Catalysing (organo-)catalysis: Trends in the application of machine learning to enantioselective organocatalysis

• Stefan P. Schmid,
• Leon Schlosser,
• Frank Glorius and
• Kjell Jorner

Beilstein J. Org. Chem. 2024, 20, 2280–2304, doi:10.3762/bjoc.20.196

Non-noble metal-catalyzed cross-dehydrogenation coupling (CDC) involving ether α-C(sp³)–H to construct C–C bonds

• Hui Yu and
• Feng Xu

Beilstein J. Org. Chem. 2023, 19, 1259–1288, doi:10.3762/bjoc.19.94

• , tetrahydrofuran or tetrahydropyran can smoothly react with many methyl aryl ketones to obtain the desired coupling products (Scheme 6a) [54]. The mechanism of the dehydrogenation cross-coupling reaction may undergo a radical pathway. Initially, the tert-butoxy radical produced by the dissociation of t-BuOOH may

• , pyrazines, pyridines, quinolines, isoquinolines, benzothiazoles, benzoquinones, etc. Under the reaction conditions, various ethers such as 1,4-dioxane, tetrahydropyran, tetrahydrofuran, diethyl ether, etc. are suitable substrates. Immediately thereafter, various photocatalytic catalysts were developed for

Discrimination of β-cyclodextrin/hazelnut (Corylus avellana L.) oil/flavonoid glycoside and flavonolignan ternary complexes by Fourier-transform infrared spectroscopy coupled with principal component analysis

• Nicoleta G. Hădărugă,
• Gabriela Popescu,
• Dina Gligor (Pane),
• Cristina L. Mitroi,
• Sorin M. Stanciu and
• Daniel Ioan Hădărugă

Beilstein J. Org. Chem. 2023, 19, 380–398, doi:10.3762/bjoc.19.30

• , leading to high water solubility. On the other hand, the tetrahydropyran moieties of the Glcp units provide the hydrophobic property of the CD cavity [4]. As a consequence of their unique structure, CDs can encapsulate hydrophobic molecules or hydrophobic moieties of geometrically compatible bioactive

Advances in mercury(II)-salt-mediated cyclization reactions of unsaturated bonds

• Sumana Mandal,
• Raju D. Chaudhari and
• Goutam Biswas

Beilstein J. Org. Chem. 2021, 17, 2348–2376, doi:10.3762/bjoc.17.153

• reaction conditions leads to the formation of 2.5-disubstitued-furan 147 rather than mono-unsaturated spiroketals [100]. Interestingly when 1.4-dihydroxy-5-alkyne derivatives were subjected to a Hg(OTf)2-catalyzed cyclization then oxacyclization takes place to form tetrahydropyran derivatives (Scheme 43

• vinylmercury intermediate (Scheme 55). For the synthesis of stereoselective tetrahydropyran derivatives 184, Hg(II)-catalyzed cyclization proved to be more effective than silver(I)-salt-mediated cyclization. It showed that methyl-substituted allenes undergo efficient cyclization to form polycyclic ethers under

• treatment with Hg(OTf)2. Hg(TFA)2-mediated cyclization of allene. Hg(II)-catalyzed intramolecular trans-etherification reaction of 2-hydroxy-1-(γ-methoxyallyl)tetrahydropyran derivatives. a) Cyclization of alkene derivatives by catalytic Hg(OTf)2 salts and b) mechanism of cyclization. a) Synthesis of 1,4

Recent advances in palladium-catalysed asymmetric 1,4–additions of arylboronic acids to conjugated enones and chromones

• Jan Bartáček,
• Jan Svoboda,
• Martin Kocúrik,
• Jaroslav Pochobradský,
• Alexander Čegan,
• Miloš Sedlák and
• Jiří Váňa

Beilstein J. Org. Chem. 2021, 17, 1048–1085, doi:10.3762/bjoc.17.84

• arylboronic acids [59]. Attempt to use the catalytic system L2/Pd(TFA)2 for the addition of phenylboronic acid to 3-methyl-2-cyclohexenone [14]. Ring opening of an enantioenriched tetrahydropyran-2-one derivative as alternative strategy to linear products [14]. Synthesis of biologically active compounds from

