Search results
Search for "building block" in Full Text gives 362 result(s) in Beilstein Journal of Organic Chemistry. Showing first 200.
Vicinal ketoesters – key intermediates in the total synthesis of natural products
- Marc Paul Beller and
- Ulrich Koert
Beilstein J. Org. Chem. 2022, 18, 1236–1248, doi:10.3762/bjoc.18.129
- diesters and ester amides as key intermediates (+)-Awajanomycin Diethyl mesoxalate (90a) is a valuable building block due to the high density of carbon atoms in high oxidation states. As a vic-tricarbonyl compound, its central keto group is an especially potent electrophile. The Koert group used this
Graphical Abstract
Scheme 1: Structures of vicinal ketoesters and examples for their typical reactivity.
Scheme 2: Doyle’s diastereoselective intramolecular aldol addition of α,β-diketoester.
Scheme 3: Synthesis of euphorikanin A (16) by intramolecular, nucleophilic addition [6].
Scheme 4: Ketoester cycloisomerization for the synthesis of preussochromone A (24) [10].
Scheme 5: Diastereoselective, intramolecular aldol reaction of an α-ketoester 28 in the synthesis of (−)-preu...
Scheme 6: Synthesis of an α-ketoester through Riley oxidation and its use in an α-ketol rearrangement in the ...
Scheme 7: Azomethine imine cycloaddition towards the synthesis of the proposed structure of palau’amine (44) [19]....
Scheme 8: Intramolecular diastereoselective carbonyl-ene reaction of an α-ketoester in the synthesis of jatro...
Scheme 9: Grignard addition to an α-ketoester and subsequent Friedel–Crafts cyclization in the synthesis of (...
Scheme 10: Diastereoselective addition to an auxiliary modified α-ketoester in the formal synthesis of (+)-cam...
Scheme 11: Intramolecular photoreduction of an α-ketoester in the synthesis of (rac)-isoretronecanol (69) [26].
Scheme 12: α-Ketoester as nucleophile in a Tsuji–Trost reaction in the synthesis of (rac)-corynoxine (76) [27].
Scheme 13: Mannich reaction of an α-ketoester in the synthesis of (+)-gracilamine (83) [28].
Scheme 14: Enantioselective aldol reaction using an α-ketoester in the synthesis of (−)-irofulven (87) [29].
Scheme 15: Allylboration of a mesoxalic acid ester in the synthesis of (+)-awajanomycin (92) [30,31].
Scheme 16: Condensation of a diamine with mesoxolate in the synthesis of (−)-aplaminal (96) [32].
Scheme 17: Synthesis of mesoxalic ester amide 102 and its use in the synthesis of (rac)-cladoniamide G (103) [33].
Scheme 18: The thermodynamically controlled, intramolecular aldol addition of a vic-tricarbonyl compound in th...
Mechanochemical bottom-up synthesis of phosphorus-linked, heptazine-based carbon nitrides using sodium phosphide
- Blaine G. Fiss,
- Georgia Douglas,
- Michael Ferguson,
- Jorge Becerra,
- Jesus Valdez,
- Trong-On Do,
- Tomislav Friščić and
- Audrey Moores
Beilstein J. Org. Chem. 2022, 18, 1203–1209, doi:10.3762/bjoc.18.125
- constitutes the building block of g-CN, as opposed to in a linking position. Computational studies by Hartley and Martsinovich have investigated the influence of various linkers, including phosphorus atoms, on both the structure and optical behavior of heptazine-based graphitic carbon nitrides [3]. Yet
Graphical Abstract
Scheme 1: a) Mechanochemical synthesis of g-PCN from sodium phosphide and trichlorotriazine (previous work [38]) ...
Figure 1: PXRD patterns of g-h-PCN (green) and g-h-PCN300 (teal).
Figure 2: XPS scans of a) C 1s, b) N 1s and c) P 2p for the pre-annealed g-h-PCN and d) C 1s, e) N 1s and f) ...
Figure 3: 31P MAS NMR of a) g-h-PCN and b) g-h-PCN300. Asterisks denote spinning sidebands.
Figure 4: Calculated structures for a) corrugated (edge facing), b) corrugated (single layer), c) layered g-h...
Reductive opening of a cyclopropane ring in the Ni(II) coordination environment: a route to functionalized dehydroalanine and cysteine derivatives
- Oleg A. Levitskiy,
- Olga I. Aglamazova,
- Yuri K. Grishin and
- Tatiana V. Magdesieva
Beilstein J. Org. Chem. 2022, 18, 1166–1176, doi:10.3762/bjoc.18.121
- provides targeted pharmacophoric properties of the bio-active molecule [23] but also opens a route to its further functionalization, being a building block with wide variety of reactivity. A donor–acceptor cyclopropane concept suggested in the 1980s [24] became extremely popular in the recent decade [25
Graphical Abstract
Figure 1: Cyclic voltammograms obtained for complexes 1 (black), 2 (blue), 3 (green), 4 (red) (MeCN, 0.05 M Bu...
Scheme 1: Synthesis of complex 4.
Figure 2: Key correlations in the NOESY spectrum of complex (S)-4 and the corresponding characteristic fragme...
Scheme 2: Reductive three-membered ring-opening and follow-up chemical steps.
Figure 3: Correlations in the HMBC spectra of 6a and 6b and spin coupling constants in the 1H NMR spectrum of ...
Scheme 3: Electrochemically induced ring-opening followed by intramolecular cyclization.
Scheme 4: One-pot multistep approach to the cysteine derivatives.
Figure 4: Characteristic correlations in the NOESY spectra of diastereomeric complexes 10 and the correspondi...
Synthesis of protected precursors of chitin oligosaccharides by electrochemical polyglycosylation of thioglycosides
- Md Azadur Rahman,
- Kana Kuroda,
- Hirofumi Endo,
- Norihiko Sasaki,
- Tomoaki Hamada,
- Hiraku Sakai and
- Toshiki Nokami
Beilstein J. Org. Chem. 2022, 18, 1133–1139, doi:10.3762/bjoc.18.117
- . Contrary, thioglycoside 1c (Ar = 4-MeC6H4, Eox = 1.47 V vs SCE), which had the lowest oxidation potential, showed the lowest conversion (51%) and the lowest yield of tetrasaccharide 4c (2%) [8]. This being the case, lower conversion of the building block 1c and lower yield of oligosaccharides 2c–4c
- , building block 1a (0.20 mmol, 109 mg) per cycle as 0.2 M solution in dry CH2Cl2. Electrochemical dimerization of tetrasaccharide 4a. Supporting Information Supporting Information File 240: Additional experimental details and compound characterization data. Funding T. N. acknowledges financial support
Graphical Abstract
Figure 1: Structures of chitin and chitosan oligosaccharides.
Figure 2: Effect of the anomeric leaving group on the yield of oligosaccharides.
Figure 3: Influence of the glycosylation temperature (T2) on the yield of oligosaccharides.
Figure 4: Influence of temperatures of anodic oxidation (T1) and glycosylation (T2).
Figure 5: MALDI–TOF MS spectra of oligosaccharides.
Figure 6: Proposed structures of byproducts of electrochemical polyglycosylation.
Figure 7: Proposed mechanisms of electrochemical polyglycosylation.
Figure 8: Oxidative potential of monosaccharide 1a, disaccharide 2a, and trisaccharide 3a.
Scheme 1: Electrochemical dimerization of tetrasaccharide 4a.
Figure 9: Influence of cycle number on the yield of longer oligosaccharides 5a (n = 5)–8a (n = 8). Conditions...
The stereochemical course of 2-methylisoborneol biosynthesis
- Binbin Gu,
- Anwei Hou and
- Jeroen S. Dickschat
Beilstein J. Org. Chem. 2022, 18, 818–824, doi:10.3762/bjoc.18.82
- from Micromonospora humi can convert DMAPP into (R)-2-Me-IPP with a methyltransferase [27], naturally providing the C6 building block for this hypothetical alternative pathway towards 1 (Scheme 1B). Today the genomes of many bacteria from the genus Streptomyces have been made available, showing that
Graphical Abstract
Scheme 1: Biosynthesis of 2-MIB (1). A) Naturally observed pathway through methylation of GPP to 2-Me-GPP by ...
Figure 1: A) Active site of 2MIBS with the bound substrate surrogate 2FGPP (generated with Pymol from the cry...
Scheme 2: Synthesis of (R)- and (S)-2-Me-LPP.
Figure 2: Structures of 2MIBS side products and spontaneous degradation products of 2-Me-LPP. The enantiomers...
Figure 3: Total ion chromatograms of extracts from an incubation of A) enantiomerically pure (R)-2-Me-LPP wit...
Scheme 3: Hypothetical mechanism for the isomerization of (S)-2-Me-LPP through 2-Me-GPP to (R)-2-Me-LPP.
Heteroleptic metallosupramolecular aggregates/complexation for supramolecular catalysis
- Prodip Howlader and
- Michael Schmittel
Beilstein J. Org. Chem. 2022, 18, 597–630, doi:10.3762/bjoc.18.62
- that the chiral moiety should be incorporated in the ligand unit in order to provide an enantiopure assembly with an asymmetric cavity. 1,1'-Binaphthol (BINOL) is one such chiral building block, which has been successfully utilized to carry out numerous asymmetric catalytic reactions [74]. Keeping this
Graphical Abstract
Figure 1: Butterfly 1 (Figure was reprinted with permission from [45]. Copyright 2012 American Chemical Society. ...
