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

• crucial, while the urea analog of the catalysts proved less efficient and led to diminished reactivity and stereoselectivity. Further mechanistic studies corroborated this hypothesis as more electron-rich allylsilane derivatives were consumed slower despite being inherently more nucleophilic. Another

• macrocycle 81 (Scheme 17a) [78]. Compared to bis-thiourea 80, the higher rigidity in the macrocycle 81 not only enforces halide abstraction significantly, but also allowed for a better control of the stereoselectivity in the glycosylation of glycosyl halides 78 with a variety of coupling partners. In this

Enantioenriched α-substituted glutamates/pyroglutamates via enantioselective cyclopropenimine-catalyzed Michael addition of amino ester imines

• Zara M. Seibel,
• Jeffrey S. Bandar and
• Tristan H. Lambert

Beilstein J. Org. Chem. 2021, 17, 2077–2084, doi:10.3762/bjoc.17.134

• , stereoselectivity, and selectivity for the Michael addition versus cycloaddition (Figure 2). The optimal substituent in this regard proved to be p-chlorophenyl 1, which resulted in the yield and selectivities using catalyst 5 as already discussed in Table 1. The o-chlorophenyl imine 12 was equally reactive, but led

Progress and challenges in the synthesis of sequence controlled polysaccharides

• Giulio Fittolani,
• Theodore Tyrikos-Ergas,
• Denisa Vargová,
• Manishkumar A. Chaube and
• Martina Delbianco

Beilstein J. Org. Chem. 2021, 17, 1981–2025, doi:10.3762/bjoc.17.129

• polymerization [18], C) chemical synthesis. The use of enzymes has undeniable advantages because it offers the possibility to use unprotected sugars as substrates and guarantees remarkable control of the regio- and stereoselectivity during glycosylation. Mono- or oligosaccharides bearing a reactive leaving group

• for the introduction of unnatural modifications. However, the control over the length and substitution pattern remains poor. To ensure good regio- and stereoselectivity, the starting material, often a polycyclic compound, has to be designed with suitable protecting groups (PGs). These structures can

• . Several oligosaccharides have been prepared to identify the best PG pattern ensuring a proper balance between BB reactivity, stereoselectivity, and simplicity of deprotection [113][114][115][116][117][118][119][120][121][122][123][124][125]. Ester groups are commonly employed at C-2 position to ensure

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

• (dimethylamino)titanium [Ti(NMe2)4] and tetrabenzyltitanium [TiBn4], and it was observed that a better stereoselectivity was achieved by using the first catalyst while a better yield was obtained when the second catalyst was applied (Scheme 8B). Although the authors did not explore any possible biological

• described the dehydrosilylation and hydrosilylation of alkenes to afford silylated alkanes and alkenes in excellent yields and stereoselectivity, depending on the phosphine-based ligand employed. The reaction proved to work through a redox-neutral path, being considered an atom-economical process

• -component reaction in which a cobalt-Cp*-catalyzed C–H bond addition afforded complex scaffolds in good yields (Scheme 37B and C) [193]. The authors explained the stereoselectivity by means of a mechanism involving a hydride migration suffering influence of steric effects related not only to the catalyst

Sustainable manganese catalysis for late-stage C–H functionalization of bioactive structural motifs

• Jongwoo Son

Beilstein J. Org. Chem. 2021, 17, 1733–1751, doi:10.3762/bjoc.17.122

• tryptophan-containing peptides (Scheme 13). A wide variety of complex peptides was explored, affording glycosylated conjugates with high stereoselectivity. The free NH functional group was tolerated in the manganese catalysis protocol, suggesting that the chemoselectivity was controlled by chelation of 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

• oxidant (Scheme 30) [99]. Bicycle units 82 founded in natural products could be synthetized under Co(II) salen complex 80 catalysis at room temperature with excellent stereoselectivity. Only trans-decalins 82 were observed in the presence of secondary OTBS groups in the substrate backbone; this was not

• stereoselectivity, and olefin 84h containing a biologically relevant steroid moiety was successfully hydroalkylated under these conditions. This confirmed the potential of this strategy to forge challenging carbon sp3–sp3 bonds. The proposed mechanism starts with a Ni(I) species (A), which acts as a radical

Breaking paracyclophane: the unexpected formation of non-symmetric disubstituted nitro[2.2]metaparacyclophanes

