Letter Cite This: Org. Lett. XXXX, XXX, XXX−XXX
pubs.acs.org/OrgLett
Sulfur Ylide Initiated [4 + 1]/[4 + 2] Annulation Reactions: A One-Pot Approach to Dibenzofuran Acrylate Derivatives Jiaan Shao,*,† Wenteng Chen,*,‡ Zhimin Ying,‡ Shuangrong Liu,‡ Feng Luo,‡ and Lili Ou§ †
School of Medicine, Zhejiang University City College, Hangzhou, 310015, P. R. China College of Pharmaceutical Science, Zhejiang University, Hangzhou, 310058, P. R. China § Hangzhou Zhongmei Huadong Pharmaceutical Co., Ltd., Hangzhou, 310011, P. R. China ‡
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S Supporting Information *
ABSTRACT: A one-pot approach has been developed for the synthesis of polysubstituted dibenzofuran acrylate derivatives from (E)-2-(2-nitrovinyl)phenols, sulfur ylides, and alkynes. This protocol was carried out under mild reaction condition without any precious catalysts in generally moderate to good yields. Additionally, a plausible mechanism for the transformation was proposed.
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Scheme 1. Reactions of Sulfur Ylides with Nitroolefins
ue to the diverse chemical or biological properties, dibenzofurans are considered as a privileged class of structural motifs in numerous natural products, bioactive molecules, and functional materials.1 As a result, a variety of dibenzofuran-containing compounds were discovered and developed, such as drug candidates exhibiting antibiosis, antimalarial, antiallergy, anti-inflammatory and anticancer activities, photoelectronic materials in phosphorescent organic light-emitting diodes (PhOLEDs), and chemical probes in the biological process investigation.2−8 The common strategies for the construction of a dibenzofuran nucleus were based on intramolecular ring closure of functionalized diaryl ethers or o-arylphenols through C−C or C−O bond formations.1a,9,10 However, these methods are often restricted in the limited substrate scope, required harsh reaction conditions, and use transition metal catalysts or photocatalysts. Although other approaches to synthesize dibenzofurans have been developed,11 it is still advantageous to develop new means with mild reaction conditions, enhanced scope, better generality, and lower cost for the synthesis of polyfunctional dibenzofuran skeletons. Sulfur ylides are easily prepared and widely used as effective one-carbon synthons in a variety of cyclic compounds constructions.12−15 Considering the reactivity and synthetic diversities of sulfur ylides, ylide-initiated reactions remain an attractive option to develop a variety of organic transformations and provide functionalized complex products. Cascade reactions between sulfur ylides and nitroolefins are a classic protocol to construct dihydroisoxazole N-oxide or oxazolidin-2-one derivatives (Scheme 1, eqs 1 and 2).14b−d,16−18 In these chemical processes, a 1,4-Michael addition involved formal [4 + 1] cyclization is crucial to the transformation. Inspired by these previous studies, we assumed to introduce an ortho-hydroxyl at the benzene ring of nitroolefins. Due to the stronger nucleophilic activity of phenolic hydroxyl, a different [4 + 1] cyclization reaction between sulfur ylides and nitroolefins © XXXX American Chemical Society
may occur and result in dihydrobenzofurans, which can further react with two-carbon synthons to afford polyfunctional dibenzofurans under mild conditions (Scheme 1, eq 3). In order to demonstrate the assumption, reaction of nitroolefin 1a, stabilized sulfur ylide 2a, and dimethyl acetylenedicarboxylate (DMAD) 3a was selected as a model to check the reaction progress (Table 1). 1a and 2a were pretreated before DMAD and K2CO3 were added into the reaction mixture. To our surprise, when the 1:1:1 mixture of above substrates were stirred in DMF at 35 °C for 12 h, dibenzofuran compound 4a′ was obtained with an isolated yield of 23% while another product was gained in 29% yield. Further analysis showed the unidentified product might be a dibenzofuran acrylate compound 4a (Table 1, entry 1). Unfortunately, the yield of 4a′ could not be improved to an acceptable level though a number of solvents were screened (Table 1, entries 2−6). However, to our delight, the yield of 4a was significantly Received: July 1, 2019
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DOI: 10.1021/acs.orglett.9b02260 Org. Lett. XXXX, XXX, XXX−XXX
Letter
Organic Letters Table 1. Optimization of the Reaction Conditionsa,b
Scheme 2. Synthesis of Dibenzofuran Acrylate Derivativesa
yield (%) entry
solvent
ratio (1a:2a:3a)
base/equiv
4a
4a′
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17c 18d
DMF CH3CN THF MeOH DCE TFE CH3CN CH3CN CH3CN CH3CN CH3CN CH3CN CH3CN CH3CN CH3CN CH3CN CH3CN CH3CN
1:1:1 1:1:1 1:1:1 1:1:1 1:1:1 1:1:1 1:1:2.1 1:1:2.1 1:1:2.1 1:1:2.1 1:1:2.1 1:1:2.1 1:1:2.1 1:1:3 1:1:2.1 1:1:2.1 1:1:2.1 1:1:2.1
K2CO3/1.0 K2CO3/1.0 K2CO3/1.0 K2CO3/1.0 K2CO3/1.0 K2CO3/1.0 K2CO3/1.0 KHCO3/1.0 Na2CO3/1.0 NaOH/1.0 Cs2CO3/1.0 DBU/1.0 Et3N/1.0 − K2CO3/0.5 K2CO3/1.5 K2CO3/1.0 K2CO3/1.0
29 41 33 7 18
