An efficient method for the one-pot construction of the 1H-naphtho[2,3-c]pyran-5,10-dione system

Abstract

2-(1-Hydroxyalkyl)-1,4-naphthoquinones are found to react with pyrrolidino enamines in toluene to give 1H-naphtho[2,3-c]pyran-5,10-diones in good yields via a tandem conjugate addition-cyclization sequence, followed by an elimination of pyrrolidine. 2-Hydroxymethyl-1,4-naphthoquinone and morpholino enamines undergo a similar sequence, without loss of morpholine, to yield 3-morpholino-3,4-dihydro-1H-naphtho[2,3-c]pyran-5,10-diones. The 3-morpholino group of these products can be replaced with a hydro, a hydroxy, or a methoxy group. Imines also react with 2-(1-hydroxyalkyl)-1,4-naphthoquinones to give the corresponding 1H-naphtho[2,3-c]pyran-5,10-diones, including a natural product (pentalongin). The utility of these reactions is demonstrated in the synthesis of pyranonaphthoquinone antibiotics, viz. (±)-eleutherin and (±)-isoeleutherin.

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

“…The observed selectivity for the cis-fusion of the B/C rings is not surprising, being the result of a 6-exo-trig-nucleophilic addition on a fivemembered electrophilic substrate. This is also in line with the work of Kobayashi and co-workers, 18 who showed that the treatment of 2-hydroxymethyl-1,4-naphthoquinone with morpholine enamines afforded exclusively cis-3-morpholino-3,4-dihydro-1H-naphthopyran-5,10-diones.…”

“…We believe that the mechanism of this reaction involves the initial conjugate addition of enamine 2a to the ZnBr 2activated MBH adduct 3a to afford the corresponding iminium intermediate I, followed by intramolecular addition 25,26 of the zinc alkoxide function to the transiently formed iminium ion to give the N,O-ketal zinc enolate II. Final hydrolytic quench affords the N,O-ketal 4a 18,27 (Scheme 3, Table 2, entry 4). From a mechanistic viewpoint, it is worth noting that the role of ZnBr 2 in the present reaction is different from that of our previous study.…”

“…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. The reaction involves an intermolecular 1,4-addition of the enamine to the enone moiety, followed by a spontaneous intramolecular addition of the hydroxyl group to the transiently generated iminium ion.…”

Synthesis and anticancer properties of new (dihydro)pyranonaphthoquinones and their epoxy analogs

“…9 A synthetically different approach comprised transformation of 2-bromo-1,4-naphthoquinone into 3-allyl-2-(1-hydroxyethyl)-1,4-dimethyoxynaphthalene via a number of steps, which then underwent subsequent Lemieux-Johnson oxidation, oxidative demethylation and acid-catalyzed dehydration to produce 1-methylpentalongin. 10 Other routes toward the 1H-benzo[g]isochromene-5,10-dione scaffold involve for example the reaction of imines with 2-(1-hydroxyalkyl)-1,4-naphthoquinones 11 and an intramolecular Heck reaction of 3-bromo-2-formyl-1,4-dimethoxynaphthalene with 3-hydroxybut-1-ene. 12 Intensive efforts have also been devoted to the synthesis of diverse pyranonaphthoquinone natural products, such as 9-demethoxy(iso)eleutherin, 13 crisamicin A, 14 kalafungin, 15 and many others.…”

“…18 Oxidative demethylation of this 1,4-dimethoxynaphthalene system 9 upon treatment with cerium ammonium nitrate (CAN, 2 equiv) in a CH 3 CN/H 2 O (1:1) solvent mixture afforded 2-hydroxymethyl-1,4-naphthoquinone 10 in 92% yield. 11 Subsequently, the introduction of acylmethyl groups onto 2-hydroxymethyl-1,4-naphthoquinone 10 was effected by employing N-acylmethylpyridinium ylides (1 equiv) in CH 3 CN in the presence of triethylamine, 9 providing a clean and high-yielding access to 1H-benzo[g]isochromene-5,10-diones 13 upon p-toluenesulfonic acid-catalyzed dehydratation in toluene. 19 Apparently, the initially formed addition products 11 spontaneously cyclized to give hemiacetals 12, which underwent an acid-promoted elimination of water to afford 3-substituted pyranonaphthoquinones 13a-h in excellent yields (Scheme 1).…”