Sulfur-containing spiroketals from Breynia disticha and evaluations of their anti-inflammatory effect

• Ken-ichi Nakashima,
• Naohito Abe,
• Masayoshi Oyama,
• Hiroko Murata and
• Makoto Inoue

Beilstein J. Org. Chem. 2023, 19, 1604–1614, doi:10.3762/bjoc.19.117

• the ethyl acetate fraction (Figure 1). The structures of known compounds 5–7 were identified based on 1H and 13C NMR data [2][3][10]. Breynin J (1) was isolated as an amorphous, colorless powder. The HRESIMS spectrum exhibited a sodium adduct ion peak at m/z 1107.3177, consistent with a molecular

• isolated as an amorphous, colorless powder. Because the sodium adduct ion peak at m/z 1107.3178 in the HRESIMS spectrum gave the same molecular formula as that of 1 (C45H64O28SNa, calcd 1107.3197), compounds 1 and 2 were determined to be isomers. The 1D and 2D NMR spectroscopic data indicated that the

• compounds 2 and 7 were determined to be 1S,3R,4R,6S,7R,9S,11S,12R,16S,17S (Figure 3c). Probreynogenin (3) was isolated as an amorphous, colorless solid. The molecular formula of 3 was determined to be C23H27NO11S based on the sodium adduct ion peak at m/z 548.1197 [M + Na]+ (calcd 548.1197) observed by

Morpholine-mediated defluorinative cycloaddition of gem-difluoroalkenes and organic azides

• Tzu-Yu Huang,
• Mario Djugovski,
• Sweta Adhikari,
• Destinee L. Manning and
• Sudeshna Roy

Beilstein J. Org. Chem. 2023, 19, 1545–1554, doi:10.3762/bjoc.19.111

• their 3JH−F coupling constants in the 1H NMR spectra, circa 32.0 Hz for Z-isomers and 8.0 Hz for E-isomers [33]. A peak was observed at −158.2 ppm in the 19F NMR spectrum after 2 h of the reaction, which could be the fluoride salt of the dimorpholine adduct. This peak was also found when the reaction

Synthesis and biological evaluation of Argemone mexicana-inspired antimicrobials

• Jessica Villegas,
• Bryce C. Ball,
• Katelyn M. Shouse,
• Caleb W. VanArragon,
• Ashley N. Wasserman,
• Hannah E. Bhakta,
• Allen G. Oliver,
• Danielle A. Orozco-Nunnelly and
• Jeffrey M. Pruet

Beilstein J. Org. Chem. 2023, 19, 1511–1524, doi:10.3762/bjoc.19.108

• effects of each modification. It was found that the acetone adduct B9 and the partially reduced variant B10 were more potent, while the fully reduced variant B11 was significantly less active (Table 2). These results suggested the activity of B1 could be similarly altered by the same modifications to the

α-(Aminomethyl)acrylates as acceptors in radical–polar crossover 1,4-additions of dialkylzincs: insights into enolate formation and trapping

• Angel Palillero-Cisneros,
• Paola G. Gordillo-Guerra,
• Fernando García-Alvarez,
• Olivier Jackowski,
• Franck Ferreira,
• Fabrice Chemla,
• Joel L. Terán and
• Alejandro Perez-Luna

Beilstein J. Org. Chem. 2023, 19, 1443–1451, doi:10.3762/bjoc.19.103

• protodemetalation to provide ultimately the 1,4-addition adduct. In the presence of carbonyl acceptors, aldol condensation occurs providing overall a tandem 1,4-addition–aldol process. When a tert-butanesulfinyl moiety is present on the nitrogen atom, these electrophilic substitution reactions occur with good

• )acrylates in hands, we carried out an initial survey of their reaction with Et2Zn in CH2Cl2 at −33 °C on addition of air. In these conditions, acrylate 10 led to the recovery (following aqueous work-up) of sulfinamide 9 without traces of formation of the 1,4-adduct (Scheme 4). By contrast, 1,4-addition

• without subsequent fragmentation was observed starting from α-(aminomethyl)acrylates having free N–H bonds (Table 2). The reaction of Et2Zn with acrylates 5–7 afforded the desired 1,4-addition products 11–13 in 42–55% yield. Better results were obtained starting from 8a, which delivered adduct 14a in 79

Metal catalyst-free N-allylation/alkylation of imidazole and benzimidazole with Morita–Baylis–Hillman (MBH) alcohols and acetates

