2-Azaanthraquinones

The regiochemistry of the Diels-Alder reaction of l-alkoxy-3-(rm-butyldimethylsilyl)oxy-2-azadienes and naphthoquinones, as a route to 2-azaanthraquinon-3-ones, has been investigated (91H915). 

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]. 

Choshi, T., Kumemura, T., Nobuhiro, J., and Hibino, S. 2008. Novel synthesis of the 2-azaanthraquinone alkaloid, scorpinone, based on two microwave-assisted pericyclic reactions. Tetrahedron Letters, 49 3725-28. 

Aza-Wittig reactions in fused pyrimidine synthesis, 55, 159 synthetic uses, 57, 37 2-Azaanthraquinone, synthesis, 56, 275... 

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-... 

Choshi et al. (2008) have developed a novel method for the total synthesis of the 2-azaanthraquinone alkaloid in nine steps, out of which, one key step involves a microwave-assisted [4+2] cycloaddition reaction for the constriction of a 2-azaanthraquinone frame work. 

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). 

Pummerer reaction conditions was followed by cycUzation to isomilnchnone 292 and hence to cycloadduct 293, which loses water to form a-pyridone 294. Subsequent manipulation involving deoxygenation and debenzylation completed the synthesis. In similar fashion, the azaanthraquinone alkaloid dielsiquinone was synthesized for the first time. Also, the quinolizidine alkaloids ( )-lupinine and ( )-anagyrine, and the ergot alkaloid ( )-costaclavine were synthesized using this Pummerer cyclization-cycloaddition cascade of imidosulfoxides and isomiinch-nones. 

Benzo[g]quinolines, e.g. (40), and benzo[g]isoquinolines are oxidized to the corresponding azaanthraquinones using, for example, chromium trioxide in acetic acid (Scheme 28) (79KGS517). 

Lewis acid catalysis for aza Diels-Alder reactions of 2-aza-l,3-butadienes [254], In analogy to the hitherto discussed aza Diels-Alder reactions, evidence for a non-concerted mechanism of these transformations has emerged. Thus, Mellor et al. have found that under suitable conditions azaanthraquinone 3-34 does not only form the expected cycloadduct 3-37 upon treatment with a-methylstyrene and formaldehyde, but the tertiary alcohol 3-36 is also generated presumably via cation 3-35. Alcohol 3-36 is easily converted into the cycloadduct 3-37 and 3-35 is therefore supposed to act as intermediate in a non-concerted multistep sequence (Fig. 3-12) [255,256]. More recent studies on N-arylimines performed by Laschat et al. have corrobated the assumption that non-concerted processes represent a noteworthy mechanistic pathway in reactions of 2-aza-l,3-buta-dienes with suitable dienophiles [257]. 

Ghosez et al. could also achieve high asymmetric inductions by reacting electron-rich 2-aza-l,3-butadienes with a,/J-unsaturated chiral oxazolines [283]. Other applications of electron-rich 2-aza-l,3-butadienes in normal electron demand aza Diels-Alder reactions have been aimed at the preparation of natural cibrostatines [284] and azaanthraquinones [285]. 

In the laboratory of D.W. Cameron the total synthesis of the azaanthraquinone natural product bosttycoidin was undertaken using the Minisci reaction and the intramolecular Houben-Hoesch reaction as the key steps. It is worth noting that the synthesis of specific di- and trihydroxyazaanthraquinones by the Friedel-Crafts acylation is very limited due to the lack of orientational specificity and the lack of reactivity of pyridine derivatives in acylation reactions. 

Oxidation of liriodenine with chromic acid gave 1-azaanthraquinone-... 

Guatteria psilopus Mart. (Anonaceae) along with, the aporphine guatter-ine (3a). It was noted that atherospermidine (3) was formed from guat-terine using chromium trioxide in pyridine. Further oxidation of atherospermidine by chromium trioxide in sulfuric acid yielded 1-azaanthraquinone-4-carboxylic acid (la). 

Scheme 4. Proposed biogenetic origin of azafluorenones from azaanthraquinones.

Diels-Alder Reactions. Bp3-OEt2 is used to catalyze and reverse the regiospecificity of some Diels-Alder reactions, e.g. with pen-hydroxylated naphthoquinones, sulfur-containing conpounds, the reaction of 1-substituted trans-1,3-dienes with 2,6-dimethylbenzoquinones, and the reaction of 6-inethoxy-l-vinyl-3,4-dihydronaphthalene with p-quinones. BFs-OEta has a drastic effect on the regioselectivity of the Diels-Alder reaction of quinoline- and isoquinoline-5,8-dione with piperylene, which produces substituted azaanthraquinones. This Lewis acid is the most effective catalyst for the Diels-Alder reaction of furan with methyl acrylate, giving high endo selectivity in the 7-oxabicyclo[2.2.1]heptene product (eq 35). ... 

The reader should always bear in mind diat spontaneous oxidation in air can occur if a l droquinone is sufficiently activated towards oxidation. An example of diis is exemplified by KeUy et al in a short synthesis of diazaquinomycin A (68). The synthesis incorporates die first reported use of a double Knorr cyclization. The key intermediate (66) was prqiared in just two steps from die MOM-protected hydro-quinone (65). Cyclization of the compound (66) then gave diazaquinomycin B (67), which either under die reaction conditions or by careful isolation prior to simply stirring the solution in an open flask afforded the antibiotic diazaquinomycin A (68), thereby confirming the structure of the < y recorded example of the tricyclic 1,8- azaanthraquinone ring system (Scheme 14). 

Cycloadditions of crotonaldehyde N,N-dimethylhydrazone 154 with naphthoquinone 155 at room temperature afforded cycloadduct 156 in yields superior to atmospheric pressure conditions (Scheme 38) [59]. Interestingly, elongation of pressurizing time from 6 to 24 h diminishes the yield of azaanthraquinone, as aminoquinone side products 157 and 158 are formed. 

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