Metal-free synthesis of phosphinoylchroman-4-ones via a radical phosphinoylation–cyclization cascade mediated by K₂S₂O₈

• Qiang Liu,
• Weibang Lu,
• Guanqun Xie and
• Xiaoxia Wang

Beilstein J. Org. Chem. 2020, 16, 1974–1982, doi:10.3762/bjoc.16.164

• Qiang Liu Weibang Lu Guanqun Xie Xiaoxia Wang Dongguan University of Technology, Dongguan 523808, P. R. China Department of Applied Chemistry, School of Science, Xi’an Jiaotong University, Xi’an 710049, P. R. China 10.3762/bjoc.16.164 Abstract A variety of chroman-4-ones bearing phosphine oxide

• afforded the title compounds in moderate yields. Keywords: chroman-4-ones; diphenylphosphine oxide; metal-free; potassium persulfate; radical cyclization; Introduction The chroman-4-one framework is a privileged structural motif found in numerous natural products and pharmaceuticals with extraordinary

• biological and pharmaceutical activities such as anticancer activities and anti-HIV activity among others (Figure 1) [1][2][3]. Therefore, the preparation of functionalized chroman-4-one derivatives has attracted great attention of experts and scientists in the field of organic synthesis and pharmaceutical

Steroid diversification by multicomponent reactions

• Leslie Reguera,
• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Daniel G. Rivera

Beilstein J. Org. Chem. 2019, 15, 1236–1256, doi:10.3762/bjoc.15.121

• -secocholestan-5-ol 33 in such a metal-catalyzed MCR led to the steroidal chroman-ketal 34 as a mixture of epimers at the center bearing the methoxy group, instead of the expected chroman spiroketal. The authors proposed the initial formation of a 6-membered enol ether, which may subsequently undergo either a

Studies directed toward the exploitation of vicinal diols in the synthesis of (+)-nebivolol intermediates

• Runjun Devi and
• Sajal Kumar Das

Beilstein J. Org. Chem. 2017, 13, 571–578, doi:10.3762/bjoc.13.56

• asymmetric synthesis of (R)-1-((R)-6-fluorochroman-2-yl)ethane-1,2-diol, (R)-1-((S)-6-fluorochroman-2-yl)ethane-1,2-diol and (S)-6-fluoro-2-((R)-oxiran-2-yl)chroman, which have been used as late-stage intermediates for the asymmetric synthesis of the antihypertensive drug (S,R,R,R)-nebivolol. Noteworthy is

• chromans have become attractive synthetic targets in academia and pharmaceutical industry [1]. Nebivolol (1, Figure 1) is a chroman-based antihypertensive drug that was first reported in the racemic form [2][3]. Chiral HPLC was subsequently employed to access various stereoisomers of 1 in enantiomerically

• have demonstrated that the synthesis of 1a could be achieved using the 2-substituted chroman derivatives (R)-1-((R)-6-fluorochroman-2-yl)ethane-1,2-diol (2) and (R)-1-((S)-6-fluorochroman-2-yl)ethane-1,2-diol (3) or the corresponding chroman epoxides 4 and 5 as late-stage intermediates. Although the

cis-Diastereoselective synthesis of chroman-fused tetralins as B-ring-modified analogues of brazilin

• Dimpee Gogoi,
• Runjun Devi,
• Pallab Pahari,
• Bipul Sarma and
• Sajal Kumar Das

Beilstein J. Org. Chem. 2016, 12, 2816–2822, doi:10.3762/bjoc.12.280

• been reductively removed by a diastereoselective method which should be useful in future for preparing libraries of chroman-fused tetralins with trans-stereochemistry at the ring junction. Keywords: brazilin; chroman; epoxy-arene cyclization; natural-product-like molecules; tetralin; Findings The

• chroman unit occurs widely as a privileged framework in a large number of natural products (NPs), natural product-like molecules (NPLMs) and pharmaceuticals, possessing diverse biological activities [1]. (+)-Brazilin (1) and (−)-haematoxylin (2) are two structurally-related tetracyclic homoisoflavonoid

