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

• dissociation energy (ΔΔG) by 10.6 kcal/mol. The formation of the neighboring group stabilized the oxocarbenium ion (dioxolenium ion) and its reaction with alcohol leads to the experimentally observed glycosides and the FSO2H adduct. We assume that due to the formation of the latter also substrates, which do

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

• inhibited the desired phosphinylphosphination (see, alkyne 2f), probably because of the decomposition of Ph2P(O)PPh2. Furthermore, an electron-deficient alkyne such as methyl propiolate (2h) failed to provide the desired adduct (3h) [61]. 3-Phenyl-1-propyne (2i) and cyclohexylacetylene (2j) gave 3i and 3j

• phosphinylphosphination of some internal alkynes, 2p and 2q, with Ph2P(O)PPh2, but did not afford any adduct (the starting alkynes were recovered unchanged) (Scheme 4). This is most probably because the internal alkynes are sterically bulkier than terminal alkynes, and therefore, the addition did not proceed (Scheme 4

• was complete, sulfur (3 equiv) was added under inert atmosphere and then the mixture was stirred at 60 °C for 6 h to provide the stable adduct 3. The purification of the products was performed by silica gel column chromatography using isohexane/MeOAc as an eluent. Radical addition of Ph2PPPh2 and Ph2P

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

• the involvement of an elementary formation of Knoevenagel adduct A from the reaction between the aldehyde and 11. This adduct undergoes an intermolecular Michael addition to naphthylamine resulting in the formation of B. A subsequent intramolecular nucleophilic cyclization leads C followed by

• proposed two different mechanisms in which the first mechanism involved two subsequent reactions. The first one being a Knoevenagel condensation between aromatic aldehyde and ethyl cyanoacetate to yield a Knoevenagel intermediate A which upon subsequent reaction with benzamidine, forms Michael adduct B. A

• consecutive ring closure yields the desired product 75 aided by the attack of nitrogen lone pair in Michael’s adduct C via a sequential ethanol elimination (E) from D followed by aerial oxidation of intermediate F. Another proposed mechanism follows the formation of imine derivative G produced by the reaction

Synthetic reactions driven by electron-donor–acceptor (EDA) complexes

• Zhonglie Yang,
• Yutong Liu,
• Kun Cao,
• Xiaobin Zhang,
• Hezhong Jiang and
• Jiahong Li

Beilstein J. Org. Chem. 2021, 17, 771–799, doi:10.3762/bjoc.17.67

• of N-heterocyclic compounds. In 2017, Wu and colleagues [58] uncovered the use of the bis(sulfur dioxide) adduct of DABCO, 1,4-diazabicyclo[2.2.2]octane·(SO2)2, as sulfone source in the EDA complex formation by 4-methyl-1-(p-tolyl)pentan-1-one O-(2,4-dinitrophenyl)oxime (11) towards the

• -bond adduct. The first light-promoted three-component reaction has been realized by a halogen-bond adduct, forming perfluoroalkylated pyrimidines 26 (Scheme 8). A variety of perfluorinated chains were assembled with methylene compounds and guanidines or amidines, giving the corresponding

• perfluoroalkyl iodide form a halogen-bond adduct, and then light-induced electron transfer happens in order to give a perfluoroalkyl radical. The protocol can realize alkene- and alkyne iodide perfluoroalkylation and C–H perfluoroalkylation of electron-rich heteroaromatic hydrocarbons, providing a novel protocol

Synthesis of dibenzosuberenone-based novel polycyclic π-conjugated dihydropyridazines, pyridazines and pyrroles

• Ramazan Koçak and
• Arif Daştan

Beilstein J. Org. Chem. 2021, 17, 719–729, doi:10.3762/bjoc.17.61

• cycloaddition reaction, a retro Diels–Alder reaction of the resulting adduct, and a final 1,3-prototropic hydrogen shift took place to afford cycloadducts 3a,b [55] and 3c–f (87–96% yield) (Scheme 1 and Table 1). As shown by the reaction conditions in Table 1, the reactions of tetrazine derivatives with

α,γ-Dioxygenated amides via tandem Brook rearrangement/radical oxygenation reactions and their application to syntheses of γ-lactams

