Formal total synthesis of macarpine via a Au(I)-catalyzed 6-endo-dig cycloisomerization strategy

• Jiayue Fu,
• Bingbing Li,
• Zefang Zhou,
• Maosheng Cheng,
• Lu Yang and
• Yongxiang Liu

Beilstein J. Org. Chem. 2022, 18, 1589–1595, doi:10.3762/bjoc.18.169

• ring smoothly, leading to the exclusive formation of biaryl intermediate 11 in a yield of 82%. It is worth noting that the methoxy substitution in the substrate played a crucial role in controlling the selectivity of the cycloisomerization according to our previous study [15]. It was rationalized that

Functionalization of imidazole N-oxide: a recent discovery in organic transformations

• Koustav Singha,
• Imran Habib and
• Mossaraf Hossain

Beilstein J. Org. Chem. 2022, 18, 1575–1588, doi:10.3762/bjoc.18.168

• summarized so that the chemists, researchers, and pharmaceutical industries find its effectiveness in near future for the synthesis of potent, novel, and non-toxic drug molecules. Keywords: functionalization; imidazole N-oxide; mechanistic insights; multicomponent reaction; nucleophilic substitution

• substitution reactions Metal-free coupling reaction through nucleophilic substitution of H-atom (SNH) In 2020, a C–H/C–Li coupling reaction between 2H-imidazole 1-oxides and pentafluorophenyllithium under transition metal-free conditions was reported by Timofey D. Moseev and co-workers [17]. The reaction

• proceeds through the nucleophilic substitution of a H-atom (SNH) at the C-5 position of the imidazole N-oxides. This reaction methodology can be considered as suitable process for the syntheses of bioactive imidazole compounds containing (poly)fluoroaryl moieties. Interestingly, in some of the

Efficient synthesis of aziridinecyclooctanediol and 3-aminocyclooctanetriol

• Emine Salamci and
• Ayse Kilic Lafzi

Beilstein J. Org. Chem. 2022, 18, 1539–1543, doi:10.3762/bjoc.18.163

• group in compound 10 was converted to the corresponding alcohol 11 as the sole isomer via SN2 substitution by hydrolysis. In the azidolysis reaction of compound 8, we propose that because the azide group is bulkier than the water molecule, it could not substitute the second mesylate group, and therefore

• have achieved the synthesis of 3-aminocyclooctanetriol 13 and aziridinecyclooctanediol 16 starting from cis,cis-1,3-cyclooctadiene. The nitrogen functionalities were introduced by the substitution with NaN3 of the corresponding mesylate. Reduction of the azido functionalities gave monoaminocyclitol and

Design, synthesis, and evaluation of chiral thiophosphorus acids as organocatalysts

• Karen R. Winters and
• Jean-Luc Montchamp

Beilstein J. Org. Chem. 2022, 18, 1471–1478, doi:10.3762/bjoc.18.154

• cross-coupling [34] in excellent yield. Esterification of 6 with monomethyl H-phosphonate tert-butylamine salt [35] resulted in the mixed H-phosphonate ester 7 in excellent yield. Cyclization using our homolytic aromatic substitution methodology [36] gave P-heterocycle 8 in modest yield. Other methods

• -catalyzed hydrophosphinylation [45]. The key heterocyclization of 11 into 12 was accomplished using silver-promoted homolytic aromatic substitution [46], which was superior to our own manganese methodology (43% yield) [36]. Copper-catalyzed arylation [34] of 12 with iodobenzene and 4-nitroiodobenzene gave

• synthesized from 2-aminobiphenyl according to the literature [47]. Subsequent reaction with phosphorus trichloride and electrophilic aromatic substitution gave a chlorophosphine intermediate, which was directly reacted with (S)-1-phenylethylamine, then hydrogen peroxide. Phosphonamide diastereoisomers 17 were

Naphthalimide-phenothiazine dyads: effect of conformational flexibility and matching of the energy of the charge-transfer state and the localized triplet excited state on the thermally activated delayed fluorescence

• Kaiyue Ye,
• Liyuan Cao,
• Davita M. E. van Raamsdonk,
• Zhijia Wang,
• Jianzhang Zhao,
• Daniel Escudero and
• Denis Jacquemin