• (containing a chroman unit) natural products (Figure 1) [2][3][4]. Their synthetic des-(angular)hydroxy derivatives (+)-brazilane (3) and haematoxylane (4) have also been mentioned in the literature [2][3][4]. Among them, brazilin (1), the most-studied member of this group, has been proved to have a number of

Chemical probes for competitive profiling of the quorum sensing signal synthase PqsD of Pseudomonas aeruginosa

• Michaela Prothiwa,
• Dávid Szamosvári,
• Sandra Glasmacher and
• Thomas Böttcher

Beilstein J. Org. Chem. 2016, 12, 2784–2792, doi:10.3762/bjoc.12.277

• synthesized from the chroman-4-one 8 which was produced by base-catalyzed Knoevenagel reaction from 2-hydroxyacetophenone with octanal. Although the starting material was readily available, the reaction gave the product only in low yield (20–30%) and separation of the starting material from the product could

• be difficult especially for multigram scale approaches. Since 1-O-HHQ (4) was now easily available, we used 4 as starting point for the 1-O-PQS (13) synthesis by two different approaches. First, we tried to synthesize chroman-4-one 8 by hydrogenation of 4. We found that ammonium formate (NH4HCO2) as

• mild hydrogen source with Pd/C gave chroman-4-one 8 in a clean reaction with a good yield of 76% whereas the direct use of H2 with Pd/C gave mainly the fully reduced 2-heptylchromane. Compound 8 can be applied for the synthesis of 1-O-PQS (13) as described in [33]. A new, direct way in which 1-O-HHQ (4

New metathesis catalyst bearing chromanyl moieties at the N-heterocyclic carbene ligand

• Agnieszka Hryniewicka,
• Szymon Suchodolski,
• Agnieszka Wojtkielewicz,
• Jacek W. Morzycki and
• Stanisław Witkowski

Beilstein J. Org. Chem. 2015, 11, 2795–2804, doi:10.3762/bjoc.11.300

• weak), 122.9 (IIICHAr), 122.4 (IIICHAr), 117.1 (IVCAr weak), 112.8 (IIICHAr), 74.7 (CHIPr), 73.3 (Cchroman-2), 53.1 and 51.8 (N-(CH2)2-N), 33.1 (Cchroman-3), 27.9 (Cchroman-2a and 2b), 25.7 (CH3 IPr), 21.2 (Cchroman-4), 18.3 (CH3 chroman weak), 15.2 (CH3 chroman weak), 12.0 (CH3 chroman) ppm; EIMS m/z

Synthesis of the furo[2,3-b]chromene ring system of hyperaspindols A and B

• Danielle L. Paterson and
• David Barker

Beilstein J. Org. Chem. 2015, 11, 265–270, doi:10.3762/bjoc.11.29

• to the large number of conformations available [24][25][26]. However, with the relatively fixed geometry for the five membered ring in 7a and 7b due to the fused chroman ring and the quarternary centre at C-11, analysis of the coupling constants was considered viable. In isomer 7a the coupling

• of the stereochemistry at C-10 during the formation of the furo[2,3-b]chromene. Indeed, one possible mechanism for the formation of isomers 7a and 7b is initial protonation of ketone 8, attack of phenol on the activated carbonyl resulting in formation of chroman-hemiketal 23, where the large C-11

The unexpected influence of aryl substituents in N-aryl-3-oxobutanamides on the behavior of their multicomponent reactions with 5-amino-3-methylisoxazole and salicylaldehyde

• Volodymyr V. Tkachenko,
• Elena A. Muravyova,
• Sergey M. Desenko,
• Oleg V. Shishkin,
• Svetlana V. Shishkina,
• Dmytro O. Sysoiev,
• Thomas J. J. Müller and
• Valentin A. Chebanov