Figure 2: Synthesis of the three-component heteroleptic molecular boat 8 and its use as a catalyst for the Kn...
Figure 3: Synthesis of the two-component triangle 14 and three-component heteroleptic prism 15 [59]. Figure was a...
Figure 4: Catalytic Michael addition reaction using the urea-decorated molecular prism 15 [59].
Figure 5: Self-assembly of two-component tetragonal prismatic architectures with different cavity size. Figur...
Figure 6: Construction of artificial LHS using rhodamine B as an acceptor and 24b as donor generating a photo...
Figure 7: Synthesis of supramolecular spheres with varying [AuCl] concentration inside the cavity. Figure was...
Figure 8: Hydroalkoxylation reaction of γ-allenol 34 in the presence of [AuCl]-encapsulated molecular spheres ...
Figure 9: Two-component heteroleptic triangles of different size containing a BINOL functionality. Figure was...
Figure 10: Asymmetric conjugate addition of chalcone 42 with trans-styrylboronic acid (43) catalyzed by BINOL-...
Figure 11: Encapsulation of monophosphoramidite-Rh(I) catalyst into a heteroleptic tetragonal prismatic cage 47...
Figure 12: (a) Representations of the basic HETPYP, HETPHEN, and HETTAP complex motifs. (b) The three-componen...
Figure 13: Two representative four-component rotors, with a (top) two-arm stator and (bottom) a four-arm stato...
Figure 14: Four-component rotors with a monohead rotator. Figure was adapted with permission from [94]. Copyright ...
Figure 15: (left) Click reaction catalyzed by rotors [Cu2(55)(60)(X)]2+. (right) Yield as a function of the ro...
Figure 16: A supramolecular AND gate. a) In truth table state (0,0) two nanoswitches serve as the receptor ens...
Figure 17: Two supramolecular double rotors (each has two rotational axes) and reference complex [Cu(78)]+ for...
Figure 18: The slider-on-deck system (82•X) (X = 83, 84, or 85). Figure is from [98] and was reprinted from the jo...
Figure 19: Catalysis of a conjugated addition reaction in the presence of the slider-on-deck system (82•X) (X ...
Figure 20: A rotating catalyst builds a catalytic machinery. For catalysis of the catalytic machinery, see Figure 21. F...
Figure 21: Catalytic machinery. Figure was adapted from [100] (“Evolution of catalytic machinery: three-component n...
Figure 22: An information system based on (re)shuffling components between supramolecular structures [99]. Figure ...
Figure 23: Switching between dimeric heteroleptic and homoleptic complex for OFF/ON catalytic formation of rot...
Figure 24: A chemically fueled catalytic system [112]. Figure was adapted from [112]. Copyright 2021 American Chemical S...
Figure 25: (Top) Operation of a fuel acid. (Bottom) Knoevenagel addition [112].
Figure 26: Development of the yield of Knoevenagel product 118 in a fueled system [112]. Figure was reprinted with ...
Figure 27: Weak-link strategy to increased catalytic activity in epoxide opening [119]. Figure was adapted from [24]. C...
Figure 28: A ON/OFF polymerization switch based on the weak-link approach [118]. Figure was reprinted with permissi...
Figure 29: A weak-link switch turning ON/OFF a Diels–Alder reaction [132]. Figure was reprinted with permission fro...
Figure 30: A catalyst duo allowing selective activation of one of two catalytic acylation reactions [133] upon subs...
Figure 31: A four-state switchable nanoswitch (redrawn from [134]).
Figure 32: Sequential catalysis as regulated by nanoswitch 138 and catalyst 139 in the presence of metal ions ...
Figure 33: Remote control of ON/OFF catalysis administrated by two nanoswitches through ion signaling (redrawn...
Chemistry of polyhalogenated nitrobutadienes, 17: Efficient synthesis of persubstituted chloroquinolinyl-1H-pyrazoles and evaluation of their antimalarial, anti-SARS-CoV-2, antibacterial, and cytotoxic activities
- Viktor A. Zapol’skii,
- Isabell Berneburg,
- Ursula Bilitewski,
- Melissa Dillenberger,
- Katja Becker,
- Stefan Jungwirth,
- Aditya Shekhar,
- Bastian Krueger and
- Dieter E. Kaufmann
Beilstein J. Org. Chem. 2022, 18, 524–532, doi:10.3762/bjoc.18.54
- synthetic building block 2-nitroperchlorobutadiene (1). 3-(Alkyl)(2-hydroxyethyl)aminopyrazoles 7 are accessible from the reaction of oxazolidine derivative 6 with 7-chloro-4-hydrazinylquinoline. Oxidation of sulfane 9d led to the formation of the pharmacologically interesting sulfoxide 10d. The newly
Graphical Abstract
Figure 1: The structures of chloroquine, hydroxychloroquine, and amodiaquine.
Scheme 1: Synthesis of 3-azolylpyrazoles 3a–c.
Scheme 2: Assumed mechanism for the formation of 1H-pyrazoles 3a–c.
Scheme 3: Synthesis of 3-aminopyrazoles 5b–k and 5-aminopyrazoles 5a and 5l–o.
Scheme 4: Orientation of nucleophilic attack of 7-chloro-4-hydrazinylquinoline on nitrobutadienes 4.
Scheme 5: Synthesis of oxazolidine 6 and pyrazole 7.
Scheme 6: A plausible mechanism for the formation of pyrazole 7.
Scheme 7: Synthesis of pyrazoles 9 and sulfoxide 10d.
Scheme 8: Synthesis of pyrazole 11.
Borylated norbornadiene derivatives: Synthesis and application in Pd-catalyzed Suzuki–Miyaura coupling reactions
- Robin Schulte and
- Heiko Ihmels
Beilstein J. Org. Chem. 2022, 18, 368–373, doi:10.3762/bjoc.18.41
- congested derivative 2b has significantly suppressed reactivity, the monosubstituted derivative 2a was shown to be a very useful and complementary building block for the synthesis of monoarylated norbornadiene derivatives that carry no further substituents. It should be noted, however, that the inverse
Graphical Abstract
Scheme 1: Synthesis of the borylated norbornadienes 2a,b and 3.
Scheme 2: Suzuki–Miyaura coupling reactions of borono-norbornadienes 2a and 2b with selected haloarenes 4a–k.
Figure 1: Photometric monitoring of the photoisomerization of 2-(1-naphthyl)norbornadiene (5b) in MeCN, c = 2...
Scheme 3: Photo-induced, reversible conversion of the naphthylnorbornadiene 5b to quadricyclane 6b in CH3CN (...
Synthesis and late stage modifications of Cyl derivatives
- Phil Servatius and
- Uli Kazmaier
Beilstein J. Org. Chem. 2022, 18, 174–181, doi:10.3762/bjoc.18.19
- suitable protected linear precursor A (Scheme 2, PG: protecting group), the resulting carboxylic acid obtained can directly be activated and subjected to cyclization. If the glycine allyl ester is incorporated as the last building block into the C-terminus of the peptide, this concept should provide a high
Graphical Abstract
Figure 1: Naturally occurring HDAC inhibitors.
Figure 2: Naturally occurring HDAC inhibitors with different zinc-binding motifs.
Scheme 1: Planned syntheses of Cyl-1 derivatives.
Scheme 2: Cyl-1 derivatives via peptide Claisen rearrangement.
Scheme 3: Synthesis of tetrapeptide allyl esters 8.
Scheme 4: Synthesis and late stage modifications of Cyl derivatives.
Synthesis and bioactivity of pyrrole-conjugated phosphopeptides
- Qiuxin Zhang,
- Weiyi Tan and
- Bing Xu
Beilstein J. Org. Chem. 2022, 18, 159–166, doi:10.3762/bjoc.18.17
- similar activity compared to their phosphorylated counterparts. These results indicate that these peptide assemblies are rather compatible with cells. Compounds 13 and 14, both possessing a pyrrole building block on the side chain, hardly inhibit the HeLa cells. While 15a and 15b exhibit slight
Graphical Abstract
Scheme 1: Molecular structures of the parent phosphopeptide 1 and its pyrrole-conjugated analogs 2–14.
Figure 1: Cell viability of HeLa cells treated with 200 μM of each compound for 24 h.
Figure 2: Cell viability of HeLa cells treated with 20 μM, 50 μM, 100 μM, 200 μM and 400 μM of 1, 4a and 6b f...
Figure 3: A) TEM images of 1 before and after addition of ALP (0.5 U/mL) in PBS buffer (pH 7.4). Scale bar is...
High-speed C–H chlorination of ethylene carbonate using a new photoflow setup
- Takayoshi Kasakado,
- Takahide Fukuyama,
- Tomohiro Nakagawa,
- Shinji Taguchi and
- Ilhyong Ryu
Beilstein J. Org. Chem. 2022, 18, 152–158, doi:10.3762/bjoc.18.16
- [14][15][16][17][18][19][20]. Vinylene carbonate also serves as a useful synthetic building block for Diels–Alder reactions [21][22][23][24][25] and polymerization [26][27][28][29][30]. Results and Discussion Using a PTFE tube and PTFE connectors, we connected the photoflow setup with a chlorine gas
Graphical Abstract
Scheme 1: Radical chain mechanism for a photo-induced C–H chlorination reaction.
Figure 1: Components for photoflow setup: (a) MiChS LX-1 reactor and (b) MiChS LED-s (365 ± 5 nm, 60–600 W).
Scheme 2: Model reaction: photoflow C–H chlorination of ethylene carbonate (1) to chloroethylene carbonate (2...
