Homo-Diels-Alder reaction product

As mentioned in the previous section, substituted norbornadienes can proceed [2+2] cycloaddition with highly reactive dienophiles (maleic imide or strained alkene) in the presence of a nickel (0) catalyst leading to the formation of cyclobutane derivatives. With less reactive dienophiles, the reaction seems to be prone to [2+ 2+ 2] cycloaddition giving homo-Diels-Alder reaction products. These two types of reactions appear to be competitive in certain cases to give a mixture of products [130-133]. 

An unusual nickel-catalyzed [2+2+2] homo-Diels-Alder reaction of norbomadiene (140) with (S)-(-)-p-tolyl vinyl sulfoxide (141), which yielded deltacyclane (142), has been reported (Scheme 38).85 A high degree of stereoselectivity was observed, with mainly the exo-product being formed. 

The Homo Diels-Alder Reaction of Norbomadiene with Acetylenes. [2 + 2+2] Cycloadditions of dienes such as norbomadiene with the double bonds in 1,4-position are called homo Diels-Alder reactions. Using an in situ catalyst (consisting of Co(acac)3-Et2AlCl-bis(diphenylphosphino)ethane) the products obtained with monosubstituted acetylenes, such as phenyl, i-propyl-, n-butyl-, t-butyl-, and trimethylsilylacetylene, are 4-substituted deltacyclenes. - In the formation of the polycyclic deltacyclene skeleton, six new stereo centers are generated in one step. Thus enantiocontrol by using optically active phosphine ligands as cocatalysts allows the synthesis of optically active cycloadducts, as shown for the reaction of norbomadiene with phenylacetylene to give 4-phenyldeltacyclene (eq 1). 

An investigation of the homo-Diels-Alder reaction between norbornadiene and different dienophiles showed general endo selectivity in the products 1 for R = H however, when... 

The main product in the reaction of norbornadiene with buta-1,3-diene resulted from a 1,4-cycloaddition onto the conjugated diene (for extended homo-Diels-Alder reactions, vide infra). On the other hand, the 1,2-homo-Diels-Alder adduct 4 was obtained when bisfcycloocta-tetraenejiron [or iron(III) chloride/isopropylmagnesium chloride] was used as the catalyst. ... 

Yield improvements and changes in selectivity were observed by using nickel, cobalt or manganese catalysts in this cycloaddition. Noteworthy is the formation of a new isomer, 8-ethylidenetetracyclo[4.3.0.0 . 0 ]nonane, shown to be the primary product (8%) of the homo-Diels-Alder reaction when a nickel catalyst was used." ... 

The use of nickel catalysts allows the homo-Diels-Alder reaction to occur between norbornadiene and a-unsaturated ketones and sulfoxides to give the products 8 often with excellent yield and stereoselectivity. Whereas the exo preference, usual in the catalytic homo-Diels-Alder reactions, is here evident for the open-chain dienophiles, the endo selectivity observed with cyclopentenone could be due to its s-trans conformation." ... 

The use of transition metal complexes as catalysts allows 1,4-cycloadditions to be involved as the major pathway in several cases when conjugated dienes are reacted with norbornadiene. No normal homo-Diels-Alder reaction was observed by reaction of the latter with buta-1,3-diene in the presence of an iron complex catalyst, the main product obtained was such a 1,4-adduct 2f the same adduct 2 was obtained in good yield and selectivity when a catalyst formed from cobalt(II) chloride, diethylaluminum chloride and bis(l,2-diphenylphos-phinojethane was used. ... 

Albeit not as popular as the homo-Diels-Alder reaction, the hetero [4+2] cycloaddition, possessing all of the features of the homo version, offers a significant potential for the synthesis of the six-membered hetero rings constituents of several natural products e.g., carbohydrates and alkaloids. 

Cobalt(II) iodide-triphenylphosphine-zinc systems catalyse the homo-Diels-Alder reaction of norbornadiene with alkynes R C=CR (R = Bu, Ph or SiMe3 R = H, Me or Et) to give the tetracyclic adducts 512. Asymmetric induction has been reported for the cobalt acetylacetonate-catalysed homo-Diels-Alder addition of 1 -hexyne to norbornadiene in the presence of the diphosphine (R)-(+)-Ph2PCH2CHMePPh2 to yield the dextrorotatory product 513 in 78% enantiomeric excess. Six new stereocentres are created in this... 

Homo-Diels-Alder reactions have also been achieved with, in some cases, very high selectivity. In 1990, two groups independently reported achieving the homo-Diels-Alder reaction between norbornadiene (8.88) and phenylacetylene (8.89), affording the deltacyclene product (8.90). ° When the phosphine used in this reaction was Norphos, the product was formed with remarkable selectivity. 

CH-acidic component (R ==CO Et), none of the desired products could be isolated, even within extended reaction times of up to 240 min instead, only the Knoevenagel condensation product with the aldehyde and the shown by-product 326 were formed. The latter one arises from a dimerization of compound 323 in a homo-Diels-Alder reaction. 