Beilstein J. Org. Chem. 2014, 10, 3019–3030, doi:10.3762/bjoc.10.320

• 48 h the reaction proceeded to form mainly two compounds – Knoevenagel adduct 7 and Schiff base 8 (Scheme 3). Trace amounts of 2-hydroxy-N-(2-methoxyphenyl)-2-methyl-4-(3-methylisoxazol-5-ylamino)chroman-3-carboxamide (4a) were detected in the reaction mixture as well. Furthermore, both conventional

• alia, ultrasonic activation was applied to promote this multicomponent reaction. It was established that the three-component cyclocondensation of the starting compounds under ultrasonication at room temperature for 4 h led to the selective formation of the substituted chroman-3-carboxamide 4a in 58

• at room temperature for 4 h without catalyst always led to the selective formation of the corresponding chroman-3-carboxamides 4a–h (Table 3, entries 1, 4, 7, 10, 13, 16, 19, 22). However, to our surprise, the ytterbium triflate-catalyzed three-component reaction of 5-amino-3-methylisoxazole (1

Gold(I)-catalysed one-pot synthesis of chromans using allylic alcohols and phenols

• Eloi Coutant,
• Paul C. Young,
• Graeme Barker and
• Ai-Lan Lee

Beilstein J. Org. Chem. 2013, 9, 1797–1806, doi:10.3762/bjoc.9.209

• chroman-containing targets [19][20][21]. Nevertheless, there are still a few drawbacks with these methods, for example, they usually require a large excess of substrate (e.g. ~30-fold excess), and in the case of acid catalysis, also poor yields when the phenol is not para-substituted. Therefore, it would

• , a wide range of primary, secondary and tertiary alcohols were successfully employed as nucleophiles [61][62][63][64][65][66][67][68][69][70][71][72], but our one attempt employing a phenol 5 as a nucleophile surprisingly produced chroman 6 instead (Scheme 1, reaction 2). Although gold(III)-catalysed

• solvents and inert air atmosphere are not required, and the chroman is formed directly in a mild one-pot procedure with only water as the byproduct, we decided to investigate the chroman-forming reaction in more detail, beyond the sole example previously reported (Scheme 1, reaction 2). In this paper, we

Catalytic asymmetric tandem Friedel–Crafts alkylation/Michael addition reaction for the synthesis of highly functionalized chromans

• Jiahuan Peng and
• Da-Ming Du

Beilstein J. Org. Chem. 2013, 9, 1210–1216, doi:10.3762/bjoc.9.137

• diphenylamine-linked bis(oxazoline)-Zn(OTf)2 complex was investigated. This tandem reaction afforded functionalized chiral chromans in good yields with moderate to high stereoselectivities (up to 95:5 dr, up to 99% ee). Keywords: asymmetric catalysis; bis(oxazoline); chroman; Friedel–Crafts alkylation; tandem

Intramolecular carbolithiation of N-allyl-ynamides: an efficient entry to 1,4-dihydropyridines and pyridines – application to a formal synthesis of sarizotan

• Wafa Gati,
• Mohamed M. Rammah,
• Mohamed B. Rammah and
• Gwilherm Evano

Beilstein J. Org. Chem. 2012, 8, 2214–2222, doi:10.3762/bjoc.8.250

• of the 3,5-disubstituted pyridine core of the antidyskinetic drug, 5-HT1A receptor agonist, dopamine D2 receptor ligand sarizotan 19 (Scheme 6). The pyridinyl-chroman sarizotan (also called EMD-128130) was originally developed by Merck KGaA in the late 1990’s [44] and was found to be a dual selective

Organocatalytic tandem Michael addition reactions: A powerful access to the enantioselective synthesis of functionalized chromenes, thiochromenes and 1,2-dihydroquinolines

• Chittaranjan Bhanja,
• Satyaban Jena,
• Sabita Nayak and
• Seetaram Mohapatra

Beilstein J. Org. Chem. 2012, 8, 1668–1694, doi:10.3762/bjoc.8.191

• cascade reaction starts in an analogous manner to that previously mentioned, although the first oxa-Michael step is followed by a second Michael addition to form the chroman unit. A series of α,β-unsaturated aldehydes were reacted with the o-hydroxy-β-nitrostyrene as shown in Scheme 11. Except for the