Beilstein J. Org. Chem. 2022, 18, 1435–1453, doi:10.3762/bjoc.18.149

• NI-PTZ dyads, and the synthesis route is mentioned in the following section of molecular design and structural confirmation. These dyads are different from the previously reported dyads by the substitution position, and the number of PTZ moieties attached on the NI unit, as well as the redox

• potential of the PTZ moiety. NI-PTZ has a linkage at the 3-position of the NI moiety, for the recently reported analogous dyad, however, the substitution is at the 4-position [20]. For the current NI-PTZ dyad, the torsion between the NI and PTZ has a larger freedom, due to the reduced steric hindrance

1,4,6,10-Tetraazaadamantanes (TAADs) with N-amino groups: synthesis and formation of boron chelates and host–guest complexes

• Artem N. Semakin,
• Ivan S. Golovanov,
• Yulia V. Nelyubina and
• Alexey Yu. Sukhorukov

Beilstein J. Org. Chem. 2022, 18, 1424–1434, doi:10.3762/bjoc.18.148

• , deprotection reactions were performed at low temperatures to prevent degradation of the aminal fragments. Indeed, treatment of Bn-4c with hydrochloric acid at 0 °C resulted in a substitution of one NNH2 unit with the oxygen atom producing product 22, having a hitherto undescribed 4-oxa-1,6,10-triazaadamantane

Synthesis of C6-modified mannose 1-phosphates and evaluation of derived sugar nucleotides against GDP-mannose dehydrogenase

• Sanaz Ahmadipour,
• Alice J. C. Wahart,
• Jonathan P. Dolan,
• Laura Beswick,
• Chris S. Hawes,
• Robert A. Field and
• Gavin J. Miller

Beilstein J. Org. Chem. 2022, 18, 1379–1384, doi:10.3762/bjoc.18.142

• , syntheses of C6-modified mannose 1-phosphates 13 and 17 were developed (Scheme 1). The synthesis of 6-amino-6-deoxymannose 1-phosphate 13 started from protected thioglycoside 10 [6]. A two-step modification using Appel halogenation followed by nucleophilic substitution with azide furnished 11. Conversion of

• deprotection with concomitant azide reduction was completed using hydrogen and Pd/C and Pd(OH)2/C catalysts, affording 13 as the disodium salt in 90% yield, after anion exchange chromatography. Synthesis of 6-deoxy-6-thio-ᴅ-mannose 1-phosphate (18) was completed from 14 via C6 substitution with thioacetate and

On drug discovery against infectious diseases and academic medicinal chemistry contributions

• Yves L. Janin

Beilstein J. Org. Chem. 2022, 18, 1355–1378, doi:10.3762/bjoc.18.141

• systematically identify promising chemical space, for instance heterocyclic derivatives or heterocyclic systems featuring substitution patterns which have not been prepared yet. Such identification could probably benefit from computer-assisted data mining although this is definitively not the area of expertise

Synthesis and electrochemical properties of 3,4,5-tris(chlorophenyl)-1,2-diphosphaferrocenes

• Almaz A. Zagidullin,
• Farida F. Akhmatkhanova,
• Mikhail N. Khrizanforov,
• Robert R. Fayzullin,
• Tatiana P. Gerasimova,
• Ilya A. Bezkishko and
• Vasili A. Miluykov

Beilstein J. Org. Chem. 2022, 18, 1338–1345, doi:10.3762/bjoc.18.139

• para-substitution of the Cl atoms in the aryl fragments did not significantly effect the oxidation potentials of 1,2-diphosphaferrocenes 8, while the reduction potential of 8b was shifted by 0.33 V to a more negative region as compared to 8c. ORTEP representations for cations 5c (a) and 6c (b) at the

B–N/B–H Transborylation: borane-catalysed nitrile hydroboration

• Filip Meger,
• Alexander C. W. Kwok,
• Franziska Gilch,
• Dominic R. Willcox,
• Alex J. Hendy,
• Kieran Nicholson,
• Andrew D. Bage,
• Thomas Langer,
• Thomas A. Hunt and
• Stephen P. Thomas

