Benzannulation cross

The aryl bromide 40, prepared from cross-coupling between 1,2-dibromobenzene and (trimethylsilyl)acetylene, was converted to the corresponding arylzinc halide 41a and arylboronic acid 41b for subsequent coupling with the haloallenes 42 to produce the benzannulated enyne-allene 43 in -40% yield (Scheme 20.10) [38]. Desilylation with tetrabutylammonium fluoride (TBAF) then afforded 44 in 67% yield. 

The use of l-iodo-9-fluorenone (59) for cross-coupling with phenylacetylene produced 60, which on treatment with 51 gave the benzannulated enyne-allenes 61 (Scheme 20.14) [43], Thermolysis of 61 in 1,4-CHD at 75 °C promoted the Myers-Saito cyclization reaction, leading to 63 in excellent yields. Again, the benzylic radical center in 62 is a stabilized triarylmethyl radical. 

A palladium-catalyzed intramolecular benzannulation of bis-enynes 1135 proceeds chemoselectively to afford dihydroisocoumarins 1136 (Equation 441) <2002JOC2653>. A reaction sequence involving ruthenium-catalyzed yne-ene cross-metathesis of a polystyrene supported undecynoic acid ester followed by a Diels-Alder cycloaddition reaction with DMAD provides the basis for a combinatorial approach to dihydroisocoumarins featuring a variety of side chains at C-6 and C-8 <1999SL1879>. 

The scope and value of the benzannulation reaction is further increased by the substitution pattern of the arene ring, which can be modified by the incorporation of allcynes bearing additional functional groups such as silyl, stannyl, or boryl substituents. These functional groups have been used in various palladium-catalyzed (cross)-coupling reactions [63, 64]. Further structural elaboration may be based on benzannulation followed by nucleophilic aromatic addition [63b]. 

More vigorous oxidation leads directly to quinones. This approach has been employed in a regioselective synthesis of polysubstituted quinones based on benzannulation with trime-thylsilyl allcynes followed by oxidation, iododesilylation, and cross-coupling [66]. 

Finally, benzenepolycarboxylates were obtained by ruthenium-catalyzed cross-benzannulation of acetylenedicarboxylates with allylic compounds [52] (Eq. 39). A ruthenacyclopentene is postulated to occur via oxidative coupling of one molecule of alkyne with allylic alcohol. Subsequent insertion of another molecule of alkyne gives the corresponding polysubstituted benzene derivatives. 

Another method of benzannulation to a furan ring uses precursors of type 59, which are available by cross-coupling reaction with the corresponding 3-bromofuran. Upon treatment with ethyl chloroformate and triethylamine, a pyrocarbonate is formed which acylates the furan nucleus in an intramolecular reaction. With an excess base the 7-hydroxybenzofurans are obtained (Equation 123) <1998TL5609>. 

The regiochemical product distribution of the co-cyclization of two or three different alkynes occurs statistically. In some cases carefully controlled reaction conditions allow isolation of a main product from mixed cyclotrimerizations. For example, l,2,3,4-tetraphenyl-5,6-diethylbenzene can be obtained from cobalt-catalyzed reaction of tolane and 3-hexyne in good yield [62]. The first example of an intermolecular, regiospecific cross-benzannulation reaction catalyzed by Pd(PPh3)4 was reported by Yamamoto [63]. The reaction of 2-alky 1-but-l-ene-3-yne with disubstituted diynes leads exclusively in high yields to... 

The aniline derivative 208 was obtained by cross-benzannulation of the amino-enyne 207 with dodeca-5,7-diyne (50) [64]. Cross-benzannulation of the 1,4-disubstituted enyne 209 with fte diyne 50 afforded the 1,2,3,4-tetrasubstituted benzene 210 [63]. Pentasubstituted benzene 212 can be synthesized by the coupling of the trisubstituted l-buten-3-yne 211 with the diyne 50 [63]. 

Intermolecular enyne-diyne cross-benzannulation offers a convenient synthetic method for cyclophanes. The cyclic enyne 213 reacted smoothly with 12-carbon-tethered cyclic diyne 214, and the meto-cyclophane having both 15- and 16-membered rings 215 was prepared in high yield (72 %) [65],... 

TABLE 4. Pd-Catalyzed Cross-Benzannulation Between 4-Snbstitnted Conjngated Enynes... 

Another type of benzannulation, which might be related to the benzannulation of conjugated enynes, is the Pd-catalyzed cyclotrimerization of 1,3-diynes (Scheme 1,3-Diynes cyclotrimerize in the presence of a Pd catalyst to give 1,3.5-trisubstituted benzene derivatives. In this reaction, too, the regioselectivity is perfectly controlled as shown in Scheme 4, and other products were never isolated. The reaction of various diynes is summarized in Table 7. Some functional groups such as olefins and ether linkages may be present in the side chain. An example for the cross-cyclotrimerization of a diyne and an aUcyne has also been reported (Scheme... 

D. [4 + 2] ANNULATION OF CONJUGATED ENYNES WITH DIYNES (CROSS-BENZANNULATION)... 

The scope of the reaction discussed in Sect. B is somewhat limited since the only practical synthetic procedure consists of the cyclodimerization of the two identical enynes, and therefore the same substituents are attached at the phenyl group and the vinyl group of the reaction product. The attempted cross-annulation of conjugated enynes with alkynes or dienes turned out to be unsuccessful. However, the scope of the benzannulation reaction could be extended significantly by introducing conjugated... 

TABLE 9. Pd-Catalyzed Cross-Benzannulation of Conjugated Enynes with Diynes (2)... 

Although a mechanism of the above palladium-catalyzed cross-benzannulation between conjugated enynes and diynes is not perfectly understood, the reaction may proceed via not a concerted mechanism but a stepwise mechanism [48]. 

Figure 4.32 A cross-section of results for the biotinylated Rh(lll)-catalyzed enantioselective benzannulation synthesis as reported by Rovis, Ward, and coworkers [64].

The Pd(0)-catalysed 4 -i- 2-cross-benzannulations of conjugated enynes (167) with diynes (166) and triynes yield substituted benzene derivatives (168) (Scheme 64). " Monosubstituted conjugated enynes readily undergo 4 - - 2-homodimerization in the presence of Pd catalyst to produce 4,o - and 2,6-disubstituted styrenes. ... 

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