Concerted Pericyclic Cycloaddition Reactions

Pericyclic reactions have cyclic transition states and electron flow paths that appear to go around in a loop. There are three main types of pericyclic reactions cycloaddition 

Chapter 12 Qualitative Molecular Orbital Theory Pericyclic Reactions 

The Diels-Alder reaction is an allowed thermal six-electron (4 + 2) cycloaddition reaction between a diene (contributing four pi electrons to the transition state) and dienophile (contributing two pi electrons). It is an extremely useful cycloaddition because it goes in high yield and with predictable stereochemistry. The stereochemistry of both the starting pieces is preserved in the product for example, if two groups on the dienophile are cis, they remain cis in the product. 

The five-membered transition state 4 + 2 cycloaddition is less common than the six. The four-pi electron piece is called a 1,3-dipole because it reacts as if it has a minus and a plus separated by one atom, A-B-C . The orbital arrangement for the 1,3-dipolar addition is similar to that for the Diels-Alder reaction  

Cycloreversions are the reverse of cycloadditions and occur by the same mechanism. Because the cycloreversion breaks the molecule into two pieces, increasing degrees of freedom and therefore disorder, the AS of reaction is positive. The A G for the cycloreversion process becomes favorable (negative) with increased temperature because the -TAS term dominates over the Aff term (recall AG = A/f - TAS). The reverse Diels-Alder reaction of dicyclopentadiene into two cyclopentadienes is a common example  

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Cycloaddition reactions involve the combination of two molecules to form a new ring. Concerted pericyclic cycloadditions involve reorganization of the Tr-electron systems of the reactants to form two new a bonds. Examples might include cyclodimerization of alkenes, cycloaddition of allyl cation to an alkene, and the addition reaction between alkenes and dienes (Diels-Alder reaction). 

Pericyclic reactions in which p-orbitals at the ends of the rt-component of each system overlap and form the new a-bonds on the same surface are called suprafacial cycloaddition. Almost aU pericyclic cycloaddition reactions are suprafacial on both systems and thus the stereochemistry is maintained due to their concerted nature. This specification is usually made by placing a suitable subscript (s or a) after the number referring to the Tr-component. For example,... 

Mechanistically the observed stereospecificity can be rationalized by a concerted, pericyclic reaction. In a one-step cycloaddition reaction the dienophile 8 adds 1,4 to the diene 7 via a six-membered cyclic, aromatic transition state 9, where three r-bonds are broken and one jr- and two cr-bonds are formed. The arrangement of the substituents relative to each other at the stereogenic centers of the reactants is retained in the product 10, as a result of the stereospecific y -addition. 

An explanation for the finding that concerted [4 -I- 2] cycloadditions take place thermally, while concerted [2 + 2] cycloadditions occur under photochemical conditions, is given through the principle of conservation of orbital symmetry. According to the Woodw ard-Hofmann rules derived thereof, a concerted, pericyclic [4 -I- 2] cycloaddition reaction from the ground state is symmetry-allowed. 

The Diels-Alder reaction is a pericyclic cycloaddition when bond-forming and bond-breaking processes are concerted in the six-membered transition state... 

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. 

The [3+2] cycloaddition strategy provides an effective method to access valuable intermediates for the construction of biologically important alkaloids, amino acids, amino carbohydrates and P-lactams [58-62]. The reaction involves the concerted pericyclic addition of a dipole and a dipolarophile and considerable efforts have been made to render these reactions asymmetric nsing Lewis acid catalysis and chiral anxiliaries [63]. 

The interpretation of chemical reactivity in terms of molecular orbital symmetry. The central principle is that orbital symmetry is conserved in concerted reactions. An orbital must retain a certain symmetry element (for example, a reflection plane) during the course of a molecular reorganization in concerted reactions. It should be emphasized that orbital-symmetry rules (also referred to as Woodward-Hoffmann rules) apply only to concerted reactions. The rules are very useful in characterizing which types of reactions are likely to occur under thermal or photochemical conditions. Examples of reactions governed by orbital symmetry restrictions include cycloaddition reactions and pericyclic reactions. 

The concerted reactions presented in this chapter are called pericyclic reactions. They are divided into electrocyclic reactions, cycloaddition reactions, and sigmatropic rearrangements. Some occur when energy is supplied in the form of heat others require light energy to occur. Most have strict stereochemical requirements. 

This [2 + 2] cycloaddition requires the HOMO of one of the ethylenes to overlap with the LUMO of the other. Figure 15-20 shows that an antibonding interaction results from this overlap, raising the activation energy. For a cyclobutane molecule to result, one of the MOs would have to change its symmetry. Orbital symmetry would not be conserved, so the reaction is symmetry-forbidden. Such a symmetry-forbidden reaction can occasionally be made to occur, but it cannot occur in the concerted pericyclic manner shown in the figure. 

The mechanism of 1,3-cycloaddition of nitrile oxides has been a subject of sometimes bitter controversy. While these reactions displayed the regioselec-tivity and stereoselectivity appropriate to concerted pericyclic mechanisms,62 it was suggested that the results were equally in accord with a diradical mechanism.86 However, no direct evidence for a diradical intermediate has been produced, and the balance of the theoretical argument now favors the... 

Cycloaddition reactions are a very important class of pericyclic reactions in which two unsaturated molecules join by converting two tt-bonds into two new a-bonds between their termini. Although cycloaddition reactions are concerted (no intermediate species are formed), the two new bonds in a few cases may be formed in an asynchronous fashion. Depending on partial charge distribution in both reactants, the formation of one bond may lead to the development of the other. 

A unified picture of the mechanism of this cycloaddition for various structural types of nitroso dienophiles is not available. Depending upon the electronic and steric nature of the particular nitroso compound, the reaction apparently may vary from a concerted pericyclic process to one involving discrete dipolar intermediates. The net result of this mechanistic diversity is a few anomalous regiochemi-cal results in the cycloaddition. 

Two studies on the mechanism of this type of [4 + 2] cycloaddition which have led to very di erent interpretations have appeared. Mock and Nugent suggested that the Diels-Alder reactions of N-sulfi-nyl-p-toluenesulfonamide are stepwise, ionic processes. On the other hand, Hanson and Stockbum prefer a concerted, pericyclic mechanism in accord with frontier molecular orbital theory. Both proposals satisfactorily rationalize the observed regioselectivity of these reactions. 

There are two different modes of cyclizations in hetero [4+2] cycloadditions involving Danishefsky s diene 1) concerted (pericyclic) and 2) stepwise. When carbonyl compounds are reacted with Danishefsky s diene, the stepwise pathway is often referred to as the Mukaiyama aldol reaction pathway. The concerted process is called the Diels-Alder pathway. The mode of cyclization in the case of Lewis acid catalyzed reactions depends on the Lewis acid itself and whether it is present in stoichiometric or catalytic amounts. The Mukaiyama aldol pathway has been... 

Regioselectivity has been previously described in terms of a local hard and soft acid and base (HSAB) principle, and some empirical rules have been proposed to rationalize the experimental regioselectivity pattern observed in some DA reactions.71,72 There is not a single criterion, however, to explain most of the experimental evidence accumulated in cycloaddition processes involving four centre interactions. An excellent source for the discussion of regioselectivity in concerted pericyclic reactions is given in reference.73... 

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