Isobenzofurans cycloaddition reactions

Benzo[c]furans (isobenzofurans) are very reactive but generally unstable dienes which are prepared in situ and trapped. The in ihu-generated isobenzo-furan 33 was trapped by cycloaddition reaction with bis(methyl (S)-lactyl) ester 34 to afford [32] optically active naphthols (Equation 2.12). The cycloaddition was carried out in the presence of a catalytic amount of glacial acetic acid and represents a facile one-pot procedure to synthesize substituted naphthols. 

Cycloaddition reactions of the C = N bond of azirines are common, e.g. Scheme 31 (71AHC(13)45, B-83MI 101-03, 84CHEC(7)47). Azirines can also participate in [4 + 2] cycloadditions with cyclopentadie-nones, isobenzofurans, triazines, and tetrazines. 

A review article summarizing various aspects of the chemistry of benzo[f]furans (isobenzofurans) bridging the gap between these theoretically interesting but usually fugitive molecules and natural products was published . Another review deals with the recent advances in the chemistry of these molecules <1999AHC1>. The main reactions of benzo[cycloaddition reactions, which are summarized in Section 3.06.2.3.1. 

There are general reviews on heterocyclic syntheses by cycloaddition reactions of isocyanates and on the use of heterocyclic cations in preparative organic chemistry. More specific topics are 5-hydroxymethylfuran-2-carb-aldehyde, isobenzofurans and related ort/io-quinonoid systems, the conversion of 2//-cyclohepta[Zj] furan-2-one (1) into derivatives of azulene, the synthesis of indoles from o-alkylphenyl isocyanides, and abnormal Fischer indolization reactions of o-methoxyphenylhydrazones. Two reviews on isoindoles have appeared and a lecture on highly conducting charge-transfer complexes that are based on heterocyclic selenium and tellurium donors has been reprinted.Recent advances in the chemistry of imidazole and in the use of nitro-imidazoles as radiosensitizers have been summarized. There have been reviews on benzimidazole A -oxides and on dihydrobenzimidazoles, benzimidazolones, benzimidazolethiones, and related compounds. Other topics are synthetic applications of 1,3-dithiolium and 1,3-oxathiolium salts and of isoxazoles, the chemistry of benzisoxazoles, 2-amino-oxazoles, 5-oxazolones (2), furoxans, benzofuroxans, and related systems, the synthesis of five-membered meso-ionic compounds, and tetrazoles. ... 

A new cathodic cyclodimerisation of 4-pyrones yields either (90) or (91) depending on conditions,88 2-Benzopyran-3-one has been isolated at low temperature and intercepted by NPM as the adduct (92) 88 high-pressure cycloaddition reactions of 2H-pyran-3-ones with a variety of dienophiles have been recorded.88 Cycloaddition reactions of furans and isobenzofurans continue to dominate this section. Dienophiles whose reactions with furan have been studied recently include phenylsulphonylpropadiene (giving predominantly the endo-adduct (93) 8b. benzynes (derived from aryloxazoli nesJ.8 and... 

Isobenzofurans have long been recognized as outstanding dienes for the Diels-Alder and other cycloaddition reactions leading to oxabicyclo products. A 1988 review appeared in which the progress in the chemistry of isobenzofurans and the chemical transformations of oxabicyclo adducts has been intensively discussed <88X2093 >. 

Higher homologues of linear acenes have been synthesized using the isobenzofuran cycloaddition method as illustrated in the following schemes (Schemes 16.26 and 16.27) [29]. The cycloadduct of tetracyclone shown in Scheme 16.26 (in the box) is a synthetic equivalent of benzodifuran, and on heating, it releases 1,2,3,4-tetraphenylbenzene by a retro Diels-Alder reaction generating isobenzofuran in situ, probably in a sequential manner. 

Isobenzofurans have the useful property of undergoing cycloaddition reactions with dienophiles, and this has been exploited in many elegant reaction schemes. Hence, new routes to suitably substituted derivatives are always welcome. It has been known for some time that strong base induced 1,4-elimination of allylic ethers is a general reaction and this reaction has now been applied to the synthesis of isobenzofuran in solution (99) (Scheme 11). Keay et al. have... 

Use in Isobenzofuran Synthesis. 1,2,4,5-Tetrazine has also been involved in multiple cascade cycloaddition reactions to generate complex substrates. The reactivity of isobenzofuran was delineated with Cgo (eq 5). Starting from a [4+2] cycloaddition between 19 and 1,2,4,5-tetrazine, intermediate 20 was generated. Next, a retro-[4+2] produced the desired isobenzofuran, which... 

