Diels-Alder reactions anthraquinone synthesis

Scheme 12. Synthesis of benzo[a]anthraquinone by Diels-Alder reaction using styrene as the diene [51]...

It has been reported that several transition metal complexes catalyze the hetero-Diels-Alder reaction between a variety of aldehydes, in particular benzaldehyde, and Danishefsky s diene (Sch. 52). With the [CpRu(CHIRAPHOS)] complex the ee is modest (25 %) (entry 1) [192]. The chiral complex VO(HFBC)2 performs better in this reaction (entry 2) [193]. In experiments directed towards the synthesis of anthra-cyclones, this complex was used in cycloadditions between anthraquinone aldehydes with silyloxy dienes. One example is shown in Sch. 53 [194]. Compared with the chiral aluminum catalyst developed earlier by Yamamoto and co-workers [195], the vanadium catalyst results in lower enantioselectivity but has advantages such as ease of preparation, high solubility, stability towards air and moisture, and selective binding to an aldehyde carbonyl oxygen in the presence of others Lewis-basic coordination sites on the substrate. 

Anthraquinones. A regioselective synthesis of polyhydroxyanthraquinones is based on Diels-Alder reactions of 1 with chloro-substituted naphthoquinones. An example is the synthesis of 1,6-dihydroxyanthraquinone (3) from 3-chlorojuglone (2). Analogous syntheses are possible by use of vinylogous ketene acetals related to... 

Diels-Alder reactions of 1235 synthesis of 1228, 1231, 1250, 1335 Quinone oxime tautomers 251, 252 Quinones—see also Aminoquinones, Anthraquinones, Arenolquinones, Benzoquinones, CaUxquinones, Hydroquinones, Hydroxyquinones, Naphthoquinones, Perylenequinones, Scabequinone reduction of 1108 Quinone units 1396... 

Rubiaceaous plants are usually rich in anthraquinones. The first four anthraquinones, 2-methyl-3-methoxyanthraquinone (7), 2-methyl-3-hydroxyanthraquinone (8), 2-methyl-3-hydroxy-4-methoxyanthraquinone (9) and 2,3-dimethoxy-6-methylanthra-quinone (10) reported in genus Hedyotis were isolated from H. diffusa [26]. All the compounds except for (10) are substituted only in ring C. The structure of (10) has been later confirmed by synthesis based on Diels-Alder reaction. This anthraquinone has been the only one reported from a natural source until today. Other anthraquinones possessing the same substitution pattern are synthetic products [27]. 

At this point, all that remained to complete the targeted natural product (1) was the attachment of the anthraquinone system, which, as discussed above, projected a Diels—Alder reaction with an isobenzofiiran (i. e. 13). Thus, a synthesis of its precursor, phtha-lide 67, was developed as shown in Scheme 9. Since most of these transformations are relatively routine, we will not describe them in any detail here, except to note that the ability to incorporate several different protecting groups for the phenol functions at different stages of the synthesis (cf. 62, 63, 67) was a critical element for the completion of dynemicin A (1). As we shall see, only 67 ultimately proved capable of both participating in the desired Diels—Alder reaction and being elaborated to the complete DE anthraquinone system. 

SCHEME 16.33 Double Diels-Alder/elimination reaction toward highly substituted anthraquinone synthesis. 

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