Tropone cycloadditions

We have described the cycloadditions of a variety of dienes, ranging from cyclo-pentadiene to cyclopentadienones with alkyl and aryl fulvenes80-82. In these cases, only the [4 + 2] cycloadducts across the 2 and 3 positions are observed. Similarly, 1,3-dipoles such as nitrones and nitrile oxides add in this fashion, as well. We discovered the first authentic [6 + 4] cycloaddition of a fulvene in 197083. The cycloadditions of tropone to fulvenes, which we originally suggested involved [6-fulvene + 4-tropone] cycloadditions, now appear to be [6-tropone + 4-fulvene] cycloadditions8... 

Lead tetraacetate has also used to generate 4,5-dehydrotropone 168 from the A -aminotriazole 167 in the presence of several 4-phenyloxazoles (Fig. 3.51). In this case, the 1 1 oxazole-tropone cycloaddition adducts were not observed and only the furo[3,4-ii]tropones 169 were isolated in 20-57% yields. 

The prediction of the Woodward-Hofrmann rules that thermal concerted cycloadditions are allowed for combinations in which 4 -1- 2 7c electrons are involved has stimulated the search for combinations with 10 and larger numbers of participating electrons. An example of a [6 -1- 4] cycloaddition is the reaction of tropone with 2,5-dimethyl-3,4-diphenylcyclopentadienone ... 

Nine-membered ring systems are potentially accessible via a TMM cycloaddition with conjugated trienes in a [6-1-3] fashion. However, tropone is the only reported system that undergoes such a reaction. Interestingly, these cydoadditions are remarkably selective in that only nine-memhered ring products are formed. 

Scheme 2.33 Carboxylative TMM [4-r3] cycloadditions with tropone in the synthetic study of sanadaol (123)...

Trichlorinated tropones [10] have been prepared by a one-pot procedure based on thermal cycloaddition of tetrachlorocyclopropene 9 with electron-rich butadienes (Scheme 2.6) followed by spontaneous ring-expansion/dehydro-chlorination of the resulting cycloadducts. 

Whereas tropones usually act as dienes in cycloaddition reactions (Section 5.4), tricarbonyl (tropone) iron 59 displays a reactivity that is almost identical to that of a normal enone. High pressure cycloadditions of 59 with 1-oxygen substituted dienes 60 gave the desired cycloadducts 61 in good to excellent yields (Equation 5.9). The subsequent decomplexation of the cycloadducts has been accomplished by treatment with CAN [20]. 

The study of high pressure cycloaddition reactions of tropone (125) with maleic anhydride and norbornene allowed the reaction activation volumes to be measured and showed that they are large, negative and solvent-dependent (Scheme 5.17) [43a]. 

Tropone (125) and the 2-substituted tropones showed a different reactivity in the cycloaddition with 2-cyclopentenone (28). Whereas tropone itself (125) and the 2-methoxytropone (126) reacted at lOkbar, giving a mixture of four and three products, respectively (Scheme 5.18), 2-hydroxy- and 2-chloro-tropone failed to react at all [43b]. Compound 127 does not have the expected dihydro-homobarrelenone framework it is probably derived from the cycloaddition of 125 and 1,4-cyclopentadien-l-ol, the enol form of 28. 

Similar results were obtained in the cycloadditions of 2-cyclopentenone 28 with 2-methoxy-4-isopropyl-tropone (128) and 2-methoxy-6-isopropyl-tropone (129) (Equations 5.14 and 5.15). 

Another versatile two-step synthesis of homobarrelenones [45] is based on the high pressure cycloaddition of tropone (125) and its 2-methoxy-, 2-hydroxy- and 2-chloro-derivatives with 2,3-bis(methoxycarbonyl)-7-oxabicyclo[2.2. l]hepta 2,5-diene (133) followed by thermolysis of the cycloadducts at 130 °C with the... 

Cycloaddition of 125 with buckminsterfullerene (Ceo) at 3 kbar allowed the adduct [48] to be obtained, preventing a retro Diels-Alder process (Scheme 5.19). Cycloadditions of tropone (125) with furans 134 gave mixtures of 1 1 endo-dcad exo-monocycloadducts 135 and 136, respectively [49a], together with some bisadducts. In this case furan reacts solely as the 27t component in spite of its diene system. Whereas 2-methoxy furan gave mainly the kinetically controlled product 135 (R= OMe Ri =R2 =H), under the same conditions 3,4-dimethoxy furan afforded the thermodynamically controlled cycloadduct 136 (R=H Ri =R2 =OMe) as the major product (Scheme 5.19). 

