Dienes donor substituents

Both the reactivity data in Tables 11.3 and 11.4 and the regiochemical relationships in Scheme 11.3 ean be understood on the basis of frontier orbital theory. In reactions of types A and B illustrated in Seheme 11.3, the frontier orbitals will be the diene HOMO and the dienophile LUMO. This is illustrated in Fig. 11.12. This will be the strongest interaction because the donor substituent on the diene will raise the diene orbitals in energy whereas the acceptor substituent will lower the dienophile orbitals. The strongest interaction will be between j/2 and jc. In reactions of types C and D, the pairing of diene LUMO and dienophile HOMO will be expected to be the strongest interaction because of the substituent effects, as illustrated in Fig. 11.12. 

With certain donor substituents at C-3 the experimental findings may be rationalized rather by a diradical mechanism, where formation of the new carbon-carbon single bond leads to a diradical species 6, which further reacts by bond cleavage to give the diene 2 ... 

Danishefsky s diene).46 The two donor substituents provide strong regiochemical control. The D-A adducts are trimethylsilyl enol ethers that can be readily hydrolyzed to ketones. The (3-methoxy group is often eliminated during hydrolysis, resulting in formation of cyclohexenones. 

Diethoxyphosphoryloxy)-1,3-butadiene and 2-(diethoxyphosphoryloxy)-1,3-pentadiene are good dienes and are compatible with Lewis acid catalysts.50 They exhibit the regioselectivity expected for a donor substituent and show a preference for endo addition with enones. 

Entry 7 features a quinone dienophile. The reaction exhibits the expected selectivity for the more electrophilic quinone double bond (see p. 506). The reaction is also regioselective with respect to the diene, with the methyl group acting as a donor substituent. The enantioselectivity is 80%. 

Because of the strong rr-deficiency of most six-membered heteroaromatic compounds, cycloadditions of this type belong to Diels-Alder reactions with inverse electron demands in other words, they are LUMO -HOMOp, controlled reactions (for review see (B-87MI 502-08)). Acceptor substituents in the heterocyclic diene and donor substituents in the dienophile accelerate the reaction, as shown by kinetic data (83TL1481,84TL2541,90TL6851). 

A donor substituent may be represented by a doubly occupied orbital D, at (a + 2/3) for O and at (a + 1.5/ ) for N. Hence D always lies lower than the HOMOs of the diene and the dienophile. Scheme c illustrates the tricky case involving a first-order D-rc interaction and a second-order D- 2 term. One may wonder if the HOMO of the substituted dienophile cannot be higher than that of the diene. In fact, we just need to take a double bond for D to see that the HOMO of hexatriene lies higher than the butadiene HOMO when n is raised to the level of 2, the latter rises further, so that the diene always has the higher energy. 

Ghosez and co-workers used standard electron-poor dienophiles (quinone, acrylonitrile, methyl acrylate, maleic anhydride) for their experiments, hence the choice of donor substituents to increase the electron density of the azadiene (Alder s rule). However, the intrinsically electron-deficient diene can only be made sufficiently nucleophilic by the presence of exceptionally good donors. The oxygen lone pair is relatively low-lying (a+ 2/3), so it does not confer sufficient reactivity for the oxime to react. AMI calculations validate this qualitative reasoning the oxime B HOMO lies at -9.47 eV versus -8.56 eV for A s HOMO. 

The highest HOMO coefficient in a diene will be localized on position 4 if a donor substituent is present at Cv but on position 1 if the donor appears at C2. 

An increase in reactivity also can be observed in Diels-Alder reactions with normal electron demand if a given dienophile is reacted with a series of more and more electron-rich dienes. The reaction rates of the Diels-Alder reactions of Figure 15.22 show that the substituents MeO > Ph > alkyl are such reactivity-enhancing donors. The tabulated rate constants also show that a given donor substituent accelerates the Diels-Alder reaction more if located in position 1 of the diene than if located in position 2. 

Fig. 15.22. Diels-Alder reactions with normal electron demand reactivity increase by the use of donor-substituted 1,3-dienes (Do refers to a donor substituent).

Diels-Alder reactions of the type shown in Table 12.1, that is, Diels-Alder reactions between electron-poor dienophiles and electron-rich dienes, are referred to as Diels-Alder reactions with normal electron demand. The overwhelming majority of known Diels-Alder reactions exhibit such a normal electron demand. Typical dienophiles include acrolein, methyl vinyl ketone, acrylic acid esters, acrylonitrile, fumaric acid esters (fnms-butenedioic acid esters), maleic anhydride, and tetra-cyanoethene—all of which are acceptor-substituted alkenes. Typical dienes are cy-clopentadiene and acyclic 1,3-butadienes with alkyl-, aryl-, alkoxy-, and/or trimethyl-silyloxy substituents—all of which are dienes with a donor substituent. 

Diels-Alder reactions also may occur when the electronic situation of the substrates is completely reversed, that is, when electron-rich dienophiles react with electron-poor dienes. [4+2]-Cycloadditions of this type are called Diels-Alder reactions with inverse electron demand. 1,3-Dienes that contain heteroatoms such as O and N in the diene backbone are the dienes of choice for this kind of cycloaddition. The data in Figure 12.22 show the rate-enhancing effect of the presence of donor substituents in the dienophile. 

LUMO. These two effects reinforce and favour dienophile attack from the face anti to the better electron donor substituent, in this case the C-Me. In summary, the most electron-donating rr-bond (i.e., that which possesses the higher cr-orbital energy and/or the cr -orbital nearest in energy to the diene orbital) will block attack from that face, because as the reaction occurs the cyclopentadiene develops an envelope conformation and the electron-donating group (i.e. C-Me in the case discussed) is pseudo-axial. The HOMO/LUMO energy difference is less than for attack from the other face anti to C-X. 

The regiochemistry of the Diels-Alder reaction is also sensitive to the nature of substituents on the diene and dienophile. The combination of an electron donor in the diene and an electron acceptor in the dienophile gives rise to caseA 4 atid B. The preferred orientations are shown in Scheme 11.3. There are also examples where the substituents are reversed so that the electron donor substituent is on the diefiopTiHe and the elecTfon-accepting su is on the diene. These are called... 

Pd(ll)-catalyzed Cope rearrangement most probably proceeds through a Pd-bound six-membered carbenium ion intermediate to afford the [3,3] rearranged products. A donor substituent is required at either C-2 or C-5 of 1,5-dienes for the rearrangement in order to stabilize the carbenium cation. 

The Diels-Alder reactions we have considered thus far are typical and are described as having normal electron demand. Acceptor substituents on the dienophile accelerate the reaction, as do donor substituents on the diene. The primary interaction is diene HOMO and dienophile LUMO. However, in cases where there is a donor group on the dienophile and an acceptor on the diene, the result is an inverse electron demand Diels-Alder reaction. Now the key interaction is dienophile HOMO and diene LUMO. These reactions are less common, but are sometimes useful. 

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