Beilstein J. Org. Chem. 2022, 18, 1332–1337, doi:10.3762/bjoc.18.138

• in excellent yield (92%). The reaction was successfully applied to the hydroboration of aryl nitriles; benzonitrile was reduced to benzylamine hydrochloride (1e, 92%) in good yield. The reaction tolerated substitution in the ortho- (1f, 86%, 1g, 65%, 1h, 83%), meta- (1i, 82%, 1k, 75%), and para- (1j

Ferrocenoyl-adenines: substituent effects on regioselective acylation

• Mateja Toma,
• Gabrijel Zubčić,
• Jasmina Lapić,
• Senka Djaković,
• Davor Šakić and
• Valerije Vrček

Beilstein J. Org. Chem. 2022, 18, 1270–1277, doi:10.3762/bjoc.18.133

• . may influence the regioselectivity of the ferrocenoylation reaction. While the N9-position of the purine ring is a typical site of substitution, the N7-position may be preferred in some situations. In any case, the interplay between steric and electronic effects of selected substituents is crucial to

Modular synthesis of 2-furyl carbinols from 3-benzyldimethylsilylfurfural platforms relying on oxygen-assisted C–Si bond functionalization

• Sebastien Curpanen,
• Per Reichert,
• Gabriele Lupidi,
• Giovanni Poli,
• Julie Oble and
• Alejandro Perez-Luna

Beilstein J. Org. Chem. 2022, 18, 1256–1263, doi:10.3762/bjoc.18.131

• on the SiMe(OSiMe3)2 unit, which were readily converted through Pd- or Cu-catalyzed electrophilic substitution reactions into an array of furfurals decorated at C3 with carbon- or heteroatom-containing substituents (Scheme 1). Conversely, all of our subsequent efforts to achieve cross-coupling

• activation [19]. Thereby, C3-triorganosilyl-substituted furfurals could be suitable platforms to develop a two-step modular approach to 3-substituted 2-furyl carbinols, entailing nucleophilic addition to the aldehyde function and oxygen-assisted electrophilic substitution of the C–Si bond (Scheme 1). Results

• ). With the 3-silylated 2-furyl carbinol substrates at hand, we then considered C–Si bond activation strategies relying on the assistance of the oxygen atom to promote electrophilic substitution reactions with carbon electrophiles. C3–Si bond functionalization through intramolecular activation by

A one-pot electrochemical synthesis of 2-aminothiazoles from active methylene ketones and thioureas mediated by NH₄I

• Shang-Feng Yang,
• Pei Li,
• Zi-Lin Fang,
• Sen Liang,
• Hong-Yu Tian,
• Bao-Guo Sun,
• Kun Xu and
• Cheng-Chu Zeng

Beilstein J. Org. Chem. 2022, 18, 1249–1255, doi:10.3762/bjoc.18.130

• produce α-iodo ketone with the molecular I2 produced by anodic oxidation. Subsequently, the nucleophilic substitution between intermediate 4 and thiourea tautomer gives α-sulfur substituted ketone 5. Intermediate 5 undergoes intramolecular nucleophilic addition to the carbonyl group and followed by

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

• -substitution. Subsequent transesterification gave the α-ketoester 75, which was used in a Wittig reaction. The undesired Z-configured double bond was isomerized to the E-alkene and final hydrogenation delivered corynoxine (76). (+)-Gracilamine The Mannich reaction was also used by Nagasawa et al. as a key step

A Streptomyces P450 enzyme dimerizes isoflavones from plants

• Run-Zhou Liu,
• Shanchong Chen and
• Lihan Zhang

Beilstein J. Org. Chem. 2022, 18, 1107–1115, doi:10.3762/bjoc.18.113

• explored the substrate scope of the catalyst using a variety of plant-derived polyketides (Scheme 1). The results revealed that the 5-OH substitution on isoflavone (see compound 6) was tolerable for dimerization (Figure S15, Supporting Information File 1), whereas the additional 4’-methoxyl group at the B

Scope of tetrazolo[1,5-a]quinoxalines in CuAAC reactions for the synthesis of triazoloquinoxalines, imidazoloquinoxalines, and rhenium complexes thereof

