Arynes 4+2 cycloadditions, furan

The elusive dibenzannulated dimethyldihydro-pyrene 69 was prepared by the group of Mitchell (Scheme 16) [48]. A Diels-Alder cycloaddition between an aryne and furan was employed to introduce the key benzene rings to the metacyclo-phanediene framework 68. The colorless 68 switches to green 69 on UV irradiation, and 69 reverts thermally or photochemically. More recently, the same group reported the synthesis of the three-way molecular switch 70 [49]. 

Aryne cycloadditions to furans have been employed in the synthesis of bio-related molecules. For example, adduct 272 served as the starting point for the preparation of the aromatic segment of rifamycin W (an antibiotic). Previously unreported benzyne 274 (its precursor 273 was prepared in several steps from piperonal) readily gave cycloadduct 275 with furan, but unfortunately for a proposed route to podophyllotoxin, did not undergo... 

Aryne cycloadditions have been coupled with radical cyclizations to rapidly assemble multiring systems For example, benzyne addition to furan 278 followed by radical cyclization onto the newly formed double bond gave 280 in two steps and fair yield. 

The synthesis of benzo[l, 2-c 3,4-c 5,6-c"]trifuran 459 (the furan analog of triphenylene) was accomplished by three aryne cycloadditions onto a single benzene ring. The arynes were generated by two different methods. The dibromodiazonium carboxylate hydrochloride 455 and furan gave adduct 456, which was then treated with excess potassium amide. 

Thiophenes undergo Diels-Alder reactions, but their diene reactivity is lower than that of furans. The [4+2] cycloaddition occurs, therefore, only with very reactive dienophiles (arynes and alkynes with acceptor substituents) or under high pressure (example 3). 1,2-Disubstituted benzene derivatives 2 are formed with alkynes, as the primary Diels-Alder adduct 1 eliminates sulfur ... 

Pyrroles, like furans, undergo [4+2] cycloadditions with arynes. For good yields, however, it is important to have some functionality other than hydrogen attached to the nitrogen. A variety of 7-azabenzonorbornenes have been prepared in this way 54... 

Interestingly, when the number of equivalents of t-butyllithium was reduced from 4.0 to 1.1, all three benzyne-furan cycloadducts (i.e., 97a, 102, and 103) resulting from the three possible dibromoindole starting materials (lOOa-c) were isolated in excellent yields (Scheme 28). It is noteworthy that while the ortho dichlOTO- and dibromo-substituted indoles (94, lOOa-c) resulted in clean formation of the aryne species, the ortho difluoro derivatives lOOd-f did not behave in the same way. The attempted Diels-Alder reactions with 4,5 and 6,7-difluoroindoles lOOe and lOOf resulted only in the recovery of starting material. However, in the case of 5,6-difluoroindole lOOd, the cycloaddition resulted in the formation of 103,... 

Arynes, such as benzyne (1,2-dehydrobenzene), also undergo Diels-Alder cycloaddition reactions. Benzyne, CelTj, is a highly reactive species and can be prepared by elimination of a suitably substituted benzene derivative. It reacts in situ with various dienes such as furan, cyclopentadiene, cyclohexadiene and even benzene and naphthalene to give bicyclic or polycyclic cycloadducts (3.15). Analogous addition reactions are shown by dehydroaromatics in the pyridine and thiophene series. 

Arynes with their reactive triple bond would be expected to participate readily in cycloaddition reactions. However, as demonstrated in the previous section, the addition of nucleophiles is extremely facile, and therefore reactions with non-nucleophilic reagents cannot usually be observed unless the aryne is generated in the absence of nucleophiles. In practice this usually means that routes involving the treatment of aryl halides with nucleophilic bases cannot be used. The first cycloaddition reaction of ortho-benzyne, the Diels-Alder reaction with furan was observed in 1955 by Wittig and used 2-fluorobromobenzene as the precursor. The cycloadduct was obtained in almost 90% yield, and the reaction has formed the basis for numerous synthetically useful Diels-Alder cycloadditions involving arynes. Tetrabromobenzene reacts with butyllithium to give the diaryne intermediate with furan to form a tetrahydroanthracene. The mixture of syn and anti conformers can be separated based on differences in methanol solubility (Scheme 7.26). 

During the course of the total synthesis of rubromycins, Reipig and coworkers have employed an aryne-furan cycloaddition to construct the key building block naphthaldehyde 120 (Scheme 12.39) [71]. 

While preparing benzonorbornadienes by the Diels-Alder cycloaddition of substituted benzyne intermediates with furan. Caster and coworkers discovered significantly differentregiochemistries be tween bromobenzene 121 and chlorobenzene 124 in the n-BuIi induced metallation step (Schemes 12.40 and 12.41) [72]. In the case of bromobenzene 121, benzyne intermediate 122 was generated via bromine-Uthium exchange, followed by elimination of UF trapping by furan then afforded 6-fluoro-9-oxabenzonorbornadiene (123). In contrast, aryne 125 was produced... 

The Diels-Alder cycloaddition between 5,6-bis(trimethylsilyl)benzo[c]furan (130) and arynes has been demonstrated by Wong et al. in the synthesis of linear polycyclic aromatic compounds, such as 131 and 132 (Scheme 12.42) [74]. 

Besides furan, the Diels-Alder reaction between other heteroaromatics and arynes is also known. The [A+2] cycloaddition of benzyne with 3,4-dimethylphos-phole pentacarbonylmolybdenum complexes 133 has recently been reported by Mathey (Equation 12.37) [75]. The cycloaddition mainly takes place on the less-hindered side of the phosphole ring, affording 2,3-benzo-7-phosphanorbornadiene complexes 134 in moderate yields. 

The cycloadditions of substituted furans with various arynes afforded a variety of multifunctionalized polycyclic compounds (13S1843,13T4338, 13T6144,13OL2806). 

Arynes are generated by formal 1,2-elimination reachons from 1,2-disubstituted arenes like 27a-c. Trapping of benzyne by cycloaddition to furan goes back to the pioneering... 

The Diels-Alder reaction ([4+2] cycloaddition) [8] provides one of the most powerful methods for the constmc-tion of PAHs because it affords one-step formation of the six-membered ring framework, the basic unit of these derivatives. This chapter, based on the results of our work, will highUght the synthesis of substituted oligoacenes including anthracene (1), tetracene (2), and pentacene (3) cores by Diels-Alder reactions using arynes and quinones as dienophile components and furans, thiophene-1,1-dioxides, and o-quinodimethane as diene components. The synthetic methodology will be accompanied by discussions on molecular and packing stmctures as weU as solid-state optical properties. 

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