Woodward and Hoffmann pointed out that the Diels-Alder reaction involved bonding overlap of the highest-occupied molecular orbital (HOMO) on the diene and the lowest-unoccupied molecular orbital (LUMO) on the dienophile. Display the HOMO for 2-methoxybutadiene. Where is it localized Display the LUMO for acrylonitrile. Where is it localized Orient the two fragments such that the HOMO and LUMO best overlap (A clearer picture is provided by examining-the HOMO map for 2-methoxybutadiene and the LUMO map for acrylonitrile.) Which product should result ... 

In the Diels-Alder reaction a double bond adds 1,4 to a conjugated diene (a 2 + 4 cycloaddition), so the product is always a six-membered ring. The double-bond compound is called a dienophile. The reaction is easy and rapid and of very broad scope and reactivity of dienes and dienophiles can be predicted based on analysis of the HOMOs and LUMOs of these species. Ethylene and simple alkenes make poor dienophiles, although the reaction has been carried out with these compounds. 

Despite the fact that the exo adduct is likely to be the more stable of the two thermodynamically, it is often (though not universally) found in Diels-Alder reactions that the endo adduct is the major, if not the sole, product. To explain this, it has been suggested that in endo addition stabilisation of the T.S. can occur (and the rate of reaction thereby speeds up) through secondary interaction of those lobes of the HOMO in, e.g. (32) and of the LUMO in (33) that are not themselves involved directly in bond-formation, provided these are of the same phase. Such interaction would not, of course, be possible in the T.S. for exo addition because the relevant sets of centres in (32) and (33) will now be too far apart from each other the endo adduct is thus the kinetically controlled product. It is significant in this connection that the relative proportion of exo... 

In the [4 + 2] cycloadditions discussed so far, the enol ether double bond of alkoxyallenes is exclusively attacked by the heterodienes, resulting in products bearing the alkoxy group at C-6of the heterocycles. This regioselective behavior is expected for [4+2] cycloadditions with inverse electron demand considering the HOMO coefficients of methoxyallene 145 [100]. In contrast, all known intramolecular Diels-Alder reactions of allenyl ether intermediates occur at the terminal C=C bond [101], most probably because of geometric restrictions. 

The Diels-Alder reaction is the reaction of a diene with a mono-ene to form a cyclohexene derivative, an important reaction for the construction of organic intermediates. One of its attractions is the atom efficiency of 100%, no by-products being formed. The mono-ene, or dienophile which may also be an alkync, has a LUMO of low energy while the diene is usually electron rich with a high lying HOMO. The interaction of these two orbitals starts the reaction between the two molecules (Figure 2.33) [26],... 

The explanation of the regiospecificity of Diels-Alder reactions requires knowledge of the effect of substituents on the coefficients of the HOMO and LUMO orbitals. In the case of normal electron demand, the important orbitals are the HOMO on the diene and the LUMO on the dienophile. It has been shown that the reaction occurs in a way which bonds together the terminal atoms with the coefficients of greatest magnitude and those with the coefficients of smaller magnitude [18]. The additions are almost exclusively cis and with only a few exceptions, the relative configurations of substituents in the components is kept in the products [19]. 

The essential features of the Diels-Alder reaction are a four-electron n system and a two-electron it system which interact by a HOMO-LUMO interaction. The Diels-Alder reaction uses a conjugated diene as the four-electron n system and a it bond between two elements as the two-electron component. However, other four-electron it systems could potentially interact widi olefins in a similar fashion to give cycloaddition products. For example, an allyl anion is a four-electron it system whose orbital diagram is shown below. The symmetry of the allyl anion nonbonding HOMO matches that of the olefin LUMO (as does the olefin HOMO and the allyl anion LUMO) thus effective overlap is possible and cycloaddition is allowed. The HOMO-LUMO energy gap determines the rate of reaction, which happens to be relatively slow in this case. 

Cycloaddition reactions are those in which two unsaturated molecules add together to yield a cyclic product. For e.xample, Diels-Alder reaction between a diene (four tt electrons) and a dienophile (two tt electrons) yields a cyclohexene. Cycloadditions can take place either by suprafacial or antarafacial pathways. Suprafacial cycloaddition involves interaction between lobes on the same face ol one component and on the same face of the second component. Antarafacial cy cloaddition involves interaction between lobes on the same face of one component and on opposite laces of the other component. The reaction course in a specific case can be found by looking at the symmetry of the HOMO of one component and the lowest unoccupied molecular orbital (LUMO) of the other component. 

The complementary substitution of the heterodiene with one or more strongly electron-donating substituents raises the heterodiene homo and in selected instances has proven sufficient to promote its 4or participation in HOMOdtene-controlled Diels-Alder reactions. The combined use of a nucleophilic heterodiene and reactive, electrophilic alkenes, e.g. ketenes, permits the observation of Diels-Alder products often formed in competition with [2 + 2] cycloaddition products and represents examples of stepwise [4 + 2] cycloaddition reactions proceeding with zwitterionic intermediate generation. 

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