Benzocyclobutanes

Tan et al. investigated polymers made from bis-benzocyclobutenes [13-15]. As the benzocyclobutane is analogous to tbe dien, tbe Diels-Alder addition takes place. This reaction is applied to the preparation of polyimides. The advantage of this system is that the resultant polymer is oxidized to form thermally stable aromatic polyimides (Fig. 7). 

Fluonnation and skeletal transformation of fluorinated cycloalkanes occurs in the reaction with antimony pentafluoride at high temperature [777] In the case of perfluorinated benzocyclobutanes, an unexpected alicyclic ring cleavage has been observed Perfluorinated alkyl benzocyclobutanes, when treated with antimony pentafluoride, ean be converted to perfluorinated styrenes and then transformed to perfluorinated indans [77S, 779]... 

The presence of an substituent, found in the pyrrolidine enamine of 2-methylcyclohexanone, blocks the possibility of an intramolecular proton transfer in the zwitterionic intermediate and thus only the benzocyclobutane... 

It has long been assumed that the activity of corticoids which contain an additional ring anmilated to the 16,17 positions such a.s halcinonide (76), owed their activity to the hydrolyzed product. It is thus of note that full activity seems to be retained by a compound which incorpo-latcs a ring at that position held in place by carbon-carbon bonds. Diels-Alder condensation of halcinonide precursor 77, with benzocyclobutadiene, obtained by heating benzocyclobutane 78, Icad.s after hydrolysis of the acetate to naflocort (79) [17]. 

During investigation of the synthesis of benzocyclobutane 193, Cava and coworkers118 found that o-quinodimethane 192, generated in the pyrolysis of 1,3-dihydrobenzo[c]thiophene 2,2-dioxide (191), can be trapped by Af-phenylmaleimide to give N-phenyl-1,2,3,4-tetrahydronaphthalene 2,3-dicarboimide (194) (equation 125). 

Brook et al. 5X1 observed such reactions during the formation of siienes by photolysis. Using radiation with A > 360 nm, they photolyzed acylsi-lanes such as 127, which bears a mesityl group attached to the carbonyl carbon. On prolonged photolysis of the initially formed silene 128, the C—H bond of the ortho methyl group of the mesityl group added to the silicon-carbon double bond to form the benzocyclobutane 129. Alternatively a 1,5-H shift would lead to the species 130, which would also yield the benzocyclobutane on electrocyclic rearrangement. 

A mixture of sodamide, bromoanisole, and l-methoxy-2-methyl-l-(trimethylsilyl-oxy)-l-butene were reacted at room temperature at a 50 millimolar scale. After some two horns, with slight emission of ammonia, the reaction suddenly became exothermic, with violent gas emission and on one occasion a fire. This was a modest scale-up of a literature procedure for synthesis of 2-alky lbenzoic acids, via a benzyne intermediate. It is advised that this reaction be employed only on smaller scale, with safety precautions. The reaction must pass through a benzocyclobutane intermediate, this, or another, high energy species might accumulate and then decompose. 

Oppolzer and Robbiani have reported highly stereoselective total syntheses of alkaloids such as chelidonine by an intramolecular o-quinodimethene/nitrostyrene-cycloaddition (Scheme S.7).34 (Benzocyclobutane is used as a source of quinodimethene). The high regio- and stereoselectivity in the intramolecular cycloaddition is remarkable a strong preference for transition state, exo-N02, over transition state, emfo-N02, is responsible for the stereoselectivity. 

The complex 2 also reacts with ethylene to form the metallacycle 6, which is converted into a benzocyclobutane (8) in two steps. 

Aromatic compounds can participate in both [2+2] and [4+2] photocycloaddition reactions with uracil derivatives to give either benzocyclobutane or ethenoquinazoline (barrelene) derivatives, which can then undergo a number of subsequent photochemical reactions. The products obtained are dependent upon the reaction conditions, and thus the photocycloaddition reaction between naphthalenes 470 and l,3-dimethyl-5-fluorouracil 471 in cyclohexane gave 4a-fluoro-5,10-ethenobenzo[/]quinazolines 472 as products as a result of a [4+2] photocycloaddition (photo-Diels-Alder) reaction <2002TL3113, 2003H(61)377>. 