• Laura Holzhauer,
• Chloé Liagre,
• Olaf Fuhr,
• Nicole Jung and
• Stefan Bräse

Beilstein J. Org. Chem. 2022, 18, 1088–1099, doi:10.3762/bjoc.18.111

• hydrazine and sodium nitrite. Further derivation of 11f led to compounds 11g–l which include different substitution patterns for R2. The tetrazolo[1,5-a]quinoxaline products 11a–l were obtained in yields of 36% to 81% for all steps (see Supporting Information File 1 for the entire scheme). Starting from 11a

• - (14o) functionality can also be applied for various other reactions. Possible modifications of compounds 14 were exemplarily shown for 14j, which was converted to the amine-substituted product 14j* via nucleophilic substitution with a yield of 77% (see Scheme 3). However, alkynes 4 with reactive and

A versatile way for the synthesis of monomethylamines by reduction of N-substituted carbonylimidazoles with the NaBH₄/I₂ system

• Lin Chen,
• Xuan Zhou,
• Zhiyong Chen,
• Changxu Wang,
• Shunjie Wang and
• Hanbing Teng

Beilstein J. Org. Chem. 2022, 18, 1032–1039, doi:10.3762/bjoc.18.104

• cyanoformamides [75]. However, all of these works are primarily focused on the substitution reaction of N-substituted carbonylimidazoles. In our previous work, we conveniently prepared formamides by reducing N-substituted carbonylimidazoles with NaBH4 [62] (Scheme 1). The reaction mechanism shows that the H− ion

• acted as a nucleophile to attack the carbonyl carbon to cause the imidazolium ion to leave without reducing the carbonyl group. Although this work expands the application of N-substituted carbonylimidazoles, the reaction can still be regarded as a substitution reaction, which is attributed to the weak

Electrochemical vicinal oxyazidation of α-arylvinyl acetates

• Yi-Lun Li,
• Zhaojiang Shi,
• Tao Shen and
• Ke-Yin Ye

Beilstein J. Org. Chem. 2022, 18, 1026–1031, doi:10.3762/bjoc.18.103

• development of a green, efficient, and sustainable protocol for the synthesis of azidoketones is of great significance [7][8][9]. Retrosynthetically, the nucleophilic substitution of α-bromoketones by sodium azide [10] and oxidation of the azido alcohols [11] are among the most straightforward methods to

Automated grindstone chemistry: a simple and facile way for PEG-assisted stoichiometry-controlled halogenation of phenols and anilines using N-halosuccinimides

• Dharmendra Das,
• Akhil A. Bhosle,
• Amrita Chatterjee and
• Mainak Banerjee

Beilstein J. Org. Chem. 2022, 18, 999–1008, doi:10.3762/bjoc.18.100

• reactivity and availability of multiple sites for substitution, often leads to an inseparable mixture of halogenated products [27][28]. Thus, a cheaper and sustainable method for a regioselective halogenation in a controlled manner is a worthy pursuit. In recent times, mechanochemistry [45][46], achieved by

• addition of 1.1 equiv of NBS afforded a mixture of products with reduced regioselectivity to the expected p-bromophenol (yield: 62%). From the mechanistic point of view, it is expected that a standard electrophilic aromatic substitution pathway was followed for the halogenation using NXS (X = Br, I, or Cl

Molecular diversity of the base-promoted reaction of phenacylmalononitriles with dialkyl but-2-ynedioates

• Hui Zheng,
• Ying Han,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2022, 18, 991–998, doi:10.3762/bjoc.18.99

• , phenacylmalononitrile is also a readily available substrate, which can be easily prepared through a base-promoted substitution reaction of phenacyl bromide with malononitrile under mild conditions [11][12][13][14][15][16]. In many practical cases, phenacylmalononitriles could be conveniently generated in situ by

Electrochemical and spectroscopic properties of twisted dibenzo[g,p]chrysene derivatives

• Tomoya Imai,
• Ryuhei Akasaka,
• Naruhiro Yoshida,
• Toru Amaya and
• Tetsuo Iwasawa