• Mikhail K. Klychnikov,
• Radek Pohl,
• Ivana Císařová and
• Ullrich Jahn

Beilstein J. Org. Chem. 2021, 17, 688–704, doi:10.3762/bjoc.17.58

• for 12m. However, the coupling diastereoselectivity with TEMPO (3) amounted to 4:1 for the trans diastereomers 12nA,B and exclusive for the cis isomer 12nC. The relative configuration of diastereomer 12nA was unequivocally established by X-ray crystallography of the hydrochloride adduct of the keto

[2 + 1] Cycloaddition reactions of fullerene C₆₀ based on diazo compounds

• Yuliya N. Biglova

Beilstein J. Org. Chem. 2021, 17, 630–670, doi:10.3762/bjoc.17.55

• CBr4 or I2, 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) or NaH as the base, and a malonate-derived substrate. The adduct is synthesized in a slightly higher yield by direct treatment of fullerene with malonates. As noted above, a decrease in the strain of the fullerene core is the driving force of its

• ethereal solution of diazomethane in toluene at 0 °C resulted in pyrazoline derivative C [81]. The adduct isolated chromatographically was exposed to ultraviolet (UV) irradiation for 25 min at 25 °C in a quartz tube. The resulting isomers 3 and 4 were separated by reversed-phase high-performance liquid

• adduct 8 and diethyl dicarboxymethanofullerene 11 were synthesized in Rh2(OAc)4-catalyzed reactions. Using Rh2(OAc)4, the selectivity of the process was improved, and the yield of the target products slightly increased to 42 and 32%, respectively [85]. The ability of derivatives to effectively preserve

Valorisation of plastic waste via metal-catalysed depolymerisation

• Francesca Liguori,
• Carmen Moreno-Marrodán and
• Pierluigi Barbaro

Beilstein J. Org. Chem. 2021, 17, 589–621, doi:10.3762/bjoc.17.53

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

• , respectively) gave the two highest results, but the use of dioxane is best avoided due to its toxicity. Except for hexane (only 6% ee, Table 1, entry 13), which resulted in an almost racemic product presumably due to solubility issues, all other solvents afforded the target SMA adduct with similar moderate ee

• the chalcone derivatives employed in the model reaction, the best result in terms of enantioselectivity was attained with 4-methyl-substituted chalcone, which allowed the synthesis of the corresponding SMA adduct 12d with an excellent ee of 91% (Table 3, entry 4). Good to moderate results were

• unexpected result, we decided to revisit the solvent screening. For this purpose, the sulfa-Michael addition of naphthalene-1-thiol to 11c was carried out again in toluene, dioxane, DCM and THF (Table 4). In DCM, 93% ee was attained for adduct 12c. In the light of this striking result, we decided to repeat

Synthesis of trifluoromethyl ketones by nucleophilic trifluoromethylation of esters under a fluoroform/KHMDS/triglyme system

• Yamato Fujihira,
• Yumeng Liang,
• Makoto Ono,
• Kazuki Hirano,
• Takumi Kagawa and
• Norio Shibata

Beilstein J. Org. Chem. 2021, 17, 431–438, doi:10.3762/bjoc.17.39

• that is used as a hemiaminaloate adduct [Me2NCH(O)CF3]- (Scheme 1b) [19][20][21][22][23][24][25][26][27][28]. Although the taming CF3 anion had been an elusive problem for decades, it has been dramatically progressed in recent years by the substantial works by Grushin [51][52][53] and Prakash [54]. Our

• . Trifluoromethyl ketones. a) Hydrolysis of trifluoromethyl ketones. b) Selected examples of biologically active trifluoromethyl ketones. Chemistry of the CF3 anion generated from HCF3. a) Decomposition of the trifluoromethyl anion to difluorocarbene and fluoride. b) A hemiaminaloate adduct of CF3 anion to DMF. c

Annulation of a 1,3-dithiole ring to a sterically hindered o-quinone core. Novel ditopic redox-active ligands

• Sergey V. Norkov,
• Anton V. Cherkasov,
• Andrey S. Shavyrin,
• Maxim V. Arsenyev,
• Viacheslav A. Kuropatov and
• Vladimir K. Cherkasov