• Olfa Mhasni,
• Jalloul Bouajila and
• Farhat Rezgui

Beilstein J. Org. Chem. 2023, 19, 1251–1258, doi:10.3762/bjoc.19.93

• , the use of DABCO, commonly used as a powerful catalyst or a nucleophilic additive in the reaction of acyclic MBH adducts with various nucleophiles [21][34][35][36][37], did not afford the SN2/SN2’ products but provided the 1,4-adduct 8a in 84% yield (Table 2, entry 4). Alternatively, we also

Selective construction of dispiro[indoline-3,2'-quinoline-3',3''-indoline] and dispiro[indoline-3,2'-pyrrole-3',3''-indoline] via three-component reaction

• Ziying Xiao,
• Fengshun Xu,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2023, 19, 1234–1242, doi:10.3762/bjoc.19.91

• as Michael acceptors, 1,3-dipolarophiles, 1,4-dienophiles and other multiple substrates. They have been widely employed as key component to finish many multicomponent and domino reactions [26][27][28][29][30][31][32][33][34][35]. Recently, the Michael adduct of 3-methyleneoxindoles with various

• nucleophiles, especially active methylene compounds, have attracted much attentions [36][37][38][39][40][41]. This kind of Michael adduct has more than one reactive site and could proceed domino reactions with various electrophiles [42][43][44][45][46][47][48][49]. In this respect, several elegant domino or

• spirooxindoles, in which the in situ-generated Michael adduct of 3-ethoxycarbonylmethyleneoxindole underwent a Mannich reaction and annulation reaction with in situ-generated aldimines (reaction 1 in Scheme 1) [50][51]. Tanaka reported chiral quinidine derivative-catalyzed Michael–Henry cascade reactions of

Exploring the role of halogen bonding in iodonium ylides: insights into unexpected reactivity and reaction control

• Carlee A. Montgomery and
• Graham K. Murphy

Beilstein J. Org. Chem. 2023, 19, 1171–1190, doi:10.3762/bjoc.19.86

• , they believed that the reaction was likely initiated by either single electron transfer between the reagents (not shown), or by electrophilic addition of the olefin onto the ylide, forming intermediate adduct 17. This was followed by formation of iodocycle 18, from which reductive elimination of

• direct cycloaddition between the ylide and alkene. Murphy’s report of formal X–H insertions with iodonium ylides was similarly proposed to initiate upon complex formation with a Lewis base. Adduct formation was believed to both increase the acidity of halogen bond acceptor’s attached protons, as well as

• -derived iodonium ylide (60/I-13) (Figure 12, inset), which showed a 5.1 kcal/mol energy difference between rapidly equilibrating halogen-bonded fluoride adducts. The lower energy adduct IntA had fluoride residing in the stronger σ-hole opposite the β-dicarbonyl (syn to the arene), whereas the higher

Two new lanostanoid glycosides isolated from a Kenyan polypore Fomitopsis carnea

• Winnie Chemutai Sum,
• Sherif S. Ebada,
• Didsanutda Gonkhom,
• Cony Decock,
• Rémy Bertrand Teponno,
• Josphat Clement Matasyoh and
• Marc Stadler

Beilstein J. Org. Chem. 2023, 19, 1161–1169, doi:10.3762/bjoc.19.84

• ]. Results Structure elucidation Compound 1 was isolated as an off-white solid powder. Its molecular formula was determined to be C43H68O12 based on HRESIMS results that revealed a sodium adduct ion peak at m/z 799.4604 ([M + Na]+ calcd for C43H68O12Na+, 799.4603) indicating the presence of ten degrees of

• trivially named as forpinioside B. Compound 2 was obtained as a colourless oil and its molecular formula was determined to be C43H68O13 according to its HRESIMS spectrum that revealed a sodium adduct ion peak at m/z 815.4550 ([M + Na]+ calcd for C43H68O13Na+, 815.4552) indicating the presence of an

Photoredox catalysis harvesting multiple photon or electrochemical energies

• Mattia Lepori,
• Simon Schmid and
• Joshua P. Barham

Beilstein J. Org. Chem. 2023, 19, 1055–1145, doi:10.3762/bjoc.19.81

The unique reactivity of 5,6-unsubstituted 1,4-dihydropyridine in the Huisgen 1,4-diploar cycloaddition and formal [2 + 2] cycloaddition

