2,4-Hexadienes, cycloaddition

The vinylogous 3,5-hexadien-2-one (16) adds in a 1,4 cycloaddition with zl -dehydroquinolizidine (17) to form compound 18 (26). A similar 1,4-cycloaddition reaction takes place between pyrylium salts and the pyrrolidine or morpholine enamines of cycloalkanones (26a). 

The first studies on cation-radical Diels-Alder reactions were undertaken by Bauld in 1981 who showed [33a] the powerful catalytic effect of aminium cation radical salts on certain Diels-Alder cycloadditions. For example, the reaction of 1,3-cyclohexadiene with trans, iraw5-2,4-hexadiene in the presence of Ar3N is complete in 1 h and gives only the endo adduct (Equation 1.14) [33]. 

A one-pot procedure [9] based on the cycloaddition of 4-aryl-2-silyloxybuta-dienes 7 and bisdiene 8 with alkynes, followed by oxidative aromatization of the cycloadducts, opened a route to polycyclic phenols without isolating the cyclo-hexadiene derivative intermediates (Scheme 2.5). 

A strong acceptor TCNE undergoes [2+2] rather than [4+2] cycloaddition reactions even with dienes. 1,1-Diphenylbutadiene [20] and 2,5-dimethyl-2,4-hexadiene (Scheme 5) [21] afford mainly and exclusively vinyl cyclobutane derivatives, respectively. In the reactions of 2,5-dimethyl-2,4-hexadiene (1) the observed rate constant, is greater for chloroform solvent than for a more polar solvent, acetonitrile (2) the trapping of a zwitterion intermediate by either methanol or p-toluenethiol was unsuccessful (3) radical initiators such as benzyl peroxide, or radical inhibitors like hydroquinone, have no effect on the rate (4) the entropies of activation are of... 

As shown in Table VII, [2 + 4] cycloaddition is the most common reaction pathway followed by Me2Si=C(SiMe3)2, but it is usually accompanied by significant quantities of the product of an ene reaction. As the diene becomes more sterically hindered in its s-cis conformation, as in cis/trans-2,4-hexadiene, the product of an ene reaction predominates. With butadiene, where minimal steric effects are to be expected, the exclusive product of the reaction was found to be the [2 + 4] cycloaddition... 

Cyclopentadiene (6) reacted with 105 at 0°C to give 108 (entry 1). At 100°C, butadiene (12) afforded 109 (entry 2). No [2 + 2] cycloadduct was formed in either reaction. Perfluoromethylenecyclopropane (105) failed to react with cis,cis- or cis,trans-2,4-hexadiene at 100 °C, although 110 was readily formed from trans,frans-2,4-hexadiene (106) under these conditions [29] (entry 3). Anthracene (107) added to 105 at 100 °C. The dienophilicity of 105 is exceptional when compared with the reactivity of simple fluoroolefins, such as perfluoro-isobutylene, which require 150 and 200 °C to undergo cycloaddition to cyclopentadiene [30] and anthracene, respectively. 

The reaction kinetics between a maleimide derivative and a 3,5-hexadiene derivative varies depending on the maleimide compound being reacted. Cycloaddition yields of greater than 80 percent and often as much as 90-95 percent can be expected within 1-18 hours at room temperature or slightly elevated reaction conditions (e.g., 30°C). 

The conjugation of oligonucleotides with peptides also can be done using Diels-Alder cycloadditions in water (Tona and Haner, 2005). Marchan et al. (2006) used the same 3,5-hexadiene phosphoramidite derivative as Hill et al. (2001), but in this case used a maleimide-modified... 

Wilker and Erker92 have studied the stereochemistry of the [4+2] cycloaddition of diarylthioketones and corresponding diaryselenoketones with Irons, trans- and cis,trara,s-2,4-hexadiene, (see later Scheme 30), and found an analogous behaviour between S and Se. 

Six-membered rings. Selenoketones react as dienophiles with conjugated die-nes24,89,223 233 234 in Diels-Alder [4+2] cycloadditions to form 3,6-dihydro-2H-selenapyrans. Reaction of arylselenoketones92with /ra ,v,/ra .v-2,4-hexadiene proceeds in a completely stereospecific way to yield the corresponding cis-selenapyran, while with cw,tra i-2,4-hexadiene it proceeds stereoselectively, forming cis-selenapyran with small amounts of the /nmv-selenapyran isomers, Scheme 30. 

If the reaction is carried out at a pressure of 12 kbar, the mechanism changes, and cycloaddition with ci5,traro-2,4-hexadiene proceeds stereo specifically yielding the traws-selenapyrans as the major products along with the corresponding tetraarylethylenes. 

Some reactions via intermediate alkylideneallyl cations have been reported. Solvolysis of 3-bromo-2,5-dimethyl-2,4-hexadiene in ethanol at 100 °C for 80 min gives 5-ethoxy-2,5-dimethyl-2,3-hexadiene in quantitative yield (Scheme 2) (5). This indicates that ethanol selectively attacks the sp2 carbon of the intermediate alkylideneallyl cation. A similar selectivity has been observed in the solvolysis of 2,3-dienyl alcohols (6), and is in agreement with the charge distribution. A cycloaddition reaction via an alkylideneallyl cation intermediate has been reported as illustrated in Scheme 3(7). 

