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

• equilibrium to the adamantane form by forming a stable boronate adduct 18 having a diamantane structure through the reaction with phenylboronic acid. Note that product 18 contains an unprecedented 2,4-dioxa-1,5,7,10-tetraaza-3-boraadamantane motif (Scheme 4). This result demonstrates that N-amino-substituted

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

• reaction temperature of 60 °C means both routes are viable under the reaction conditions. It should be noted that treatment of a nitrile with excess H-B-9-BBN has been shown to form an N-B-9-BBN iminyl H-B-9-BBN adduct [43], suggesting route B may be favoured. Experimental calculation of the reaction

Cytochrome P450 monooxygenase-mediated tailoring of triterpenoids and steroids in plants

• Karan Malhotra and
• Jakob Franke

Beilstein J. Org. Chem. 2022, 18, 1289–1310, doi:10.3762/bjoc.18.135

• charge, can then efficiently bind molecular oxygen (step 3), leading to dioxygen adduct D. Transfer of an additional electron from a reducing partner such as cytochrome P450 reductase (step 4) generates peroxo intermediate E, which upon protonation (step 5) gives hydroperoxo intermediate F, also called

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

• of benzaldehyde led to the formation of adduct 14 (in 75% yield), which arose from the addition of a benzyl carbanion 17 to benzaldehyde. The generation of such a nucleophile strongly suggests the formation of pentavalent silicon intermediate 15 [27], which then produced a (stabilized) benzylic

Derivatives of benzo-1,4-thiazine-3-carboxylic acid and the corresponding amino acid conjugates

• Péter Kisszékelyi,
• Tibor Peňaška,
• Klára Stankovianska,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2022, 18, 1195–1202, doi:10.3762/bjoc.18.124

• either the salt 16a·HCl or the free amine 16a in good to excellent yield (Scheme 3). We also explored the asymmetric catalytic hydrogenation of adduct 14. Our first attempt at the reduction using organocatalyzed transfer hydrogenation was unsuccessful (see Supporting Information File 1). The (R)-Ru(OAc)2

Lewis acid-catalyzed Pudovik reaction–phospha-Brook rearrangement sequence to access phosphoric esters

• Jin Yang,
• Dang-Wei Qian and
• Shang-Dong Yang

Beilstein J. Org. Chem. 2022, 18, 1188–1194, doi:10.3762/bjoc.18.123

• the standard substrates to test the suitable conditions for the O-phosphination product 3aa. Delightfully, in the presence of 10 mol % Cu(OTf)2 in toluene at 100 °C, the desired product 3aa was obtained in 62% yield, and no Pudovik adduct 4aa was detected (Table 1, entry 1). Inspired by this result

• . Additional experiments were conducted in order to clarify the reaction mechanism. Under standard conditions, only pyridin-2-ylmethyl diphenylphosphinate (3aa) was produced, and the Pudovik adduct (hydroxy(pyridin-2-yl)methyl)diphenylphosphine oxide (4aa) was not detected (Scheme 4a). The control experiment

• (1a) and 2-pyridinecarboxaldehyde (2a) undergo the Pudovik reaction to produce the intermediate adduct 4aa. Then, Cu(OTf)2 coordinates with 4aa to form the intermediate Int-A, which goes through the phospha-Brook rearrangement process to form Int-B. Finally, Int-B is transformed into the product 3aa

Electro-conversion of cumene into acetophenone using boron-doped diamond electrodes

• Mana Kitano,
• Tsuyoshi Saitoh,
• Shigeru Nishiyama,
• Yasuaki Einaga and
• Takashi Yamamoto

Beilstein J. Org. Chem. 2022, 18, 1154–1158, doi:10.3762/bjoc.18.119

• propose a reaction mechanism (Table 2). First, we carried out the electrolysis of 1 in MeCN–MeOH to confirm whether the reaction intermediate is a radical or cationic species (Table 2, entry 1). As a result, methyl cumyl ether, a methoxy adduct to the benzyl position of 1, was obtained as the main product

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

• -deficient alkyne resulted in adduct B. Thirdly, the intramolecular addition of the carbanion to the carbonyl group afforded species C, which in turn converted to the final product 3 by the protonation of the species C. The protonated species 5 could be successfully isolated in 12% yield after six hours when

Cathodic generation of reactive (phenylthio)difluoromethyl species and its reactions: mechanistic aspects and synthetic applications

