Cycloadditions tropolones

Cyclo ddltion. Ketenes are ideal components ia [2 + 2] cycloadditions for additions to the opposite sides of a TT-system as shown ia the cyclobutane product (2) ia Figure 1. Electron-rich double bonds react readily with ketenes, even at room temperature and without catalysts. In conjugated systems, ketenes add ia a [2 + 2] fashion. This is illustrated ia the reaction foUowiag, where the preferential orientation of L (large substituent) and S (small substituent) is seen (40). This reaction has been used ia the synthesis of tropolone [533-75-5]. 

The present procedure, based on the last method, is relatively simple and uses inexpensive starting materials. Step A exemplifies the 2 + 2 cycloaddition of dichloroketene to an olefin, " and the specific cycloadduct obtained has proved to be a useful intermediate in other syntheses. Step B has been the subject of several mechanistic studies, and its yield has been greatly improved by the isolation technique described above. This synthesis has also been extended to the preparation of various tropolone derivatives. " ... 

Tropolones are readily accessible from the [3-1-4] cycloadditions of vinylcarbenoids with the highly oxygenated diene 58, as illustrated in Scheme 14.5 [79]. Treatment of the cyclic vinyldiazoacetate 59 with diene 58 in the presence of Rh2(OPiv)4 affords the fused cycloheptadiene product 60 in 68% yield. Deprotection followed by oxidation gives the single regioisomeric methyl tropolone 61 in 80% yield. 

Theoretically, the regioselectivity observed in photochemical [2 + 2] cycloaddition of 56 with 1,1-dimethoxyethene is in good agreement with experimental results and has been explained on the basis of pertubational molecular orbital theory." Hartke and co-workers" described an interesting contrast in the reactivity of tropolones in an intramolecular Diels-Alder reaction (Scheme 6.18). Thus, alkylation of 64a and 64b with 65 gave 66a and 66b, respectively, that were subjected to cyclization in refluxing toluene. Whereas 66a decomposed under the reaction conditions, 66b afforded 67b in high yield. 

Tropolone has been made from 1,2-cycloheptanedione by bromination and reduction, and by reaction with N-bromosuccinimide from cyclo-heptanone by bromination, hydrolysis, and reduction from diethyl pimelate by acyloin condensation and bromination from cyclo-heptatriene by permanganate oxidation from 3,5-dihydroxybenzoic acid by a multistep synthesis from 2,3-dimethoxybenzoic acid by a multistep synthesis from tropone by chlorination and hydrolysis, by amination with hydrazine and hydrolysis, or by photooxidation followed by reduction with thiourea from cyclopentadiene and tetra-fluoroethylene and from cyclopentadiene and dichloroketene. - The present procedure, based on the last method, is relatively simple and uses inexpensive starting materials. Step A exemplifies the 2 + 2 cycloaddition of dichloroketene to an olefin, " and the specific oycloadduot obtained has proved to be a useful intermediate in other syntheses. " Step B has been the subject of several mechanistic studies, " and its yield has been greatly improved by the isolation technique described above. This synthesis has also been extended to the preparation of various tropolone derivatives. - " ... 

The bicyclic ketone (44), obtained from the Fe2(CO)9-promoted [3 + 4] cycloaddition reaction of a,a,a, a -tetrabromoacetone and 2-isopropylfuran followed by Zn-Cu couple reduction, has been converted to the naturally occurring troponoid, /3-thujaplicin (46) (75JOC806). Hydrogenation of (44), ether cleavage, bromination and dehydrobromination gave the tropone (45), an intermediate easily converted into the tropolone (46) by a standard procedure (Scheme 10). A related [3 + 4] cycloaddition reaction of oxyallyl metallic with furan has been used to assemble the antibiotic C-nucleosides (78JA2561). 

Didehydrotropone, prepared by oxidation of l-amino[4,5-d]-1,2,3-triazole with lead tetraacetate, undergoes cycloaddition reactions with pyridazine M-oxides <94H(38)957>. Loss of nitrogen by the cycloadduct results in the formation of tropono[4,5-b]oxepines (Scheme 10). The electron deficient nature of the tropolone ring precludes the formation of [4 + 2]jt cycloaddition products by the oxepine ring, in contrast to the reactivity of benz[l>]oxepines. 

Imembrine, a tropolone natural product related to colchicine was also synthesized via an oxazole-acetylene Diels-Alder reaction followed by a [4 -H 3]-oxyallyl cycloaddition.Here, 8-iodo-5,6,7-trimethoxyisoquinoline 269 was converted to 5-substituted oxazole 270 in four steps and 42% overall yield (Fig. 3.81). Thermolysis of 270 in refluxing o-dichlorobenzene effected the desired intramolecular Diels-Alder cycloaddition with concomitant loss of the Boc-protecting group to afford the tetracyclic furan 271 in 90% yield. At this point, 271 was subjected to the [4 + 3] cycloaddition in the presence of l,3,3-trichloro-2-propanone and 2,2,2-trifluoroethanol. Subsequent dechlorination of the intermediate (not shown) with zinc provided the oxabicyclic 272 as a single regioisomer in 73% yield. The synthesis of imembrine was completed in three steps from 272. 

Another useful method for the preparation of tropolone utilises the cycloaddition reaction of dichloroketene with cyclopentadicne to give a bicyclo[3.2.0]heptenone derivative which can be transformed into tropolone [251,252]... 

Cyaloaddition Reactions. Tropolones may react as dienes or as 2-TT-dienophiles in cycloaddition reactions. Thus tropolone reacts as a diene with maleic anhydride [321] or with benzyne [322] ... 

Strategy of Rh-triggered qrcloaddition cascade. In this case, the Rh-catalyzed transformation of a-diazoketone 132 into an oxatetracycUc key cycloadduct 133 through intramolecular [3+2]-cycloaddition of an in-situ generated carbonyl yUde was achieved. Further, the regioselective conversion of the cycloadduct 133 into a tropolone derivative led to an efficient enantioselective access to colchicine (Scheme 40). 

Cycloadditions and Rearrangements. The addition of 2-oxyallyl cations to furan provides a route to oxabicyclo[3,2,l]octanes complementary to the cycloaddition of cyclopropanones to furan. Careful experimental studies have led to yields of preparative importance both with furan and with cyclopentadiene. Following the route to azabicyclo-octanes, dipolar addition to the pyrylium betaine (99) affords oxa-analogues (Scheme 23). Also reported are the addition of fiiran to 1-cyanonaphthalene, the formation of various cycloadducts of tropone and tropolone (Scheme 24), and the phototransformations of (100) (Scheme 25) and (101) (Scheme 26). Thermal addition gives (102) from (103) and similarly other 8-oxabicyclo-octanes are prepared from acyclic precursors. ... 

The synthetic method for tropolone involving 1,2-cycloaddition of halogenated ketenes to cyclopentadiene followed by solvolytic fragmentation of the resulting adduct provides a very convenient synthesis of tropolone derivatives from readily available starting materials. The synthesis of -thujaplicin (hinokitiol) illustrates this approach. ... 

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