Beilstein J. Org. Chem. 2021, 17, 273–282, doi:10.3762/bjoc.17.26

• . Heating the mixture at 60 °C for 4 h does not result in any change of the color from that characteristic of o-quinone 4. After cooling of the solution red crystals of adduct 8 were isolated (see Figure 2 and Figure S6 in Supporting Information File 1). The X-ray diffraction study reveals that adduct 8 is

• -quinone 4. Each o-quinone molecule bridges two adjacent sodium ions. The bond lengths distribution in the o-quinone moiety in 8 is typical of sterically hindered o-quinones (Table S1 in Supporting Information File 1). According to 1H and 13C NMR spectroscopy data, adduct 8 in CD3OD solution exists as

• stoichiometric mixture of 4 and monosodium salt of hfac, so that adduct 8 forms in a crystal phase only. Our studies indicate that the interaction of 4 with stable gem-dithiolates, such as sodium trithiocarbonate, malononitrile gem-dithiolate or 2,6-di-tert-butylphenol gem-dithiolate proceeds in a predictable

Insight into functionalized-macrocycles-guided supramolecular photocatalysis

• Minzan Zuo,
• Krishnasamy Velmurugan,
• Kaiya Wang,
• Xueqi Tian and
• Xiao-Yu Hu

Beilstein J. Org. Chem. 2021, 17, 139–155, doi:10.3762/bjoc.17.15

• between them. These nonbonding interactions could allow the double bonds to be placed at an optimal distance for the efficient [2 + 2]-photoadduct. However, this adduct could not be observed in the absence of the metal cation, indicating the importance of the preorganization of the substrates with Ba2

Facile preparation and conversion of 4,4,4-trifluorobut-2-yn-1-ones to aromatic and heteroaromatic compounds

• Takashi Yamazaki,
• Yoh Nakajima,
• Minato Iida and
• Tomoko Kawasaki-Takasuka

Beilstein J. Org. Chem. 2021, 17, 132–138, doi:10.3762/bjoc.17.14

• ]. As expected for this model system, a very efficient addition was observed within a period of 0.5 h at 0 °C, leading to an isolated yield of 69% for the adduct 3aa when 1.5 equiv of acetylacetone and NaH in Et2O were used (Table 2, entries 1−3), which unambiguously demonstrated the high potency of 2a

• to proceed under the action of a catalytic amount of a base, and only 2 mol % of t-BuOK led to the formation of the desired adduct 3aa as a sole stereoisomer in 84% isolated yield under the same reaction conditions (Table 2, entries 6−8). The E-stereochemistry of 3aa was deduced from the NMR data of

Progress in the total synthesis of inthomycins

• Bidyut Kumar Senapati

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

• %). Deprotection of the TBDMS ether of stannane 40 with tetra-n-butylammonium fluoride (TBAF) in THF and then subsequent Swern oxidation of the crude alcohol gave aldehyde 41 in 71% yield. The aldehyde 41 was treated with ethyl isobutyrate (42) in the presence of LDA to afford the aldol adduct (Z)-(rac)-43 in the

• diastereoisomers. Then, the key aldol reaction of 123 with silyl enol ether 53 under optimized Mukaiyama–Kiyooka conditions, followed by TIPS deprotection, afforded adduct (3R)-(+)-11 in 63% yield and with 94% ee. Ester hydrolysis followed by acetylation of (3R)- (+)-11 produced acid derivative (+)-76 [50] in 87

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

• tricyclic adduct (+)-23b, a precursor to (−)-adaline (1). This methodology, based on the synthesis of optically active β-sulfinyl nitrones, was proved to be efficient in the synthesis of (+)-euphococcinine (2) in 7 steps from piperidine (17), in an overall yield of 2.1%. Specific rotation for (+)-2 was [α

• –dehydration reactions, via intermediate anti-aldol (−)-67 (Scheme 8). The addition of Grignard reagent to the enone (E)-(−)-68 occurred anti to the group TpMo(CO)2 to give adduct (E)-69, which was used in the next step without purification. The treatment of this adduct with HCl in dioxane promoted

