Chemical and chemoenzymatic routes to bridged homoarabinofuranosylpyrimidines: Bicyclic AZT analogues

• Sandeep Kumar,
• Jyotirmoy Maity,
• Banty Kumar,
• Sumit Kumar and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2022, 18, 95–101, doi:10.3762/bjoc.18.10

• -glucofuranose following chemoenzymatic and chemical routes in 34–35% and 24–25% overall yields, respectively. The quantitative and diastereoselective acetylation of primary hydroxy over two secondary hydroxy groups present in the key nucleoside precursor was mediated with Lipozyme® TL IM in 2

Iron-catalyzed domino coupling reactions of π-systems

• Austin Pounder and
• William Tam

Beilstein J. Org. Chem. 2021, 17, 2848–2893, doi:10.3762/bjoc.17.196

• provided the desired carboamination product 164. By using methyl cinnamate derivatives, the reactions were highly diastereoselective for the formation of 1,2-anti carboamination products. Notably, the Ritter reaction was found to be the origin of diastereoselectivity on the basis of a density functional

• electron-withdrawing substituents on the oxime; however, the reaction required highly activated alkenes to proceed. 1,2-Disubstituted alkenes were tolerated and were diastereoselective for the anti-addition product. When maleimides 171 were used as the 2-carbon coupling partner, a [5 + 1] annulation was

Highly stereocontrolled total synthesis of racemic codonopsinol B through isoxazolidine-4,5-diol vinylation

• Lukáš Ďurina,
• Anna Ďurinová,
• František Trejtnar,
• Ľuboš Janotka,
• Lucia Messingerová,
• Jana Doháňošová,
• Ján Moncol and
• Róbert Fischer

Beilstein J. Org. Chem. 2021, 17, 2781–2786, doi:10.3762/bjoc.17.188

• Bratislava, Radlinského 9, 81237 Bratislava, Slovak Republic 10.3762/bjoc.17.188 Abstract A new highly diastereoselective synthesis of the polyhydroxylated pyrrolidine alkaloid (±)-codonopsinol B and its N-nor-methyl analogue, starting from achiral materials, is presented. The strategy relies on the trans

• human cancer cell lines has never been described. In view of this, we have developed an efficient and highly diastereoselective approach towards codonopsinol B (1) and its N-nor-methyl analogue 2 from achiral starting materials and evaluated their anticancer activity using four different cancer cell

• isoxazolidine-4,5-diols in the presence of anhydrous cerium chloride [17], which proceeded in a highly syn-diastereoselective manner due to the presence of the unprotected hydroxy group in the α-position. Accordingly, the diol 3 will be examined in the reaction with vinylmagnesium bromide with an emphasis on

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

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

• -sulfinylurea as bifunctional organocatalyst [23]. The enantio- and diastereoselective addition of Meldrum’s acids to nitroalkenes via N-sulfinylurea catalysis gave products that were readily converted to pharmaceutically relevant compounds [24][25]. A sulfinylurea organocatalyst catalyzed a highly selective

Recent advances in organocatalytic asymmetric aza-Michael reactions of amines and amides

• Pratibha Sharma,
• Raakhi Gupta and
• Raj K. Bansal

Beilstein J. Org. Chem. 2021, 17, 2585–2610, doi:10.3762/bjoc.17.173

• -nitrophthalimide to α,β-unsaturated ketones. Diastereoselective synthesis of bridged 1,2,3,4-tetrahydroisoquinoline derivatives using modularly designed organocatalyst. Synthesis of spiro[pyrrolidine-3,3'-oxindoles] via asymmetric cascade aza-Michael reaction catalyzed by squaramide. Asymmetric aza-Michael

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

• promotes the Hg(II)-salt-catalyzed cyclization of allenes in most circumstances. In cyclization reactions, Hg(OTf)2 showed to be the most effective and versatile of all Hg(II) salts. Mercury(II) salts can also be used to cyclize unsaturated bonds in a regio- and diastereoselective manner. Apart from

Halides as versatile anions in asymmetric anion-binding organocatalysis

• Lukas Schifferer,
• Martin Stinglhamer,
• Kirandeep Kaur and
• Olga García Macheño

Beilstein J. Org. Chem. 2021, 17, 2270–2286, doi:10.3762/bjoc.17.145

• diastereoselective glycosylation reaction. b) Competing SN1 vs SN2 reactivity. a) Folding mechanism of oligotriazoles upon anion recognition. b) Representative tetratriazole 82 catalyzed enantioselective Reissert-type reaction of quinolines and pyridines with various nucleophiles. Switchable chiral tetratriazole