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

Beilstein J. Org. Chem. 2023, 19, 982–990, doi:10.3762/bjoc.19.73

• gives the well-known Huisgen 1,4-dipole A. Secondly, Michael addition of the 1,4-dipole A to 5,6-unsubstituted 1,4-dihydropyridine gives the adduct intermediate B. At last, the intramolecular coupling of the negative and the positive charges in intermediate B directly affords isoquinolino[1,2-f][1,6

• acetylenedicarboxylate to give the adduct C. Then, the direct coupling of the positive charge and the negative charge affords the 2-azabicyclo[4.2.0]octa-3,7-diene 5. On the other hand, a carbenium ion D can be formed by migration of a hydrogen atom in intermediate C, which in turn converts into a fused bicyclic

First synthesis of acylated nitrocyclopropanes

• Kento Iwai,
• Rikiya Kamidate,
• Khimiya Wada,
• Haruyasu Asahara and
• Nagatoshi Nishiwaki

Beilstein J. Org. Chem. 2023, 19, 892–900, doi:10.3762/bjoc.19.67

• ) halogenation, and 3) ring closure (Scheme 2). β-Nitrostyrene 2 serves as an appropriate acceptor for conjugate addition by diethyl malonate (3a) to afford adduct 4a, in which the methine group flanked by two carbonyl groups is readily halogenated, and the subsequent intramolecular nucleophilic substitution by

• substrates, almost equal amounts of diastereomers were formed. Whereas 4b was isolated by recrystallization of the reaction mixture from ethanol, the other adducts 4c–g were easily isolated by column chromatography. For comparison with previously reported results, adduct 4b, derived from acetylacetone (3b

• ), was subjected to cyclopropanation according to a method described in the literature [13]. To a solution of adduct 4b in toluene, (diacetoxyiodo)benzene and tetrabutylammonium iodide were added, and the resulting mixture was stirred at room temperature for 14 h. Unexpectedly, from the reaction mixture

Pyridine C(sp²)–H bond functionalization under transition-metal and rare earth metal catalysis

• Haritha Sindhe,
• Malladi Mounika Reddy,
• Karthikeyan Rajkumar,
• Akshay Kamble,
• Amardeep Singh,
• Anand Kumar and
• Satyasheel Sharma

Beilstein J. Org. Chem. 2023, 19, 820–863, doi:10.3762/bjoc.19.62

• regioselectively at the C4 position of the organoborate intermediate 60 delivering the σH-adduct intermediates 62 and 63. Subsequently, hydride elimination with the help of the organoborane gave the desired alkylated product 59 and regenerates the hydride catalyst. Further enantioselective pyridine C–H alkylation

Photocatalytic sequential C–H functionalization expediting acetoxymalonylation of imidazo heterocycles

• Deepak Singh,
• Shyamal Pramanik and
• Soumitra Maity

Beilstein J. Org. Chem. 2023, 19, 666–673, doi:10.3762/bjoc.19.48

• (Scheme 3A). Upon analyzing the reaction mixture of 1a and 2a under standard conditions in the presence of TEMPO, we found only a trace of the desired product 4a. At the same time, a TEMPO-DEM adduct 7 and TEMPO-OAc adduct 8 were identified by the HRMS analysis of the crude reaction mixture, indicating

Cassane diterpenoids with α-glucosidase inhibitory activity from the fruits of Pterolobium macropterum

• Sarot Cheenpracha,
• Ratchanaporn Chokchaisiri,
• Lucksagoon Ganranoo,
• Sareeya Bureekaew,
• Thunwadee Limtharakul and
• Surat Laphookhieo

Beilstein J. Org. Chem. 2023, 19, 658–665, doi:10.3762/bjoc.19.47

• a Diels–Alder adduct, thus displaying the same relative configuration found in pterolobirin B [11]. The absolute configuration of 3 was thus elucidated as 5S,6R,8R,9S,10R,15R,5′S,6′R,8′R,9′S,10′R,12′S,13′R,14′R,15′S,16′S and the measured ECD spectrum (Figure 4b) with the positive at 243 nm and

Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles

• Péter Kisszékelyi and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44

• reaction with the α-aminoether 118. This reagent released an iminium ion into the reaction medium that reacted with the Al enolate 117 [66]. Furthermore, the Mannich adduct was then reacted with Grignard reagents that replaced the dimethylamino group (Scheme 30). Alexakis and co-workers also investigated

• acryloyloxazolidinone 183, the reaction gave the expected aldol product 184 in good yields and diastereomeric ratios with a preference toward the syn-adduct (Scheme 47A). Interestingly, when they used methacryloyloxazolidinone 185 as a Michael acceptor, the X-ray analysis of the product showed a rearranged structure