Prins cyclization-mediated stereoselective synthesis of tetrahydropyrans and dihydropyrans: an inspection of twenty years

• Asha Budakoti,
• Pradip Kumar Mondal,
• Prachi Verma and
• Jagadish Khamrai

Beilstein J. Org. Chem. 2021, 17, 932–963, doi:10.3762/bjoc.17.77

• Asha Budakoti Pradip Kumar Mondal Prachi Verma Jagadish Khamrai Division of Molecular Synthesis & Drug Discovery, Centre of Biomedical Research (CBMR), SGPGIMS Campus Raebareli Road, Lucknow, 226014 Uttar Pradesh, India 10.3762/bjoc.17.77 Abstract Functionalized tetrahydropyran (THP) rings are

• important building blocks and ubiquitous scaffolds in many natural products and active pharmaceutical ingredients (API). Among various established methods, the Prins reaction has emerged as a powerful technique in the stereoselective synthesis of the tetrahydropyran skeleton with various substituents, and

• ; Prins cyclization; stereoselective; tetrahydropyran; Introduction 6-Membered saturated oxygen heterocycles, known as tetrahydropyran (THP), are recognized as privileged scaffolds, present in a variety of biologically important natural products, such as polyether antibiotics, marine toxins, pheromones

Syntheses of spliceostatins and thailanstatins: a review

• William A. Donaldson

Beilstein J. Org. Chem. 2020, 16, 1991–2006, doi:10.3762/bjoc.16.166

• compounds. These compounds generally contain 9 stereocenters spread over a common (2Z,4S)-4-acetoxy-2-butenamide fragment, an (all-cis)-2,3,5,6-tetrasubstituted tetrahydropyran fragment and a terminal oxane ring joined by a dienyl chain. Due to the impressive antitumor properties of these compounds, along

• all contain a common (2Z,4S)-4-acetoxy-2-butenamide fragment (in green, Figure 1), appended to an (all-cis)-2,3,5,6-tetrasubstituted tetrahydropyran fragment (in red, Figure 1). The members of this family primarily differ with respect to the terminal oxane ring (in blue, Figure 1) which is attached to

• catalyst. Of the asymmetric strategies, Jacobsen’s and Ghosh’s routes proceeded with the highest enantioselectivity; the catalyst loading was lower for the Jacobsen route (0.5 mol %) compared to the Ghosh route (20 mol %). Synthesis of the (all-cis)-2,3,4,5-tetrasubstituted tetrahydropyran fragment

Aldehydes as powerful initiators for photochemical transformations

• Maria A. Theodoropoulou,
• Nikolaos F. Nikitas and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2020, 16, 833–857, doi:10.3762/bjoc.16.76

• excellent yields. However, benzyl and vinyl bromides did not prove efficient for this coupling reaction. Common cyclic and acyclic ethers, symmetric or nonsymmetric, such as oxetane, tetrahydropyran, dioxane, 2-methyltetrahydrofuran, and 2-methoxy-2-methylpropane, were found compatible, affording the

Arylisoquinoline-derived organoboron dyes with a triaryl skeleton show dual fluorescence

• Vânia F. Pais,
• Tristan Neumann,
• Ignacio Vayá,
• M. Consuelo Jiménez,
• Abel Ros and
• Uwe Pischel

Beilstein J. Org. Chem. 2019, 15, 2612–2622, doi:10.3762/bjoc.15.254

• . The addition of 1-bromo-4-methoxynaphthalene (1, 0.9 equiv) and K3PO4, and stirring overnight at 110 ºC, afforded the biaryl methyl ether 5 in an 82% yield (Scheme 1). Similarly, Buchwald´s methodology [41] was applied in the synthesis of 7, which was obtained in 70% yield after tetrahydropyran (THP

• Frontier Scientific. All reagents were used as received. 1-Bromo-4-methoxynaphthalene (1) [47], 1-chloroanthracene (4) [48], and 1‐(tetrahydropyran‐2’‐yloxy)‐4‐bromonaphthalene (6) [49] were synthesized according to literature procedures. The solvents for the photophysical measurements were purchased from