Figure 2: Photoflow setup for the C–H chlorination of ethylene carbonate (1).
Regioselective synthesis of methyl 5-(N-Boc-cycloaminyl)-1,2-oxazole-4-carboxylates as new amino acid-like building blocks
- Jolita Bruzgulienė,
- Greta Račkauskienė,
- Aurimas Bieliauskas,
- Vaida Milišiūnaitė,
- Miglė Dagilienė,
- Gita Matulevičiūtė,
- Vytas Martynaitis,
- Sonata Krikštolaitytė,
- Frank A. Sløk and
- Algirdas Šačkus
Beilstein J. Org. Chem. 2022, 18, 102–109, doi:10.3762/bjoc.18.11
- ppm appeared, implying chemical exchange and therefore the presence of rotamers (Supporting Information File 1 in Figure S53b). The synthesis of methyl 5-(N-Boc-piperidin-4-yl)-1,2-oxazole-4-carboxylate (4h), a nonchiral amino acid-like building block, was obtained by the reaction of β-enamino
Graphical Abstract
Figure 1: Examples of amino-functionalized 1,2-oxazole derivatives I–VIII.
Scheme 1: Conversion of cyclic amino acids to 1,2-oxazole derivatives.
Scheme 2: Plausible mechanisms for the formation of 1,2-oxazoles 4a–h and VII from β-enamino ketoesters 3a–h ...
Figure 2: (a) 1H NMR (italics), 13C NMR (normal), and 15N NMR (bold) chemical shifts (ppm) of compound 3a in ...
Scheme 3: Synthesis of compound 15N-1,2-oxazole 5. The coupling constants of JHN and JCN from 15N2 are indica...
Figure 3: Stacked chromatogram view of pairs of enantiomers with area, %: (R)-4b, ee 100% (tR = 10.1 min) and...
Figure 4: (a) Structure of 4b with syn- and anti-conformers; (b) superimposed 1H NMR and 1D gradient NOE spec...
Scheme 4: Synthesis of 2-[4-(methoxycarbonyl)-1,2-oxazol-5-yl]cycloaminyl-1-ium trifluoroacetates 6a,b.
Figure 5: ORTEP diagram of the asymmetric unit consisting of two cations 6b(A) and 6b(B) and triflate anions.
Selective sulfonylation and isonitrilation of para-quinone methides employing TosMIC as a source of sulfonyl group or isonitrile group
- Chuanhua Qu,
- Run Huang,
- Yong Li,
- Tong Liu,
- Yuan Chen and
- Guiting Song
Beilstein J. Org. Chem. 2021, 17, 2822–2831, doi:10.3762/bjoc.17.193
- standard conditions, the desired products 3b or 4b were obtained with yields of 92% and 88%, respectively. Second, the sulfonylated diarylmethane 3b obtained through the C–S bond-cleavage sulfonylation reaction is a versatile building block for preparing diarylmethane derivatives through a nucleophilic
Graphical Abstract
Figure 1: Selected bioactive compounds.
Scheme 1: The chemistry of TosMIC in the reactions with olefins.
Scheme 2: ZnI2-catalyzed C–S-bond cleavage of TosMIC for the synthesis of diarylmethyl sulfones 3a–m. Reactio...
Scheme 3: Cases encountered by other p-QMs examinations.
Figure 2: Crystal structure of diarylmethyl sulfone 3e.
Scheme 4: DBU-catalyzed 1,6-conjugate addition for the synthesis of isonitrile diarylmethanes 4a–h. Reaction ...
Scheme 5: Synthetic applications of the synthesized compound 3b.
Scheme 6: Mechanistic studies and proposed mechanism.
The ethoxycarbonyl group as both activating and protective group in N-acyl-Pictet–Spengler reactions using methoxystyrenes. A short approach to racemic 1-benzyltetrahydroisoquinoline alkaloids
- Marco Keller,
- Karl Sauvageot-Witzku,
- Franz Geisslinger,
- Nicole Urban,
- Michael Schaefer,
- Karin Bartel and
- Franz Bracher
Beilstein J. Org. Chem. 2021, 17, 2716–2725, doi:10.3762/bjoc.17.183
- [15]. In this work we took advantage of the hitherto less explored N-acyl-Pictet–Spengler reaction and related chemistry based on the seminal work of Speckamp [16], where an N-acyl residue at the arylethylamine building block leads to enhanced cyclization rates due to the acid-mediated formation of
- reduction of the intermediate nitrostyrenes and N-ethoxycarbonylation of the resulting primary amines [15]. For the synthesis of the alkaloids rac-reticuline (2e) and rac-orientaline (2f) we used a carbamate building block A3 without protection of the phenolic group, since our previous work [10
- ] demonstrated that this building block is compatible with N-acyl-Pictet–Spengler cyclization conditions. The structures of the utilized building blocks are shown in Figure 4. The N-acyl-Pictet–Spengler cyclizations of appropriate pairs of the building blocks with TFA in dichloromethane at 0 °C for 19–90 h (TLC
Graphical Abstract
Figure 1: Prominent synthetic approaches to 1-benzyltetrahydroisoquinolines: Bischler–Napieralski, Pictet–Spe...
Figure 2: Structures of N-methylcoclaurine (1) and the ten 1-benzyl-1,2,3,4-tetrahydroisoquinoline alkaloids ...
Figure 3: Two routes using N- and O-alkoxycarbonylated building blocks for the synthesis of phenolic N-methyl...
Figure 4: Structures of the building blocks A1–A4 (N-ethoxycarbonyl phenethylamines) and B1–B3 (ω-methoxystyr...
Figure 5: Biological activity. Antiproliferative effects of the 1-benzyltetrahydroisoquinoline alkaloids in A...
Synthetic strategies toward 1,3-oxathiolane nucleoside analogues
- Umesh P. Aher,
- Dhananjai Srivastava,
- Girij P. Singh and
- Jayashree B. S
Beilstein J. Org. Chem. 2021, 17, 2680–2715, doi:10.3762/bjoc.17.182
- nucleoside analogues. The enantiomerically pure 1,3-oxathiolane core has been an important building block in precursors that result in a defined stereochemistry of the resultant nucleoside product after N-glycosylation. Dynamic kinetic resolution (DKR) is a processes that interconverts a racemic mixture into
Graphical Abstract
Figure 1: Representative modified 1,3-oxathiolane nucleoside analogues.
Figure 2: Mechanism of antiviral action of 1,3-oxathiolane nucleosides, 3TC (1) and FTC (2), as chain termina...
Figure 3: Synthetic strategies for the construction of the 1,3-oxathiolane sugar ring.
Scheme 1: Synthesis of 4 from benzoyloxyacetaldehyde (3a) and 2-mercapto-substituted dimethyl acetal 3na.
Scheme 2: Synthesis of 8 from protected glycolic aldehyde 3b and 2-mercaptoacetic acid (3o).
Scheme 3: Synthesis of 20 from ᴅ-mannose (3c).
Scheme 4: Synthesis of 20 from 1,6-thioanhydro-ᴅ-galactose (3d).
Scheme 5: Synthesis of 8 from 2-(tert-butyldiphenylsilyloxy)methyl-5-oxo-1,2-oxathiolane (3m).
Scheme 6: Synthesis of 20a from ʟ-gulose derivative 3f.
Scheme 7: Synthesis of 31 from (+)-thiolactic acid 3p and 2-benzoyloxyacetaldehyde (3a).
Scheme 8: Synthesis of 35a from 1,4-dithiane-2,5-diol (3q) and glyoxylic acid (3g) hydrate.
Scheme 9: Synthetic routes toward 41 through Pummerer reaction from methyl 2-mercaptoacetate (3j) and bromoac...
Scheme 10: Strategy for the synthesis of 2,5-substituted 1,3-oxathiolane 41a using 4-nitrobenzyl glyoxylate an...
Scheme 11: Synthesis of 44 by a resolution method using Mucor miehei lipase.
Scheme 12: Synthesis of 45 from benzoyloxyacetaldehyde (3a) and 2-mercaptoacetaldehyde bis(2-methoxyethyl) ace...
Scheme 13: Synthesis of 46 from 2-mercaptoacetaldehyde bis(2-methoxyethyl) acetal (3nc) and diethyl 3-phosphon...
Scheme 14: Synthesis of 48 from 1,3-dihydroxyacetone dimer 3l.
Scheme 15: Approach toward 52 from protected alkene 3rb and lactic acid derivative 51 developed by Snead et al....
Scheme 16: Recent approach toward 56a developed by Kashinath et al.
Scheme 17: Synthesis of 56a from ʟ-menthyl glyoxylate (3h) hydrate by DKR.
Scheme 18: Possible mechanism with catalytic TEA for rapid interconversion of isomers.
Scheme 19: Synthesis of 35a by a classical resolution method through norephedrine salt 58 formation.
Scheme 20: Synthesis of 63 via [1,2]-Brook rearrangement from silyl glyoxylate 61 and thiol 3nb.
Scheme 21: Combined use of STS and CAL-B as catalysts to synthesize an enantiopure oxathiolane precursor 65.
Scheme 22: Synthesis of 1 and 1a from glycolaldehyde dimer 64 and 1,4-dithiane-2,5-diol (3q) using STS and CAL...
Scheme 23: Synthesis of 68 by using Klebsiella oxytoca.
Scheme 24: Synthesis of 71 and 72 using Trichosporon taibachii lipase and kinetic resolution.
Scheme 25: Synthesis of 1,3-oxathiolan-5-ones 77 and 78 via dynamic covalent kinetic resolution.
