Combretastatins D series and analogues: from isolation, synthetic challenges and biological activities

• Jorge de Lima Neto and
• Paulo Henrique Menezes

Beilstein J. Org. Chem. 2023, 19, 399–427, doi:10.3762/bjoc.19.31

• called cyclic diaryl ether heptanoids (DAEH). This review is intended to highlight the structure elucidation, biosynthesis, and biological activity of these compounds as well as the use of different strategies for their synthesis. Keywords: combretastatin D; corniculatolide; isocorniculatolide

• macrocycles and their synthesis finds several examples described in the literature and has already been the subject of review articles [2][3][4]. More recently, cyclic diaryl ether heptanoids (DAEH) [5], another class of macrocycles has been attracting attention not only because of their structural and

• would give compounds 12 and 13. A coupling reaction would give the corresponding diaryl ether Int-2, in a similar way to that suggested by Pettit, which could be selectively reduced to afford the corresponding seco-acid (intermediates Int-3 and Int-4). Subsequent macrolactonization would give the

Synthesis of six-membered silacycles by borane-catalyzed double sila-Friedel–Crafts reaction

• Yafang Dong,
• Masahiko Sakai,
• Kazuto Fuji,
• Kohei Sekine and
• Yoichiro Kuninobu

Beilstein J. Org. Chem. 2020, 16, 409–414, doi:10.3762/bjoc.16.39

• initially investigated using diaryl ether 1a and dihydrodiphenylsilane (2a) as model substrates (Table 1). Under the optimized reaction conditions used for the synthesis of silafluorenes in our previous report [40] (B(C6F5)3 (5.0 mol %) and 2,6-lutidine (7.5 mol %) in chlorobenzene at 100 °C), the desired

• 9,9-dihydro-5-silafluorene (2f), which gave the spiro-type phenoxasilin 3f in 96% yield. We then investigated the scope of the starting biaryl ethers used in the reaction as well as related derivatives thereof using dihydrodiphenylsilane (2a, Scheme 3). Pyrrolidine-substituted diaryl ether 1b was

• transformed into phenoxasilin 3g in 80% yield. Also, the chloro-substituted diaryl ether gave its corresponding phenoxasilin 3h in 94% yield without affecting the chlorine substituent. The methyl-substituted phenoxasilin derivatives 3i and 3j were formed in good yield despite of the steric hindrance of the

Metal-free formal synthesis of phenoxazine

• Gabriella Kervefors,
• Antonia Becker,
• Chandan Dey and
• Berit Olofsson

Beilstein J. Org. Chem. 2018, 14, 1491–1497, doi:10.3762/bjoc.14.126

• a high-yielding O-arylation of a phenol with an unsymmetrical diaryliodonium salt to provide an ortho-disubstituted diaryl ether. This species was cyclized to acetylphenoxazine in moderate yield. The overall yield in the three-step sequence is 72% based on recovered diaryl ether. An interesting

• , unusually stable iodine(III) intermediate in the O-arylation was observed by NMR and could be converted to the product upon longer reaction time. Keywords: arylation; cyclization; diaryl ether; diaryliodonium salt; phenol; Introduction Phenoxazine (1) is a tricyclic compound consisting of an oxazine ring

• commercially available starting materials. According to the retrosynthesis depicted in Scheme 2, target 1 would be formed from acetyl derivative 2, which can be derived from the functionalized diaryl ether 3 using Bolm’s N-arylation (see Scheme 1c) [18]. The synthesis of diaryl ether 3 is the key step of the

Atom-economical group-transfer reactions with hypervalent iodine compounds

• Andreas Boelke,
• Peter Finkbeiner and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2018, 14, 1263–1280, doi:10.3762/bjoc.14.108

• ) [44]. The reaction presumably proceeds via an ortho-addition of the λ3-iodane 20b, followed by an iodine-to-oxygen 1,3-aryl migration via a concerted mechanism through the five-membered intermediate TS2 to afford the corresponding diaryl ether 24. A mechanistically similar ortho-iodination/O-arylation

Recent advances in copper-catalyzed asymmetric coupling reactions

• Fengtao Zhou and
• Qian Cai

Beilstein J. Org. Chem. 2015, 11, 2600–2615, doi:10.3762/bjoc.11.280

• reactions, including the Ullmann [1], Ullmann–Goldberg [2][3], Ullmann diaryl ether formation [4] and Ullmann–Hurtley condensation [5], have been reported several decades before Pd and Ni-catalyzed reactions. However, the application of these methods was limited due to their disadvantages such as the

• -catalyzed asymmetric diaryl ether formation in the synthesis of (−)-myricatomentogenin, (−)-jugcathanin, (+)-galeon and (+)-pterocarine [52]. However, the enantioselectivity was poor in most cases. In 2013, Cai and co-workers [53] reported the first Pd-catalyzed highly enantioselective intermolecular aryl C

Total synthesis of ochnaflavone

• Monica M. Ndoile and
• Fanie R. van Heerden

Beilstein J. Org. Chem. 2013, 9, 1346–1351, doi:10.3762/bjoc.9.152

• moieties, and the permethyl ether of 2,3,2'',3''-tetrahydroochnaflavone have been achieved. The key steps in the synthesis of ochnaflavone were the formation of a diaryl ether and ring cyclization of an ether-linked dimeric chalcone to assemble the two flavone nuclei. Optimal experimental conditions for

