3-Cyanophthalides

Substituted derivatives of 3,4-didehydropyridine have also been prepared, and these have been utilized in a variety of cycloaddition and nucleophilic addition reactions (82T427 89ACR275). A recent example involves the synthesis of azaanthraquinones by reaction of the pyridyne with the lithium salt of 3-cyanophthalide (Scheme 156), in a sequence that also involves the intermediacy of a 3-pyridyl carbanion (88H2643). 

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]. 

In a clever, convergent and regiospecific route to the aklavinone ring system, it was shown that treatment of the lithio anion of the cyanophthalide 1 with the enone lactone 2 in THF/HMPA gave the tetracyclic quinone 3 directly (25% yield after conversion to the methyl ester and purification). 

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

An annelation reaction of a,3-unsaturated carbonyl compounds with cyanophthalides (34) can be used for the construction of naphthoquinone and antlnaquinone systems in biologically active natural... 

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... 

The carbanion of 3-cyanophthalide cf 534) cycloadds to 3-pyridynes to give 2-azaanthraquinones in good yield. The mechanism is as shown for 535 533. With 7-... 

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