• Suraj Patel,
• Tyson N. Dais,
• Paul G. Plieger and
• Gareth J. Rowlands

Beilstein J. Org. Chem. 2021, 17, 1518–1526, doi:10.3762/bjoc.17.109

• % probability level [63]. Crystal structure of 15. Ellipsoids are drawn at a 50% probability level [63]. Possible origin of stereoselectivity. Nitration of [2.2]paracyclophane (1) and the synthesis of 4-hydroxy-5-nitro[2.2]metaparacyclophane (5) and the cyclohexadienone cyclophane 6 (average yield from more

Cascade intramolecular Prins/Friedel–Crafts cyclization for the synthesis of 4-aryltetralin-2-ols and 5-aryltetrahydro-5H-benzo[7]annulen-7-ols

• Jie Zheng,
• Shuyu Meng and
• Quanrui Wang

Beilstein J. Org. Chem. 2021, 17, 1481–1489, doi:10.3762/bjoc.17.104

• -product for the reaction with furan further verified the oxophilic character of the employed BF3, although the stereoselectivity considerably decreased in comparison with the formation of tetralin ring system as the distance between the reaction sites is increased. It is worth mentioning that the

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

• NaHCO3 to prevent poising from moisture and acids. Once mixed with the nitroethane, the mixture was directed into the catalyst. The catalyst was found to be highly efficient operating at high conversion (96–91%) for 30 hours (TON = 204) with high enantio- and stereoselectivity (96:4 anti/syn, 91–92% ee

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

• solvents, such as toluene and dichloromethane, took place with high diastereoselectivity. However, solvents such as ether and THF had a negative impact on stereoselectivity [15]. On the other hand, recent studies developed by Sirvent and Foubelo demonstrated the influence of the solvents in both the yield

Metal-free glycosylation with glycosyl fluorides in liquid SO₂

• Krista Gulbe,
• Jevgeņija Lugiņina,
• Edijs Jansons,
• Artis Kinens and
• Māris Turks

Beilstein J. Org. Chem. 2021, 17, 964–976, doi:10.3762/bjoc.17.78

• glucosyl fluoride gave better yields (18a and 18d) than with the corresponding acylated analogues β-9 and α-11 described above. It was also found that the glycosylation stereoselectivity with glucosyl fluoride 16 did not depend on the anomeric ratio of glucosyl fluoride 16: both anomers of 16 yielded

• characterized by lithium cation basicity (LiCB) liquid SO2 (76.3) is similar to DCM (83) [67]. Thus, liquid SO2 could be classified as a non-coordinating solvent that unlikely coordinates to the oxocarbenium ion intermediate and affects the glycosylation stereoselectivity [1]. As a result, we can conclude that

• the stereoselectivity of the glycosylation in liquid SO2 is substrate-controlled and approaches a thermodynamic equilibrium determined by the anomeric effect or interference of both the anomeric effect and the assistance of the neighboring ester-type protecting group. Next, we have also observed that

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

• ion intermediate in a stereoselective manner for THP ring formation as shown in Scheme 3. The outcome of exclusive cis-stereoselectivity in the Prins cyclization might be attributed to the most favorable conformation adopted by 12 with equatorial orientation of the 2,6-substituents (R1 and R2). Alder

• construct tetrasubstituted cis-2,6-disubstituted 4,5-dibromotetrahydropyran 124 with high stereoselectivity using γ-brominated homoallylic alcohol (Z)-122 and aldehyde 123 in the presence of InBr3 and TMSBr in CH2Cl2 at 0 °C (Scheme 29) [65]. Metzger and co-workers reported an AlCl3-catalyzed cyclization of

• THPs was exclusively generated via Prins reaction using FeCl3 as a Lewis acid catalyst. Excellent stereoselectivity was obtained for a remarkably broad range of substrates under mild reaction conditions (Scheme 64) [106]. The authors proposed fundamental insights into the mechanism of the reaction

Highly regio- and stereoselective phosphinylphosphination of terminal alkynes with tetraphenyldiphosphine monoxide under radical conditions

• Dat Phuc Tran,
• Yuki Sato,
• Yuki Yamamoto,
• Shin-ichi Kawaguchi,
• Shintaro Kodama,
• Akihiro Nomoto and
• Akiya Ogawa

Beilstein J. Org. Chem. 2021, 17, 866–872, doi:10.3762/bjoc.17.72

• previously reported radical addition reactions of Ph2P(S)PPh2 and Ph2P(S)P(S)Ph2 to alkynes [44], the E/Z ratios were about 9:1 and 8:2, respectively, it should be noted that the present addition of Ph2P(O)PPh2 1 to alkynes afforded (E)-isomers with an excellent stereoselectivity (greater than 95:5) [60