• Sadanobu Iwase,
• Shinsuke Inagi and
• Toshio Fuchigami

Beilstein J. Org. Chem. 2022, 18, 872–880, doi:10.3762/bjoc.18.88

• the radical trapping reagent, the expected radical adduct 4 was formed in reasonable yield of ca. 30% (Table 1, run 1). A platinum cathode is more suitable for the formation of adduct 4 compared to a glassy carbon cathode (Table 1, run 2). Dolbier et al. reported that electron-poor perfluoroalkyl

• radicals such as n-perfluoropropyl radical have high reactivity to electron-rich olefins such as α-methylstyrene and styrene [26]. In fact, our cathodically generated reactive species also reacted with α-methylstyrene. However, electron-rich dihydrofuran did not provide any radical adduct at all (Table 1

• , run 4). The reason is not clear at present. Thus the obtained results indicate that the cathodically generated reactive species would be the (phenylthio)difluoromethyl radical. In order to increase the yield of adduct 4, the cathodic reduction of 1 was performed in other solvents such as DMF and

Post-synthesis from Lewis acid–base interaction: an alternative way to generate light and harvest triplet excitons

• Hengjia Liu and
• Guohua Xie

Beilstein J. Org. Chem. 2022, 18, 825–836, doi:10.3762/bjoc.18.83

• temperatures from 230 to 300 K (see Figure 9) [43]. As shown in Figure 9a, when the temperature reached 280 K, the aromatic resonances became intense, implying the appearance of a new species, which was assigned to the Lewis acid–base adduct. Fifteen new resonance peaks were also observed in the 19F NMR

Synthesis of bis-spirocyclic derivatives of 3-azabicyclo[3.1.0]hexane via cyclopropene cycloadditions to the stable azomethine ylide derived from Ruhemann's purple

• Alexander S. Filatov,
• Olesya V. Khoroshilova,
• Anna G. Larina,
• Vitali M. Boitsov and
• Alexander V. Stepakov

Beilstein J. Org. Chem. 2022, 18, 769–780, doi:10.3762/bjoc.18.77

• studied in the reaction with 1 to determine whether these 1,3-DC reactions would similarly proceed with high diastereofacial selectivity. The reaction of 3-methyl-3-phenylcyclopropene (2j) [36] with ylide 1 resulted in the formation of a 1:1 adduct and the cycloaddition with cyclopropene 2j occurred at

Complementarity of solution and solid state mechanochemical reaction conditions demonstrated by 1,2-debromination of tricyclic imides

• Petar Štrbac and
• Davor Margetić

Beilstein J. Org. Chem. 2022, 18, 746–753, doi:10.3762/bjoc.18.75

• ] could be simplified by in situ generation of the catalyst. Moreover, in the debromination of norbornene imide 11, the expected Diels−Alder adduct with furan was not obtained, but compound 12 incorporating a tetrahydrofuran ring at position 2, presumably by radical reaction (Figure 2) [19][20]. We

• (0.6:1), and slightly more in favor of the unsymmetrical adduct 20. On the other hand, the reaction of cyclopentadiene (21) provided the linear exo,exo-cycloadduct 22 as the major product, together with the 2:1 adduct 23. In this reaction, identical stereospecificity was obtained by employment of the

• Zn/Ag couple in THF [19]. Linear exo,exo-product 25 was obtained exclusively in the reaction with DPIBF 24, which is in accordance to the stereospecificity of cycloadditions reported by Sasaki [25] where the linear adduct is greatly preferred over bent. An interesting feature of the 1H NMR spectrum

Inductive heating and flow chemistry – a perfect synergy of emerging enabling technologies

• Conrad Kuhwald,
• Sibel Türkhan and
• Andreas Kirschning

Beilstein J. Org. Chem. 2022, 18, 688–706, doi:10.3762/bjoc.18.70

• reactions (anthracene (33) and maleic anhydride (34) to the cycloaddition adduct 35 and chromene carbaldehyde 36 and enol ether 37 to the diastereomeric pyrano-chromenes 38), Alder-En reactions (oxomalonate diethyl ester (39) and β-pinene (40) to give the α-pinene derivative 41), and the thermal

Tri(n-butyl)phosphine-promoted domino reaction for the efficient construction of spiro[cyclohexane-1,3'-indolines] and spiro[indoline-3,2'-furan-3',3''-indolines]

