Diynes cross-benzannulation with enynes

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],... 

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

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 14.24 Synthesis of aryl ethers via Pd-catalyzed cross-benzannulation of enynes with diynes. 

SCHEME 14 JO S5mthesis of cyclophanes via Pd-catalyzed [4 -I- 2] cross-benzannulation of enynes with diyne. 

Scheme 2.75 Palladium-catalyzed cross-benzannulation of enynes 2.218 with diynes 2.219.

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]. 

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

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. ... 

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

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). 

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],... 

Different types of cyclophanes, such as ortho-, meta-, or paracyclophanes, were obtained via the intermolecular Pd-catalyzed [4 - - 2] cross-benzannulation of cyclic enynes with diynes [2Id]. For example, cyclophane-type compound 78, containing both meta- and orthocyclophane motifs, was synthesized upon reaction of enyne 79 and diyne 80 (Scheme 14.30). 

Gevorgyan, V., Takeda, A., Homma, M., Sadayori, N., Radhakrishnan, U. and Yamamoto, Y. (1999) Palladium-catalyzed [4-1-2] cross-benzannulation reaction of conjugated enynes with diynes and triynes. Journal of the American Chemical Society, 121(27), 6391-6402. 

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