Figure 4: Pathway for glycosidic bond formation.
Scheme 26: First synthesis of (±)-BCH-189 (1c) by Belleau et al.
Scheme 27: Enantioselective synthesis of 3TC (1).
Scheme 28: Synthesis of cis-diastereomer 3TC (1) from oxathiolane propionate 44.
Scheme 29: Synthesis of (±)-BCH-189 (1c) via SnCl4-mediated N-glycosylation of 8.
Scheme 30: Synthesis of (+)-BCH-189 (1a) via TMSOTf-mediated N-glycosylation of 20.
Scheme 31: Synthesis of 3TC (1) from oxathiolane precursor 20a.
Scheme 32: Synthesis of 83 via N-glycosylation of 20 with pyrimidine bases.
Scheme 33: Synthesis of 85 via N-glycosylation of 20 with purine bases.
Scheme 34: Synthesis of 86 and 87 via N-glycosylation using TMSOTf and pyrimidines.
Scheme 35: Synthesis of 90 and 91 via N-glycosylation using TMSOTf and purines.
Scheme 36: Synthesis of 3TC (1) via TMSI-mediated N-glycosylation.
Scheme 37: Stereoselective N-glycosylation for the synthesis of 1 by anchimeric assistance of a chiral auxilia...
Scheme 38: Whitehead and co-workers’ approach for the synthesis of 1 via direct N-glycosylation without an act...
Scheme 39: ZrCl4-mediated stereoselective N-glycosylation.
Scheme 40: Plausible reaction mechanism for stereoselective N-glycosylation using ZrCl4.
Scheme 41: Synthesis of enantiomerically pure oxathiolane nucleosides 1 and 2.
Scheme 42: Synthesis of tetrazole analogues of 1,3-oxathiolane nucleosides 97.
Scheme 43: Synthetic approach toward 99 from 1,3-oxathiolane 45 by Camplo et al.
Scheme 44: Synthesis of 100 from oxathiolane phosphonate analogue 46.
Scheme 45: Synthetic approach toward 102 and the corresponding cyclic thianucleoside monophosphate 102a by Cha...
Scheme 46: Synthesis of emtricitabine (2) from 1,4-dithiane-2,5-diol (3q) and glyoxylic acid (3g).
Scheme 47: Synthesis of 1 and 2, respectively, from 56a–d using iodine-mediated N-glycosylation.
Scheme 48: Plausible mechanism for silane- and I2-mediated N-glycosylation.
Scheme 49: Pyridinium triflate-mediated N-glycosylation of 35a.
Scheme 50: Possible pathway for stereoselective N-glycosylation via in situ chelation with a metal ligand.
Scheme 51: Synthesis of novel 1,3-oxathiolane nucleoside 108 from oxathiolane precursor 8 and 3-benzyloxy-2-me...
Scheme 52: Synthesis of 110 using T-705 as a nucleobase and 1,3-oxathiolane derivative 8 via N-glycosylation.
Scheme 53: Synthesis of 1 using an asymmetric leaving group and N-glycosylation with bromine and mesitylene.
Scheme 54: Cytidine deaminase for enzymatic separation of 1c.
Scheme 55: Enzymatic resolution of the monophosphate derivative 116 for the synthesis of (−)-BCH-189 (1) and (...
Scheme 56: Enantioselective resolution by PLE-mediated hydrolysis to obtain FTC (2).
Scheme 57: (+)-Menthyl chloroformate as a resolving agent to separate a racemic mixture 120.
Scheme 58: Separation of racemic mixture 1c by cocrystal 123 formation with (S)-(−)-BINOL.
N-Sulfinylpyrrolidine-containing ureas and thioureas as bifunctional organocatalysts
- Viera Poláčková,
- Dominika Krištofíková,
- Boglárka Némethová,
- Renata Górová,
- Mária Mečiarová and
- Radovan Šebesta
Beilstein J. Org. Chem. 2021, 17, 2629–2641, doi:10.3762/bjoc.17.176
- /mismatched combination of chirality, we employed both enantiomers of tert-butyl sulfinamide with the (S)-enantiomer of the pyrrolidine building block. The introduction of green chemistry principles into chemical transformations is an important goal toward sustainable production and manufacturing. Asymmetric
Graphical Abstract
Figure 1: Catalyst design principles.
Scheme 1: Synthesis of isothiocyanate 3a and isocyanate 3b.
Scheme 2: Synthesis of sulfinylthioureas C1 and ureas C2.
Scheme 3: Synthesis of adducts 8a,d,f in solution.
Figure 2: DFT-calculated (PBEh-3c/def2-SV(P)//M06-2X/def2-TZVP) structures of catalyst (S,R) and (S,S)-C2, en...
Figure 3: a) Arrangements of reactants in the transition states; b) DFT-calculated (PBEh-3c/def2-SV(P)//M06-2...
Figure 4: DFT-calculated (PBEh-3c/def2-SV(P)//M06-2X/def2-TZVP) reaction profile for the Michael addition of ...
Chemical syntheses and salient features of azulene-containing homo- and copolymers
- Vijayendra S. Shetti
Beilstein J. Org. Chem. 2021, 17, 2164–2185, doi:10.3762/bjoc.17.139
- synthesis of azulene-bithiophene copolymers 61–65 in which varied ratios of different regioisomers of azulene (1,3- and 4,7-connected) were present (Scheme 13). The synthesis of the key building block 5,5’-bis(trimethylstannyl)-3,3’-didodecyl-2,2’-bithiophene (60) is shown in Scheme 13A. The reaction of the
- -dialkylfluorene-2,7-bis(trimethyleneborate) 102–105 under Suzuki reaction conditions (Scheme 19A). To make the other two polymers, poly{[1,3-bis(9,9’-dihexylfluoren-2’-yl)azulenyl]-alt-[2”,7”-(9”,9”-dialkylfluorenyl]}, 115 and 116, a key azulene-containing building block, 1,3-bis(7-bromo-9,9-dihexylfluoren-2-yl
- degree of regioisomers of same building block. Further, in 2019, Gao and co-workers [41] disclosed the synthesis of azulene-fluorene conjugated polymers connected via 2,6-positions of the azulene ring (Scheme 21). The key starting material to make these polymers was 2,6-dibromoazulene (125), which was
Graphical Abstract
Figure 1: Chemical structure, numbering scheme, and resonance form of azulene.
Scheme 1: Synthesis of polyazulene-iodine (PAz-I2) and polyazulene-bromine (PAz-Br2) complexes.
Scheme 2: Synthesis of ‘true polyazulene’ 3 or 3’ by cationic polymerization.
Scheme 3: Synthesis of 1,3-polyazulene 5 by Yamamoto protocol.
Scheme 4: Synthesis of 4,7-dibromo-6-(n-alkyl)azulenes 12–14.
Scheme 5: Synthesis of (A) 4,7-diethynyl-6-(n-dodecyl)azulene (16) and (B) 4,7-polyazulene 17 containing an e...
Scheme 6: Synthesis of directly connected 4,7-polyazulenes 18–20.
Scheme 7: Synthesis of (A) tert-butyl N-(6-bromoazulen-2-yl)carbamate (27), (B) dimeric aminoazulene 29, and ...
Figure 2: Iminium zwitterionic resonance forms of poly[2(6)-aminoazulene] 31.
Scheme 8: Synthesis of poly{1,3-bis[2-(3-alkylthienyl)]azulene} 33–38.
Scheme 9: Synthesis of polymer ruthenium complexes 40–43.
Scheme 10: Synthesis of 4,7-polyazulenes 45 containing a thienyl linker.
Scheme 11: Synthesis of azulene-bithiophene 48 and azulene-benzothiadiazole 52 copolymers. Conditions: (a): (i...
Scheme 12: Synthesis of azulene-benzodithiophene copolymer 54 and azulene-bithiophene copolymer 56.
Scheme 13: Synthesis of (A) 5,5’-bis(trimethylstannyl)-3,3’-didodecyl-2,2’-bithiophene (60) and (B) azulene-bi...
Scheme 14: Synthesis of 1,3-bisborylated azulene 67.
Scheme 15: Synthesis of D–A-type azulene-DPP copolymers 69, 71, and 72. Conditions: (a) Pd(PPh3)4, K2CO3, Aliq...
Scheme 16: Synthesis of the key precursor TBAzDI 79.
Scheme 17: Synthesis of TBAzDI-based polymers 81 and 83. Conditions: (a) P(o-tol)3, Pd2(dba)3, PivOH, Cs2CO3, ...
Scheme 18: Synthesis of (A) 1,3-dibromo-2-arylazulene 92–98 and (B) 2-arylazulene-thiophene copolymers 99–101.
Scheme 19: Synthesis of (A) poly[2,7-(9,9-dialkylfluorenyl)-alt-(1’,3’-azulenyl)] 106–109, (B) 1,3-bis(7-bromo...
Scheme 20: Synthesis of azulene-fluorene copolymers 117–121 containing varying ratios of 1,3- and 4,7-connecte...
Scheme 21: Synthesis of (A) 2,6-dibromoazulene (125), (B) azulene-fluorene copolymer 126, and (C) azulene-fluo...
Scheme 22: Synthesis of 2-arylazulene-fluorene copolymers 131–134.
Scheme 23: Synthesis of azulene-fluorene-benzothiadiazole terpolymers 136–138.
Scheme 24: Synthesis of azulene-carbazole-benzothiadiazole-conjugated polymers 140–144.
