Ethylene as dienophiles

A large number of pyridazines are synthetically available from [44-2] cycloaddition reactions. In one general method, azo or diazo compounds are used as dienophiles, and a second approach is based on the reaction between 1,2,4,5-tetrazines and various unsaturated compounds. The most useful azo dienophile is a dialkyl azodicarboxylate which reacts with appropriate dienes to give reduced pyridazines and cinnolines (Scheme 89). With highly substituted dienes the normal cycloaddition reaction is prevented, and, if the ethylenic group in styrenes is substituted with aryl groups, indoles are formed preferentially. The cycloadduct with 2,3-pentadienal acetal is a tetrahydropyridazine derivative which has been used for the preparation of 2,5-diamino-2,5-dideoxyribose (80LA1307). 

Due to the low reactivity of ethylene and acetylene as dienophiles, forcing conditions, such as high temperature and high pressure, are necessary for [4 + 2]cycloaddition. The hazards associated with handling acetylene under these conditions are well known and... 

While (Z)-l,2-bis(phenylsulfonyl)ethylene (140) does not add to dienes such as furan, cyclopentadiene, cyclo-octatetraene, indene and )S-naphthol, ( )-l,2-bis(phenylsulfonyl)ethylene (141) is more reactive and the reaction with furan proceeds at room temperature for 2 h to give the adduct in 95% yield. The reactivity of dienophiles having sulfonyl group in the [4 -t- 2]cycloaddition is shown in equation 103 °X Due to the low reactivity of ethylene and acetylene as dienophiles, forcing conditions, such as high temperature and high pressure, are necessary for [4 -1- 2]cycloaddition. The hazards associated with handling acetylene under these conditions are well known and... 

Vinyl sulfones are reactive as dienophiles. The sulfonyl group can be removed reductively with sodium amalgam (see Section 5.6.2). In this two-step reaction sequence, the vinyl sulfone functions as an ethylene equivalent. The sulfonyl group also permits alkylation of the adduct, via the carbanion. This three-step sequence permits the vinyl sulfone to serve as the synthetic equivalent of a terminal alkene.68... 

Examples of some compounds which exhibit a high level of reactivity as dienophiles are collected in Table 6.1. Scheme 6.1 presents some typical Diels-Alder reactions. Each of the reactive dienophiles has at least one strongly electron-attracting substituent on the double or triple carbon-carbon bond. Ethylene, acetylene, and their alkyl derivatives are poor dienophiles and react only under extreme conditions. 

Since most of the dienophiles considered are substituted ethylenes, we can take ethylene as a reference to discuss the variations in local reactivity induced by chemical substitution. Ethylene (29) presents a local electrophilicity value tok = 0.37eV at the equivalent carbon atoms Cl and C2. Note that acetylene (32), having equivalent Fukui functions for both electrophilic and nucleophilic attacks, presents a lower electrophilicity pattern as compared with that of ethylene (tok = 0.27 eV at the equivalent carbon centres of structure 29). 

Furan, pyrrole, and thiophene as dienophiles in reaction with acetylene, ethylene, and cyclopentadiene... 

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... 

To confirm this assumption, we have computed activation barriers for acetylene, ethylene and cyclopropene addition to 4,4-dimethyl-[4H]-l,2-diazole. To our delight, the B3LYP/6-31G(d)/AMl computed activation barrier for ethylene addition to 4,4-dimethyl-[4//]-1,2-diazole is almost identical (Table 47) to the value obtained with full B3LYP/6-31+G(d) calculation on [4H]-1,2-diazole as dienophile (Table 44). The activation barrier for the acetylene addition is 22.3 kcal/mol indicating that this reaction should be also experimentally feasible. As indicated... 

Cycloaddition reactions, [3 + 2] or [2 + 2] depending on L, of TpRe(CO)(L) (f/ -furan) complexes have been reported. The electrophilic alkene tetracyano-ethylene (TCNE) and the alkyne dimethylacetylenedicarboxylate (DMAD) were used as dienophiles. For L = PMcs and BuNC, 1,3-dipolar cycloaddition of TCNE to / -furan gives [3 + 2] products via a carbonyl ylide (Scheme 47). Addition of... 

In all cases, the double or triple bond of the dienophile is adjacent to the positively polarized carbon of an electron-withdrawing substituent. As a result, the double-bond carbons in these substances are substantially less electron-rich than the carbons in ethylene, as indicated by the electrostatic potential maps in Figure 14.8. 

Compounds containing a double or triple bond, usually activated by additional unsaturation (carbonyl, cyano, nitro, phenyl, etc.) In the ap position, add to the I 4-positions of a conjugated (buta-1 3-diene) system with the formation of a ax-membered ring. The ethylenic or acetylenic compound is known as the dieTwphile and the second reactant as the diene the product is the adduct. The addition is generally termed the Diels-Alder reaction or the diene synthesis. The product in the case of an ethylenic dienophile is a cyctohexene and in that of an acetylenic dienophile is a cyctohexa-1 4-diene. The active unsaturated portion of the dienophile, or that of the diene, or those in both, may be involved in rings the adduct is then polycyclic. 

The simplest of all Diels-Alder reactions cycloaddition of ethylene to 1 3 butadi ene does not proceed readily It has a high activation energy and a low reaction rate Substituents such as C=0 or C=N however when directly attached to the double bond of the dienophile increase its reactivity and compounds of this type give high yields of Diels-Alder adducts at modest temperatures... 

Let us now examine the Diels-Alder cycloaddition from a molecular orbital perspective Chemical experience such as the observation that the substituents that increase the reac tivity of a dienophile tend to be those that attract electrons suggests that electrons flow from the diene to the dienophile during the reaction Thus the orbitals to be considered are the HOMO of the diene and the LUMO of the dienophile As shown m Figure 10 11 for the case of ethylene and 1 3 butadiene the symmetry properties of the HOMO of the diene and the LUMO of the dienophile permit bond formation between the ends of the diene system and the two carbons of the dienophile double bond because the necessary orbitals overlap m phase with each other Cycloaddition of a diene and an alkene is said to be a symmetry allowed reaction... 

Conjugation as well as geometric and positional isomerization occur when an alkadienoic acid such as linoleic acid is treated with a strong base at an elevated temperature. CycHc fatty acids result from isomerization of linolenic acid ia strong base at about 250°C (58). Conjugated fatty acids undergo the Diels-Alder reaction with many dienophiles including ethylene, propylene, acryUc acid, and maleic anhydride. 

Cycloaddition involves the combination of two molecules in such a way that a new ring is formed. The principles of conservation of orbital symmetry also apply to concerted cycloaddition reactions and to the reverse, concerted fragmentation of one molecule into two or more smaller components (cycloreversion). The most important cycloaddition reaction from the point of view of synthesis is the Diels-Alder reaction. This reaction has been the object of extensive theoretical and mechanistic study, as well as synthetic application. The Diels-Alder reaction is the addition of an alkene to a diene to form a cyclohexene. It is called a [47t + 27c]-cycloaddition reaction because four tc electrons from the diene and the two n electrons from the alkene (which is called the dienophile) are directly involved in the bonding change. For most systems, the reactivity pattern, regioselectivity, and stereoselectivity are consistent with describing the reaction as a concerted process. In particular, the reaction is a stereospecific syn (suprafacial) addition with respect to both the alkene and the diene. This stereospecificity has been demonstrated with many substituted dienes and alkenes and also holds for the simplest possible example of the reaction, that of ethylene with butadiene ... 

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