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

Methodologies for the synthesis of quaternary carbon centers via hydroalkylation of unactivated olefins: twenty years of advances

• Thiago S. Silva and
• Fernando Coelho

Beilstein J. Org. Chem. 2021, 17, 1565–1590, doi:10.3762/bjoc.17.112

• , was the only example reported of a quaternary carbon center synthesis (Scheme 12). The observations that no reaction was detected in the absence of AgOCl and that only an aza-Michael adduct was observed in the absence of the gold(I) complex led the authors to propose that the silver(I) salt promoted

Breaking paracyclophane: the unexpected formation of non-symmetric disubstituted nitro[2.2]metaparacyclophanes

• Suraj Patel,
• Tyson N. Dais,
• Paul G. Plieger and
• Gareth J. Rowlands

Beilstein J. Org. Chem. 2021, 17, 1518–1526, doi:10.3762/bjoc.17.109

• observed (Figure 6). As with the oxidation, we assume that the lower deck blocks approach from one face. Protonation of the adduct also occurs anti to the para ring. We suspect that this second addition favors the trans product over the cis rather than the para ring influencing the approach of the proton

Icilio Guareschi and his amazing “1897 reaction”

• Gian Cesare Tron,
• Alberto Minassi,
• Giovanni Sorba,
• Mara Fausone and
• Giovanni Appendino

Beilstein J. Org. Chem. 2021, 17, 1335–1351, doi:10.3762/bjoc.17.93

• Guareschi imides, which, under the original protocol, is limited to ketones as the carbonyl component. When aldehydes are used, the adduct is aromatized to the corresponding 2-hydroxypyridone [50][51]. Finally, a modification of the type-IV Guareschi reaction that involves the condensation of two moles of

• reacts with aldehydes and eventually regenerates a triphenylmethane dye from the sulfite adduct [22]. The study of old color reactions has not only mechanistic interest but can lead to new drug candidates, as shown by the

A new glance at the chemosphere of macroalgal–bacterial interactions: In situ profiling of metabolites in symbiosis by mass spectrometry

• Marine Vallet,
• Filip Kaftan,
• Veit Grabe,
• Fatemeh Ghaderiardakani,
• Simona Fenizia,
• Aleš Svatoš,
• Georg Pohnert and
• Thomas Wichard

Beilstein J. Org. Chem. 2021, 17, 1313–1322, doi:10.3762/bjoc.17.91

• both profiling and imaging MS spectra as the [M + Na]+ adduct at m/z 165.0633. Ectoine was mainly found around the rhizoid in elevated amounts. Thus, Roseovarius sp. MS2 became visible in the rhizoidal zone and on the thallus due to the exclusive production of ectoine within the tripartite community

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

• -nucleoside reverse transcriptase inhibitor (NNRTI) doravirine (49) in flow (Scheme 5) [100]. The aldol reaction of an aromatic ester 44 with a vinylogous ester 45 was achieved in a continuous manner, yielding the hydroxyl adduct, 46, in 85% yield within just a 15 second residence time. Here, a slightly

• of the catalyst in less polar solvents (Scheme 11). Thus, a stream of 2,6-dichlorobenzaldehyde (70) and cyclohexanone (65) along with 10 mol % of AcOEt and 3 mol % H2O were directed as a flow stream into the loaded column to partake in the aldol reaction to furnish adduct 71 in 95% yield and

• (Scheme 12) [113]. The reactor output reached a maximum conversion of 64%, generating a 1:1 ratio of the aldol adduct 39 and the further condensation product 72. It was also shown that the selectivity for 39 could be improved by increase the flow rate, although this also coincided with a lower conversion

N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

Synthetic accesses to biguanide compounds

• Oleksandr Grytsai,
• Cyril Ronco and
• Rachid Benhida

Beilstein J. Org. Chem. 2021, 17, 1001–1040, doi:10.3762/bjoc.17.82

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

Prins cyclization-mediated stereoselective synthesis of tetrahydropyrans and dihydropyrans: an inspection of twenty years

• Asha Budakoti,
• Pradip Kumar Mondal,
• Prachi Verma and
• Jagadish Khamrai

Beilstein J. Org. Chem. 2021, 17, 932–963, doi:10.3762/bjoc.17.77

• an intimate ion pair 51. The proximal addition of a bromide ion to 51 produces axial adduct 56 exclusively. However, when SnBr4 is used as a Lewis acid, oxocarbenium ion 52 is formed via 50. The counterion SnBr4− being much less nucleophilic than the Br− ion allows the formation of a solvent

• formal 2-oxonia-[3,3]-sigmatropic rearrangement. Furthermore, Markó and co-workers successfully synthesized 2,6-anti-configured THP starting from allylsilane 245, following diethylaluminium chloride-promoted ene reaction and condensation with an aldehyde 246 [102]. Expected ene adduct 247 was obtained as

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