Cycloaddition reactions definition

Most of the reactions described in this chapter would fall under Huisgen s definition of a cycloaddition reaction (/, la). However some of the reactions described would not be considered cycloaddition reactions according to this restrictive definition. Therefore, the more liberal definition given by Baldwin will be used as a guideline, namely, Cycloadditions are chemical transformations giving at least one product having at least two new bonds as... 

Since Huisgen s definition of the general concepts of 1,3-dipolar cycloaddition, this class of reaction has been used extensively in organic synthesis. Nitro compounds can participate in 1,3-dipolar cycloaddition as sources of 1,3-dipoles such as nitronates or nitroxides. Because the reaction of nitrones can be compared with that of nitronates, recent development of nitrones in organic synthesis is briefly summarized. 1,3-Dipolar cycloadditions to a double bond or a triple bond lead to five-membered heterocyclic compounds (Scheme 8.12). There are many excellent reviews on 1,3-dipolar cycloaddition, in particular, the monograph by Torssell covers this topic comprehensively. This chapter describes only recent progress in this field. Many papers have appeared after the comprehensive monograph by Torssell. Here, the natural product synthesis and asymmetric 1,3-dipolar cycloaddition are emphasized.630 Synthesis of pyrrolidine and -izidine alkaloids based on cycloaddition reactions are also discussed in this chapter. 

On the basis of available experimental data, it is impossible to choose a definite pathway of elimination of silanol. However, study of silylation of methyl P -nitropropionate (411) with BSA in the presence of trapping agents rigorously proved that silyl nitronate D is initially formed. This compound can be detected in the [3 + 2]-cycloaddition reaction with methyl acrylate product (413). If silylation of AN (411) is performed in the presence of ethyl vinyl ether, a-nitrosoalkene E can be successfully trapped in as heterodiene a Diels-Alder reaction. Dihydroox-azine (414) is formed, and its silylation affords isolable product (415). 

Cyclobutanes may be converted to alkenes thermally, the reverse of the [2 + 2] cycloaddition reaction. These retroaddition or cycloreversion reactions have important synthetic applications and offer further insights into the chemical behavior of the 1,4-diradical intermediates involved they may proceed to product alkenes or collapse to starting material with loss of stereochemistry. Both observations are readily accommodated by the diradical mechanism. Generation of 1,4-tetramethylene diradicals in other ways, such as from cyclic diazo precursors, results in formation of both alkenes and cyclobutanes, with stereochemical details consistent with kinetically competitive bond rotations before the diradical gives cyclobutanes or alkenes. From the tetraalkyl-substituted systems (5) and (6), cyclobutane products are formed with very high retention stereospecificity,while the diradicals generated from the azo precursors (7) and (8) lead to alkene and cyclobutane products with some loss of stereochemical definition. ... 

In contrast with the cycloaddition reactions, no definite conclusion is available for the ene reaction . These reactions can be rationalized as proceeding via either a one- or a two-step reaction... 

Obviously, the appropriate application of the Woodward-Hoffmann rules to transition metal complex reactions involving metal carbon bonds requires information about the mechanistic and stereochemical details which is not easy to come by and definitely not yet sufficiently available for photochemical cycloaddition reactions of complexed olefinic systems. 

As mentioned above, the cycloaddition reaction with 1,3,4-oxadiazole is predicted to be LUMO diene (heterocycle) controlled. That definitely suggests that with electron-withdrawing substituents in the two and five positions of the heterocycle ring, the heterocycle should become more reactive as a diene for Diels-Alder reactions. To study the usefulness of 1,3,4-oxadiazole and its derivatives as dienes for the Diels-Alder reaction, we are presenting the results of our theoretical study of the cyclopropene addition to 2,5-di(trifluoromethyl)-l,3,4-oxadiazole. The AMI computed FMO energy gap for this reaction pair was only 8.00266 eV in comparison to 9.64149 eV FMO energy gap between LUMO of 1,3,4-oxadiazole and HOMO of cyclopropene. Therefore, the computed activation barrier for the cyclopropene addition to 2,5-bis(trifluoromethyl)-1,3,4-oxadiazole should be very... 

Another example demonstrating the difference in reactivity is the ozonolysis reactions of acetylene and ethylene. Ozonolysis of ethylene is a classical 1,3-dipolar cycloaddition reaction with an activation energy of 5 kcal/mol [106], whereas a larger activation energy of 11 kcal/mol was measured for the reaction of ozone with acetylene [107]. The 1,3-dipolar cycloaddition adduct, 1,2,3-trioxolene, has not been definitively observed as an intermediate involved in the acetylene ozonolysis. Nevertheless, according to the combined microwave and ab-initio calculation studies, the formation of similar van der Waals complexes in the course of ozonolysis has been established for both acetylene and ethylene [108]. 

