3-Cyanophthalides anthraquinones

A method for synthesis of anthraquinones is by reaction of cyanophthalide carban-ions with benzynes [162], It is particularly useful for the access of 2 aza-l,3,8-trimeth-oxyanthraquinone because of the high regioselectivity imposed by the methoxy groups and the nitrogen atom of the pyridine. 

Direct formation of aza-anthraquinones 181 has been achieved using in situ generated lithio cyanophthalide 177 (a 1,4-dipole equivalent) and 3,4-pyridyne 178 (Scheme 52) [88H(27)2643]. Thus, addition of 3-bromopyridine derivative to a solution of LDA and 177 at -40°C leads, when warmed to room temperature, to aza-anthraquinones 181 in good yields via intermediates 179 and 180. This type of reaction has also been applied to 4-bromoquinoline to give benzo[rf]-2-azaanthraquinone in 60% yield [88H(27)2643]. 

Both o- and p-quinone acetals, also prepared in situ, reacted with 3-cyanophthalide affording hydroxy-anthraquinones [38],... 

The annulation of these oxidation products 9, 10 with the anion of 3-cyanophthalide 105 affords access to a range of anthraquinones 106 ° (equation 43). 

The easily available protected phenol ether 83 was subjected to anodic oxidation (-bl.3 V V5. SCE) in MeOH containing NaOAc and LiC104 as a supporting electrolyte to afford in 53% yield quinone monoketal 84, which reacted with 5-fluoro-3-cyanophthalide (85) in the presence of LDA to give anthraquinone 86. This quinone was converted... 

As already shown in Scheme 16, the electrochemically generated /t-quinone monoacetal (84) reacted with 3-cyanophthalide anion 85 to give the anthraquinone 86. Similarly, PhI(OAc)2-promoted oxidation of 4-substituted phenols in MeOH provides the corresponding cyclohexa-2,5-dienones, which react with the anion of 3-cyanophthalide to yield a variety of anthraquinones . A-Acetyltyrosine ethyl ester 456 was subjected to... 

Two modifications which lead directly to anthraquinones without the need for the final oxidation step have been described. In one , the phthalide carries a phenylsulfonyl substituent in the 3-position, whereas in the other a 3-cyanophthalide is used. In this way the intermediate 535 formed by attack of the phthalide on the benzyne can collapse directly to an anthraquinone. A number of naturally occurring anthraquinones have been prepared this way h252... 

An annelation reaction of a,p-unsaturated carbonyl compounds with cyanophthalides (34) can be used for the construction of naphthoquinone and anthraquinone systems in biologically active natural... 

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