Asymmetric organocatalyzed synthesis of coumarin derivatives

• Natália M. Moreira,
• Lorena S. R. Martelli and
• Arlene G. Corrêa

Beilstein J. Org. Chem. 2021, 17, 1952–1980, doi:10.3762/bjoc.17.128

• form the product of interest, which could be obtained with moderate to excellent yields and enantioselectivities. The protocol used allowed obtaining hydrocoumarins with a wide structural variety and with a diastereoselective control, as shown in Scheme 24. In 2016, Albrecht et al. [60] published the

Methodologies for the synthesis of quaternary carbon centers via hydroalkylation of unactivated olefins: twenty years of advances

• Thiago S. Silva and
• Fernando Coelho

Beilstein J. Org. Chem. 2021, 17, 1565–1590, doi:10.3762/bjoc.17.112

• addition products 10 and 12 (Scheme 7A). In both cases, a low diastereoselective control was observed. Control experiments revealed that, under these reaction conditions, the hydroalkylation was reversible (Scheme 7B), indicating the participation of the silver salt in the C(sp3)–C(sp3)-bond cleavage

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

• , an immunoactivating natural product (substrate 37) [97][98]. In 2015, the diastereoselective synthesis of (E,S)-3-hydroxy-7-tritylthio-4-heptenoic acid 43, a key component of cyclodepsipeptide histone deacetylase (HDAC) inhibitors, was achieved in flow (Scheme 4) [99]. Acetyloxazolidinone 41 was used

N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

• generated, taking place a diastereoselective nucleophilic dichloromethylation of the imine. The addition took place almost exclusively to the Re face of the imine (RS)-14, which is the less sterically hindered in the most stable s-cis conformation (see Scheme 2). The second intramolecular N-alkylation step

• described the diastereoselective synthesis of aziridines 42 in one-step using the Cu(I)/ʟ-proline complex as a catalyst and N-tert-butasulfinylamide in an aminotrifluoromethylation reaction of alkenes. All the aziridines 42 were obtained with high diastereoselectivity (dr > 25:1) and good yields (56–98

• by the group of Reddy [81] starting from ethyl cyclobutanecarboxylate 43 and chiral N-tert-butanesulfinyl aldimines (RS)-14. In this three-step procedure, a highly diastereoselective addition of the ethyl cyclobutanecarboxylate anion occurred first, followed by the reduction of the ester group, and

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

•  18). A sequence of reactions involving elimination of a proton from 83, treatment of 84 with an alkoxide, and protonation of the resulting enolate delivered thermodynamically favored equatorial ester 80 and 81. The highly diastereoselective Brønsted superacid-catalyzed Prins cyclization of

• , followed by removal of trimethylsilane (Scheme 50). The authors further explored this strategy for the asymmetric synthesis of 3-vinylidene-substituted tetrahydropyran by taking the chiral propargylsilane. A diastereoselective route to cis-2,6-disubstituted tetrahydropyran-4-one 215 was explored by

• ion, which was followed by a completely diastereoselective Friedel–Crafts reaction (Scheme 70). List and co-workers devised a strategy employing highly acidic confined iminoimidodiphosphate (iIDP) Brønsted acids 308 that catalyzed asymmetric Prins cyclizations of both aliphatic and aromatic aldehydes

Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects

• Shivani Gulati,
• Stephy Elza John and
• Nagula Shankaraiah

Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71

• ] tailored a microwave-assisted multicomponent reaction for fast and efficient generation of diastereoselective dibenzo[c,e]azepinones. The protocol utilized substituted 2'-formylbiphenyl-2-carboxylic acid 19, benzylamines 20, and isocyanides 21 in TFE and Na2SO4 as drying agent for the construction of

• co-workers [50] demonstrated an aqueous phase, diastereoselective, multicomponent reaction involving substituted isatins 35, β-nitrostyrene 36 and benzylamine (20) or α-amino acids 37 using microwave irradiation to afford a library of spirooxindoles 38 in good yields under catalyst-free conditions

• -alkenyloxindole 43 were considered to be the building blocks united in ethanol as solvent (Scheme 15). The notable highlights of the described methodology are diastereoselective C–C and C–N bond formation, high yields, non-toxic product, and cost-effectiveness along with a greener approach. The synthetic strategy