Azulene quinones [49b] are compounds related to the family of tropones and are considered to possess great biological and physiological potential. Several polycyclic compounds have been prepared by high pressure (3kbar, PhCl, 130°C, 15h) Diels-Alder reaction of 3-bromo-l,5-azulene quinone (137) and 3-bromo-l,7-azulene quinone (138) with several dienophiles. The cycloadditions were regioselective and afforded cycloadducts in reasonable to good yields (Scheme 5.20). 

Diels-Alder cycloadditions involving norbomene 57 [34], benzonorbomene (83), 7-isopropylidenenorbomadiene and 7-isopropylidenebenzonorbomadiene (84) as dienophiles are characterized as inverse-electron-demand Diels-Alder reactions [161,162], These compounds react with electron-deficient dienes, such as tropone. In the inverse-electron-demand Diels-Alder reaction, orbital interaction between the HOMO of the dienophile and the LUMO of the diene is important. Thus, orbital unsymmetrization of the olefin it orbital of norbomene (57) is assumed to be involved in these top selectivities in the Diels-Alder cycloaddition. 

Several unusual cycloaddition reactions of 9 with unsaturated ketones should be mentioned in conclusion the heterocumulene generated photolytically from 7 undergoes [8 + 2]-cycloaddition with tropone to form 33 (40%) the structure of the product has been unequivocally established by X-ray structure analysis 22,23). Once again, the affinity of phosphorus for oxygen is manifested an entirely analogous cycloaddition reaction is known for diphenylketene 26). 

INVERSE ELECTRON-DEMAND DIELS-ALDER CYCLOADDITION OF A KETENE DITHIOACETAL. COPPER HYDRIDE-PROMOTED REDUCTION OF A CONJUGATED ENONE. 9-DITHIOLANOBICYCLO[3.2.2]NON-6-EN-2-ONE FROM TROPONE... 

In addition to 534, further [4+2]-cycloadducts of 5 were prepared by using 1,3-dienes, some of which are well known as trapping reagents of short-lived cyclic allenes and cycloalkynes. Further, cycloadditions could be achieved with tropone and several 2-substituted tropones, 8,8-dicyanoheptafulvene, 1,3,5-cycloheptatriene and a few of its 7-substituted derivatives. The products of these reactions are represented in Scheme 6.108. 

Due to the high conformational demands which are imposed on higher-order cycloadditions, fulvenes, heptafulvenes and tropones have been mostly applied in uncatalyzed [6 + 4] cycloadditions. The scope of metal-promoted cycloadditions, however, is much broader due to the preorganized orientation of the reactants which are both co-ordinated to the metal center. 

Cycloaddition reactions using tropone or another cyclic triene as the 6ji partner have been abundantly described in the literature. It has been found that virtually all metal-free [6 + 4] cycloadditions of cyclic trienes afford predominantly exo adducts. This has been rationalized by consideration of the HOMO-LUMO interactions between the diene and triene partners. An unfavorable repulsive secondary orbital interaction between the remaining lobes of the diene HOMO and those of the triene LUMO develops during an endo approach. The exo transition state is devoid of this interaction (Figure 9). 

The periselectivity of the tropone-diene cycloaddition is dependent on the reaction temperature. The exo [6 + 4] cycloadduct is considered to be the kinetic product, the endo [4 + 2] cycloadduct being the thermodynamic product291. 

Mahon and colleagues297 studied the cycloaddition reactions of substituted cis-1,2-isopropylidenedioxycyclohexadienes. The reaction of tropone (471) with cyclohexadiene 472, for example, afforded the expected exo cycloadduct 473 with good yield (equation 140). 

Rigby and coworkers305,309 also performed metal mediated [6 + 4] cycloadditions of heterocyclic trienes and tropones with various dienes. In concurrence with the all-carbon trienes, the electronic nature of the diene partners generally had little influence on the cycloaddition efficiency. The only reported exceptions are the reactions of thiepin-1,1-dioxides. Lower yields were observed in the reactions involving electron-deficient dienes in comparison with the reactions with electron-rich dienes. The reaction of complex 514... 

Tropone itself gives with diazomethane a 3 1 mixture of 1- and 2-methylcycloheptapyrazol-4-ones (143a,b), along with cyclooctatrienone and 2,3-homotropone (72TL1925). Here the regiochemistry of cycloaddition is the reverse of that of diazomethane with simple a,/3-unsaturated carbonyl compounds (80MI1, p.282). The different behavior of tropone and, e.g.. 

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