Scheme 6.21 Steric course of the [4 + 2]-cycloaddition of 1,2-cyclo-hexadiene (6) to (Z,Z)-1,4-dideutero-l, 3-butadiene.

The reaction of thioacetyl cations with 2,5-dimethyl-l,5-hexadiene under low-pressure conditions in an FT-ICR mass spectrometer leads to elimination of propene. At variance from the [4 + 2+] polar cycloadditions observed under high-pressure conditions in the QqQqQ instrument, Caserio and coworkers220 invoked electrophilic attack of the CE CS"1"... 

Depending on the trapping reagents, various reactions have been observed an ene reaction between propene, isobutene, and 2231 or 27,34 a [2 + 4] cycloaddition between butadiene and 12,21 22,31 and 27,34 or both an ene reaction and a [2 + 4] cycloaddition between 2,3-dimethylbutadiene and 2231 or 27,34 and between piperylene or hexadiene and 22.31 Some of these reactions are summarized in Scheme 8. By contrast, 27 does not react with the C = C double bond of an alkene such as CH2 = CH-OMe.34... 

This section is devoted to cyclizations and cycloadditions of ion-radicals. It is common knowledge that cyclization is an intramolecular reaction in which one new bond is generated. Cycloaddition consists of the generation of two new bonds and can proceed either intra- or intermolecularly. For instance, the transformation of 1,5-hexadiene cation-radical into 1,4-cyclohexadienyl cation-radical (Guo et al. 1988) is a cyclization reaction, whereas Diels-Alder reaction is a cycloaddition reaction. In line with the consideration within this book, ring closure reactions are divided according to their cation- or anion-radical mechanisms. 

Backvall and Plobeck reported a formal synthesis of ellipticine (228) starting from indole (707). The [4+2] cycloaddition of 1-indolylmagnesium iodide (1208) with 3-(phenylsulfonyl)-2,4-hexadiene (1209) afforded the tetrahydrocarbazole... 

In a thorough study on photooxidation of 2,5-dimethyl-2,4-hexadiene (455) it was found that 1,2-dioxene 456, 1,2-dioxetane 457, hydroperoxy dienes 458 and 459 and, when methanol was used as solvent, also hydroperoxy(methoxy)octene 460 are formed (Scheme 124) . Product distribution was found to be highly solvent dependent. These results led investigators to postulate a mechanism involving the intermediacy of perepoxide 461 and zwitterion 462 (Scheme 124). Accordingly, the product of [4-1-21-cycloaddition 456, the product of [2 + 2]-cycloaddition 457, as well as the products 458 and 459 deriving from ene-addition would originate from polar intermediates 461 and... 

Silylene addition to dienes was first reported in 1968 (Scheme 17) (68JA3438). The l-silacyclopent-3-ene produced is again thought to result from a silirane intermediate, as a concerted 1,4-cycloaddition can be ruled out. Thermally generated silylene SiH2 does not add stereospecifically to trans,trans- and cis,trans-2,4-hexadiene but gives a mixture of the two silacyclopentenes (6 1 and 2 1 ratio) in each case (Scheme 18) (74JA6198). 

Pyridine 20 has been prepared by the silver- or acid-catalyzed isomerization of 1-aza-bicyclo[2.2.0]hexadiene 22, which in turn was obtained in a [2 + 2]-cycloaddition reaction of tris(to7-butyl)azete with hexafluorobut-2-yne. Irradiation of Dewar pyridine 22 gives a high yield of azaprismane 23, which isomerizes thermally to rearranged pyridine 24. Finally, pyridine 24 yields 1-aza Dewar pyridine 25 photolytically.34... 

Diels-Alder reactions. Although 2,4-hexadiene shows only slight regioselec-tivity in Diels-Alder reactions, the 1-acetoxy derivative (1) undergoes regioselective cycloaddition with a variety of dienophiles.1... 

Figure 21-17 Schematic representation of the energy of the stepwise addition of CH2=CF2 to fra/7s,frans-2,4-hexadiene. The lower diagram is a schematic cross section" that shows everything in two dimensions. If 48 and 49 dissociate to CF2=CF2 and diene, 48 will return the trans.trans isomer, but 49 will go to the cis,trans diene through the transition state represented by the dashed line. In some [2 + 2] cycloadditions of this type, trans.trans to cis.cis isomerizations are observed in competition with cycloaddition, as expected for breaking apart the intermediate corresponding to 49.

Photochemical cycloaddition reactions of t-1 and several of its analogues with conjugated dienes have been reported. The reaction of 1-t with 2,5-dimethyl-2,4-hexadiene yields the isomeric [2+2] cycloadducts 49 and 50 in a 1.2 1 ratio with a... 

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