Scheme 25: Synthesis of (A) azulene-2-yl methacrylate (146) and (B) the triazole-containing azulene methacryla...
Scheme 26: Synthesis of (A) azulene methacrylate polymer 151 and (B) triazole-containing azulene methacrylate ...
Scheme 27: Synthesis of azulene methyl methacrylate polymers 154, 155 (A and B) and azulene-sulfobetaine metha...
On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets
- Renato L. Carvalho,
- Amanda S. de Miranda,
- Mateus P. Nunes,
- Roberto S. Gomes,
- Guilherme A. M. Jardim and
- Eufrânio N. da Silva Júnior
Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126
Graphical Abstract
Scheme 1: Schematic overview of transition metals studied in C–H activation processes.
Scheme 2: (A) Known biological activities related to benzimidazole-based compounds; (B and C) an example of a...
Scheme 3: (A) Known biological activities related to quinoline-based compounds; (B and C) an example of a sca...
Scheme 4: (A) Known biological activities related to sulfur-containing compounds; (B and C) an example of a s...
Scheme 5: (A) Known biological activities related to aminoindane derivatives; (B and C) an example of a scand...
Scheme 6: (A) Known biological activities related to norbornane derivatives; (B and C) an example of a scandi...
Scheme 7: (A) Known biological activities related to aniline derivatives; (B and C) an example of a titanium-...
Scheme 8: (A) Known biological activities related to cyclohexylamine derivatives; (B) an example of an intram...
Scheme 9: (A) Known biologically active benzophenone derivatives; (B and C) photocatalytic oxidation of benzy...
Scheme 10: (A) Known bioactive fluorine-containing compounds; (B and C) vanadium-mediated C(sp3)–H fluorinatio...
Scheme 11: (A) Known biologically active Lythraceae alkaloids; (B) synthesis of (±)-decinine (30).
Scheme 12: (A) Synthesis of (R)- and (S)-boehmeriasin (31); (B) synthesis of phenanthroindolizidines by vanadi...
Scheme 13: (A) Known bioactive BINOL derivatives; (B and C) vanadium-mediated oxidative coupling of 2-naphthol...
Scheme 14: (A) Known antiplasmodial imidazopyridazines; (B) practical synthesis of 41.
Scheme 15: (A) Gold-catalyzed drug-release mechanism using 2-alkynylbenzamides; (B and C) chromium-mediated al...
Scheme 16: (A) Examples of anti-inflammatory benzaldehyde derivatives; (B and C) chromium-mediated difunctiona...
Scheme 17: (A and B) Manganese-catalyzed chemoselective intramolecular C(sp3)–H amination; (C) late-stage modi...
Scheme 18: (A and B) Manganese-catalyzed C(sp3)–H amination; (C) late-stage modification of a leelamine deriva...
Scheme 19: (A) Known bioactive compounds containing substituted N-heterocycles; (B and C) manganese-catalyzed ...
Scheme 20: (A) Known indoles that present GPR40 full agonist activity; (B and C) manganese-catalyzed C–H alkyl...
Scheme 21: (A) Examples of known biaryl-containing drugs; (B and C) manganese-catalyzed C–H arylation through ...
Scheme 22: (A) Known zidovudine derivatives with potent anti-HIV properties; (B and C) manganese-catalyzed C–H...
Scheme 23: (A and B) Manganese-catalyzed C–H organic photo-electrosynthesis; (C) late-stage modification.
Scheme 24: (A) Example of a known antibacterial silylated dendrimer; (B and C) manganese-catalyzed C–H silylat...
Scheme 25: (A and B) Fe-based small molecule catalyst applied for selective aliphatic C–H oxidations; (C) late...
Scheme 26: (A) Examples of naturally occurring gracilioethers; (B) the first total synthesis of gracilioether ...
Scheme 27: (A and B) Selective aliphatic C–H oxidation of amino acids; (C) late-stage modification of proline-...
Scheme 28: (A) Examples of Illicium sesquiterpenes; (B) first chemical synthesis of (+)-pseudoanisatin (80) in...
Scheme 29: (A and B) Fe-catalyzed deuteration; (C) late-stage modification of pharmaceuticals.
Scheme 30: (A and B) Biomimetic Fe-catalyzed aerobic oxidation of methylarenes to benzaldehydes (PMHS, polymet...
Scheme 31: (A) Known tetrahydroquinolines with potential biological activities; (B and C) redox-selective Fe c...
Scheme 32: (A) Known drugs containing a benzofuran unit; (B and C) Fe/Cu-catalyzed tandem O-arylation to acces...
Scheme 33: (A) Known azaindolines that act as M4 muscarinic acetylcholine receptor agonists; (B and C) intramo...
Scheme 34: (A) Known indolinones with anticholinesterase activity; (B and C) oxidative C(sp3)–H cross coupling...
Scheme 35: (A and B) Cobalt-catalyzed C–H alkenylation of C-3-peptide-containing indoles; (C) derivatization b...
Scheme 36: (A) Cobalt-Cp*-catalyzed C–H methylation of known drugs; (B and C) scope of the o-methylated deriva...
Scheme 37: (A) Known lasalocid A analogues; (B and C) three-component cobalt-catalyzed C–H bond addition; (D) ...
Scheme 38: (A and B) Cobalt-catalyzed C(sp2)–H amidation of thiostrepton.
Scheme 39: (A) Known 4H-benzo[d][1,3]oxazin-4-one derivatives with hypolipidemic activity; (B and C) cobalt-ca...
Scheme 40: (A and B) Cobalt-catalyzed C–H arylation of pyrrole derivatives; (C) application for the synthesis ...
Scheme 41: (A) Known 2-phenoxypyridine derivatives with potent herbicidal activity; (B and C) cobalt-catalyzed...
Scheme 42: (A) Natural cinnamic acid derivatives; (B and C) cobalt-catalyzed C–H carboxylation of terminal alk...
Scheme 43: (A and B) Cobalt-catalyzed C–H borylation; (C) application to the synthesis of flurbiprofen.
Scheme 44: (A) Benzothiazoles known to present anticonvulsant activities; (B and C) cobalt/ruthenium-catalyzed...
Scheme 45: (A and B) Cobalt-catalyzed oxygenation of methylene groups towards ketone synthesis; (C) synthesis ...
Scheme 46: (A) Known anticancer tetralone derivatives; (B and C) cobalt-catalyzed C–H difluoroalkylation of ar...
Scheme 47: (A and B) Cobalt-catalyzed C–H thiolation; (C) application in the synthesis of quetiapine (153).
Scheme 48: (A) Known benzoxazole derivatives with anticancer, antifungal, and antibacterial activities; (B and...
Scheme 49: (A and B) Cobalt-catalyzed C–H carbonylation of naphthylamides; (C) BET inhibitors 158 and 159 tota...
Scheme 50: (A) Known bioactive pyrrolo[1,2-a]quinoxalin-4(5H)-one derivatives; (B and C) cobalt-catalyzed C–H ...
Scheme 51: (A) Known antibacterial cyclic sulfonamides; (B and C) cobalt-catalyzed C–H amination of propargyli...
Scheme 52: (A and B) Cobalt-catalyzed intramolecular 1,5-C(sp3)–H amination; (C) late-stage functionalization ...
Scheme 53: (A and B) Cobalt-catalyzed C–H/C–H cross-coupling between benzamides and oximes; (C) late-state syn...
Scheme 54: (A) Known anticancer natural isoquinoline derivatives; (B and C) cobalt-catalyzed C(sp2)–H annulati...
Scheme 55: (A) Enantioselective intramolecular nickel-catalyzed C–H activation; (B) bioactive obtained motifs;...
Scheme 56: (A and B) Nickel-catalyzed α-C(sp3)–H arylation of ketones; (C) application of the method using kno...
Scheme 57: (A and B) Nickel-catalyzed C(sp3)–H acylation of pyrrolidine derivatives; (C) exploring the use of ...
Scheme 58: (A) Nickel-catalyzed C(sp3)–H arylation of dioxolane; (B) library of products obtained from biologi...
Scheme 59: (A) Intramolecular enantioselective nickel-catalyzed C–H cycloalkylation; (B) product examples, inc...
Scheme 60: (A and B) Nickel-catalyzed C–H deoxy-arylation of azole derivatives; (C) late-stage functionalizati...
Scheme 61: (A and B) Nickel-catalyzed decarbonylative C–H arylation of azole derivatives; (C) application of t...
Scheme 62: (A and B) Another important example of nickel-catalyzed C–H arylation of azole derivatives; (C) app...
Scheme 63: (A and B) Another notable example of a nickel-catalyzed C–H arylation of azole derivatives; (C) lat...
Scheme 64: (A and B) Nickel-based metalorganic framework (MOF-74-Ni)-catalyzed C–H arylation of azole derivati...
Scheme 65: (A) Known commercially available benzothiophene-based drugs; (B and C) nickel-catalyzed C–H arylati...
Scheme 66: (A) Known natural tetrahydrofuran-containing substances; (B and C) nickel-catalyzed photoredox C(sp3...
Scheme 67: (A and B) Another notable example of a nickel-catalyzed photoredox C(sp3)–H alkylation/arylation; (...
Scheme 68: (A) Electrochemical/nickel-catalyzed C–H alkoxylation; (B) achieved scope, including three using na...
Scheme 69: (A) Enantioselective photoredox/nickel catalyzed C(sp3)–H arylation; (B) achieved scope, including ...
Scheme 70: (A) Known commercially available trifluoromethylated drugs; (B and C) nickel-catalyzed C–H trifluor...