• %, respectively) with excellent stereoselectivity (E/Z = 95:5–99:1). Terminal alkylalkynes with chloro (2d), cyano (2e), and ester (2g) groups provided the corresponding adducts 3d, 3e, and 3g in 33%, 41%, and 54% yields, respectively (E/Z = 94:6–100:0). In sharp contrast, the presence of a hydroxy group

• in 41% and 65% yields, respectively. Again, an excellent stereoselectivity was observed. Moreover, terminal arylalkynes 2k–o were also tolerated under the conditions to afford the desired adducts 3k–o in moderate to good yields with high stereoselectivity. We also investigated the

The synthesis of chiral β-naphthyl-β-sulfanyl ketones via enantioselective sulfa-Michael reaction in the presence of a bifunctional cinchona/sulfonamide organocatalyst

• Deniz Tözendemir and
• Cihangir Tanyeli

Beilstein J. Org. Chem. 2021, 17, 494–503, doi:10.3762/bjoc.17.43

• -Michael addition (SMA) reactions remain a rather less explored reaction among asymmetric organocatalytic transformations, mainly because of the high nucleophilicity of thiols causing difficulties in controlling the stereoselectivity [21], despite C–S bond-forming reactions are of great interest in

• organocatalysts 8d and 9a,b in the literature [30][41]. Among the 11 screened organocatalysts, the ones with amino-substituted DMAP cores gave unimpressive ee values (Table 1, entries 2–5). The quinine-derived organocatalysts 8a–d failed to attain striking stereoselectivity (25–43% ee). The popular urea–quinine

Diels–Alder reaction of β-fluoro-β-nitrostyrenes with cyclic dienes

• Savva A. Ponomarev,
• Roman V. Larkovich,
• Alexander S. Aldoshin,
• Andrey A. Tabolin,
• Sema L. Ioffe,
• Jonathan Groß,
• Till Opatz and
• Valentine G. Nenajdenko

Beilstein J. Org. Chem. 2021, 17, 283–292, doi:10.3762/bjoc.17.27

• structures using 1H NMR spectroscopy (Scheme 3). Larger values of 3JH6-F were observed for the exo-F isomers. The presence of a strong EWG on the aryl substituent led to higher stereoselectivity. For example, approximately a 2:1 ratio was observed for the nitro- and carboxymethyl-substituted products 3b, 3c

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

• (Scheme 23) [64]. Fürstner et al. [67] showed that (trifluoromethyl)gold(I)triphenylphosphine in dichloromethane can be used for the production of difluorocyclopropanes at low temperatures. The advantage of the method is its stereoselectivity. The disadvantages include the stoichiometric use of gold, low

Direct synthesis of anomeric tetrazolyl iminosugars from sugar-derived lactams

• Michał M. Więcław and
• Bartłomiej Furman

Beilstein J. Org. Chem. 2021, 17, 115–123, doi:10.3762/bjoc.17.12

• the light of Woerpel’s model, which characterizes the direction of nucleophilic addition to oxocarbenium ions [41][42][43]. According to this concept, the conformational stability of the compound in question is the key property to consider when predicting the reaction’s stereoselectivity. When the

Progress in the total synthesis of inthomycins

• Bidyut Kumar Senapati

Beilstein J. Org. Chem. 2021, 17, 58–82, doi:10.3762/bjoc.17.7

• , it was transformed into (E)-vinylboronate (+)-145b in perfect stereoselectivity by using the recently developed boron-Wittig reaction with bis[(pinacolato)boryl]methane (144) [79]. By applying the Corey–Fuchs dibromoolefination and followed by Pd-catalyzed hydrogenolysis under Uenishi's conditions

• [80], compound (Z)-(+)-143a delivered the bromodiene (Z,Z)-(+)-145a in good yield and stereoselectivity. Isomerization of (Z)-(+)-143a to (E)-(+)-143b was carried out successfully using sterically hindered base DBU or DABCO. Treatment of (E)-(+)-143b with 144 using the boron-Wittig reaction [79

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

• hydrogenation occurred with high stereoselectivity producing a single diastereoisomer of 29. Then, the amide was treated with methyllithium at −78 °C to provide ketone 30 in 85% yield. Subsequently, the intramolecular Mannich reaction was carried out, leading to the desired alkaloid, via precursor 32. Ketone 30