• the oxidative cyclization to form ochnaflavone were established. Keywords: biflavone; diaryl ether; natural products; nucleophilic aromatic substitution; ochnaflavone; tetrahydroochnaflavone; Introduction Biflavonoids are a class of compounds that are receiving increasing attention because of their

• nucleophilic substitution and chalcone formation as the key steps. Results and Discussion Our synthesis of 1 is summarized in Scheme 1. The two most important steps in the synthesis of 1 are the formation of the diaryl ether linkage and the assembly of the flavone nuclei. The most logical approach to the

Palladium-catalyzed C–N and C–O bond formation of N-substituted 4-bromo-7-azaindoles with amides, amines, amino acid esters and phenols

• Rajendra Surasani,
• Dipak Kalita,
• A. V. Dhanunjaya Rao and
• K. B. Chandrasekhar

Beilstein J. Org. Chem. 2012, 8, 2004–2018, doi:10.3762/bjoc.8.227

• -substituted 7-azaindole fails to provide the desired product under similar conditions [48]. Further, on utilizing palladium or copper-mediated cross-coupling reactions of N-protected amino-2-fluorophenol with 4-chloro- or 4-bromo-1H-pyrrolo[2,3-b]pyridine, the desired diaryl ether could not be isolated in

• at 100 °C in 10 h of time provided 70% of the desired diaryl ether 9a (Table 7, entry 3). The reaction rate is slow, i.e., when run for 3 h at 100 °C, only 30% product was obtained (Table 7, entry 2). But upon continuous heating for 7 h we observed 70% (Table 7, entry 3) of the expected product

Screening of ligands for the Ullmann synthesis of electron-rich diaryl ethers

• Nicola Otto and
• Till Opatz

Beilstein J. Org. Chem. 2012, 8, 1105–1111, doi:10.3762/bjoc.8.122

• Nicola Otto Till Opatz Institute of Organic Chemistry, University of Mainz, Duesbergweg 10–14, 55128 Mainz, Germany 10.3762/bjoc.8.122 Abstract In the search for new ligands for the Ullmann diaryl ether synthesis, permitting the coupling of electron-rich aryl bromides at relatively low

• formation; diaryl ethers; nucleophilic aromatic substitution; Ullmann-type coupling; Introduction The diaryl ether linkage is a common structural motif encountered in numerous classes of natural products. Moreover, various diaryl ethers have been shown to possess antibacterial, anti-inflammatory

• Cu-catalyzed reaction in recent years [14]. It is known that certain additives, such as N,N- and N,O-chelating ligands, accelerate the Ullmann diaryl ether synthesis and permit a considerable reduction of the reaction temperature [15][16][17]. Successful approaches towards a mild coupling were, e.g

Translation of microwave methodology to continuous flow for the efficient synthesis of diaryl ethers via a base-mediated S_NAr reaction

• Charlotte Wiles and
• Paul Watts

Beilstein J. Org. Chem. 2011, 7, 1360–1371, doi:10.3762/bjoc.7.160

• ] (Figure 1). Installation of the diaryl ether can, however, be synthetically challenging, and this is illustrated by the wide number of techniques developed, which include Ullmann ether synthesis [6], Pummerer-type rearrangements [7], Buchwald–Hartwig couplings [8], phenolic additions to amines [9

• reaction of chloroarenes to a series of para-substituted phenols to afford a general and efficient route to the diaryl ether subunit. Results and Discussion With the optimised conditions from Marafie and Moseley’s [15] stopped-flow investigation taken as a starting point, the synthesis of diaryl ethers

• not require a 10 min reaction time, with quantitative conversion of DCNB (4) to the diaryl ether 7 achieved in 60 s. It is important to note that no degradation of the diaryl ether 7 was observed when extended reaction times of up to 45 min were employed. The ability to decrease the reaction time

Carbamate-directed benzylic lithiation for the diastereo- and enantioselective synthesis of diaryl ether atropisomers

• Abigail Page and
• Jonathan Clayden

Beilstein J. Org. Chem. 2011, 7, 1327–1333, doi:10.3762/bjoc.7.156

• diethyl ether. Enantioselective deprotonation of one of the two benzylic positions leads to atropisomeric products with ca. 80:20 e.r.; an electrophilic quench typically provides functionalised atropisomeric diastereoisomers in up to 97:3 d.r. Keywords: configurational stability; diaryl ether

• sterically hindered diaryl ether linkage. Results An aryloxy group is a weak director of metallation [20][23], but in preliminary studies we were able to deprotonate and methylate the hindered diaryl ether 6 [10] by treatment with n-BuLi in ether at 0 °C with or without (−)-sparteine (Scheme 2). Methylation

• of the resulting organolithium returned the product 7 in up to 88% yield as a mixture of diastereoisomers (by NMR). Previous data on the conformational stability of related diaryl ether [10], coupled with our inability to separate these diastereoisomers, and the invariant ratio in which they were