Absolute rate coefficients and Arrhenius parameters have been obtained for the cycloaddition reaction of S( F2,1,0) atoms with a representative series of olefins and acetylenes. The activation energies are small, and they exhibit a trend with molecular structure which is expected for an electro-philic reagent The A-factors show a definite trend which can be attributed to steric repulsions and a generalized secondary a-isotope effect explained by activated complex theory. Secondary a-H/D kinetic isotope effects have been measured and their origin discussed. Hartree-Fock type MO calculations indicate that the primary product of the S( F) + olefin reaction is a ring-distorted, triplet state thi-irane, with a considerable energy barrier with respect to rotation around the C-C bond. 

In a study described by Kappe et al. (Section 11.4.1) [58], the intermolecular Diels-Alder cycloaddition reaction of the pyrazinone heterodiene 52 with ethylene led to the bicyclic cycloadduct S3 (Scheme 11.15). Under conventional conditions these cycloaddition reactions must be conducted in an autoclave at an ethylene pressure of 25 bar at 110 °C for 12 h. In contrast, under the action of microwaves, he Diels-Alder addition of pyrazinone precursor 52 to ethylene in a sealed vessel flushed with ethylene before sealing was complete after 140 min at 190 °C. It was not, however, possible to further increase the reaction rate by increasing the temperature. At temperatures above 200 °C an equilibrium between the cycloaddition 52 S3 and the competing retro Diels-Alder fragmentation process was observed (Scheme 11.15) [58]. By use of a microwave reactor enabling pre-pressurization of the reaction vessel with 10 bar ethylene, however, the Diels-Alder addition 52 S3 was definitely more efficient at 190 °C 85% yield of adduct 53 was obtained within 20 min [65b]. 

A cycloaddition reaction is actually a type of pericydic reaction, but the term peri-cyclic includes other types of reactions. The textbook definition of pericydic is a reaction whose transition state has a cyclic structure (i.e., the electrons are flowing in a closed loop). In addition to cycloaddition reactions (which exchange two Jt-bonds for two o-bonds, or vice versa), pericydic reactions include sigmatropic reactions, electro-cyclic reactions, and cheletropic reactions (and a few others which we ll ignore). 

To understand this definition, it is useful to depict cycloaddition reactions with dashed lines representing bonding interactions that will be present in the product of the reaction.The effect of the cycloaddition shown for the [ 2j -I- process in Figure 11.84(a) is to pull up the inner lobe of the sp hybrid orbital on C3 so that it overlaps with the upper lobe of the p orbital... 

While photocycloadditions are typically not concerted, pericyclic processes, our analysis of the thermal [2+2] reaction from Chapter 15 is instructive. Recall that suprafacial-suprafacial [2+2] cycloaddition reactions are thermally forbidden. Such reactions typically lead to an avoided crossing in the state correlation diagram, and that presents a perfect situation for funnel formation. This can be seen in Figure 16.17, where a portion of Figure 15.4 is reproduced using the symmetry and state definitions explained in detail in Section 15.2.2. The barrier to the thermal process is substantial, but the first excited state has a surface that comes close to the thermal barrier. At this point a funnel will form allowing the photochemical process to proceed. It is for this reason that reactions that are thermally forbidden are often efficient photochemical processes. It is debatable, however, whether to consider the [2+2] photochemical reactions orbital symmetry "allowed". Rather, the thermal forbiddenness tends to produce energy surface features that are conducive to efficient photochemical processes. As we will see below, even systems that could react via a photochemically "allowed" concerted pathway, often choose a stepwise mechanism instead. 

The most general definition of click chemistry is a reaction which proceeds at room temperature, often without a solvent or catalyst, to give the reaction product in close to quantitative yields. The yields in the reactions in this book are by no means optimized, but they often approach quantitative. As an industrial chemist I am well aware that yields can be dramatically increased with modest process development efforts. Sometimes, a change of reaction temperature can have a dramatic effect, as demonstrated by Wilson and Fu who obtained a < 2 % yield of -lactones in their [2+2] cycloaddition reaction of ketenes with aldehydes at room temperature, while at —78 °C a 92 % yield of the cycloadduct is obtained... 

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