Benzannulation diynes

Aryl- and alkenylcarbene complexes are known to react with alkynes through a [3C+2S+1C0] cycloaddition reaction to produce benzannulated compounds. This reaction, known as the Dotz reaction , is widely reviewed in Chap. Chromium-Templated Benzannulation Reactions , p. 123 of this book. However, simple alkyl-substituted carbene complexes react with excess of an alkyne (or with diynes) to produce a different benzannulated product which incorporates in its structure two molecules of the alkyne, a carbon monoxide ligand and the carbene carbon [128]. As referred to before, this [2S+2SH-1C+1C0] cycloaddition reaction can be carried out with diyne derivatives, showing these reactions give better yields than the corresponding intermolecular version (Scheme 80). 

Also, the [4+2] benzannulation of enyne 154 with diyne 155 proceeds chemo- and regioselectively to afford 156 [66], A similar reaction of enyne silyl enol ether 157 with the diyne offers a good synthetic route to polysubstituted phenols 159 via 158 [67]. In this reaction enol silyl ethers having the (E) configuration as shown in 157 give satisfactory results. 

Saito S, Yamamoto Y (2002) Palladium-Catalyzed Benzannulation Reactions of Conjugated Enynes and Diynes. In Negishi E, de Meijere A (eds) Handbook of Organopalladium Chemistry for Organic Synthesis. Wiley, New York, p 1635... 

However, starting with 2-iodo-phenyl Z-3-bromo-acrylalc (151) and bu-tadiynes two subsequent Sonogashira coupling reactions and a benzannulation give rise to the formation of the diynes 152 in moderate yields (Scheme 58). 

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],... 

IV.10.2 Palladium-Catalyzed Benzannulation Reactions of Conjugated Enynes and Diynes... 

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)... 

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]. 

Scheme 17 Transfer hydrogenative cycloaddition of a-ketols with benzannulated 1,5-diynes or ortho-acetylenic benzaldehydes. Yields are of material isolated by flash chromatography on silica gel...

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. ... 

Shortly after palladium-catalyzed [4-1-2] homo-benzannulation reaction of two enynes was discovered [4], a cross-benzannulation of enynes with diyne enynophiles was developed [13], thus substantially expanding the scope of this transformation. Similar to the homo-benzannulation reaction, the cross-benzannulation reaction occurs in a highly regioselective manner, offering easy access to densely substituted arylacetylenes 10 as solo regioisomers (Scheme 14.17) [13,14]. In most cases, the reaction is chemoselective, providing a product of cross-benzannulation reaction only. 

SCHEME 14.17 Scope of the Pd-catalyzed [4 + 2] cross-benzannulation reaction of enyne with diyne. 

TABLE 14.3 Pd-Catalyzed [4 + 2] cross-Benzannulation Reaction of 2-Methylbut-l-en-3-yne with Unsymmetrically Substituted Diynes... 

In a manner analogous to the palladium-catalyzed [4 -l- 2] benzannulation reaction of two enynes, the stannylative version of the benzannulation reaction of enyne with diyne was also successful, providing 3-alkynylarylstannane 40 in 85% yield [10] (Scheme 14.18). Notably, the metallative version of this reaction made it possible to introduce substitution at the mefa-position to the alkynyl moiety, which is the only nonfunctionalizable position via the nonmetallative method. 

Two possible approaches were shown for the Sonogashira cross-coupling/ benzannulation of enyne with diyne cascade transformation (Scheme 14.19) [11a]. Accordingly, three-component coupling between dihalide 41 and two molecules of terminal diyne produced phenanthren-9(10//)-one derivatives 43 with modest yields under Sonogashira cross-coupling conditions (path A). Incorporation of two different substituents to the final product 46 was achieved via a stepwise addition of terminal alkynes (path B). 

A highly atom-economical cascade transformation employs Trost s Pd-catalyzed dimerization of alkynes [15] and consequent Pd-catalyzed benzannulation reaction [16] (Scheme 14.20). A formal [2 - - 2 - - 2] cycloaddition reaction proceeded through the formation of 2,4-enyne followed by a formal [4 - - 2] benzannulation reaction with diyne, representing a highly chemo- and regioselective trimerization reaction of alkynes. Homo-dimerization of terminal acetylenes followed by a benzannulation... 

Similarly, a variety of aryl ethers can be obtained via the [4-1-2] cross-benzannulation reaction of enynes with diynes (Scheme 14.24) [18]. Notably, using this strategy, alkoxy substituent can be introduced at positions 2, 4, and 6 of ary-lacethylene 65 with the use of appropriate coupling partners. Moreover, starting from silyl ethers, the corresponding p-alkynylphenols can be synthesized after deprotection in either a stepwise or a one-pot fashion [18b],... 

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