Cycloaddition reactions feasibility

Since 1,3-dipolar cycloadditions of diazomethane are HOMO (diazomethane)-LUMO (dipolarophile) controlled, enamines and ynamines with their high LUMO energies do not react (79JA3647). However, introduction of carbonyl functions into diazomethane makes the reaction feasible in these cases. Thus methyl diazoacetate and 1-diethylaminopropyne furnished the aminopyrazole (620) in high yield. 

The photochemical dimerization of unsaturated hydrocarbons such as olefins and aromatics, cycloaddition reactions including the addition of 02 ( A ) to form endoperoxides and photochemical Diels-Alders reaction can be rationalized by the Woodward-Hoffman Rule. The rule is based on the principle that the symmetry of the reactants must be conserved in the products. From the analysis of the orbital and state symmetries of the initial and final state, a state correlation diagram can be set up which immediately helps to make predictions regarding the feasibility of the reaction. If a reaction is not allowed by the rule for the conservation of symmetry, it may not occur even if thermodynamically allowed. 

In another attempt, we reached the tetracyclic structure 42 via two consecutive [4 + 2] cycloaddition reactions. Reaction of 3-cyano-4-benzopyrone 31 with Danishefsky s diene 38 in toluene at 300 °C for 96 h provided the desired cycloadduct 39 in 80% yield with an endo exo ratio of 1 2 [Scheme 8]. Hydrolysis of the silyl enol ether in 39 using TMSBr in CH3CN at room temperature proved to be feasible but slow, and afforded the enone 40 in 90% yield. Reaction of diene 41 with enone 40 in the presence of 2.5 equiv of BF3-Et20 yielded tetracycle 42 in 25% yield with an endo exo ratio of 1 1 after 120 h at room temperature.49... 

Utilization of a,(3-unsaturated amides derived from the chiral amine, namely, camphor sultam, has been made by several groups to test the feasibility of [l,3]dipolar cycloaddition reactions with these chiral systems. This methodology has been applied to the synthesis of (35,4/ )ethyl-l-azabicyclo[2.2.1]heptane-3-carboxylate (see above for non-specific syntheses).433... 

It has become clear from the Woodward-Hoffmann-rules how orbital symmetry controles in an easily discernible manner the feasibility and stereochemical consequences of every concerted reaction 239>. For cycloaddition reactions of a m-ji-electron system to a M-jr-electron molecule the following stereochemical selection rules have been established (q = 0,1,2,...) ... 

Although the [2 + 2] photocycloaddition is preferably prevented in the synthesis of PAHs, it has been proven to be a very feasible approach in the selective synthesis of syn-[2.2]cyclophanes [86,87]. Topological reaction control in solution has been achieved for a multistep intramolecular [2 + 2] cycloaddition reaction in the photochemical formation of [n]-ladderanes from pseudo-gem-bis(polyene) substituted [2.2]paracyclophanes [88]. The probably most well-known example of an intramolecular photocycloaddition process is one of the... 

Reaction of pyridine JV-imines with 2H-azirines gives pyrido[l,2-h]triazine derivatives 38.162,163 Substituted pyridine, quinoline, and isoquinoline JV-imines react in an analogous manner. Although, in principle, two modes of cycloaddition are feasible with 3-substituted pyridine JV-imines, the reaction of the 3-methyl derivative involves cycloaddition at the more hindered site. 

In a few cases [2 + 2] cycloadditions are feasible, particularly with ketenes, and these reactions are dealt with in Section 10.4. 

To determine the reliability of these computational approaches, we have computed activation barriers for these reactions at both AMI ab initio and B3LYP/6-31G(d) DFT theory levels (Table 30). Knowing that activation barriers for the addition of cyclopropene to furan computed at the B3LYP/6-31G(d)/AMl theory level were 18.7 and 18.4 kcal/mol for an endo and exo cycloaddition reaction (Table 8) and it is experimentally feasible, it becomes obvious that none of the cycloaddition reactions presented in Table 25 should be able to be accomplished experimentally. All activation barriers were around 40 kcal/mol or higher, with the exception of the cyclopropane addition to 1,2-oxazole (Table 31). The comparison... 

The bond order uniformity for the transition state with those heterocycles is not an adequate approach for evaluation of their reactivity because their transition state structures are highly asynchronous. Therefore, we have evaluated their reactivity by estimating the activation barriers for the cycloaddition reactions with acetylene, ethylene, and cyclopropene as dienophiles (Table 39). All computed activation barriers were very high and are not expected to be experimentally feasible. That is fully supported by the fact that, at this moment, there is no experimental evidence that five-membered heterocycles with... 

Q ,/i-Unsaturated complexes undergo a number of facile cycloaddition reactions to produce more elaborate complexes. For example, cycloadditions using diazoalkanes, nitrileimines, alkylnitrones, azomethine ylids (see Ylide), and imines are feasible. For example, reaction of the chiral carbene (9) with trimethylsilyldia-zometathane gave the heterocyclic-substituted carbene (10) (Scheme 15). ... 

The cycloaddition reaction of dipoles has been known since the 18th century, later, Huisgen introduced the concept of a 1,3-dipole [30]. One of the earhest examples of copper(II) acetylacetonate [Cu(acac)2] catalyzed 1,3-dipole formation involved the controlled decomposition of an a-diazo ketone [31]. Some cases utilized copper as the metal species and demonstrated the feasibility of cycloaddition reactions and these 1,3-dipoles with dipolarophiles. These reactions set the stage for the evaluation of additional transition metals capable of catalyzing this transformation. The earliest example of rhodium(II)-catalyzed a-diazo ketone decomposition to form a 1,3-dipole was described by Teyssie and co-workers [32]. Despite this promising beginning, it was not until many years later that rhodium(II) was used generally for the formation of such 1,3-dipoles [6-12,21,29,30] (Fig. 1). 

The feasibility of cycloaddition reactions can be easily predicted on the basis of three methods, namely, orbital symmetry correlation-diagram method. 

According to this method, the feasibility of a cycloaddition reaction depends upon the symmetry properties of the highest occupied molecular orbital (HOMO) of one reactant and the lowest unoccupied molecular orbital (LUMO) of the other. A favorable bonding interaction is possible only when the phases of the lobes of the interacting orbitals in the HOMO and LUMO are the same. 

Later, Narasaka and coworkers reported that the scope of this transformation could be substantially improved with the use of Mn(III) catalysis [313]. These new reaction conditions allowed highly efficient employment of differently substituted simple non-activated alkyl-, aryl-, hetaryl- and even cydic vinyl azides 328 (Scheme 8.117). In addition, previously unreactive 1,3-diketones 33S could serve as feasible 1,3-dicarbonyl components in this formal [3 + 2] cycloaddition reaction, affording 2,3,5-tri-and 2,3,4,5-tetra-substituted pyrroles 336 in moderate to excellent yields... 

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