Beilstein J. Org. Chem. 2022, 18, 963–971, doi:10.3762/bjoc.18.96

• states. Herein, we report on the electrochemical and spectroscopic properties of the DBC derivatives, where the effects of substituents and torsion were examined with the aid of DFT calculations. Consequently, the findings revealed that the substitution at the Z position induces a change in the

Electroreductive coupling of 2-acylbenzoates with α,β-unsaturated carbonyl compounds: density functional theory study on product selectivity

• Naoki Kise and
• Toshihiko Sakurai

Beilstein J. Org. Chem. 2022, 18, 956–962, doi:10.3762/bjoc.18.95

• –3), and conversely, when ∆G is large and positive, product 4 is selectively produced (Table 4, entries 5 and 6). On the other hand, when ∆G is close to zero, both products 3 and 4 are generated simultaneously (Table 4, entry 4). These results suggest that the substitution of the methoxy group at the

• 6-position tends to suppress the cyclization of D to E (Table 4, entries 4–6), since its electron-donating property reduces the electrophilicity of the ester carbonyl group. In contrast, the substitution of the methoxy group at the 5-position tends to promote the cyclization of D, owing to its

Synthetic strategies for the preparation of γ-phostams: 1,2-azaphospholidine 2-oxides and 1,2-azaphospholine 2-oxides

• Jiaxi Xu

Beilstein J. Org. Chem. 2022, 18, 889–915, doi:10.3762/bjoc.18.90

• presence of sodium hydride in dioxane, affording tricyclic γ-phosphonolactams 74, 78, and 81 in low to moderate yields (Scheme 14) [34]. In 2005, Aladzheva and co-workers prepared γ-phosphonolactams 85 from the substitution of ethyl 2-(3-chloropropyl)aminoalkanoates 82 derived from glycine and ᴅʟ-alanine

• )aminoalkanoic acids 86 (Scheme 15) [35][36]. This is a convenient way to synthesize γ-phosphonolactams 85. They further extended their method to synthesize cyclic O,O- and O,S-bidentate ligands with a P–N–P backbone. The substitution reaction of 3-bromopropylamine hydrogen bromide (87) and chloroethoxyphosphine

• with the generated styrene in the reaction mixture (Scheme 18) [42]. One year later, the same group investigated the influence of the double bond geometry and the substitution pattern on the alkene. The results indicated that the double bond geometry plays a moderate role, while the bulkiness of the R

Synthesis of novel alkynyl imidazopyridinyl selenides: copper-catalyzed tandem selenation of selenium with 2-arylimidazo[1,2-a]pyridines and terminal alkynes

• Mio Matsumura,
• Kaho Tsukada,
• Kiwa Sugimoto,
• Yuki Murata and
• Shuji Yasuike

Beilstein J. Org. Chem. 2022, 18, 863–871, doi:10.3762/bjoc.18.87

• inexpensive and easy to handle Se powder as the Se source. The reaction proceeded with terminal alkynes having various substitutions, such as aryl, vinyl, and alkyl groups. The obtained alkynyl imidazopyridinyl selenide was found to undergo nucleophilic substitution reaction on Se atom using organolithium

• phenyllithium in THF at −78 °C led to a nucleophilic substitution reaction with the elimination of the ethynyl group to form the desired phenylimidazopyridinyl selenide 6a in 49% yield. In the reaction with n-butyllithium, alkyl derivative 6b was isolated in the same way. The reaction of 4aa with the Ruppert

• synthesized using a simple operation that can be performed under aerobic conditions. Moreover, the results showed that the obtained compounds underwent nucleophilic substitution reactions involving the elimination of the alkyne moiety on Se atoms to form aryl or alkyl imidazopyridinyl selenides and

Palladium-catalyzed solid-state borylation of aryl halides using mechanochemistry

• Koji Kubota,
• Emiru Baba,
• Tamae Seo,
• Tatsuo Ishiyama and
• Hajime Ito

Beilstein J. Org. Chem. 2022, 18, 855–862, doi:10.3762/bjoc.18.86

• organic materials, typically through Suzuki–Miyaura coupling [1][2][3][4][5][6][7]. The palladium-catalyzed boryl substitution of aryl halides with boron reagents, termed Miyaura–Ishiyama borylation, is an efficient method for synthesizing arylboronates with high functional group compatibility [8][9][10