Acetylene derivs benzofurans

The 2a,7b-dihydrocyclobuta[7>]benzofuran structure, obtained by addition of activated acetylenes to benzofurans (see Houben-Weyl, Vol.E6b, p 148), isomerizes thermally to a 1-benz-oxepin182 184 185 which reacts further to 1-naphthol derivatives at higher temperature182,185 (see Section 1.2 ). Under photochemical conditions, the 1-benzoxepins undergo ring contraction to the starting material.182 184... 

When the unsaturated substrate is an acetylene derivative, furans - or benzo-furans- may be produced. For instance, 2-aminoethyl-benzofuran 190 (Fig. 67) is obtained at pH 7 from the acetylenic alcohol 189 instead of the expected Mannich base, which is produced at a higher pH value. 

In the exceptional case, the reaction of the cation with the nucleophile occurs intramolecularly. Irradiation of the /3,/3-bis(o-methoxyphenyl)vinyl bromide 75 yields a benzofuran derived from 76, next to a benzofuran and an acetylene derived from 77 (Scheme 45). Here, the reaction of the primary vinyl cation 76 with the internal nucleophile can compete with the 1,2-shift across the C=C double bond, yielding the a-aryl-substituted vinyl cation 77. 

The mass spectra of indole and its alkyl derivatives reveal a close relationship to those of corresponding benzofurans and pyrroles (Beynon,13 p. 397 Beynon and Williams43). A major degradation path is the formation of quinolinium ions, which may decompose further by expulsion of one molecule of HCN and one of acetylene, (59)—>[60]—>[61]—>[62] ... 

Annulation to carbonyl functions has also been achieved with Trost s bifunctional reagents. Whereas the parent silyl acetate (97) yields only simple alkylation products with aldehydes under normal conditions, addition of only a few mole % of trimethyltin acetate to the reaction mixture results in facile formation of methylenetetrahydrofurans Furthermore, excellent diastereoselectivity is observed in the cycloaddition to a galactose-derived aldehyde (125) (equation 136). The tin acetate co-catalyst also promotes addition to relatively unreactive ketone carbonyls, such as in the case of benzofuran (126) and the acetylenic ketone (127) (equations 137, 138). It is remarkable that even the sterically hindered enone (128) reacts preferentially at the ketone function (equation 139). A tributyltin analog (129) of (97) has been used in the stepwise formation of a methylenetetrahydrofuran from aldehydes. Similarly, pyrrolidines can be prepared from the corresponding imines in two steps via a Lewis acid-catalyzed 1,2-addition of the tin reagent, which is then followed by a Pd-catalyzed cyclization (equation 140). Direct formation of pyrrolidine from the imine is possible if one uses a mesylate analog of (97) and a nickel(O) catalyst (equation 141). ... 

Irradiation of 2-(2-hydroxyphenyl)-3-phenylcyclopropenones with a high pressure mercury lamp in acetonitrile produced the corresponding acetylenes 3 and benzofuran derivatives 4. ... 

Acetylenes, beta-carboline alkaloids, furocoumarins and lignans occur widely among the families listed in Table 1. Acetophenones (benzofurans and benzopyrans) and extended quinones have a much more limited distribution while furochromones, furoquinoline alkaloids and thiophenes are apparently restricted to single families. It should be mentioned that although acetylenic polylnes are phytochemical components of plants from numerous families (4), only those derivatives produced by members of the Asteraceae have been shown to be phototoxic Q). 

This methodology was later extended by Owen [117] and Nilsson [78] to the employment of o-iodo- and -bromophenols and terminal acetylenes in the presence of stoichiometric amounts of Cu(I) oxide in pyridine or Cu(I) terf-butoxide to generate acetylide 55, allowing the achievement of typically higher or comparable yields (60-82%) of thecorresponding benzofurans 57. Ohemeng [118] and Scammells [119] effectively employed the first catalytic system in the synthesis of biologically active benzofuran derivatives, whereas Nilsson succeeded in the assembly of... 

Rostami-Charati and Hossaini reported the multicomponent synthesis of phosphonates on water by the reaction of activated acetylenes 143, 4-hydroxycoumarin/l-(6-hydroxy-2-isopropenyl-1 -benzofuran-yl)-1 -ethanone (142), and trialkylphosphites 144 [78], The reaction mixtures were heated at 70°C to render the corresponding phosphate derivatives 145 in good yields (Scheme 11.29). 

As shown in Scheme 1.46, a simple synthesis of complex fused 1,4-benzoxaz-epin-2-one derivatives 86 and 87 was aehieved via a three-component leaction of quinoline or isoquinoline, acetylene dicaiboxylic esters and l-(6-hydioxy-2-isopio-penyl-l-benzofman-yl)-l-ethanone in water, in the absence of aiy catalyst [68]. Presumably, this transformation proceeds via the initial formation of a 1 1 zwitter-ionic intermediate 88 from the Michael addition of isoquinohne (or quinolone) to the activated ester. A proton transfer reaction takes then place in which this species is protonatedby the phenol group in the l-(6-hydroxy-2-isopropenyl-l-benzofuran-yl)-l-ethanone substrate, and this is followed by a second Michael addition of the resulting phenoxide anion to the isoquinohnium ion to afford intermediate 88, containing benzofuryl and isoquinoline ring systems. This intermediate then undergoes... 

The [Pd(NH3)4] /NaY was prepared by above procedure (ion exchange method) and Pd/Cald was obtained commercially. After the reaction the [Pd(NH3)4]/NaY and Pd/CALO catalysts were recovered following the above procedure using only DMF instead of mixture of DMF and water for three times and dried for overnight. Both catalysts have shown high recyclability up to fiftii cycle without any significant loss of catalytic activity. However, the reaction between o-iodo phenol and diphenyl acetylene failed to provide benzofuran derivative in the presence of above two catalysts. 

Heterocyclic acetylenes also worked very well. Alkynes bearing on the backbones of quinoline, isoquinoline, benzothiophene, benzofuran, dibenzofiuan, and pyrazole were converted to heterocyclic nitriles (109-114) in 63-86 % yields. Interestingly, this nitrile synthesis could be applied to natural product derivatives. For example, the alkynyl ester of Vitamin E gave nitrile 115 in 45 % yield (in 80 % yield based on recovered starting material) the alkynyl ester of oleic acid gave nitrile in 68 % isolated yield. 

---