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

• cyclopropane formation did not require Et3B (Scheme 25). The work was extended to include boron-free, diastereoselective versions incorporating N-acylimidazolidinone chiral auxiliaries (Scheme 26). Cyclization reaction of phenylacetonitrile and 1,2-dibromo-1,1-difluoroethane: Kagabu et al. showed that the

A sustainable strategy for the straightforward preparation of 2H-azirines and highly functionalized NH-aziridines from vinyl azides using a single solvent flow-batch approach

• Michael Andresini,
• Leonardo Degannaro and
• Renzo Luisi

Beilstein J. Org. Chem. 2021, 17, 203–209, doi:10.3762/bjoc.17.20

• % yield. Moreover, the reaction was found fully diastereoselective when HexLi or iBuLi were added to 2m. In fact, only products deriving from the attack of the organolithium on the less hindered face (i.e., anti with respect to the phenyl substituent at C3), leading to 3k (52%), and 3l (45%), were

Recent progress in the synthesis of homotropane alkaloids adaline, euphococcinine and N-methyleuphococcinine

• Dimas J. P. Lima,
• Antonio E. G. Santana,
• Michael A. Birkett and
• Ricardo S. Porto

Beilstein J. Org. Chem. 2021, 17, 28–41, doi:10.3762/bjoc.17.4

• amide, confirming to be a sample with a high level of enantiomeric purity. As in Murahashi’s synthesis, Meyers also utilized a chiral auxiliary for asymmetric induction. Nonetheless, this method differed from Murahashi's by presenting a diastereoselective intramolecular Mannich cyclization to form the

All-carbon [3 + 2] cycloaddition in natural product synthesis

• Zhuo Wang and
• Junyang Liu

Beilstein J. Org. Chem. 2020, 16, 3015–3031, doi:10.3762/bjoc.16.251

• complex B (Scheme 11B). A facile migration–fragmentation process of complex B eliminates a ketone through fragmentation and produces metal-carbene intermediate C. The freshly prepared metal-carbene C is equilibrated to stabilized 1,3-dipole D. D undergoes a diastereoselective [3 + 2] cycloaddition to give

Ring-closing metathesis of prochiral oxaenediynes to racemic 4-alkenyl-2-alkynyl-3,6-dihydro-2H-pyrans

• Viola Kolaříková,
• Markéta Rybáčková,
• Martin Svoboda and
• Jaroslav Kvíčala

Beilstein J. Org. Chem. 2020, 16, 2757–2768, doi:10.3762/bjoc.16.226

• order to obtain enantiomerically pure compounds by enyne metathesis, a diastereoselective approach starting from chiral substrates is by far the most common. It was frequently used in the construction of chiral compounds, e.g., the mansamine framework [27], anatoxin [28] or sulfoximines [29]. A

• metathesis or enantioselective RCEYM reactions catalyzed by ruthenium complexes are known (Scheme 3). The only RCEYM of a system containing two triple and one double bonds has been described by Gouverneur et al., who synthesized a series of dihydrooxaphosphinines by the diastereoselective metathesis of

• and Mo catalysts. Beneficial effect of ethene atmosphere. Enantioselective dienyne metathesis [21]. Diastereoselective endiyne metathesis [31]. Synthesis of hepta-1,6-diyn-4-ol (4a). Protection of hepta-1,6-diyn-4-ol (4a). Alkylation of the protected diynols 7a and 8a. Deprotection of protected

A heterobimetallic tetrahedron from a linear platinum(II)-bis(acetylide) metalloligand

• Matthias Hardy,
• Marianne Engeser and
• Arne Lützen

Beilstein J. Org. Chem. 2020, 16, 2701–2708, doi:10.3762/bjoc.16.220

• Figure S1 in Supporting Information File 1 and also Figure 5 below) shows signals that clearly indicate the presence of various diastereomeric cages, and thus, the self-assembly does not occur in a diastereoselective manner. Unfortunately, the superposition of these signals made it impossible to clearly

• -carbaldehyde and iron(II) cations in a subcomponent self-assembly approach. Unfortunately, the self-assembly process in solution did not occur in a diastereoselective manner as all possible diastereomers were observed. However, the DOSY and mass spectra clearly identified the tetrahedral cage 4 as the

Vicinal difluorination as a C=C surrogate: an analog of piperine with enhanced solubility, photostability, and acetylcholinesterase inhibitory activity

• Yuvixza Lizarme-Salas,
• Alexandra Daryl Ariawan,
• Ranjala Ratnayake,
• Hendrik Luesch,
• Angela Finch and
• Luke Hunter

