Tropone as diene

SCHEME 11. Diels-Alder reactions of tropones as dienes... 

During our recent study on utilizing tropone as diene for platencin synthesis [52], many other types of Lewis acid catalysts including the above mentioned oxazaborolidine catalysts all failed to promote the desired inverse-electron-demand Diels-Alder reaction. Fortunately, the dinucleus BINOL-aluminum catalysts were found to give very nice yields and enantioselectivities (Fig. 11) [53]. Activation mode in this reaction can be either intramolecular LLA assembly or double aluminum coordination to carbonyl substrate. Future research efforts are directed toward more applications with this type of catalyst, and more detailed understanding of the nature of this type of catalysts. 

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]. 

All Diels-Alder reactions of tropones 51 as dienes with different types of dienophiles shown in Scheme 11 are accelerated by pressure, so that in some cases the desired cycloadducts are only formed at high pressure. An interesting synthetic equivalent of the unreactive acetylene in Diels-Alder syntheses is the oxanorbomadiene derivative 52 (Scheme 11 entry 2). 52 reacts with tropones forming the adducts 53, 54 and 55, which undergo a retro-Diels-Alder reaction leading to 56 and 57, the formal [4+2] cycloadducts of tropones to acetylene. 

The periselectivity of the reaction of a given diene with tropone is critically dependent on temperature. The variable course of the cycloaddition of ( )-l-trimethylsilyloxybutadiene with tropone as a function of reaction temperature is a Carnatic illustration of this phenomenon. At 80 C the major adduct is bicy-clo[4.4.1]undecenone (10), whereas in refluxing xylene the [4 + 2] cycloadduct (11) prevails as a mixture of regioisomers. A further example of the dichotomy between [6 + 4] and [4 + 2] reaction pathways can be seen with (Z)-l-acetoxybutadiene, which provides some [6 + 4] cycloadduct along with larger quantities of various [4 -i- 2] pr ucts as depicted in equation (1). In contrast to these results, dienes such as ethyl 2,4-hexadienoate and furan do not yield any [6 + 4] or [4 2] products when heated with tropone. The latter result, in particular, may be reflective of the reversibility of the furan cycloadducts. Various furan derivatives do provide modest yields of mixtures of endo and exo [4 + 2] cycloadducts with tropone when reacted together at 3 kbar and 130 C. ... 

It is interesting that iron carbonyl can be used as a protecting group for dienes. Iron diene complex 491, for example, reacted with 492 in a Mukaiyama aldol reaction (sec. 9.4,C), giving an 81% yield of 493 and 494 in an 84 16 ratio.32 in a synthesis of heptitol derivatives,322 Pearson protected tropone as the iron tricarbonyl derivative (495), and prepared 496 using a multistep sequence before deprotecting the diene to give 497. 

An ingenious approach to the synthesis of steroids incorporating a tropone A ring has been developed by Birch and co-workers. Addition of dibromocarbene to 3-methoxyestra-2,5(10)-dien-17-one 17-ethylene ketal (42) gives a monodibromocarbene adduct formulated as (43) accompanied by a minor amount of a bisadduct. This confirms earlier observations that electrophilic halocarbenes add mainly to 2,3- or 2,5-dihydroanisoles at the double bond bearing the methoxyl group. 

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). 

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. 

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. 

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). 

Other imino derivatives arise, as by-products or in side reactions, on heterocyclization. Thus, the treatment of cinnamoyltropolones 75 with hy-droxylamine (Scheme 19) yields, in the case of the 5-nitro derivative, the corresponding isoxazolotroponeoxime (89JHC371). The formation of oximes and several hydrazones from 3-acetyltropolone or its derivatives has also been mentioned (Section II,A,3,c). Moreover, an azine was obtained in addition to quinoxalotropone 213 (Section II,B,2,c) a tropone immonium salt was isolated after an extremely complex diene reaction of an 6-amino-2-azaazuIene (93CB441). 

Besides the common oleftnic dipolarophiles, other unsaturated systems have been evaluated in cycloaddition reactions of zwitterionic TMM-Pd complexes, including polyenes and acetylenes. While acyclic electron-poor dienes generally gave mixtures of five- and seven-membered rings [48], a limited number of selective [3 + 4] and [3 + 6] cycloaddition reactions have been achieved with cyclic polyenic substrates as illustrated by formation of cycloadducts 41 and 42 from pyrone [49] and tropone [50], respectively (Scheme 16). On the other hand, activated alkynes have failed to produce the corresponding cyclopentene derivatives [51]. 

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... 

Another special case, in which the unsymmetrical diene is part of a conjugated system which cannot easily be placed in any of the categories, C-, Z- or X-substituted, is tropone 6.173 when it reacts as a diene. On account of its symmetry, we have to work out the coefficients of the atomic orbitals by some other means than by the simple arguments used above and in Chapter 2 (pp. 60-65). The coefficients of the HOMO and LUMO are shown in Fig. 6.28. The numbers for the HOMO are not easily guessed at, and we must be content, in this more complicated situation, to accept the calculation which led to them. 

With this pattern in mind, we can see that the regioselectivity shown when tropone reacts as a diene with styrene to give the adduct 6.174 and with acrylonitrile to give the adduct 6.175 is readily explained, whichever pair of frontier orbitals we take in the second case. 

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