Benzocyclobutene synthesis

The versatile benzocyclobutene synthesis using the dicarbonyl-r) -cyclopenta-dienylcobalt-catalysed acetylene cyclizations has also been applied in a synthesis of (170). Reaction of the acetylene (171) with hexa-l,5-diyne gave the substituted benzocyclobutene (172) which was converted into (170). Use of bistrimethylsilyl-acetylene in the cyclization gave the benzocyclobutene (173). The trimethylsilyl groups are replaceable by electrophiles, and do not impair the ability of the benzocyclobutene to function as an o-xylylene synthon. Reaction of (173) with maleic anhydride gave the adduct (174) quantitatively. 

Two approaches to convergent steroid syntheses are based on the thermal opening of benzocyclobutenes to the o-quinodimethane derivatives (see p. 80 W. Oppolzer, 1978 A) and their stereoselective intramolecular Diels-Alder cyclizations. T, Kametani (1977 B, 1978) obtained (+ )-estradiol in a six-step synthesis. The final Diels-Alder reaction occurred regio- and stereoselectively in almost quantitative yield, presumably because the exo transition state given below is highly favored over the endo state in which rings A and D would stcrically inter-... 

A similar synthesis starts from commercially available 1,5-hexadiyne and 2-methyl-cyclopent-2-enone. The benzocyclobutene is obtained from a bis-acetylene in a cobalt-catalyzed reaction. It rearranges regio- and stereoselectively to a 3-deoxy steroid derivative. The overall yield from the cyclopentenone was 40% (R.L. Funk, 1977). 

The Diels-Alder reaction of o-quinodimethanes (from benzocyclobutenes) with nitrogen-ubstituted enes has also been applied to alkaloids synthesis (see p. 280f. T. Kametani, 1972, 1973, 1974 W. Oppolzer, 1978 A). 

As exemplified in the present procedure, the reaction has been optimized and extended in scope it affords functionalized benzocyclobutenes as well as substituted isoquinolines in high yields. Benzocyclobutenes have been used as intermediates in the synthesis of many naturally occurring alkaloids, - steroids,polycyclic terpenoids,and anthracycline antibiotics. The traditional routes leading to the preparation of benzocyclobutenes have been... 

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

Further examples of the use of the hDA reaction in dihydropyran synthesis include the formation of the fused pyrans 18 from vinylallenes 17 and aldehydes (Scheme 8) <00TL6781> and a trans-fused dihydropyran containing a phosphonate group 19 . A total synthesis of the 11-oxa steroid system is based on an intramolecular Diels-Alder reaction involving an orthoquinodimethane derived from a benzocyclobutene (Scheme 9) <00TL1767>. 

Cyclization by addition of a side-chain carbanion to an aryne bond has been proposed as the method of choice for synthesis of the versatile 1-substituted benzocyclobutene system.7 This general procedure now has been modified to permit convenient large-scale preparations utilizing a commercially available base, a minimum amount of liquid ammonia, and distillation for isolation of the product. 

The thermal reaction of the compound (318) may be chosen as an example to show the usefulness of the benzocyclobutene — o-xylylene rearrangement in alkaloid synthesis U1). On heating (318) at 120 °C, an intermediate product (319) was formed, which cyclized to give the compound (320). This method formulated the key step in the total synthesis of the alkaloid chelidonine (321) ni). 

In the late 1970s, Kirchhoff at Dow Chemical Company developed the use of benzocyclobutenes in polymer synthesis and modification. These efforts culminated in 1985 with the issuance of the first patent describing the use of benzocyclobutene in the synthesis of high-molecular-weight polymer.27 Similar work that involved a thermosetting system based on Diels-Alder cycloaddition between terminal benzocyclobutene and alkyne groups,28,29 was reported separately and independently by Tan and Arnold.28 Since these initial discoveries, the field of benzocyclobutene polymers has expanded rapidly and benzocyclobutene chemistry constitutes the basis of a new and versatile approach to the synthesis of high-performance polymers for applications in the electronics and aerospace industries.30... 

Using a fluorinated benzocyclobutene-based monomer (Figure 18.4) should provide at least one advantage over the already promising properties of fluorinated poly(j9-xylylene). All the desirable properties such as low dielectric constant and low affinity for water should remain but the thermal stability should be enhanced because of the cross-linking that would accompany the generation of these films. The synthesis and polymerization paths for poly(octafluorobisbenzocyclobutene) are depicted in Scheme 5. 

The synthesis and proposed cure mechanisms of this resin are described in reference 2. While the cure mechanism of the BCB terminated resin is not yet known, it is speculated that it reacts via one of two different routes. Initially the strained four member ring of the benzocyclobutene undergoes a thermally Induced ring opening. The opened rings then react with one another by a linear type addition to form a network type of structure or by cycloaddition to form linear polymer chains. An Illustration of the proposed polymerization mechanism of benzocyclobutene (BCB) terminated resins is shown below. 

Tan and Arnold have reported on the synthesis of several novel maleimido benzocyclobutene monomers and their conversion into homopolymers (Fig. 41) [14, 103]. 

AB maleimide benzocyclobutene monomers and polymers have also been actively studied and developed by researchers at the Dow Chemical Co. The first AB maleimide type benzocyclobutene monomer prepared and polymerized by Kirchhoff was the benzocyclobutenyl maleamic acid 106 [6]. The detailed synthesis of 106 is shown in Fig 44. 

The UDRI synthesis began by reacting benzocyclobutene with 4-nitroben-zoyl chloride 108 in the presence of a stoichiometric amount of the Lewis Acid, antimony pentachloride, at low temperature. The route pursued by Dow researchers utilized higher temperatures and 1 mole % of ferric oxide as the catalyst (Fig. 45) [46, 47, 102],... 

Oppolzer W (1978) A review on the use of intramolecular ring closures of benzocyclobutenes to synthesize natural products, Synthesis, p 794... 

Kametani T (1979) A review on the use of benzocyclobutenes in natural product synthesis, Pure Appl Chem 51 747... 

Very interesting Diels Alder comonomers for BMI are the bis(benzocyclobutenes). Under appropriate thermal conditions, the strained four-membered ring of benzocyclobutene undergoes electrocylic ring opening to generate, in situ, o-quinodimethane, which, in the presence of BMI, reacts via a Diels-Alder reaction (83). The chemical structure of a bis(benzocyclobutene-imide) is provided in Fig. 28. The synthesis and properties of BCB and BMI/BCB blend systems is described in detail in chapter I of this book. 

A novel cure chemistry employed for addition poly(imides) has recently been published. The successful preparation of 4-aminobenzocyclobutene allowed the synthesis of benzocyclobutene-terminated imide oligomers and bisfbenzocylobutenes) (17). The benzocyclobutene group is a latent diene which isomerizes to o-guinodimethane at temperatures of about 200 °C and may homo- and/or co-polymerize for example with bismaleimide (83). Details on the benzocyclobutene chemistry are described in chapter I of this book. 

In some instances the relatively easy homolytic cleavage of the C-SOz bond could be used for an efficient synthesis of polycyclic hydrocarbons, particularly cyclophanes and benzocyclobutene via pyrolysis of sulfones at temperatures of 300-900°C (see [203] for references on these reactions). An example [399] is ... 

---