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

Beilstein J. Org. Chem. 2022, 18, 669–679, doi:10.3762/bjoc.18.68

• this work. Firstly, the nucleophilic addition of tributylphosphine to the bis-chalcone gives the active zwitterionic species (A). Secondly, the Michael addition of the zwitterionic species (A) to isatylidene malononitrile at the C3-position of the oxindole scaffold results in adduct (B). Thirdly, the

• reaction, the nucleophilic addition of the zwitterion (A) to this compound takes place at the exocyclic position giving the adduct (E), which in turn proceeds with the intermediates (F) and (G) according to the above mentioned similar processes to give the spiro compound 5. The different addition direction

• mechanism has been proposed and is shown in Scheme 2. At first, the nucelophilic addition of tributylphosphine to isatylidene cyanoacetate gives a zwitterionic salt (H). Secondly, the addition of the carbanion to the carbonyl group of the isatin affords the adduct (I). Then, the intramolecular attack of the

Menadione: a platform and a target to valuable compounds synthesis

• Acácio S. de Souza,
• Ruan Carlos B. Ribeiro,
• Dora C. S. Costa,
• Fernanda P. Pauli,
• David R. Pinho,
• Matheus G. de Moraes,
• Fernando de C. da Silva,
• Luana da S. M. Forezi and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 381–419, doi:10.3762/bjoc.18.43

• irradiation, generating the reduced adduct in 79% yield (Scheme 20). Depending on the type of solvent used, the yield may vary due to oxidation of the alcohol 14 back to 10 because of its low stability in solution. The pegylation strategy involved monomethoxypoly(ethyleneglycol)succinimide carbonate (mPEG-SC

Site-selective reactions mediated by molecular containers

• Rui Wang and
• Yang Yu

Beilstein J. Org. Chem. 2022, 18, 309–324, doi:10.3762/bjoc.18.35

• (1) and N-cyclohexylphthalimide (2) went smoothly at 80 °C for 5 hours with near quantitative yield (Figure 1b). Only the syn-isomer of the 1,4-adduct 3 was detected after the reaction, which was determined by X-ray crystallographic analysis of A•3. It was also shown that the product was tightly

• accommodated in the cavity of A through π–π stacking interactions between the naphthalene ring of 3 and a triazine ligand of A from the X-ray crystallographic analysis. In the control experiment, without host A, only 44% yield of the conventional 9,10-adduct 4 was produced without any 1,4-adduct product

• the sterically less demanding N-propylphthalimide was used, only the 9,10-adduct was formed, which indicated that the steric bulkiness of the N-substituent in the dienophile also affected the 1,4-site-selectivity. It is very intriguing that when a different kind of square-pyramidal bowl host B was

Iridium-catalyzed hydroacylation reactions of C1-substituted oxabenzonorbornadienes with salicylaldehyde: an experimental and computational study

• Angel Ho,
• Austin Pounder,
• Krish Valluru,
• Leanne D. Chen and
• William Tam

Beilstein J. Org. Chem. 2022, 18, 251–261, doi:10.3762/bjoc.18.30

• reaction (Scheme 2). Satisfyingly, the reaction exclusively afforded the C3-hydroacylated regioisomer 15 in all cases. Moreover, the reaction was stereoselective for the formation of the exo-adduct rather than a mixture of endo/exo products as previously reported by Tanaka/Suemune [65] and Bolm [66], who

• . Interestingly, C1-substitution with a trimethylsilyl (TMS) group resulted in the corresponding adduct 15k as well as the ring-opened 2,4-substituted naphthol product 16k. It was noted the insertion of a methylene unit at the C1-position allowed for electron-withdrawing substituents to be present in the reaction

Glycosylated coumarins, flavonoids, lignans and phenylpropanoids from Wikstroemia nutans and their biological activities

• Meifang Wu,
• Xiangdong Su,
• Yichuang Wu,
• Yuanjing Luo,
• Ying Guo and
• Yongbo Xue

Beilstein J. Org. Chem. 2022, 18, 200–207, doi:10.3762/bjoc.18.23

• activities. Results and Discussion Compound 1 was obtained as a yellowish, amorphous powder. Its molecular formula was determined as C29H28O15 based on the HRESIMS sodium adduct ion observed at m/z 639.1319 ([M + Na]+, calcd for C29H28O15Na+, 639.1320), indicating sixteen degrees of unsaturation. Its UV

Tenacibactins K–M, cytotoxic siderophores from a coral-associated gliding bacterium of the genus Tenacibaculum

