic reactions, cycloaddition reactions, and sigmatropic rearrangements. The stereochemistry of these reactions is controlled by the symmetry of the orbitals involved in bond reorganization. 

The following thermal isomerization occurs under relatively mild conditions. Identify the pericyclic reactions involved, and show how the rearrangement occurs. 

The following thermal rearrangement involves two pericyclic reactions in sequence. Identify them, and propose a mechanism to account for the observed result. 

Keywords Diels-Alder reactions, dipolar cycloadditions, electrocyclic reactions, ene reactions, pericyclic reactions, sigmatropic rearrangements... 

As expected, the Mobius-Hiickel method leads to the same predictions. Here we look at the basis set of orbitals shown in G and H for [1,3] and [1,5] rearrangements, respectively, A [1,3] shift involves four electrons, so an allowed thermal pericyclic reaction must be a Mobius system (p. 1070) with one or an odd number of sign inversions. As can be seen in G, only an antarafacial migration can achieve this. A [1,5] shift, with six electrons, is allowed thermally only when it is a Hiickel system with zero or an even number of sign inversions hence it requires a suprafacial migration. 

Chapter 6 looks at concerted pericyclic reactions, including the Diels-Alder reaction, 1,3-dipolar cycloaddition, [3,3]- and [2,3]-sigmatropic rearrangements, and thermal elimination reactions. The carbon-carbon bond-forming reactions are emphasized and the stereoselectivity of the reactions is discussed in detail. 

Exactly such steric repulsion seems to be responsible for the further rearrangements observed with heptaphenylborepin (109 or 114 with R = Ph). The end result of a reasonable, but amazing sequence of pericyclic reactions is 1,2,3,3a,4,5-hexaphenyl-5-bora-3a,4-dihydro-5//-benz[>]in-dene (119), whose generation is initiated with 109 and continues through 116-118 (Scheme 11). The last step, 118-119, is an impressive intramolecu-... 

Besides the obvious biological interest, chorismate mutase is important for being a rare example of an enzyme that catalyses a pericyclic reaction (the Claisen rearrangement), which also occurs in solution without the enzyme, providing a unique... 

The combination of pericyclic transformations as cycloadditions, sigmatropic rearrangements, electrocydic reactions and ene reactions with each other, and also with non-pericyclic transformations, allows a very rapid increase in the complexity of products. As most of the pericyclic reactions run quite well under neutral or mild Lewis acid acidic conditions, many different set-ups are possible. The majority of the published pericyclic domino reactions deals with two successive cycloadditions, mostly as [4+2]/[4+2] combinations, but there are also [2+2], [2+5], [4+3] (Nazarov), [5+2], and [6+2] cycloadditions. Although there are many examples of the combination of hetero-Diels-Alder reactions with 1,3-dipolar cycloadditions (see Section 4.1), no examples could be found of a domino all-carbon-[4+2]/[3+2] cycloaddition. Co-catalyzed [2+2+2] cycloadditions will be discussed in Chapter 6. 

Isopolar activated complexes differ very little or not at all in charge separation or charge distribution from the corresponding initial reactants. These complexes are formed in pericyclic reactions such as Diels-Alder cydoadditions and the Cope rearrangement. 

Chorismate mutase catalyzes the Claisen rearrangement of chorismate to prephenate at a rate 106 times greater than that in solution (Fig. 5.5). This enzyme reaction has attracted the attention of computational (bio)chemists, because it is a rare example of an enzyme-catalyzed pericyclic reaction. Several research groups have studied the mechanism of this enzyme by use of QM/MM methods [76-78], It has also been studied with the effective fragment potential (EFP) method [79, 80]. In this method the chemically active part of an enzyme is treated by use of the ab initio QM method and the rest of the system (protein environment) by effective fragment potentials. These potentials account... 

In addition to the numerous pericyclic aromatic TSs, other reactions deserve attention. These include the Cope and Claisen rearrangements, the pericyclic reactions with Mobius TSs, the Bergman cyclizations [77,116], and the TSs for 1,5-H shifts [100,117],... 

In a pericyclic reaction, the electron density is spread among the bonds involved in the rearrangement (the reason for aromatic TSs). On the other hand, pseudopericyclic reactions are characterized by electron accumulations and depletions on different atoms. Hence, the electron distributions in the TSs are not uniform for the bonds involved in the rearrangement. Recently some of us [121,122] showed that since the electron localization function (ELF), which measures the excess of kinetic energy density due to the Pauli repulsion, accounts for the electron distribution, we could expect connected (delocalized) pictures of bonds in pericyclic reactions, while pseudopericyclic reactions would give rise to disconnected (localized) pictures. Thus, ELF proves to be a valuable tool to differentiate between both reaction mechanisms. 

These include a series of pericyclic reactions initiated from Si(7t,7t ). Pericyclic reactions are concerted reactions with a cyclic transition state. While in this transition state, a concerted rearrangement of electrons takes place, which causes o- and Jt-bonds to simultaneously break and form. 

---