Isobenzofurans cycloaddition

SCHEME 16.25 Synthesis of aromatic compounds from isobenzofuran cycloaddition. 

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. 

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). 

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. 

Diphenyl cyclopropenone has been reacted with activated dienes like diphenyl isobenzofuran234 and diethylamino butadiene194. Interestingly, the isobenzofuran does not add to the CVC2 bond as in cyclopropenone, but to the C /C3 bond in a (3+4) cycloaddition as indicated by the product 363. 

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. 

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... 

Such cycloadditions are dependent on the interactions of the azepine HOMO and the diene LUMO. Theoretical consideration of these orbitals reveals that bonding overlap is favourable for C-6—C-7 and C-4—C-5 additions and that, on the basis of secondary orbital interactions, the endo product is favored. Experimentally, however, it is found that additions are periselective and C-4—C-5 addition predominates in the cycloaddition of 1//-azepines with cyclopentadienones, isobenzofurans, tetra- and hexa-chlorocyclopentadienes, 1,2,4,5-tetrazines, a-pyrones and 3,4-diazacyclopentadienones (8lH(15)1569). 

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. 

Kanematsu and co-workers devised a simple pathway to isobenzofurans and dihydroisobenzofurans starting with substituted furans of type 62. Treatment with strong base results in an alkyne-allene isomerization. Subsequent intramolecular cycloaddition, ring opening (probably oxygen lone-pair assisted), and acidic workup give 63. 

No evidence for Dewar-isobenzofuran 150 was obtained, however a small amount of o-phthalaldehyde detected in the mixture may point to 150 as an intermediate. The photoreactions of 1,3-DIBF with cycloheptatriene (74TL343 75JA355 80AHC135) have been reinvestigated (83CB618).With anthracene a [774 + 7t4] cycloadduct (56%, mp 173°C) is obtained (83CB618). A thermal cycloaddition across the 4,7-position of an isobenzofuran has been reported previously (78JHC793). 

There is only one recorded case of cycloaddition to a cycloproparene that takes place other than across the bridge bond and that is withcyclopropa[/]isobenzofuran. In this case addition of dimethyl fumarate aromatizes the six-membered ring (equation 26) but the... 

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 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. 

An example concerns the cycloaddition of buta-l,3-dicnc with (trifluoromethyl)malcic anhydride, which is exothermic and gives isobenzofuran 18. ... 

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. 

Diels-Alder cycloadditions involving thiete sulfones as dienophiles occur with butadiene,cyclopentadiene, 1,2,3,4-tetraphenylcyclopentadiene, anthracene. tetraphenylcyclopentadienone, l,3-diphenyl-2H-cyclopenta[l]-phen-anthrene-2-one, a-pyrone, l-(Af,Af-dimethyl)- and l-(7V,A -diethyl)-l,3-butadiene, furan, 2,5-dimethylfuran, l,3-diphenylisobenzofuran, isobenzofuran," and l,3-diphenylnaphtho[2,3-c]furan. Generally, thiete... 

---