Silver-catalyzed synthesis of β-fluorovinylphosphonates by phosphonofluorination of aromatic alkynes

• Yajing Zhang,
• Qingshan Tian,
• Guozhu Zhang and
• Dayong Zhang

Beilstein J. Org. Chem. 2020, 16, 3086–3092, doi:10.3762/bjoc.16.258

• vinylphosphonates from simple and commercially available alkynes proceeds under mild conditions with high stereoselectivity, and thus enabling the rapid construction of molecular complexity. Results and Discussion We investigated the reaction of phenylacetylene (1a), Selectfluor®, and diethyl phosphite to afford β

Chiral anion recognition using calix[4]arene-based ureido receptors in a 1,3-alternate conformation

• Tereza Horáčková,
• Jan Budka,
• Vaclav Eigner,
• Wen-Sheng Chung,
• Petra Cuřínová and
• Pavel Lhoták

Beilstein J. Org. Chem. 2020, 16, 2999–3007, doi:10.3762/bjoc.16.249

• moieties (the alkyl group on the calixarene and the chiral centre on the urea moiety) function synergistically, and a proper choice of both substituents can lead to an even better stereoselectivity. Conclusion In conclusion, the introduction of chiral alkyl groups into the lower rim of calix[4]arene

Fluorine effect in nucleophilic fluorination at C4 of 1,6-anhydro-2,3-dideoxy-2,3-difluoro-β-D-hexopyranose

• Danny Lainé,
• Vincent Denavit,
• Olivier Lessard,
• Laurie Carrier,
• Charles-Émile Fecteau,
• Paul A. Johnson and
• Denis Giguère

Beilstein J. Org. Chem. 2020, 16, 2880–2887, doi:10.3762/bjoc.16.237

• various deoxyfluorination reaction conditions. In our specific case, we were able to modulate the stereoselectivity of the nucleophilic fluorination at C4 with the use of Et3N·3HF. As proposed by the group of Linclau [20], we support the involvement of an oxiranium intermediate (results reinforced by

• deoxyfluorination is a difficult task to achieve. The simple synthetic approach described herein and the use of Et3N·3HF as an alternative to the unpredictable DAST looked promising. In the specific case of triflate 13, we were able to modulate the stereoselectivity of the nucleophilic fluorination at C4 using

Synthesis of novel fluorinated building blocks via halofluorination and related reactions

• Attila Márió Remete,
• Tamás T. Novák,
• Melinda Nonn,
• Matti Haukka,
• Ferenc Fülöp and
• Loránd Kiss

Beilstein J. Org. Chem. 2020, 16, 2562–2575, doi:10.3762/bjoc.16.208

• )-15b were formed as single products, without any regio- or stereoselectivity issues (Scheme 8). However, repeated N-halosuccinimide addition was necessary, and the yield of the bromofluorination reaction was still mediocre. The stereochemistry of the products (rac)-15a and (rac)-15b was determined by

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

• David Van Craen Jenny Begall Johannes Grosskurth Leonard Himmel Oliver Linnenberg Elisabeth Isaak Markus Albrecht Institute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, 52074 Aachen, Germany 10.3762/bjoc.16.195 Abstract The stereoselectivity of a Diels–Alder reaction within the

• on the results of the stoichiometric reaction, a secondary amine-catalyzed nitro-Michael reaction is performed as well which afforded reasonable diastereoselectivities. Keywords: Diels–Alder reaction; enamine catalysis; hierarchical helicates; remote-control; stereoselectivity; Introduction Carbon

• –carbon (C–C) bond-forming reactions play a key role in organic chemistry. Hereby the stereoselectivity of the reaction is highly important due to the different behavior of stereoisomers in human metabolism [1][2]. Stereocontrol was achieved either via an auxiliary [3][4][5][6][7] or a catalyst [8], both

Syntheses of spliceostatins and thailanstatins: a review

• William A. Donaldson

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

• pyrrolidine byproduct. Using the Stork–Zhao conditions [23], the Nicolaou group performed an α-methyliodomethylenation of 24 to give 33 with a good stereoselectivity (Z:E ≈ 95:5, Scheme 4) [24][25]. After the hydrolysis of the dimethylaminal and the reaction of the resultant amine with phthalic anhydride, a

• with a poor stereoselectivity, however, a similar reduction of the diethyl acetal of 38, followed by an acetal hydrolysis gave the aldehyde 39 with a good stereocontrol (>10:1). It is not possible to make a direct comparison of the efficiency of these three routes as they do not lead to an identical