Benzocyclobutene electrocyclization

Malacria and coworkers [274] used an intermolecular trimerization of alkynes to gain efficient access to the skeleton of the phyllocladane family. Thus, the Co-cata-lyzed reaction of the polyunsaturated precursor 6/4-4 gave 6/4-5 in 42% yield. Here, six new carbon-carbon bonds and four stereogenic centers are formed. The first step is formation of the cyclopentane derivative 6/4-6 by a Co-catalyzed Conia-ene-type reaction [275] which, on addition o f his( Iri me ill y I si ly 1) e thy ne (btmse), led to the benzocyclobutenes 6/4-7 (Scheme 6/4.2). The reaction is terminated by the addition of dppe and heating to reflux in decane to give the desired products 6/4-5 by an electrocyclic ring opening, followed by [4+2] cycloaddition. 

A significant acceleration of the electrocyclic ring opening of benzocyclobutene derivatives has been disclosed under the influence of a -silicon atom.55 This effect has been associated with the adjacent anion-driven electrocyclic reactions such as oxy-Cope rearrangement. 

For the synthesis of estradiol methyl ether 4-319, the cyclobutene derivative 4-317 was heated to give the orthoquinonedimethane 4-318 which cydized in an intramolecular Diels-Alder reaction [109]. The thermally permitted, conrotatory electrocyclic ring-opening of benzocyclobutenes [110] with subsequent intramolecular cycloaddition also allowed the formation of numerous complex frameworks (Scheme 4.70). 

A major initial limitation of the benzocyclobutene approach to o-quinodimethanes was the lack of efficient, large-scale syntheses for many specifically substituted derivatives. Fortunately, recent developments have lemov much of this impediment. Q>nceptually, the synthesis of benzocyclobutenes from aromatic precursors can be envisaged in only a limited number of ways. These include [2 -i- 2] cycloadditions involving benzynes and alkenes, intramolecular cyclization on to a benzyne, cyclizations involving arene anions, and electrocyclic closure of o-quinodimethanes. Benzocyclobutene derivatives can also be prepared by aromatization of bicyclo[4.2.0]octanes. Detailed discussion of variations to these approaches can be found in the cited reviews. The cobalt catalyzed co-oligomerization of 1,5-hexadiynes with al-kynes, especially bis(trimethylsilyl)acetylene, has also been employed for the preparation of specifically substituted benzocyclobutenes. In the latter case the cyclobutenes are often not isolated but converted directly to o-quinodimethanes and subsequent products. ... 

This approach to cyclohexadienes can be considered an extension of that described for the precursor to type I cyclohexadiene in which the vinyl group is part of a cyclic stmcture. An example is tte low-temperature photochemical generation of the bis-exomethylene compound (196) from the benzocyclobutene (195), which was followed by an electrocyclic reaction to give compound (197). Thermolysis of (198) also leads to an assumed bis-exo-methylene intermediate (199), wldch electrocyclizes with involvement of die pyridinium ring to afford die alkaloid ellipticene (200) after dehydrogenation. ... 

Benzocyclobutene (BCB) pciymerizBs at much lower temperatures of about 250 °C than the closely related biphenylene. The reaction undergoes electrocyclic ring ojKiung to form o-xylylene which polymerizes to produce cyclic dimer andpoly-o-xylylene [92]. 

While the electrocyclic ring opening to o-quinodimethanes is the major reaction pathway in the irradiation of substituted benzocyclobutenes (cf. Example 6.14), the irradiation of unsubstituted benzocyclobutene yields 1,2-dihydropentalene (119) and 1,5-dihydropentalene (120) as major products. The mechanism shown with prebenzvalene (118) as primary photochemical intermediate has been proposed to explain the formation of the isomeric dihydropentalenes (Turro et al.. 1988). Supporting calculations that yield the same mechanism for the benzene-to-fulvene transformation have been published (Dreyerand Klessinger, 1995). 

In the presence of very reactive dienes, such as o-quinodimethanes, even electron-rich dienophiles, such as oxime ethers, can be reacted, as exemplified in Ae intramolecular cycloaddition of (143 Scheme 65), which is created in situ by an initial (2 + 2 -t- 2] cycloaddition reaction of (140) with (141) and subsequent electrocyclic ring opening of the resulting benzocyclobutene (142). This strategy has been applied recently to a novel isoquinoline synthesis. 

The equilibrium between the cyclobutene and the 1,3-butadiene is shifted in favor of the cyclobutene in benzocyclobutenes. The electrocyclic ring opening of a benzocyclobutene, an aromatic compound, leads to an o-xylylene, a nonaromatic and reactive compound. o-Xylylenes are useful intermediates in Diels-Alder reactions. 

The electrocyclic conversion of the benzocyclobutene into the o-quinodimethane radical anion 110 111 is allowed in the conrotatory mode11 c g). 

An important electrocyclic reaction is the ring-opening of benzocyclobutenes to give o-quinodimethanes. The resulting diene is an excellent substrate for reaction with a dienophile in a Diels-Alder reaction (see Section 3.1.2). For example, in a synthesis of the steroid estrone, the benzocyclobutane 337, prepared by a cobalt-mediated cyclotrimerizafion, was converted on heating to the o-quinodimethane... 

A mechanophore (blue in Fig. 2a) is a strategically designed chemical entity which responds to mechanical force in a predictable and useful manner (Fig. 2d-f). The polymer strand here acts as an actuator to transmit macroscopic force to the target. For a fully extended polymer chain, the maximum tension force is at the middle point of the chain contour. So the mechanophore should be incorporated into the middle of the chain with its active bond along the chain contotu (Fig. 2a) [15, 29, 32]. Examples of mechanochemical reactions include homolytic scission of weak bonds (diazo [33]), electrocyclic ring-opening (benzocyclobutenes [29], spiropyrans [32, 34 5], gem-dichlorocyclopropanes [46-49], ge/n-difluorocyclo-propanes [30, 50], and epoxide [51]), cycloreversion reactions (cyclobutane derivatives [52-56], Diels-Alder adducts [57, 58], 1,3-dipolar adducts [59, 60], and 1,2-dioxetanes [61]), dative bond scission [62-64], and flex-activated reactions [34, 65, 66], as recently reviewed by Bielawski [67]. 

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