The 27T-electrons of the carbon-nitrogen double bond of 1-azirines can participate in thermal symmetry-allowed [4 + 2] cycloadditions with a variety of substrates such as cyclo-pentadienones, isobenzofurans, triazines and tetrazines 71AHC(13)45). Cycloadditions also occur with heterocumulenes such as ketenes, ketenimines, isocyanates and carbon disulfide. It is also possible for the 27r-electrons of 1-azirines to participate in ene reactions 73HCA1351). 

Bispropargyl ether 222 isomerized on treatment with tBuOK into the naphthalene 223 via the intramolecular [4+2]-cydoaddition of the phenylallene with the acetylene moiety. Similar reactions of enynyl propargyl ether 224 took place at room temperature to give two isomeric isobenzofurans, 225 and 226. The major product 226 presumably arises from the intramolecular [4 + 2]-cycloaddition of the bisallenyl ether, whereas the minor product 225 is formed by the [4 + 2]-cycloaddition of the monoallenyl ether [180]. 

One of the drawbacks associated with the cycloadditions based on 27 is the low reactivity of halogenocyclopropenes towards dienes. This may be overcome if furans or isobenzofurans are used instead. The aromatization of the adducts is, however, not straightforward. For example, reaction of the exo-a.dd iCt of 27 to diphenylisobenzofuran (DPHIBF, 44) with BuLi affords no cycloproparene, but a product 46, where the bromo substituent is replaced by hydrogen. Aromatization may, however, be effected by use of low-valent titanium. This sequence provides a simple access to 48. The parent 42 is also available by this route from 45 via 47. Exposure of adducts of furans, such as 49, to low-valent titanium leads, however, to mixtures of benzocyclopropehe (1) and 1,6-dihalogenocycloheptatriene (51). Cycloaddition of furans to tetrahalogenocyclopropenes may equally be realized, but the adducts decompose in the presence of low-valent titanium and afford no cydoproparenes. 

In order to confirm the stmcture of the tricyclic thietane 60, it underwent several reactions <20040L1313>, which were performed on the substituent of the ring carbon atom. The thietane 60 underwent hydrogenation on palladium-on-charcoal to give the fully saturated compound 61. The presence of a double bond in compound 60 was also confirmed by [4+2] Diels-Alder cycloaddition of dimethyl l,2,4,5-tetrazine-3,6-dicarboxylate as well as of diphenyl-isobenzofuran, which led to the formation of cycloadducts 62 and 63, respectively (Scheme 10) <20040L1313>. 

A one-pot synthesis of isoquinolines through coupling of 2-alkynylbenzaldehyde derivatives with chromium cyanocarbene complexes was reported. The reaction involved formation of an isobenzofuran first, which then underwent intramolecular Diels-Alder cycloaddition with the nitrile. One important feature of this process was the deoxygenation of the initial adduct to give the isoquinoline ring <03OL4261>. 

The pyridyl azirine 97 was prepared from mesitylsulfonyloxy oxime 96. This is one of the first examples of heteroaromatic substituted azirines reported. This azirine undergoes a Diels-Alder reaction with isobenzofuran to provide the rwn-cycloadduct 98 in 54% yield <2005S555>. In addition to isobenzofuran, this azirine undergoes cycloaddition with a number of different dienes, including cyclopentadiene (82%), 1-methoxy-butadiene (58%), and Danishefsky s diene (67%). 

The isobenzofuran acts as a Av electron component in a [4 + 2] cycloaddition to trap the intermediate. As usual, both components must react suprafacially. Thus, because the fusion between the six- and seven-membered rings in 6-18 is tram, it must be the tram double bond in 6-16 that reacts in this trapping reaction. 

Oxazoles ate another class of heteroaromatic dienes which readily undergo Diels-Alder reactions with benzynes. For example, slow, simultaneous injection of solutions of triazole (483) and lead tetraacetate to a solution of oxazole (515) in CH2CI2 at 0 C afforded cycloadduct (516) in essentially quantitative yield. The latter is a convenient source for the unstable isobenzofuran (517), which can be trapped by [4 + 2] cycloaddition to a variety of dienophiles, e.g. by A(-methylmaleimide (Scheme 121). 

Bicyclo[3.2.0]hept-l-ene (151) can be prepared from the tosylhydrazone of norbornan-7-one via norbornan-7-ylidene 150 in 74% as a stable olefin (144). Similarly, 152 has been obtained from norborn-2-en-7-one in a yield of 67% (144a). Introduction of a further double bond leads to the strained triene 153, which has been prepared from 105b (Scheme 3). Compound 153 dimerizes readily at room temperature to a 1 1 mixture of hydrocarbons 154 (145). The most likely structures of these dimers arise from a formal [2 + 2]cycloaddition of the bridgehead double bonds of 153 with each other. Support for the intermediacy of 153 comes from trapping experiments with 1,3-diphenyl-isobenzofuran, which yield a mixture of stereoisomers via reaction with the bridgehead double bond of 153. 

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