The thermal [4 + 2] cycloaddition of 3-acetyl-2(3F/)-oxazolone 84 to the reactive dienes, o-quinodimethane 224 and isobenzofuran 226, generated from benzocyclobutane and 1-ethoxydihydroisobenzofuran, respectively, proceeds... 

In this review, the term benzocyclobutene is used to refer to structure I, with the numbering system shown below. This was done to be as consistent as possible with the majority of the references used in the preparation of this review. It should be noted however, that according to CAS, the name benzocyclobutene actually refers to benzocyclobutadiene 130 and what is commonly called benzocyclobutene is 1,2-dihydrobenzocyclobutadiene. The prefered CAS name for what is commonly called benzocyclobutene 1 is bicyclo[4.2.0]octa-l,3,5-triene with the numbering system shown below in 130. Benzocyclobutene 1 has also been referred to as benzocyclobutane, cardene, benzocyclobutene-1,2-dihydro, cyclobutabenzene and generically as a cyclobutarene. 

Thermally induced isomerization of the benzocyclobutane (83) gives the pyrroloisoquino-line (84), the pyridine ring of which can be aromatized with iron(III) chloride (Scheme 29). Similarly, the aldehyde (85 X = 0) or its O-methyl oxime (85 X = NOMe) gives the cis-trans mixture (86). If p- toluenesulfonic acid is included in the reaction mixture the pure cis compounds are obtained (72AG(E)l03l). 

The synthetic strategies used for the preparation of pyrans on insoluble supports have mainly been hetero-Diels-Alder reactions of enones with enol ethers and ringclosing olefin metathesis (Table 15.33). Benzopyrans have been prepared by hetero-Diels-Alder reactions of polystyrene-bound o-quinodimethanes with aldehydes. The required quinodimethanes were generated by thermolysis of benzocyclobutanes, which were prepared in solution [308]. Other solid-phase procedures for the preparation of benzopyrans are the palladium-mediated reaction of support-bound 2-iodo-phenols with 1,4-dienes (Entry 5, Table 15.33) and the intramolecular Knoevenagel... 

A More Complex Benzocyclobutane To Isochroman-3-one Rearrangement (c.f. Problem 138)... 

Efficient ortho-difunctionalization of aromatics (87) can be achieved by insertion of arynes into the C-C a -bonds of /3-dicarbonyls (88), using a simple aryne source (89) under mild conditions.338 The /1-dicarbonyl reactant can be a dione (aromatic or aliphatic), or a diester (including dilactones). A mechanism involving the formation of a benzocyclobutane is proposed. 

Diazetidines. A saturated four-membered ring containing two adjacent nitrogen atoms is named a 1,2-diazetidine 1. When the two nitrogen atoms and the two carbon atoms are alternatively present in the four-membered ring, it is named a 1,3-diazetidine 2, which is also known as uretidine. Fused multinuclear heterocyclic systems are known as diazacyclobutane derivatives. For example, 3,4-benzo-l,2-diazetidine is referred to as l,2-diaza-3,4-benzocyclobutane 3. 

Benzocyclobutanes can undergo [4+2] reactions using toluenesulfonyl cyanide or A -benzylidenephenylsulfon-amide leading to tetrahydroisoquinolines and dihydroisoquinolines, respectively (Scheme 79) <2000AGE1937>. 

Isoquinolines can be generated from benzocyclobutanol and 2-cyanopyridine <1994TL9191> (Equation 185). Zirconocene-copper-mediated coupling of benzocyclobutanes in the presence of nitriles gives the isoquinoline, albeit with only select examples of 3-substitution (Scheme 116) <20030L877>. 

The curious reaction of benzyne with 1-pyrrolidinocyclohexene leads to a benzocyclobutane derivative in addition to a small amount of 2-phenylcycIohexanone.234... 

The application of RAIN is illustrated in Figure 7.9 by the rearrangement of a benzocyclobutane 8 into a isochromanone II that has recently been studied by Kametani et al (ref. 14,25). 

Fig. 7.9 Electrocyclic tandem reaction as generated by RAIN. Rearrangement of a benzocyclobutane 8 into a isochromanone lTvia intermediate compounds 9 and 10.

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