Scheme 71: (A and B) Stereoselective nickel-catalyzed C–H difluoroalkylation; (C) late-stage functionalization...
Scheme 72: (A) Cu-mediated ortho-amination of oxalamides; (B) achieved scope, including derivatives obtained f...
Scheme 73: (A) Electro-oxidative copper-mediated amination of 8-aminoquinoline-derived amides; (B) achieved sc...
Scheme 74: (A and B) Cu(I)-mediated C–H amination with oximes; (C) derivatization using telmisartan (241) as s...
Scheme 75: (A and B) Cu-mediated amination of aryl amides using ammonia; (C) late-stage modification of proben...
Scheme 76: (A and B) Synthesis of purine nucleoside analogues using copper-mediated C(sp2)–H activation.
Scheme 77: (A) Copper-mediated annulation of acrylamide; (B) achieved scope, including the synthesis of the co...
Scheme 78: (A) Known bioactive compounds containing a naphthyl aryl ether motif; (B and C) copper-mediated eth...
Scheme 79: (A and B) Cu-mediated alkylation of N-oxide-heteroarenes; (C) late-stage modification.
Scheme 80: (A) Cu-mediated cross-dehydrogenative coupling of polyfluoroarenes and alkanes; (B) scope from know...
Scheme 81: (A) Known anticancer acrylonitrile compounds; (B and C) Copper-mediated cyanation of unactivated al...
Scheme 82: (A) Cu-mediated radiofluorination of 8-aminoquinoline-derived aryl amides; (B) achieved scope, incl...
Scheme 83: (A) Examples of natural β-carbolines; (B and C) an example of a zinc-catalyzed C–H functionalizatio...
Scheme 84: (A) Examples of anticancer α-aminophosphonic acid derivatives; (B and C) an example of a zinc-catal...
Cationic oligonucleotide derivatives and conjugates: A favorable approach for enhanced DNA and RNA targeting oligonucleotides
- Mathias B. Danielsen and
- Jesper Wengel
Beilstein J. Org. Chem. 2021, 17, 1828–1848, doi:10.3762/bjoc.17.125
- nuclease stability assay showed a clear improvement relative to the control and the simple 2′-O-carbamoyluridine modification [84]. A different approach to introduce aminoalkyl groups at the 2’-position was achieved via a benzyl protected 2’-succinylamido-2’-deoxyuridine building block attached either to a
Graphical Abstract
Figure 1: A schematic representation of 16-mer ASOs in different designs. White circles represent unmodified ...
Figure 2: Structures of 5-(1-propargylamino)-2’-deoxyuridine (A) and 2’-aminoethoxy-5-propargylaminouridine (...
2,4-Bis(arylethynyl)-9-chloro-5,6,7,8-tetrahydroacridines: synthesis and photophysical properties
- Najeh Tka,
- Mohamed Adnene Hadj Ayed,
- Mourad Ben Braiek,
- Mahjoub Jabli,
- Noureddine Chaaben,
- Kamel Alimi,
- Stefan Jopp and
- Peter Langer
Beilstein J. Org. Chem. 2021, 17, 1629–1640, doi:10.3762/bjoc.17.115
- anthranilic acid with 2.2 equivalents of bromine in acetic acid as previously reported [64]. Subsequently, the POCl3-mediated cyclodehydration of 1 and cyclohexanone afforded 2 through an adapted reported procedure (Scheme 1) [65]. Tetrahydroacridine 2 represents a novel synthetic building block for Pd
Graphical Abstract
Figure 1: Applications of acridines.
Scheme 1: Synthesis of 2,4-dibromo-9-chloro-5,6,7,8-tetrahydroacridine (2).
Scheme 2: Synthesis of 2,4-bis(arylethynyl)-9-chloro-5,6,7,8-tetrahydroacridines 4a–g.
Figure 2: UV–vis absorption spectra of 4a,b and 4e–g in diluted dichloromethane solutions at room temperature...
Figure 3: Emission spectra of 4a,b and 4e–g in diluted dichloromethane solutions at room temperature (c = 1 ×...
Chemical synthesis of C6-tetrazole ᴅ-mannose building blocks and access to a bioisostere of mannuronic acid 1-phosphate
- Eleni Dimitriou and
- Gavin J. Miller
Beilstein J. Org. Chem. 2021, 17, 1527–1532, doi:10.3762/bjoc.17.110
- to explore the synthesis of a ᴅ-manno C6-tetrazole thioglycoside donor and examine subsequent installation of C1 phosphate and anomeric linker groups. Results and Discussion An initial route towards a protected C6-tetrazole building block started from known mannuronic acid thioglycoside 1 (Scheme 1
Graphical Abstract
Figure 1: a) Chemical structure of alginate showing constituent M and G residues and C2/C3 acetylation for on...
Scheme 1: a) H2N(CH2)2CN, PyBOP, DIPEA, CH2Cl2, 0 °C, 40 min, 47% (+44% 3); b) TBSOTf, imidazole, DMAP, DMF, ...
Scheme 2: a) BzCl, DMAP, pyridine, CH2Cl2, rt, 24 h, 90%; b) TBSOTf, imidazole, DMAP, DMF, 40 °C, 24 h, 78%; ...
Scheme 3: a) PMBCl, KI, K2CO3, DMF, rt, 53% for 11 and 12; b) BnBr, DMF, Et3N, DCM, rt, 31% for 13 and 14.
Scheme 4: a) DMSO, SO3·pyridine, Et3N, rt, 1 h, 96%; b) H2NOH·HCl, THF, H2O, Na2CO3, 89%; c) POCl3, MeCN, 65 ...
Design, synthesis and photophysical properties of novel star-shaped truxene-based heterocycles utilizing ring-closing metathesis, Clauson–Kaas, Van Leusen and Ullmann-type reactions as key tools
- Shakeel Alvi and
- Rashid Ali
Beilstein J. Org. Chem. 2021, 17, 1374–1384, doi:10.3762/bjoc.17.96
- hint for its utility as novel building block for the development of a range of advanced functional materials for innumerable applications [8][9][10][11][12][13][14][15][16]. Moreover, truxene has also been vividly used for the construction of fullerenes and their bowl-shaped fragments besides their
Graphical Abstract
Scheme 1: Retrosynthetic pathways to the pyrrole-based C3-symmetric truxene derivative 6.
Scheme 2: Synthesis of tripyrrolotruxene 6 via cyclotrimerization and RCM as crucial steps.
Scheme 3: Synthesis of star-shaped molecule 6 utilizing the Clauson–Kaas pyrrole strategy.
Scheme 4: Synthesis of truxene derivative 6 involving Ullmann-type cross-coupling reaction.
Scheme 5: Synthesis of imidazole and benzimidazole containing truxene derivatives 14 and 16.
Scheme 6: Construction of truxene-based di- and trioxazole derivatives 21 and 20.
Scheme 7: Synthesis of benzene-bridged rings containing trioxazolotruxene system 25.
Figure 1: Normalized absorption (left); fluorescence spectra (right) of the synthesized truxene derivatives (...
A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries
- Guido Gambacorta,
- James S. Sharley and
- Ian R. Baxendale
Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90
Graphical Abstract
Figure 1: Representative shares of the global F&F market (2018) segmented on their applications [1].
Figure 2: General structure of an international fragrance company [2].
Figure 3: The Michael Edwards fragrance wheel.
Figure 4: Examples of oriental (1–3), woody (4–7), fresh (8–10), and floral (11 and 12) notes.
Figure 5: A basic depiction of batch vs flow.
Scheme 1: Examples of reactions for which flow processing outperforms batch.
Scheme 2: Some industrially important aldol-based transformations.
Scheme 3: Biphasic continuous aldol reactions of acetone and various aldehydes.
Scheme 4: Aldol synthesis of 43 in flow using LiHMDS as the base.
Scheme 5: A semi-continuous synthesis of doravirine (49) involving a key aldol reaction.
Scheme 6: Enantioselective aldol reaction using 5-(pyrrolidin-2-yl)tetrazole (51) as catalyst in a microreact...
Scheme 7: Gröger's example of asymmetric aldol reaction in aqueous media.
Figure 6: Immobilised reagent column reactor types.
Scheme 8: Photoinduced thiol–ene coupling preparation of silica-supported 5-(pyrrolidin-2-yl)tetrazole 63 and...
Scheme 9: Continuous-flow approach for enantioselective aldol reactions using the supported catalyst 67.
Scheme 10: Ötvös’ employment of a solid-supported peptide aldol catalyst in flow.
Scheme 11: The use of proline tetrazole packed in a column for aldol reaction between cyclohexanone (65) and 2...
Scheme 12: Schematic diagram of an aminosilane-grafted Si-Zr-Ti/PAI-HF reactor for continuous-flow aldol and n...
Scheme 13: Continuous-flow condensation for the synthesis of the intermediate 76 to nabumetone (77) and Microi...
Scheme 14: Synthesis of ψ-Ionone (80) in continuous-flow via aldol condensation between citral (79) and aceton...
Scheme 15: Synthesis of β-methyl-ionones (83) from citral (79) in flow. The steps are separately described, an...
Scheme 16: Continuous-flow synthesis of 85 from 84 described by Gavriilidis et al.
Scheme 17: Continuous-flow scCO2 apparatus for the synthesis of 2-methylpentanal (87) and the self-condensed u...
Scheme 18: Chen’s two-step flow synthesis of coumarin (90).
Scheme 19: Pechmann condensation for the synthesis of 7-hydroxyxcoumarin (93) in flow. The setup extended to c...