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

• -aminoanthracene (51) for the generation of steroidal naphthoquinolines as synthetic asphaltene models for the study of their physical properties. As shown in Scheme 16, the synthetic approach was based on Kozlov–Wang MCR [52], in which an aromatic aldehyde, 2-aminoanthracene and tetrahydropyran-4-one react in the

Stereoselective nucleophilic addition reactions to cyclic N-acyliminium ions using the indirect cation pool method: Elucidation of stereoselectivity by spectroscopic conformational analysis and DFT calculations

• Koichi Mitsudo,
• Junya Yamamoto,
• Tomoya Akagi,
• Atsuhiro Yamashita,
• Masahiro Haisa,
• Kazuki Yoshioka,
• Hiroki Mandai,
• Koji Ueoka,
• Christian Hempel,
• Jun-ichi Yoshida and
• Seiji Suga

Beilstein J. Org. Chem. 2018, 14, 1192–1202, doi:10.3762/bjoc.14.100

• tetrahydropyran acetals [14]. If the Stevens’ hypothesis is true, a nucleophilic reaction with C1, having a pseudo-equatorial phenyl group, should give a trans-2,4-disubstituted product (Figure 5). Similarly, acyliminium ions C3 and C5 should give the cis-2,5- or cis-2,6-disubstituted piperidine derivatives

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation and chlorination. Part 2: Use of CF₃SO₂Cl

• Hélène Chachignon,
• Hélène Guyon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2800–2818, doi:10.3762/bjoc.13.273

• exploited for cascade chlorination/cyclisation processes. For instance, diethyl malonates substituted by an alkyl chain bearing an alcohol or ether function could give access to tetrahydropyran or -furan derivatives [55]. Furthermore, this type of process also allowed the synthesis of diverse heterocycles

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

• investigate other cyclization approaches towards these chroman derivatives. In 2005, Borhan and co-workers described the construction of tetrahydrofuran and tetrahydropyran structures from 1,2,n-triols via an elegant cyclization involving Lewis acid-mediated cyclization of in situ generated cyclic orthoesters

Diastereoselective synthesis of 3,4-dihydro-2H-pyran-4-carboxamides through an unusual regiospecific quasi-hydrolysis of a cyano group

• Mikhail Yu. Ievlev,
• Oleg V. Ershov,
• Mikhail Yu. Belikov,
• Angelina G. Milovidova,
• Viktor A. Tafeenko and
• Oleg E. Nasakin

Beilstein J. Org. Chem. 2016, 12, 2093–2098, doi:10.3762/bjoc.12.198

• ; Introduction Dihydro- and tetrahydropyran moieties are very important structural fragments in organic synthesis. They are part of many natural compounds, biologically active substances and drugs [1][2][3][4]. For instance, Zanamivir and Laninamivir which are recommended for the treatment and prophylaxis of

Biosynthesis of oxygen and nitrogen-containing heterocycles in polyketides

• Franziska Hemmerling and
• Frank Hahn

Beilstein J. Org. Chem. 2016, 12, 1512–1550, doi:10.3762/bjoc.12.148

• of a 3-hydroxythioester intermediate 25 and subsequent cyclisation to a tetrahydropyran ring 27. AmbDH3 is currently the only known case of a pyran-forming domain in a cis-AT PKS. Hahn et al. showed that AmbDH3 catalyses dehydration of only the 2-D,3-D-configured precursor 25 to the E-configured

• on the C6 and C7 hydroxy groups during this biosynthetic endgame remains enigmatic [46]. Ambruticin. Another example in which a single epoxide opening event leads to the installation of an individual ring is the formation of the western tetrahydropyran ring in the biosynthesis of the ambruticins