Beilstein J. Org. Chem. 2020, 16, 2663–2670, doi:10.3762/bjoc.16.216

• -workers have recently described a method for the one-step, diastereoselective 1,2-difluorination of alkenes, mediated by a hypervalent iodine catalyst [24]. The substrate scope of the Jacobsen method has certain constraints but their original report did include some examples of α,β-unsaturated amides, and

Hierarchically assembled helicates as reaction platform – from stoichiometric Diels–Alder reactions to enamine catalysis

• David Van Craen,
• Jenny Begall,
• Johannes Großkurth,
• Leonard Himmel,
• Oliver Linnenberg,
• Elisabeth Isaak and
• Markus Albrecht

Beilstein J. Org. Chem. 2020, 16, 2338–2345, doi:10.3762/bjoc.16.195

• (dr 83:17) at room temperature. Enantioselectivity was not achieved even with the chiral ligands 4-H2 and 5-H2. Nevertheless, the successful implementation of diastereoselective catalysis by hierarchically assembled helicates was a big step forward and will draw our focus on the development of new

Convenient access to pyrrolidin-3-ylphosphonic acids and tetrahydro-2H-pyran-3-ylphosphonates with multiple contiguous stereocenters from nonracemic adducts of a Ni(II)-catalyzed Michael reaction

• Alexander N. Reznikov,
• Dmitry S. Nikerov,
• Anastasiya E. Sibiryakova,
• Victor B. Rybakov,
• Evgeniy V. Golovin and
• Yuri N. Klimochkin

Beilstein J. Org. Chem. 2020, 16, 2073–2079, doi:10.3762/bjoc.16.174

• addition of β-keto phosphonates to nitroolefins and subsequent reductive cyclization of enantioenriched, diastereomerically pure Michael adducts was developed. The present study also demonstrates that the diastereoselective cascade Henry/acetalyzation reaction with keto nitro phosphonates and aldehydes

• ,6R)-13b. Intermolecular N-methylation of reduction product 7. Synthesis of pyrrolidinyl phosphonic acids 11a–d. Synthesis of tetrahydropyranylphosphonates 13a–f via diastereoselective Henry/acetalyzation reaction. Synthesis of (3,4-dihydro-2H-pyran-5-yl)phosphonate 14. Optimization of the conditions

Controlling the stereochemistry in 2-oxo-aldehyde-derived Ugi adducts through the cinchona alkaloid-promoted electrophilic fluorination

• Yuqing Wang,
• Gaigai Wang,
• Anatoly A. Peshkov,
• Ruwei Yao,
• Muhammad Hasan,
• Manzoor Zaman,
• Chao Liu,
• Stepan Kashtanov,
• Olga P. Pereshivko and
• Vsevolod A. Peshkov

Beilstein J. Org. Chem. 2020, 16, 1963–1973, doi:10.3762/bjoc.16.163

• diastereoselective U-4CR have been described [48][49][50][51][52][53][54]. Yet, the Ugi reaction turned out to be a rather challenging chemical transformation in terms of establishing the asymmetric version [33][34][35]. Apart from the two asymmetric three-component modifications lacking the acid component [55][56

Pauson–Khand reaction of fluorinated compounds

• Jorge Escorihuela,
• Daniel M. Sedgwick,
• Alberto Llobat,
• Mercedes Medio-Simón,
• Pablo Barrio and
• Santos Fustero

Beilstein J. Org. Chem. 2020, 16, 1662–1682, doi:10.3762/bjoc.16.138

• imine-derived CF3-containing enyne, bearing the trifluoromethylethynyl group at the ortho position (Scheme 16) [55]. One of the key steps in the preparation of the starting 1,n-enynes was a highly diastereoselective allylation reaction of chiral Ellman’s sulfinylimines. Based on this strategy, chiral

• this purpose, 1,7-enynes 48 were prepared from Ellman’s tert-butane sulfinylimines, followed by a diastereoselective addition of propargylmagnesium bromide to obtain a variety of sulfinyl amide intermediates 46 in good yields and high diastereoselectivities. Subsequent oxidation to the corresponding

• corresponding aldehyde in a 41% global yield. Bicyclic product 49a underwent diastereoselective (dr > 20:1) hydrogenation using palladium over activated charcoal under an atmosphere of hydrogen to afford saturated derivative 50 (Scheme 26). On the other hand, the tert-butanesulfonyl group could be removed