Amine–borane complex-initiated SF₅Cl radical addition on alkenes and alkynes

• Audrey Gilbert,
• Pauline Langowski,
• Marine Delgado,
• Laurent Chabaud,
• Mathieu Pucheault and
• Jean-François Paquin

Beilstein J. Org. Chem. 2020, 16, 3069–3077, doi:10.3762/bjoc.16.256

• -containing adduct, with yields of 80% and 89% with EtOAc and hexane, respectively (Table 3, entries 3 and 4). Finally, we performed the reaction in hexane with no amine–borane complex added, and only trace amounts of the final compound 2a were detected (Table 3, entry 5). We next wondered if it could be

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

• ] cycloaddition of activated octalone 26 and the trimethylenemethane precursor 27 selectively produced adduct 28 in 98% yield, which is a synthetic precursor of 3β-hydroxykemp-7(8)-en-6-one (7). Another two syntheses of (±)-hirsutene (14), after Little’s pioneering work [22], were accomplished by Krische [25] and

• give 56 in 83% yield over two steps [31] (Scheme 2C). This transformation was rationalized as follows: freshly prepared 52b was converted to diazo 53, which was subjected to [3 + 2] cycloaddition to give adduct 54. Formation of diyl 55 from 54 and subsequent [3 + 2] cycloaddition produced the

• and co-workers disclosed the palladium-catalyzed intermolecular carboxylative TMM [3 + 2] cycloaddition [36] (Scheme 3). Exposure of coumarin 61 to the silyl-substituted TMM precursor 62 in the presence of a catalytic amount of Pd(PPh3)4 afforded adduct 63 in 81% yield as a single diastereomer (Scheme

Bifurcated synthesis of methylene-lactone- and methylene-lactam-fused spirolactams via electrophilic amide allylation of γ-phenylthio-functionalized γ-lactams

• Tetsuya Sengoku,
• Koki Makino,
• Ayumi Iijima,
• Toshiyasu Inuzuka and
• Hidemi Yoda

Beilstein J. Org. Chem. 2020, 16, 2769–2775, doi:10.3762/bjoc.16.227

• sodium hydride, affording the corresponding adduct in 50% and 81% yields, respectively (Table 1, entries 6 and 7). Surprisingly, the desired allylation underwent even in the absence of palladium catalyst, probably due to high nucleophilicity of the deprotonated intermediate, to give 3b in 87% yield

Selective and reversible 1,3-dipolar cycloaddition of 6-aryl-1,5-diazabicyclo[3.1.0]hexanes with 1,3-diphenylprop-2-en-1-ones under microwave irradiation

• Alexander P. Molchanov,
• Mariia M. Efremova,
• Mariya A. Kryukova and
• Mikhail A. Kuznetsov

Beilstein J. Org. Chem. 2020, 16, 2679–2686, doi:10.3762/bjoc.16.218

• polar species in the ionic medium. Therefore, we carried out the reaction of DABCH 1a with propenone 2f in bmimCl in the presence of BF3·Et2O at 80 °C for 8 h, that led to the formation of adduct 3m and pyrazoline 4a. The reaction of DABCH 1b and propenone 2a under the same conditions resulted in the

• formation of adduct 3m and pyrazoline 4b (Scheme 3). Thus, the azomethine imine A, formed by heating of DABCH 1a, either reacts with propenone 2f giving the adduct 3m or undergoes isomerization affording pyrazoline 4a. On the basis of this observation we suppose that the reaction products undergo

• cycloreversion, i.e., under the reaction conditions the adduct 3m may undergo a ring-opening with the liberation of the starting propenone 2f and the new isomeric azomethine imine B. The latter is able to isomerize into pyrazoline 4b or it reacts with propenone 2f leading to adduct 3f (Scheme 4). To prove this

Water-soluble host–guest complexes between fullerenes and a sugar-functionalized tribenzotriquinacene assembling to microspheres

