Mol Divers (2012) 16:299–306 DOI 10.1007/s11030-012-9363-4
FULL-LENGTH PAPER
Organocatalytic three-component cascade reaction for the synthesis of spiro[indeno[1,2-b]furan]-triones Somayeh Ahadi · Maryam Abaszadeh · Ayoob Bazgir
Received: 23 October 2011 / Accepted: 13 February 2012 / Published online: 15 March 2012 © Springer Science+Business Media B.V. 2012
Abstract New methods for the synthesis of spiro compounds containing dihydrofuran and coumarin moieties from 3-bromo-4-hydroxycoumarins as cyclic α-halo compound based on a pyridinium-ylide-assisted three-component tandem reaction is investigated. To the best of our knowledge, employing cyclic α-halo compounds for the synthesis of dihydrofuran-fused coumarin via a pyridinium ylide has not been reported yet. Keywords 3-Bromo-4-hydroxycoumarin · Spiro[indeno[1,2-b]furan]-triones · Organocatalysis Introduction The principal point of research activity in the field of advanced medicinal and combinatorial chemistry refers to the discovery of novel and potent synthetic methods to promote the preparation of compound libraries [1,2]. Cascade reactions that combine two or more unlike reactions into a single transformation in a sequential process is a powerful approach toward this aim. The ability of introducing molecular complexity from readily available starting materials is the main concern of this field in modern organic chemistry [3,4]. Coumarin is a useful building block in many natural products with remarkable biological activities and unique physical properties [5,6]. For example, coumarin antibiotics, such as clorobiocin, novobiocin, and coumermycin A1, inhibit the supercoiling activity of gyrase by binding to the gyrase B (GyrB) subunit [7]. Moreover, these compounds have been reported to possess a wide spectrum of biologic activities S. Ahadi · M. Abaszadeh · A. Bazgir (B) Department of Chemistry, Shahid Beheshti University, G.C., P.O. Box 19396-4716, Tehran, Iran e-mail:
[email protected]
such as anti-angiogenesis [8], anticoagulant [9], anti-inflammatory, antinociceptive, and bronchodilator [10] activity. Biologically relevant coumarin derivatives were produced by introducing substituents at C-3 and C-4 positions [11]. For instance, 3-substituted 4-hydroxycoumarin received some attention in designing the synthesis of a number of derivatives as probable HIV protease inhibitors with high therapeutic index [12]. However, the synthetic methods of 3-substituted coumarins are limited to few examples such as ligand coupling reactions [13] and transition-metal-catalyzed crosscoupling reactions of 3-bromocoumarins with some organometallics [14]. Still, the above-mentioned methods are either poorly efficient or associated with toxic reagents [15,16]. Furans and derivatives are found in numerous natural products. Besides, the appeal of molecular scaffolds encourages researchers to consider them as potential targets for synthesizing novel biologically active molecules [17]. One of the most applicable methods for the synthesis of dihydrofurans is the interrupted Feist–Benary reaction [18–21]. This reaction is a cascade intermolecular condensation–intramolecular nucleophilic substitution of β-dicarbonyl compounds with α-halo ketones under basic condition [22,23]. Recently, improved tandem reactions initiated via the reaction of stabilized carbanions on electrophiles followed by a cyclization step have been reported [24–28]. Sulfonium [29], phosphonium [30], arsonium [31], and ammonium ylides [32] were demonstrated to be appropriate carboanionic reagents. Although there are several synthetic routes to make dihydrofuran as mentioned above, the introduction of new methods is still of much interest. Recently, the reaction involving a pyridinium salt (formed in situ by the reaction of an acyclic α-halo compound and pyridine) with aldehydes, and C–H acids has emerge as a powerful method for the synthesis of polycyclic dihydrofurans [33–35].
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Mol Divers (2012) 16:299–306
In this article, we wish to report a new method for the synthesis of spiro compounds containing dihydrofuran and coumarin moieties by 3-bromo-4-hydroxycoumarins as cyclic α-halo compound base on a pyridinium ylide-assisted three-component tandem reaction. To the best of our knowledge, employing a cyclic α-halo compound for the synthesis of dihydrofuran-fused coumarins via a pyridinium ylide assisted three-component tandem reaction has not been reported yet.
Results and discussion The considerations reported above encouraged us to investigate three-component tandem reactions of 3-bromo-4-hydroxycoumarin 1 (1 mmol), 4-nitrobenzaldehyde 2b (1 mmol), 1,3-indandione 3 (1 mmol), and pyridine (1 mmol) in the presence of various bases and solvents (Table 1). As shown in Table 1, the best result was obtained with K2 CO3 (30 mol%) in (CH3 CN) under reflux conditions and spiro[chroman-3, 2 -indeno[1,2-b]furan]-trione 4b was obtained in 65% yield after 24 h (entry 7). Higher K2 CO3 loading had no significant influence on the reaction yield (entry 8). When the model reaction was carried out in the absence of K2 CO3 , the yield was low (entry 9). When we
removed the base and investigated reaction in the presence of excess amount of pyridine, 4b was obtained in low yield (