Conjugate addition–enantioselective protonation reactions

• James P. Phelan and
• Jonathan A. Ellman

Beilstein J. Org. Chem. 2016, 12, 1203–1228, doi:10.3762/bjoc.12.116

• . However, thioacetic acid (160a) also adds in good yield and high enantioselectivity to unstrained nitroalkenes 163 (Scheme 38b). Additions to β-cyclohexyl and β-4-tetrahydropyran nitroalkenes as well as an acyclic β,β-dimethyl nitroalkene all proceeded with good conversion when the reaction temperature

Scope and mechanism of the highly stereoselective metal-mediated domino aldol reactions of enolates with aldehydes

• M. Emin Cinar,
• Bernward Engelen,
• Martin Panthöfer,
• Hans-Jörg Deiseroth,
• Jens Schlirf and
• Michael Schmittel

Beilstein J. Org. Chem. 2016, 12, 813–824, doi:10.3762/bjoc.12.80

• ; domino aldol; metal enolate; tetrahydropyran; Introduction Since its discovery in the late nineteenth century the aldol reaction has become one of the most powerful tools in the field of carbon–carbon bond formation [1][2][3][4][5]. It is widely used in the formation of many natural products [6][7][8][9

Synthesis and in vitro cytotoxicity of acetylated 3-fluoro, 4-fluoro and 3,4-difluoro analogs of D-glucosamine and D-galactosamine

• Štěpán Horník,
• Lucie Červenková Šťastná,
• Petra Cuřínová,
• Jan Sýkora,
• Kateřina Káňová,
• Roman Hrstka,
• Ivana Císařová,
• Martin Dračínský and
• Jindřich Karban

Beilstein J. Org. Chem. 2016, 12, 750–759, doi:10.3762/bjoc.12.75

• a case the reaction is unexpectedly sensitive to minor steric alterations of the substrate because the C-4 epimer 15 (Scheme 3) did not react. An internal fluorine attack from the β-face of the tetrahydropyran ring through a concerted (Scheme 4C) or contact ion-pair (Scheme 4D) SNi mechanism cannot

• -fluoro-D-galactosamine 4 [29]. The chair inversion of the tetrahydropyran ring associated with the cleavage of the 1,6-anhydro bridge is indicated by the increase in the coupling value 3JH2,H3 (1.4 → 11.6 Hz) and decrease in the coupling value 2JC5,F (27.4 → 18.4 Hz) when going from 31 to 4 (α-anomer

Synthesis of Xenia diterpenoids and related metabolites isolated from marine organisms

• Tatjana Huber,
• Lara Weisheit and
• Thomas Magauer

Beilstein J. Org. Chem. 2015, 11, 2521–2539, doi:10.3762/bjoc.11.273

• formation of the cyclooctene core was achieved via an acid-catalyzed cyclization to form tetrahydropyran 147. The following key sequence consisted of a thermal selenoxide 1,2-elimination to generate allyl vinyl ether 148 which underwent a stereoselective Claisen rearrangement [69] to furnish cyclooctenone

Structure and conformational analysis of spiroketals from 6-O-methyl-9(E)-hydroxyiminoerythronolide A

• Ana Čikoš,
• Irena Ćaleta,
• Dinko Žiher,
• Mark B. Vine,
• Ivaylo J. Elenkov,
• Marko Dukši,
• Dubravka Gembarovski,
• Marina Ilijaš,
• Snježana Dragojević,
• Ivica Malnar and
• Sulejman Alihodžić

Beilstein J. Org. Chem. 2015, 11, 1447–1457, doi:10.3762/bjoc.11.157

• tetrahydropyran ring is in a 5C8 conformation [59] and it is not anomerically stabilised. The bulky 6-OMe group and 10-C are axially oriented while 4-C, 6-Me, 8-Me and 12-O are equatorial. Experimental evidences for such 5C8 conformation is the large 3J7-H,8-H coupling constant (14 Hz) suggesting equatorial

• modelled conformation of 2 by eliminating 10-H and 11-OH, forming an endocyclic double bond. Minimization of this structure resulted, as expected, in small changes at positions 10-C and 11-C (Figure 4), while all other atoms remained in almost identical positions. The tetrahydropyran ring in 3 also assumes

