Benzofuran ring system

Bcnzofuran-4,7-dioncs have been synthesized regioselectively by [3 + 2] photoaddition of 2-hydroxy-1,4-benzoquinones with a range of alkenes (equation 185)664. The reaction occurs in 30-60% yield and is a useful method for the synthesis of the benzofuran ring system, which is important in natural products like acamelin665. Substituted naphthoquinones may also be used in this reaction666,667 and this has lead to a very simple two-step synthesis of maturinone. In a similar reaction, a [3 + 2] photoaddition reaction of 2-amino-1,4-naphthoquinones with electron-rich alkenes gave 13-82% yields of 2,3-dihydro-177-bcn/ /]indole-4,9-diones in a single-step process which involved photolysis followed by oxidation (equation 186)668,669. 

Mehta and Likhite used a Lewis acid-catalyzed cyclization route to construct the benzofuran ring system of frondosin B, an IL-8 antagonist, and an inhibitor of protein kinase C (PKC). Treatment of a highly functionalized chiral ketone precursor with boron trifluoride-diethyl etherate gave the corresponding furan in 95% yield over two steps. This strategy was also employed by Ovaska and Li in their synthesis of the same compound. ... 

Benzil 258 undergoes a novel cyclization reaction on treatinent with chlorosulfonic acid (six equivalents) at 40 °C (2 hours) to 5ueld 3-chloro-2-phenylbenzofuran-6,4 -disulfonyl chloride (259, 60%). The mechanism originally proposed for the reaction involved cyclization to the benzofuran ring system prior to sulfonation. However, this mechanism is probably incorrect and has been modified so that sulfonation occurs before cyclization as shown in Scheme 4,... 

In the synthesis of morphine, bis-cyclization of the octahydroisoqtiinolinc precursor 171 by the intramolecular Heck reaction proceeds using palladium trifluoroacetate and 1,2,2,6,6-pentamethylpiperidine (PMP). The insertion of the diene system forms the rr-allylpalladium intermediate 172, which attacks the phenol intramolecularly to form the benzofuran ring (see Section 1.1.1.3). Based on this method, elegant total syntheses of (-)- and (+ )-dihydrocodei-none and (-)- and ( + )-morphine (173) have been achieved[141]. 

Five-membered ring systems furans and benzofurans... 

Mejla-Oneto and Padwa have explored intramolecular [3+2] cycloaddition reactions of push-pull dipoles across heteroaromatic jr-systems induced by microwave irradiation [465]. The push-pull dipoles were generated from the rhodium(II)-cata-lyzed reaction of a diazo imide precursor containing a tethered heteroaromatic ring. In the example shown in Scheme 6.276, microwave heating of a solution of the diazo imide precursor in dry benzene in the presence of a catalytic amount of rhodium I) pivalate and 4 A molecular sieves for 2 h at 70 °C produced a transient cyclic carbonyl ylide dipole, which spontaneously underwent cydoaddition across the tethered benzofuran Jt-system to form a pentacyclic structure related to alkaloids of the vindoline type. 

Five-Membered Ring Systems Furans and Benzofurans... 

Benzofurans, 21 152 Benzoguanamine, 2 621 17 243 Benzoheterepine ring systems, 21 154 Benzoic acetic anhydride, 1 147 Benzoic acid, 3 625-637 12 58 antimicrobial used in cosmetics, 7 831t... 

We studied the effect of replacing the indole nucleus by other non-basic ring systems and prepared the benzofuran and benzothiophen derivatives by the standard route from the appropriate ketone. It may be seen from Table 7.5 that both derivatives were less active than ondansetron. 

Additional heterocyclic ring systems, such as benzofurans [125], dihydropyrroles and dihydroazepines [41], piperidines and dihydropyrimidines 36 [126], and fused oxazole derivatives [127], have been described (Eq. 7). The formation of epoxides and aziri-dines, formally emanating from ylides, was recently reported by Doyle et al. [77]. Rho-dium(II)-catalyzed isomiinchnone cycioaddition followed by Lewis acid-mediated ring opening has been used as an entry into the protoberberine azapolycyclic ring structure [128]. 

The chemistry of fiiians and benzofurans was a Held of lively research in the last year. There are a number of reasons for this activity. The furan ring system - both in its native as well as in its reduced form - occurs in a great number of natural products and a wide variety of these compounds has been isolated from natural sources. This subject is treated regularly with care and accuracy in Heterocycles and will not be repeated here. Therefore only a few examples will be given in this chapter. Several new furan derivatives were isolated from natural sources (-)-wistarin 1 from the marine sponge Ircinia sp. <99TA3869>,... 

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