Scheme 20: Synthesis of the dihydrojasmonate 35 exploiting nitro derivative proposed by Ballini et al.
Scheme 21: Silica-supported amines as heterogeneous catalyst for nitroaldol condensation in flow.
Scheme 22: Flow apparatus for the nitroaldol condensation of p-hydroxybenzaldehyde (102) to nitrostyrene 103 a...
Scheme 23: Nitroaldol reaction of 64 to 105 employing a quaternary ammonium functionalised PANF.
Scheme 24: Enantioselective nitroaldol condensation for the synthesis of 108 under flow conditions.
Scheme 25: Enatioselective synthesis of 1,2-aminoalcohol 110 via a copper-catalysed nitroaldol condensation.
Scheme 26: Examples of Knoevenagel condensations applied for fragrance components.
Scheme 27: Flow apparatus for Knoevenagel condensation described in 1989 by Venturello et al.
Scheme 28: Knoevenagel reaction using a coated multichannel membrane microreactor.
Scheme 29: Continuous-flow apparatus for Knoevenagel condensation employing sugar cane bagasse as support deve...
Scheme 30: Knoevenagel reaction for the synthesis of 131–135 in flow using an amine-functionalised silica gel. ...
Scheme 31: Continuous-flow synthesis of compound 137, a key intermediate for the synthesis of pregabalin (138)...
Scheme 32: Continuous solvent-free apparatus applied for the synthesis of compounds 140–143 using a TSE. Throu...
Scheme 33: Lewis et al. developed a spinning disc reactor for Darzens condensation of 144 and a ketone to furn...
Scheme 34: Some key industrial applications of conjugate additions in the F&F industry.
Scheme 35: Continuous-flow synthesis of 4-(2-hydroxyethyl)thiomorpholine 1,1-dioxide (156) via double conjugat...
Scheme 36: Continuous-flow system for Michael addition using CsF on alumina as the catalyst.
Scheme 37: Calcium chloride-catalysed asymmetric Michael addition using an immobilised chiral ligand.
Scheme 38: Continuous multistep synthesis for the preparation of (R)-rolipram (173). Si-NH2: primary amine-fun...
Scheme 39: Continuous-flow Michael addition using ion exchange resin Amberlyst® A26.
Scheme 40: Preparation of the heterogeneous catalyst 181 developed by Paixão et al. exploiting Ugi multicompon...
Scheme 41: Continuous-flow system developed by the Paixão’s group for the preparation of Michael asymmetric ad...
Scheme 42: Continuous-flow synthesis of nitroaldols catalysed by supported catalyst 184 developed by Wennemers...
Scheme 43: Heterogenous polystyrene-supported catalysts developed by Pericàs and co-workers.
Scheme 44: PANF-supported pyrrolidine catalyst for the conjugate addition of cyclohexanone (65) and trans-β-ni...
Scheme 45: Synthesis of (−)-paroxetine precursor 195 developed by Ötvös, Pericàs, and Kappe.
Scheme 46: Continuous-flow approach for the 5-step synthesis of (−)-oseltamivir (201) as devised by Hayashi an...
Scheme 47: Continuous-flow enzyme-catalysed Michael addition.
Scheme 48: Continuous-flow copper-catalysed 1,4 conjugate addition of Grignard reagents to enones. Reprinted w...
Scheme 49: A collection of commonly encountered hydrogenation reactions.
Figure 7: The ThalesNano H-Cube® continuous-flow hydrogenator.
Scheme 50: Chemoselective reduction of an α,β-unsaturated ketone using the H-Cube® reactor.
Scheme 51: Incorporation of Lindlar’s catalyst into the H-Cube® reactor for the reduction of an alkyne.
Scheme 52: Continuous-flow semi-hydrogenation of alkyne 208 to 209 using SACs with H-Cube® system.
Figure 8: The standard setups for tube-in-tube gas–liquid reactor units.
Scheme 53: Homogeneous hydrogenation of olefins using a tube-in-tube reactor setup.
Scheme 54: Recyclable heterogeneous flow hydrogenation system.
Scheme 55: Leadbeater’s reverse tube-in-tube hydrogenation system for olefin reductions.
Scheme 56: a) Hydrogenation using a Pd-immobilised microchannel reactor (MCR) and b) a representation of the i...
Scheme 57: Hydrogenation of alkyne 238 exploiting segmented flow in a Pd-immobilised capillary reactor.
Scheme 58: Continuous hydrogenation system for the preparation of cyrene (241) from (−)-levoglucosenone (240).
Scheme 59: Continuous hydrogenation system based on CSMs developed by Hornung et al.
Scheme 60: Chemoselective reduction of carbonyls (ketones over aldehydes) in flow.
Scheme 61: Continuous system for the semi-hydrogenation of 256 and 258, developed by Galarneau et al.
Scheme 62: Continuous synthesis of biodiesel fuel 261 from lignin-derived furfural acetone (260).
Scheme 63: Continuous synthesis of γ-valerolacetone (263) via CTH developed by Pineda et al.
Scheme 64: Continuous hydrogenation of lignin-derived biomass (products 265, 266, and 267) using a sustainable...
Scheme 65: Ru/C or Rh/C-catalysed hydrogenation of arene in flow as developed by Sajiki et al.
Scheme 66: Polysilane-immobilized Rh–Pt-catalysed hydrogenation of arenes in flow by Kobayashi et al.
Scheme 67: High-pressure in-line mixing of H2 for the asymmetric reduction of 278 at pilot scale with a 73 L p...
Figure 9: Picture of the PFR employed at Eli Lilly & Co. for the continuous hydrogenation of 278 [287]. Reprinted ...
Scheme 68: Continuous-flow asymmetric hydrogenation using Oppolzer's sultam 280 as chiral auxiliary.
Scheme 69: Some examples of industrially important oxidation reactions in the F&F industry. CFL: compact fluor...
Scheme 70: Gold-catalysed heterogeneous oxidation of alcohols in flow.
Scheme 71: Uozumi’s ARP-Pt flow oxidation protocol.
Scheme 72: High-throughput screening of aldehyde oxidation in flow using an in-line GC.
Scheme 73: Permanganate-mediated Nef oxidation of nitroalkanes in flow with the use of in-line sonication to p...
Scheme 74: Continuous-flow aerobic anti-Markovnikov Wacker oxidation.
Scheme 75: Continuous-flow oxidation of 2-benzylpyridine (312) using air as the oxidant.
Scheme 76: Continuous-flow photo-oxygenation of monoterpenes.
Scheme 77: A tubular reactor design for flow photo-oxygenation.
Scheme 78: Glucose oxidase (GOx)-mediated continuous oxidation of glucose using compressed air and the FFMR re...
Scheme 79: Schematic continuous-flow sodium hypochlorite/TEMPO oxidation of alcohols.
Scheme 80: Oxidation using immobilised TEMPO (344) was developed by McQuade et al.
Scheme 81: General protocol for the bleach/catalytic TBAB oxidation of aldehydes and alcohols.
Scheme 82: Continuous-flow PTC-assisted oxidation using hydrogen peroxide. The process was easily scaled up by...
Scheme 83: Continuous-flow epoxidation of cyclohexene (348) and in situ preparation of m-CPBA.
Scheme 84: Continuous-flow epoxidation using DMDO as oxidant.
Scheme 85: Mukayama aerobic epoxidation optimised in flow mode by the Favre-Réguillon group.
Scheme 86: Continuous-flow asymmetric epoxidation of derivatives of 359 exploiting a biomimetic iron catalyst.
Scheme 87: Continuous-flow enzymatic epoxidation of alkenes developed by Watts et al.
Scheme 88: Engineered multichannel microreactor for continuous-flow ozonolysis of 366.
Scheme 89: Continuous-flow synthesis of the vitamin D precursor 368 using multichannel microreactors. MFC: mas...
Scheme 90: Continuous ozonolysis setup used by Kappe et al. for the synthesis of various substrates employing ...
Scheme 91: Continuous-flow apparatus for ozonolysis as developed by Ley et al.
Scheme 92: Continuous-flow ozonolysis for synthesis of vanillin (2) using a film-shear flow reactor.
Scheme 93: Examples of preparative methods for ajoene (386) and allicin (388).
Scheme 94: Continuous-flow oxidation of thioanisole (389) using styrene-based polymer-supported peroxytungstat...
Scheme 95: Continuous oxidation of thiosulfinates using Oxone®-packed reactor.
Scheme 96: Continuous-flow electrochemical oxidation of thioethers.
Scheme 97: Continuous-flow oxidation of 400 to cinnamophenone (235).
Scheme 98: Continuous-flow synthesis of dehydrated material 401 via oxidation of methyl dihydrojasmonate (33).
Scheme 99: Some industrially important transformations involving Grignard reagents.
Scheme 100: Grachev et al. apparatus for continuous preparation of Grignard reagents.
Scheme 101: Example of fluidized Mg bed reactor with NMR spectrometer as on-line monitoring system.
Scheme 102: Continuous-flow synthesis of Grignard reagents and subsequent quenching reaction.
Figure 10: Membrane-based, liquid–liquid separator with integrated pressure control [52]. Adapted with permission ...
Scheme 103: Continuous-flow synthesis of 458, an intermediate to fluconazole (459).
Scheme 104: Continuous-flow synthesis of ketones starting from benzoyl chlorides.
Scheme 105: A Grignard alkylation combining CSTR and PFR technologies with in-line infrared reaction monitoring....