• , antiperiplanar and one weak, synclinal) suggest an axial orientation of 8-H and equatorial position of 8-Me. Similar to 2, the six-membered tetrahydropyran assumes an anomerically non-stabilised chair conformation with the larger 6-methoxy substituent in the axial position. Structure elucidation of compound 4

Cross-dehydrogenative coupling for the intermolecular C–O bond formation

• Igor B. Krylov,
• Vera A. Vil’ and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2015, 11, 92–146, doi:10.3762/bjoc.11.13

• , xylenes, 1,3,5-trimethylbenzene, 2,4-dichlorotoluene, and ethylbenzene. α-Acyloxy ethers 180 were synthesized by the oxidative coupling of benzyl alcohols 178 with ethers 179 (dioxane, tetrahydropyran, tetrahydrofuran, 1,2-dimethoxyethane) using Cu(OAc)2/t-BuOOH system [152] (Scheme 37). In a series of

Recent advances in the electrochemical construction of heterocycles

• Robert Francke

Beilstein J. Org. Chem. 2014, 10, 2858–2873, doi:10.3762/bjoc.10.303

• alcohol nucleophile, a variety of tetrahydrofuran, tetrahydropyran and oxepane structures 4 can be synthesized (Scheme 2, X = O) [34]. The reaction is initiated by single electron oxidation to generate intermediate 2, which after cyclization and deprotonation gives radical 3. Further oxidation results in

De novo macrolide–glycolipid macrolactone hybrids: Synthesis, structure and antibiotic activity of carbohydrate-fused macrocycles

• Richard T. Desmond,
• Anniefer N. Magpusao,
• Chris Lorenc,
• Jeremy B. Alverson,
• Nigel Priestley and
• Mark W. Peczuh

Beilstein J. Org. Chem. 2014, 10, 2215–2221, doi:10.3762/bjoc.10.229

• macrocycle through the C1’ (glycosidic) and C6’ oxygens. The new macrolides bear a resemblance to sophorolipid lactone 2 and to polyketide macrocycles that contain a tetrahydropyran moiety [20][21][22]. We report on the synthesis, X-ray crystal structures and antibiotic activities of the new compounds

Palladium-catalysed cyclisation of alkenols: Synthesis of oxaheterocycles as core intermediates of natural compounds

• Miroslav Palík,
• Jozef Kožíšek,
• Peter Koóš and
• Tibor Gracza

Beilstein J. Org. Chem. 2014, 10, 2077–2086, doi:10.3762/bjoc.10.216

• regeneration of the PdII-catalyst via cleavage of the C–OR bond (Scheme 6). Surprisingly, the reaction of 1,1-disubstituted alkenes 30, 35 (Table 1, entries 10 and 9) provided only chlorinated tetrahydropyran (type III) and tetrahydrofuran (type IV) derivatives. The chloroderivatives III and IV were probably

Relay cross metathesis reactions of vinylphosphonates

• Raj K. Malla,
• Jeremy N. Ridenour and
• Christopher D. Spilling

Beilstein J. Org. Chem. 2014, 10, 1933–1941, doi:10.3762/bjoc.10.201

• readily engage in the metathesis reaction. Thus, reaction of the mono-allyl vinylphosphonate 21a with 5 equivalents of styrene using 10 mol % Grubbs second generation catalyst and 10 mol % CuI in refluxing CH2Cl2 for two hours gave tetrahydropyran 25 in 82% isolated yield (Scheme 7). Similarly, reaction

• of vinylphosphonate 21a with 4-fluorostyrene and 4-benzyloxystyrene gave the tetrahydropyrans 26 and 7, respectively. Tetrahydropyran 7 is a known intermediate and can be converted to centrolobine by hydrogenation [17]. Surprisingly, the dimer 27 was isolated in small amounts (~20%) from the reaction

• ring closing metathesis (RCM) to generate the oxaphosphole 22 and a new metal alkylidene 34. The sequence is completed by reaction of the metal alkylidene 34 with the metathesis partner (styrene) to give the tetrahydropyran 25. The formation of the dimeric product 27 is probably the result of a