• Si-Yuan Liu,
• Xin-Rui Wang,
• Man-Ping Li,
• Wen-Rong Xu and
• Dietmar Kuck

Beilstein J. Org. Chem. 2020, 16, 2551–2561, doi:10.3762/bjoc.16.207

• ppm in the 13C NMR spectrum were attributed to the acetylene protons and carbons, respectively. The electrospray ionization (ESI) mass spectrum showed the most intense peak at m/z 641.1923, which corresponds to the [M + Na]+ molecular adduct ion and matches well with the calculated value (m/z 641.1935

• -hydroxycinnamic acid (CHCA) as a matrix, exhibits the base peak at m/z 2879 along with an adjacent intense peak at m/z 2896, which are assigned to the [M + Na]+ and [M + K]+ molecular adduct ions, respectively. Unfortunately, attempts to perform accurate mass measurements were unsuccessful. However, the MALDI

• peak group with the maximum component at m/z 1505.9690 and Δ(m/z) = 0.5, indicating the presence of doubly charged ions. The most intense peak is assigned to the doubly charged [M + 1] isotopolog of the molecular adduct [M + 6H2O + 2Na]2+, the theoretical value of which is calculated to be m/z

Computational tools for drawing, building and displaying carbohydrates: a visual guide

• Kanhaya Lal,
• Rafael Bermeo and
• Serge Perez

Beilstein J. Org. Chem. 2020, 16, 2448–2468, doi:10.3762/bjoc.16.199

• tool has been particularly upgraded for MS spectrum annotation by adding an intuitive interface with additional features. The upgraded version can depict bond fragmentation, repeating structural unit anomeric groups, adduct ions, different types of glycosidic linkages etc. These advanced features make

Formation of an exceptionally stable ketene during phototransformations of bicyclo[2.2.2]oct-5-en-2-ones having mixed chromophores

• Asitanga Ghosh

Beilstein J. Org. Chem. 2020, 16, 2297–2303, doi:10.3762/bjoc.16.190

• ][18] and dibenzoyl acetylene (9) followed by hydrolysis of the silyloxy adduct (Scheme 4). Both 7a and 7b showed an enhanced (n,π*) absorption band near 300 nm (log ε ≈ 3.5) along with an additional weak band near 343 nm (log ε ≈ 2.5) in their UV spectra as expected for δ-keto-α,β-enone [7

Synthetic approaches to bowl-shaped π-conjugated sumanene and its congeners

• Shakeel Alvi and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 2212–2259, doi:10.3762/bjoc.16.186

• sumanene provided the covalent adduct 171 with Cl atoms attached onto the Te atoms, confirmed by an X-ray analysis (Scheme 44). Having the quinone derivatives 166 and 167 in hands, they were next subjected to the condensation reaction with a variety of aryl-1,2-diamines 168 in the presence of AcOH to

Reactions of 3-aryl-1-(trifluoromethyl)prop-2-yn-1-iminium salts with 1,3-dienes and styrenes

• Thomas Schneider,
• Michael Keim,
• Bianca Seitz and
• Gerhard Maas

Beilstein J. Org. Chem. 2020, 16, 2064–2072, doi:10.3762/bjoc.16.173

• –Alder reaction of 1-CF3-substituted propyn-1-iminium salt 1a with cyclopentadiene was carried out in order to assess the dienophilic reactivity of the cation. High conversion into cycloaddition product 2 was observed already within one hour at 0 °C. Because of its high hydrolytic lability, adduct 2 was

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

• dichloromethane results in the assembly of an α-acyloxyamide adduct 4. Just a few protocols for the asymmetric P-3CR [37][38][39][40] and its modifications [41][42][43][44][45][46][47] have been reported over the course of the last two decades (Table 1). In the majority of those protocols [37][38][39], the

• -component reaction (U-4CR) a carboxylic acid 1, an aldehyde 2, and an isocyanide 3 are complemented by a primary amine 5 that altogether undergo a condensation into a peptide-like adduct 6. These reactions are typically conducted in polar protic solvents such as methanol or water. Several examples of

• , a cinchona alkaloid derivative was allowed to react with an electrophilic fluorinating agent to afford an N-fluoroammonium salt of the cinchona alkaloid via transfer fluorination. In the second step, the Ugi adduct 8a was added to this in situ generated N-fluorocinchona intermediate to afford the