• Yasuhiro Igarashi,
• Yiwei Ge,
• Tao Zhou,
• Amit Raj Sharma,
• Enjuro Harunari,
• Naoya Oku and
• Agus Trianto

Beilstein J. Org. Chem. 2022, 18, 110–119, doi:10.3762/bjoc.18.12

• adduct [M + Na]+ at m/z 678.4412 (Δ + 0.0 mmu for C33H61N5O8Na). Analysis of 13C NMR and HSQC spectroscopic data obtained in DMSO-d6 established the presence of five carbonyl carbons (δC 166.2, 168.6, 171.0, 171.5, 172.0), two sp2 methines (δC 119.8, 144.5), one sp3 methine (δC 27.5), two magnetically

• ) and a sodium adduct ion at m/z 680.4567 (Δ − 0.2 mmu for C33H63N5O8Na), was larger by two hydrogen atoms than that of compound 1 or 2. Indeed, olefinic resonances were absent in the NMR spectra and MS/MS fragment ions from the left half of the molecule were larger by 2 mass units than those for

1,2-Naphthoquinone-4-sulfonic acid salts in organic synthesis

• Ruan Carlos B. Ribeiro,
• Patricia G. Ferreira,
• Amanda de A. Borges,
• Luana da S. M. Forezi,
• Fernando de Carvalho da Silva and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 53–69, doi:10.3762/bjoc.18.5

• transformed into α-nitroso-β-naphthol (17); then, in a single step, a sulfonic group was added, and the nitrous group was reduced, forming compound 15, which was transformed into β-NQSNa (18) after oxidation with nitric acid. Despite not knowing exactly the structure of the adduct, Folin speculated that the

DABCO-promoted photocatalytic C–H functionalization of aldehydes

• Bruno Maia da Silva Santos,
• Mariana dos Santos Dupim,
• Cauê Paula de Souza,
• Thiago Messias Cardozo and
• Fernanda Gadini Finelli

Beilstein J. Org. Chem. 2021, 17, 2959–2967, doi:10.3762/bjoc.17.205

• could also be arylated using the same protocol (18, 34%). Mechanistic investigations were conducted to support the proposed HAT mechanism by DABCO. Radical trapping with TEMPO completely shuts down product formation, proving a radical mechanism is operating. Moreover, an acyl-TEMPO adduct was formed and

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

• the stable oxonium ion to provide an anomer, which further reacts with the presilylated nucleobase in an SN2 manner and predominantly affords the β-cytidine adduct. DKR overcomes the drawback of classical resolution since it is theoretically possible to obtain 100% yield of the desired isomer [74]. 5

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

• -nitrostyrene (7a) catalyzed by (S,R)-C2 (Scheme 3). The reaction in CH2Cl2 at 5 °C with Et3N as a base gave 45% of adduct 8a with 86:14 dr and 24:76 er for both diastereomers. Slightly better yields (63%) were achieved in CHCl3 at room temperature with Et3N or NMP as a base, but both diastereoselectivity as

• well as enantioselectivity remained unchanged. We have used thiourea (S,R)-C1 for this Michael addition, too, but the catalyst was not successful for this reaction (not shown). Only traces of the Michael adduct were obtained in the solution reaction of butanal (6a) with 1-methoxy-4-(2-nitrovinyl

• )-2-(2-nitrovinyl)furan (9) and they provided racemic adduct 12 in 14 or 64% yield with poor or no diastereoselectivity (Table 2, entries 1 and 2). The change of solvent made it possible to obtain the products in a shorter time. Reactions catalyzed with 3 mol % (S,R)-C1 and (S,S)-C1 in MeCN gave

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

• formed Michael adduct (Scheme 1) [25]. The proposed catalytic cycle involved generation of the active complex through hydrogen bonding between catalyst and aniline followed by interaction with chalcone via π–π stacking of aromatic rings and hydrogen bonding leading to the Michael adduct. Likewise, Lee et

α-Ketol and α-iminol rearrangements in synthetic organic and biosynthetic reactions

• Scott Benz and
• Andrew S. Murkin

Beilstein J. Org. Chem. 2021, 17, 2570–2584, doi:10.3762/bjoc.17.172

• and a 22% yield of the Diels–Alder adduct, showing that the first step of the cascade had near-quantitative yield, diastereoselectively and regioselectively. The authors speculated that it is possible, considering their own reaction efficiency in conditions reminiscent of natural ones, that the