Synthetic study toward tridachiapyrone B

• Morgan Cormier,
• Florian Hernvann and
• Michaël De Paolis

Beilstein J. Org. Chem. 2022, 18, 1741–1748, doi:10.3762/bjoc.18.183

• desired 1,2-adduct 17 in 50% yield [41]. To perform the anionic oxy-Cope rearrangement, alcohol 17 was exposed to t-BuOK, in the presence of 18-crown-6 ether (−78 °C to rt) [42]. However, these conditions did not trigger the rearrangement and the starting material was recovered. On the other hand

Total synthesis of grayanane natural products

• Nicolas Fay,
• Rémi Blieck,
• Cyrille Kouklovsky and
• Aurélien de la Torre

Beilstein J. Org. Chem. 2022, 18, 1707–1719, doi:10.3762/bjoc.18.181

• corresponding ketone was achieved using Dess–Martin periodinane with a pyridine buffer. Addition of Me3SiCH2Li efficiently afforded the Peterson adduct 33. The 1,1-disubtituted alkene was then submitted to Mukaiyma hydration to form the tertiary alcohol, in presence of Mn(dpm)3, PhSiH3 and O2. Then, the ketone

• was selectively reduced in the presence of LiEt3BH, while the Peterson adduct was eliminated concurrently, upon heating. Finally, treatment with H2SO4 allowed total deprotection of the MOM ethers, leading to the formation of principinol D, in complete correspondence with reported spectral data

A novel spirocyclic scaffold accessed via tandem Claisen rearrangement/intramolecular oxa-Michael addition

• Anastasia Vepreva,
• Alexander Yanovich,
• Dmitry Dar’in,
• Grigory Kantin,
• Alexander Bunev and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2022, 18, 1649–1655, doi:10.3762/bjoc.18.177

• Discussion The initial attempt to involve DAS 1b in the Rh2(esp)2-catalyzed insertion reaction with 4-(tert-butyl)phenol was successful. The initial adduct 5b was not purified and was heated at 140 °C in toluene to give compound 6b in 47% yield over two steps (Scheme 2). No further optimization of the

A novel bis-triazole scaffold accessed via two tandem [3 + 2] cycloaddition events including an uncatalyzed, room temperature azide–alkyne click reaction

• Ksenia Malkova,
• Andrey Bubyrev,
• Vasilisa Krivovicheva,
• Dmitry Dar’in,
• Alexander Bunev and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2022, 18, 1636–1641, doi:10.3762/bjoc.18.175

• scaffolds. Recently, we reported a novel, metal-free synthesis of 1,5-disubstituted 1,2,3-triazoles via a three-component reaction of α-acetyl-α-diazomethanesulfonamide (1) with aldehydes and amines [4]. The reaction proceeded, presumably, through the formation of the initial 1,2,3-triazoline adduct 2 [5

• propargylamine. The reaction was allowed to go to completion in 48 h at room temperature whereupon the reaction mixture was absorbed on silica and subjected to column chromatography for isolation of the product. To our sheer amazement, the product turned out to be not the initial adduct 4a but rather 9H-benzo[f

Synthetic study toward the diterpenoid aberrarone

• Liang Shi,
• Zhiyu Gao,
• Yiqing Li,
• Yuanhao Dai,
• Yu Liu,
• Lili Shi and
• Hong-Dong Hao

Beilstein J. Org. Chem. 2022, 18, 1625–1628, doi:10.3762/bjoc.18.173

• functional transformation from 10, which itself would be prepared through methylation and conjugate addition from Pauson–Khand adduct 11. This cyclopentenone could be readily accessed from 1,7-enyne 12 which could be obtained through the reported procedure [35] from the commercially available 5-hexenoic acid

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

• ), acted as the nucleophile to attack the C-5 position of 2H-imidazole 1-oxides 9a–h to form the σH-adduct 14. The use of a deoxygenation agent in the mixture led to the formation of the desired products 10a–h via “addition–elimination” (SNH AE, path A) from the adduct 14 with the elimination of the good

Oxa-Michael-initiated cascade reactions of levoglucosenone

• Julian Klepp,
• Thomas Bousfield,
• Hugh Cummins,
• Sarah V. A.-M. Legendre,
• Jason E. Camp and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2022, 18, 1457–1462, doi:10.3762/bjoc.18.151

• and not the 1:1 product 6a was the major product (Table 1, entry 1 and Figure 2), presumably due to the equilibria and thermodynamics favoring adduct 5. The Hantzsch dihydropyridine synthesis, and aldol/Michael sequences such as the reaction of hydroxytropolones with aromatic aldehydes give similar

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