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

Strategies for the synthesis of brevipolides

• Yudhi D. Kurniawan and
• A'liyatur Rosyidah

Beilstein J. Org. Chem. 2021, 17, 2399–2416, doi:10.3762/bjoc.17.157

• -metathesis reaction between 83 and 84 was successfully achieved utilizing Grubbs II catalyst to give the adduct 82 in 76% yield. The E/Z ratio for this compound was determined from the 1H NMR spectral analysis as >20:1. After protection of the secondary alcohol as MEM ether 88 (83%), the epoxide ring was

• expected syn adduct in 65% yield as a single diastereomer. Oxidation of this molecule under Swern conditions proceeded smoothly giving ketone 91 in 94% yield, which was highlighted as an important observation as the same transformation using the similar compound was reported to be unsuccessful [14]. Ring

Photoredox catalysis in nickel-catalyzed C–H functionalization

• Lusina Mantry,
• Rajaram Maayuri,
• Vikash Kumar and
• Parthasarathy Gandeepan

Beilstein J. Org. Chem. 2021, 17, 2209–2259, doi:10.3762/bjoc.17.143

• decatungstate 22-II undergoes a HAT process with the C(sp3)–H substrate to form a carbon-centered radical species 22-III and reduced decatungstate 22-IV. The thus formed alkyl radical 22-III adds to the alkene 92 affording the radical adduct 22-VI, which is intercepted by the nickel(0) species 22-X to generate

• adduct 23-IV. The radical adduct 23-IV is captured by nickel(0) species 23-V followed by oxidative addition to aryl bromide 3 to give the nickel(III)(alkyl)(aryl) intermediate 23-VII. Facile C–C-bond forming reductive elimination of 23-VII delivers the desired product 95 and nickel(I) species 23-VIII. A

Nomimicins B–D, new tetronate-class polyketides from a marine-derived actinomycete of the genus Actinomadura

• Zhiwei Zhang,
• Tao Zhou,
• Taehui Yang,
• Keisuke Fukaya,
• Enjuro Harunari,
• Shun Saito,
• Katsuhisa Yamada,
• Chiaki Imada,
• Daisuke Urabe and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2021, 17, 2194–2202, doi:10.3762/bjoc.17.141

• of ECD spectra between 1 and 2 was also indicative of the same absolute configuration of 2 and 4 (Figure 4). The molecular formula of nomimicin D (3) was determined to be C30H42O6 through the HRESITOFMS analysis, which gave a sodium adduct ion [M + Na]+ at m/z 519.2717 (Δ 0.0 mmu). Analysis of 1H NMR

Facile and innovative catalytic protocol for intramolecular Friedel–Crafts cyclization of Morita–Baylis–Hillman adducts: Synergistic combination of chiral (salen)chromium(III)/BF₃·OEt₂ catalysis

• Karthikeyan Soundararajan,
• Helen Ratna Monica Jeyarajan,
• Raju Subimol Kamarajapurathu and
• Karthik Krishna Kumar Ayyanoth

Beilstein J. Org. Chem. 2021, 17, 2186–2193, doi:10.3762/bjoc.17.140

• intramolecular Friedel–Crafts cyclization protocol the Morita–Baylis–Hillman adduct 5a, was surveyed as the model substrate. The optimization experiments are listed in Table 1. The cyclization of MBH adduct 5a was examined in presence of metal(III)–salen complex (5 mol %) as catalysts and BF3·OEt2 (2.5 mol %) as

• in MBH adduct 5a (Table 1, entries 14–17). Interestingly among all co-catalysts examined, boron trifluoride etherate was the found to be the suitable co-catalyst in accelerating the proposed reaction. Furthermore on screening the optimized catalytic combination in presence of alternative solvents

• standard reaction conditions. Convincingly MBH adduct 5h (10 mmol) delivered the desired product 6h in 73% yield (1.28 g). The outcome of this practical scale synthesis demonstrates the synthetic utility of the stabilized reaction for large scale synthesis. The structure of the synthesised indene compounds

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

• Michael adduct 2 was generated in a 4:1 ratio along with the cycloadduct 3 [43], which we had not observed in our previous study of glycinate imine substrates. The aminoindanol-derived catalyst 5 was more reactive and resulted in improved enantioselectivity (89% ee), but afforded the same 4:1 ratio of the

• Michael adduct to cycloaddition product (Table 1, entry 2). Interestingly, the larger ring-containing catalyst 6 improved this ratio somewhat to 6:1 while retaining the enantiomeric ratio, albeit at the expense of reactivity (Table 1, entry 3). Incorporation of additional unsaturation (catalyst 7

Recent advances in the syntheses of anthracene derivatives

• Giovanni S. Baviera and
• Paulo M. Donate

Beilstein J. Org. Chem. 2021, 17, 2028–2050, doi:10.3762/bjoc.17.131

• sequential transformations of the resulting adduct into the protected diarylmethanols 81a and 81b. The scope of the reaction consisted of five examples (82a–e) that were obtained in moderate yields (30–68%). According to the authors, the reaction conditions were the mildest ever used in this type of

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

• less reactive adduct 31. DMF-mediated glycosylations permitted access to long structures based on multiple α(1–4) linkages 33 and 34 [178] and α(1–3) linkages 35 [179] (Scheme 5B). The short oligosaccharide 36 having α(1–2) linkages was also prepared, however, in this case, the stereoselectivity

Asymmetric organocatalyzed synthesis of coumarin derivatives

• Natália M. Moreira,
• Lorena S. R. Martelli and
• Arlene G. Corrêa

Beilstein J. Org. Chem. 2021, 17, 1952–1980, doi:10.3762/bjoc.17.128

• high diastereo- and enantioselectivity and moderate to excellent yields. The authors highlighted that the catalyst also contributes to cyclization, since subjecting the isolated Michael adduct to the second conditions with iodine and K2CO3 there is a decrease in yield and enantiomeric excess when

• mechanisms occur in parallel, which results in the formation of the Michael adduct as a byproduct and the desired spirocyclopentanes 104. It is noteworthy that the mechanistic studies showed that the product is formed through a concerted mechanism and therefore is not part of an intermediate adduct. A

Development of N-F fluorinating agents and their fluorinations: Historical perspective

• Teruo Umemoto,
• Yuhao Yang and
• Gerald B. Hammond

Beilstein J. Org. Chem. 2021, 17, 1752–1813, doi:10.3762/bjoc.17.123

• reaction gave adduct 1-3 as a major product and the latter showed good fluorine-transfer to the hetero atoms. In 1972, German et al. reported the reaction with sodium phenoxide, which gave a small amount (5%) of fluorophenols 1-6 and a larger amount of adduct 1-7 (Scheme 3, entry 3) [20]. These data showed

Electron-rich triarylphosphines as nucleophilic catalysts for oxa-Michael reactions

• Susanne M. Fischer,
• Simon Renner,
• A. Daniel Boese and
• Christian Slugovc

Beilstein J. Org. Chem. 2021, 17, 1689–1697, doi:10.3762/bjoc.17.117

• the conversion is observed (Figure 1). With all other (more acidic) alcohols, the conversion is reaching completeness after 24 h. Why MMTPP is performing slightly worse than TPP as indicated by the double-bond conversion and by the higher share of the mono-adduct 3monoa–d after 1 h reaction time is