One-pot synthesis of isoquinoline-5,8-dione derivatives from acylquinones and enamines

A Survey of Synthetic Routes towards the Pyranonaphthoquinone Antibiotic Pentalongin and Syntheses of the Corresponding Nitrogen Derivatives

“…56 It has been suggested that the naturally occurring 2-aza-anthraquinones originate in vivo from the incorporation of ammonia into the skeleton of the corresponding pyranonaphthoquinone analogues. 57 With reference to this hypothesis, it was postulated that bostrycoidin (100) might be formed out of fusarubin (96), first by oxidation of the intermediate ring-opened product 97, followed by reaction with ammonia (Scheme 19). In vitro treatment of fusarubin (96) with ammonia indeed gave rise to a 100% conversion into bostrycoidin (100).…”

“…57 With reference to this hypothesis, it was postulated that bostrycoidin (100) might be formed out of fusarubin (96), first by oxidation of the intermediate ring-opened product 97, followed by reaction with ammonia (Scheme 19). In vitro treatment of fusarubin (96) with ammonia indeed gave rise to a 100% conversion into bostrycoidin (100). 57 This process of ammonia incorporation has been suggested to function as a detoxifying mechanism for high ammonia concentrations.…”

“…In view of the physiological importance of 2-aza-anthraquinones, as outlined above, considerable efforts have been devoted to establish efficient synthetic strategies of these compounds. To date, three major synthetic pathways have been developed (Scheme 20): (i) via cycloaddition reactions of suitable dienes to isoquinoline-5,8dione or naphthoquinone derivatives 115 and 116 [81][82][83][84][85][86][87] (ii) via initial acylation of pyridines or substituted arenes followed by an intramolecular condensation/cyclization of intermediates 118 or 119 [88][89][90][91][92][93][94][95][96][97] and (iii) via construction of the heterocyclic ring starting from substituted naphthoquinones 120 or 121 [cf. the biomimetic construction of bostrycoidin starting from fusarubin ( 96)].…”

“…89 An elegant variant of this synthetic route makes use of carbanions of 3-cyano-3H-isobenzofuranones (also named 3-lithio-3cyanophthalides) which react with heteroarynes to yield 2-aza-anthraquinones in one step. 72 As outlined in Scheme 20, a third synthetic approach consists of the construction of the azaheterocyclic ring using condensations of enamines 96 or aniline 97 with 2-acylnaphthoquinones 121 or via ammonia-induced cyclizations of naphthoquinones 120. [98][99][100] The latter strategy was elaborated at our Department, and resulted in efficient syntheses of various 2-aza-anthraquinones.…”

First Zinc Bromide Promoted Annulative Domino Reactions between Enamines and Cyclic Morita–Baylis–Hillman Alcohols: Synthesis of N,O-Ketals

“…3 After the pioneering work of Stork 4 in the fifties, the nucleophilic behavior of this functional group has been successfully exploited in a number of conjugate additions to electron-poor alkenes such as ,-unsaturated enones, 5,6 allenyl ketones and esters, 7 as well as methyl acrylate, 8 2formylcyclohexenones, 9 and 2-acetyl-1,4-naphthoquinones. 10 Moreover, enamines are capable of undergoing palladium-as well as iridium-catalyzed S N 2 and/or S N 2′ C-allylations in the presence of allylic acetates, 11,12 phenyl ethers, 13 benzotriazoles, 14 carbonates, 15 and even allylic alcohols. 16 In particular, Kobayashi and co-workers [17][18][19] have studied the coupling reaction between enamines and -(1-hydroxyalkyl)-1,4-naphthoquinones, as bifunctional substrates bearing an enone function juxtaposed to an allylic alcohol moiety.…”