Scheme 106: Continuous-flow preparation of 469 from Grignard addition of methylmagnesium bromide.
Scheme 107: Continuous-flow synthesis of Grignard reagents 471.
Scheme 108: Preparation of the Grignard reagent 471 using CSTR and the continuous process for synthesis of the ...
Scheme 109: Continuous process for carboxylation of Grignard reagents in flow using tube-in-tube technology.
Scheme 110: Continuous synthesis of propargylic alcohols via ethynyl-Grignard reagent.
Scheme 111: Silica-supported catalysed enantioselective arylation of aldehydes using Grignard reagents in flow ...
Scheme 112: Acid-catalysed rearrangement of citral and dehydrolinalool derivatives.
Scheme 113: Continuous stilbene isomerisation with continuous recycling of photoredox catalyst.
Scheme 114: Continuous-flow synthesis of compound 494 as developed by Ley et al.
Scheme 115: Selected industrial applications of DA reaction.
Scheme 116: Multistep flow synthesis of the spirocyclic structure 505 via employing DA cycloaddition.
Scheme 117: Continuous-flow DA reaction developed in a plater flow reactor for the preparation of the adduct 508...
Scheme 118: Continuous-flow DA reaction using a silica-supported imidazolidinone organocatalyst.
Scheme 119: Batch vs flow for the DA reaction of (cyclohexa-1,5-dien-1-yloxy)trimethylsilane (513) with acrylon...
Scheme 120: Continuous-flow DA reaction between 510 and 515 using a shell-core droplet system.
Scheme 121: Continuous-flow synthesis of bicyclic systems from benzyne precursors.
Scheme 122: Continuous-flow synthesis of bicyclic scaffolds 527 and 528 for further development of potential ph...
Scheme 123: Continuous-flow inverse-electron hetero-DA reaction to pyridine derivatives such as 531.
Scheme 124: Comparison between batch and flow for the synthesis of pyrimidinones 532–536 via retro-DA reaction ...
Scheme 125: Continuous-flow coupled with ultrasonic system for preparation of ʟ-ascorbic acid derivatives 539 d...
Scheme 126: Two-step continuous-flow synthesis of triazole 543.
Scheme 127: Continuous-flow preparation of triazoles via CuAAC employing 546-based heterogeneous catalyst.
Scheme 128: Continuous-flow synthesis of compounds 558 through A3-coupling and 560 via AgAAC both employing the...
Scheme 129: Continuous-flow photoinduced [2 + 2] cycloaddition for the preparation of bicyclic derivatives of 5...
Scheme 130: Continuous-flow [2 + 2] and [5 + 2] cycloaddition on large scale employing a flow reactor developed...
Scheme 131: Continuous-flow preparation of the tricyclic structures 573 and 574 starting from pyrrole 570 via [...
Scheme 132: Continuous-flow [2 + 2] photocyclization of cinnamates.
Scheme 133: Continuous-flow preparation of cyclobutane 580 on a 5-plates photoreactor.
Scheme 134: Continuous-flow [2 + 2] photocycloaddition under white LED lamp using heterogeneous PCN as photocat...
Figure 11: Picture of the parallel tube flow reactor (PTFR) "The Firefly" developed by Booker-Milburn et al. a...
Scheme 135: Continuous-flow acid-catalysed [2 + 2] cycloaddition between silyl enol ethers and acrylic esters.
Scheme 136: Continuous synthesis of lactam 602 using glass column reactors.
Scheme 137: In situ generation of ketenes for the Staudinger lactam synthesis developed by Ley and Hafner.
Scheme 138: Application of [2 + 2 + 2] cycloadditions in flow employed by Ley et al.
Scheme 139: Examples of FC reactions applied in F&F industry.
Scheme 140: Continuous-flow synthesis of ibuprofen developed by McQuade et al.
Scheme 141: The FC acylation step of Jamison’s three-step ibuprofen synthesis.
Scheme 142: Synthesis of naphthalene derivative 629 via FC acylation in microreactors.
Scheme 143: Flow system for rapid screening of catalysts and reaction conditions developed by Weber et al.
Scheme 144: Continuous-flow system developed by Buorne, Muller et al. for DSD optimisation of the FC acylation ...
Scheme 145: Continuous-flow FC acylation of alkynes to yield β-chlorovinyl ketones such as 638.
Scheme 146: Continuous-flow synthesis of tonalide (619) developed by Wang et al.
Scheme 147: Continuous-flow preparation of acylated arene such as 290 employing Zr4+-β-zeolite developed by Kob...
Scheme 148: Flow system applied on an Aza-FC reaction catalysed by the thiourea catalyst 648.
Scheme 149: Continuous hydroformylation in scCO2.
Scheme 150: Two-step flow synthesis of aldehyde 655 through a sequential Heck reaction and subsequent hydroform...
Scheme 151: Single-droplet (above) and continuous (below) flow reactors developed by Abolhasani et al. for the ...
Scheme 152: Continuous hydroformylation of 1-dodecene (655) using a PFR-CSTR system developed by Sundmacher et ...
Scheme 153: Continuous-flow synthesis of the aldehyde 660 developed by Eli Lilly & Co. [32]. Adapted with permissio...
Scheme 154: Continuous asymmetric hydroformylation employing heterogenous catalst supported on carbon-based sup...
Scheme 155: Examples of acetylation in F&F industry: synthesis of bornyl (S,R,S-664) and isobornyl (S,S,S-664) ...
Scheme 156: Continuous-flow preparation of bornyl acetate (S,R,S-664) employing the oscillating flow reactor.
Scheme 157: Continuous-flow synthesis of geranyl acetate (666) from acetylation of geraniol (343) developed by ...
Scheme 158: 12-Ttungstosilicic acid-supported silica monolith-catalysed acetylation in flow.
Scheme 159: Continuous-flow preparation of cyclopentenone 676.
Scheme 160: Two-stage synthesis of coumarin (90) via acetylation of salicylaldehyde (88).
Scheme 161: Intensification process for acetylation of 5-methoxytryptamine (677) to melatonin (678) developed b...
Scheme 162: Examples of macrocyclic musky odorants both natural (679–681) and synthetic (682 and 683).
Scheme 163: Flow setup combined with microwave for the synthesis of macrocycle 686 via RCM.
Scheme 164: Continuous synthesis of 2,5-dihydro-1H-pyrroles via ring-closing metathesis.
Scheme 165: Continuous-flow metathesis of 485 developed by Leadbeater et al.
Figure 12: Comparison between RCM performed using different routes for the preparation of 696. On the left the...
Scheme 166: Continuous-flow RCM of 697 employed the solid-supported catalyst 698 developed by Grela, Kirschning...
Scheme 167: Continuous-flow RORCM of cyclooctene employing the silica-absorbed catalyst 700.
Scheme 168: Continuous-flow self-metathesis of methyl oleate (703) employing SILP catalyst 704.
Scheme 169: Flow apparatus for the RCM of 697 using a nanofiltration membrane for the recovery and reuse of the...
Scheme 170: Comparison of loadings between RCMs performed with different routes for the synthesis of 709.
Application of the Meerwein reaction of 1,4-benzoquinone to a metal-free synthesis of benzofuropyridine analogues
- Rashmi Singh,
- Tomas Horsten,
- Rashmi Prakash,
- Swapan Dey and
- Wim Dehaen
Beilstein J. Org. Chem. 2021, 17, 977–982, doi:10.3762/bjoc.17.79
- , Belgium 10.3762/bjoc.17.79 Abstract Several new heterocyclic systems based on a hydroxybenzofuro[2,3-b]pyridine building block were prepared. This benzofuropyridine is easily available from the Meerwein reaction of benzoquinone and a heterocyclic diazonium salt, followed by reduction and cyclization
- converted to novel oxazole-fused derivatives 19 and 20, respectively, by condensation with benzaldehyde and subsequent 2,3-dichloro-5.6-dicyano-p-benzoquinone (DDQ)-mediated oxidation (Scheme 3). Aldehyde building block 16 was a versatile starting material for further cyclization reactions. Synthesis of
- regioselective in forming 16, which is a valuable building block for various condensation reactions to yield a diverse set of products, such as polycyclic fused nitrochromenes 21 as well as pyridopsoralens 22 and 23. All these novel scaffolds are interesting structures with potential medicinal applications, and
Graphical Abstract
Figure 1: Biologically relevant 2-oxydibenzofuran-containing structures 1–6.
Figure 2: Representative bioactive structures containing benzofuro-fused pyridine analogues 7–9.
Scheme 1: Strategy for metal-free access to benzofuropyridine 13.
Scheme 2: Electrophilic aromatic substitution of 6-hydroxybenzofuro[2,3-b]pyridine (13).
Scheme 3: Synthesis of isomeric oxazole-fused derivatives.
Scheme 4: Fused derivatives from 16.
Chiral isothiourea-catalyzed kinetic resolution of 4-hydroxy[2.2]paracyclophane
- David Weinzierl and
- Mario Waser
Beilstein J. Org. Chem. 2021, 17, 800–804, doi:10.3762/bjoc.17.68
- decades, it was shown that enantioenriched 2 may serve as a valuable building block to access more advanced chiral cyclophane ligands and catalysts [3][4][19][20][21][22] and therefore its asymmetric synthesis became an important task [3][4][18][19][20][21][22][23][24][25][26][27]. Several strategies to
Graphical Abstract
Scheme 1: Overview about established methods to access enantioenriched 2 and the herein investigated kinetic ...
Scheme 2: Use of alternative acylating agents 4 for the kinetic resolution of rac-2.
