Homo-Diels-Alder addition

Cycloaddition of benzyne occurs in two cases of homo-Diels-Alder additions (e.g., to norbomadiene) reported in Ref. 1. 

Although some l,2,4-triazoline-3,5-diones can be isolated, these reagents are generally formed in situ as mentioned earlier. TADs undergo several types of addition reactions to alkenes and/or dienes, for example, [2-1-4] Diels-Alder additions, homo Diels-Alder additions, ene reactions, and [2-1-2] additions. The adducts, in many cases, can be further used for a wide variety of chemical transformations. TADs also add to a wide range of organic compounds to give polycyclic urazoles. Very often several possible reactions compete, and under different conditions the composition of such reaction mixtures often differs. It is necessary to say that even the presence of a reactive diene system does not entirely eliminate the possibility of [2-1-2] addition and/or ene reaction as documented in the appropriate sections. 

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... 

Simultaneously examine the HOMO of 1-methylcyclo-pentadiene (the diene) and the LUMO of acrylonitrile (the dienophile). Orient the two on screen such that they are disposed for Diels-Alder addition, i.e. 

Similarly, examine the overlap between the HOMO of 1-methylcyclopentadiene and the LUMO of an acrylonitrile BF3 complex. Does the Lewis acid affect overlap Would you expect BF3 to enhance, retard, or leave unchanged the rate of Diels-Alder addition ... 

HOMO for 1 -methylcyclopentadiene donates electrons in a Diels-Alder addition. 

Ab initio calculations on aza-Diels-Alder reactions of electron-deficient imines with buta-l,3-diene show that these reactions are HOMO (diene)-LUMO(dienophile)-controlled and that electron-deficient imines should be more reactive than alkyl-or aryl-imines. The Diels-Alder reaction of r-butyl 2//-azirine-3-carboxylate (80) proceeds with high diastereoselectivity with electron-rich dienes (81) (Scheme 28). The hetero-Diels-Alder additions of imines with sterically demanding dienes yield perhydroquinolines bearing an angular methyl group. The asymmetric hetero-Diels-Alder reaction between alkenyloxazolines and isocyanates produces diastereometri-cally pure oxazolo[3,2-c]pyrimidines. °... 

The classic Diels-Alder reaction continues to be applied to steroidal dienes and has been used to prepare benzene-fused compounds (277) (from 6-methylene testosterone ), and (278) and (279) [from the furano-steroid (217) ] and adducts between A -dienes and methyl acrylate, hexafluorobut-2-yne, dimethylacetylene dicarboxylate, and methyl propiolate have been obtained. In this last reaction the mono-adduct (280) was accompanied by a diadduct, assigned the structure (281), which arises from homo-conjugate Diels-Alder addition and which appears to be the first example of homo-conjugate addition to a substituted bicyclo[2,2,l]heptadiene. The diadduct was also obtained in good yield by treatment of the mono-adduct with more methyl propiolate. 

The high endo selectivity of aromatic aldehydes is also a result of their capability to participate in secondary orbital interactions. The mixing of the LUMO of benzaldehyde with the HOMO of the diene can form secondary orbital overlap which lowers the energy of the endo transition state. The electron-withdrawing effect of the catalyst [e.g. Eu(fod)3] on the aldehyde further enhances secondary orbital overlap with aromatic aldehydes by an additional reduction of the LUMO energy (Figure 2). Similar arguments have been made to rationalize the increase in endo selectivity of homo Diels-Alder reactions when Lewis acids are used as catalysts.Secondary orbital interactions are, however, absent when the dienophile is an aliphatic aldehyde in such reactions the cis (endo) stereoselectivity is based solely on steric interactions. 

Cyclic azoalkanes continue to be of active interest because they serve as precursors to interesting diradicals and as synthons for the preparation of highly strained ring systems and sterically crowded structures. One of the most important syntheses of the azoalkanes involves the cycloaddition of TADs to a suitable substrate to give urazoles by a method mentioned in preceding parts of this review. These methods include Diels-Alder, homo Diels-Alder, and domino Diels-Alder addition, as well as the ene reaction, 1,2-cycloaddition, or other types of cycloaddition reactions. These adducts are transformed into cyclic azoalkanes by hydrolysis an oxidation. The azoalkanes are very often used for thermal or photochemical decomposition to cyclic compounds. This sequence is outlined in Scheme 79. 

It seems that the homo-Diels-Alder reactions proceed markedly more rapidly than the Diels-Alder reactions since the primary [4-1-2] adducts carmot be detected spectroscopically. Furthermore, it is noteworthy that all 1 -alkynes react regiospecifically in the initial [4-1-2]-cycloaddition process. This addition proceeds in such a way that, independent of the polarity situation of the acetylene, the carbon atom bearing the substituent is positioned in the immediate vicinity of the phosphorus atom of the phosphirane increment. This suggests that steric factors are responsible for the direction of the addition. This is further supported by the observation that 11a does not participate in cycloaddition reactions with any disubstituted triple bond system, except for cyclooctyne, which possesses the necessary reactivity for a cycloaddition on account for the cisoid-dis-... 

In addition to the assembly of various carbocyclic and heterocyclic six-membered ring assembly, nickel-catalyzed [2+2+2] homo-Diels-Alder cycloadditions have been illustrated using norbomadiene derivatives (Scheme 3-30). Electron-deficient dienophiles undergo cycloadditions with norbomadiene using catalysts prepared from Ni(cod)2 and PPI13. Chemical yields and exo-selectivities are both generally high in these processes. 

Use of a monosubstituted acetylenes, such as phenylacetylene, in the homo Diels-Alder reaction results in chiral deltacyclenes, which contain a total of 6 asymmetric carbon atoms. However, as a consequence of the two and only two different addition modes of a monosubstituted acetylene to norbomadiene, the deltacyclene is formed as a pair of enantiomers. 

The addition of thermally generated difluorocarbene to bicyclo[2,2,l]hepta-2,5-dienes has been found to give the homo-Diels-Alder product (103 R = H) in addition to the endo- and exo-tricyclo-octanes (104 R = H) and (105 R = It is thought that the homo-addition product results from concerted cheletropic reaction and, by... 

When both the 1,3-dipoIe and the dipolarophile are unsymmetrical, there are two possible orientations for addition. Both steric and electronic factors play a role in determining the regioselectivity of the addition. The most generally satisfactory interpretation of the regiochemistry of dipolar cycloadditions is based on frontier orbital concepts. As with the Diels-Alder reaction, the most favorable orientation is that which involves complementary interaction between the frontier orbitals of the 1,3-dipole and the dipolarophile. Although most dipolar cycloadditions are of the type in which the LUMO of the dipolarophile interacts with the HOMO of the 1,3-dipole, there are a significant number of systems in which the relationship is reversed. There are also some in which the two possible HOMO-LUMO interactions are of comparable magnitude. 

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