Isobenzofuran quinones

The generation and trapping of 5,6-bis(trimethylsilyl)benzo[c]furan 126 was reported by Wong utilizing Warrener s s-tetrazine methodology. The trapping of the silylated isobenzofuran with A-phenylmaleimide is illustrated below. A number of other dienophiles such as dimethyl acetylenedicarboxylate, benzoquinone, naphthoquinone and anthra-l,4-quinone have also been used <00TL5957>. 

A novel route to anthracyclinones is based on the chemistry of quinone-isobenzofuran adducts (77TL3537). The 3-methoxybenzyne-furan adduct (1) was reacted with a-pyrone to give a mixture of lactones (2). Thermolysis of this intermediate in the presence of quinone (3) gave in 93% yield the tetracyclic adduct (4) as a stereoisomeric mixture. Aromatization with sodium acetate in acetic acid gave quinone (5) which was subjected to reduction, C-ring oxidation and mild acid hydrolysis to afford a mixture of ( )-7-deoxydaunomycinone (6) and its 1-methoxy regioisomer (Scheme 1). 

The formation of the substituted dibenzofuran-l,4-dione (405) from 5,5 -dimethyl-2,2 -di-p-benzoquinone (406) can be achieved thermally or by photolysis in hydroxylic solvents such as methanol or acetic acid,421 and a related cyclization has been observed in dinaphtha-quinones.422 A dibenzofuran derivative (407) is also obtained on irradiation of the conjugated dione (408) the intermediate (409) can be isolated by maintaining a temperature of 6° in the reaction flask.423 A mechanism for the photorearrangement of 2-acetyl-3-furyl-p-benzoquinones to derivatives of isobenzofuran has been proposed424 [Eq. (109)]. 

Synthetically, compound 152 was prepared by the Friedel-Crafts procedure from furan-3,4-dicarbonyl chloride and a tetralin derivative (85JCR (S)338). 1,4-Dihydro-l,4-epoxy-5,8-naphthoquinone, when treated with 3,6-di(2-pyridyl)-l,2,4,5-tetrazine, yielded the quinone 153 (75JCS(P1)1339) derivatives of 153 are also known (74CC1034). The parent compound (153) is a stable derivative of the unstable isobenzofuran. Finally, 3-acetyl-2-furyl-1,4-benzo- (or -naphtho-) quinones are isomerized photochemically in aprotic solvents into the quionones 154 (66HCA1806). 

Recently, reactions of PQ and related quinones with 1,3-disubstituted isobenzofurans have been reported 184> to involve 1,4-cycloaddition as well as cleavage of the furan ring. 

Cycloaddition of diphenylisobenzofurans to (101), to sulphenes, to 2-phenyl-3-spirocyclopropylazirines, and to o-benzoquinonedi-imines have been reported. The preparation and trapping of 1-methoxy- and 1-benzyl-isobenzofuran have been described and a high degree of regio-and stereo-specificity is observed in the reactions of a range of 1-substituted isobenzofurans with quinone acetals, for example in the formation of... 

Most of the azulenoheterocycles having the azuleno-o-quinone dimethide structure (type 3) are less stable than the other types (87H(26)2025). o-Quinonoid azulenothiophene 44 is rather unstable even at room temperature and could not be demethoxycarbonylated (83CL1721). o-Quinonoid furan 168 is not isolable at all (83CC1025). Furans 149 (rather unstable) and 152 show bond fixation, they are more stable than isobenzofuran, but behave similarly with respect to Diels-Alder cycloaddition (03OBC2383). 

Condensed p-quinones. 2,3-Dihydroanthracene-l,4-dione in dimethyl sulfoxide added under Ng and anhydrous conditions to a cold mixture of phthalaldehyde and a soln. of Na-methoxide in methanol, and stirred 6 hrs. at room temp. -> pentacene-6,13-quinone. Y 77%. - Similarly with l,3-diphenyl-5,6-dihydro-isobenzofuran-4,7-dione l,3-diphenylanthra[2,3-c]furan-4,ll-dione. Y 50%. F. e. s. A. Verine, Y. Lepage, and B. Casteignau, Bl. 1973, 1154. 

Bloomer and Lankin also examined the behavior of isobenzofurans in the context of quinone synthesis. Lactone 198 was treated sequentially with LDA and chlorotrimethyl-silane to produce 199a (Scheme 13.48) [85]. Because C-silylation occurs preferentially over 0-silylation in this system, the bis-silylated 199 was used for cycloaddition studies. The reaction of 199a with DMAD afforded oxacycle 200, and exposure of the cmde reaction mixture to TFA produced 193a in 82% yield. The triethylsilyloxy derivative... 

Using KHMDS and TBS-Cl, however, produced only the 0-silylated isobenzofuran 512, which was immediately reacted with dimethyl quinone 513 to provide cycloadduct 514. Reaction of the crude reaction mixture with TFA afforded 515 in 74% yield from 511. 

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