• silylation/aldol cyclization sequence where the diastereoselectivity of the reaction is determined by the Si nucleophile used [90]. Using Me2PhSiZnX·2LiX in combination with ligand L21 leads to the trans adduct, while Me2PhSiBpin together with L30 provides the cis product. Consequently, the authors have

Transition-metal-catalyzed domino reactions of strained bicyclic alkenes

• Austin Pounder,
• Eric Neufeld,
• Peter Myler and
• William Tam

Beilstein J. Org. Chem. 2023, 19, 487–540, doi:10.3762/bjoc.19.38

• undergoing reductive elimination to afford to [2 + 2] adduct, β-oxygen elimination followed by E/Z isomerization and intramolecular lactonization generates the annulated coumarin scaffold. In 2003, the Cheng lab extended on this Ni-catalyzed ring-opening strategy [31]. It was noted the addition of 1.5

• final ring-opened adduct 37. Copper-catalyzed reactions In 2009, Pineschi and co-workers explored the Cu-catalyzed rearrangement/allylic alkylation of 2,3-diazabicyclo[2.2.1]heptenes 47 with Grignard reagents 48 (Scheme 8) [41]. The reaction is thought to proceed via the Lewis acid-catalyzed [3,4

• derivatives 85. The reaction was amenable for both electron-rich and deficient indoles. When the reaction was attempted on electron-deficient oxabicyclic alkene derivatives, it was observed the reaction did not undergo dehydration to give the 2-naphthyl product, rather the ring-opened 1,2-hydroxy adduct. When

Transition-metal-catalyzed C–H bond activation as a sustainable strategy for the synthesis of fluorinated molecules: an overview

• Louis Monsigny,
• Floriane Doche and
• Tatiana Besset

Beilstein J. Org. Chem. 2023, 19, 448–473, doi:10.3762/bjoc.19.35

• of adduct J. The product 26 is released via a reductive elimination step, generating at the same time the reduced cobalt Cp*Co(I), which is converted to the active catalyst after oxidation. The same year, Yoshino and Matsunaga described a similar methodology, using the cobalt(III) complex [Cp*Co

Mechanochemical solid state synthesis of copper(I)/NHC complexes with K₃PO₄

• Ina Remy-Speckmann,
• Birte M. Zimmermann,
• Mahadeb Gorai,
• Martin Lerch and
• Johannes F. Teichert

Beilstein J. Org. Chem. 2023, 19, 440–447, doi:10.3762/bjoc.19.34

• such as n-BuLi or NaOt-Bu (in various equivalents, Table 1, entries 1 and 2) or weak bases (Et3N, K2CO3 or K3PO4, Table 1, entries 3–5) either did give no conversion to 5 at all or delivered a catalytically inactive complex, which we assign to a CO2 adduct of 5 (Table 1, entry 4) [51][52]. We

• hypothesize that in this CO2 adduct, the guanidine moiety is unavailable to perform its assisting part in catalysis through hydrogen-bonding interaction [48]. As additional evidence to support the formation of the CO2 adduct of 5, we can show that bubbling of CO2 through a solution of 5 leads to catalytically

• inactive complexes (see Supporting Information File 1 for details). This also supports the notion that during catalytic ester hydrogenation, the guanidinium moiety acts as a hydrogen bond donor to the esters [48]. The formation of a CO2 adduct hinders the ability to form hydrogen bonds. Furthermore

Asymmetric synthesis of a stereopentade fragment toward latrunculins

• Benjamin Joyeux,
• Antoine Gamet,
• Nicolas Casaretto and
• Bastien Nay

Beilstein J. Org. Chem. 2023, 19, 428–433, doi:10.3762/bjoc.19.32

• (13,14)-bond of 1 and 2, respectively. Conversely, we envisaged an alternative disconnection to form the (16,17)- or the (14,15)-bond of 1 and 2, through an aldol reaction of aldehyde 8 readily available from ʟ-cysteine, leading to aldol adduct 7 (Figure 2, route B). The methyl ketone partner 9 could be

Strategies to access the [5-8] bicyclic core encountered in the sesquiterpene, diterpene and sesterterpene series

• Cécile Alleman,
• Charlène Gadais,
• Laurent Legentil and
• François-Hugues Porée

Beilstein J. Org. Chem. 2023, 19, 245–281, doi:10.3762/bjoc.19.23

• 31 and oxazolidinone 32 (Scheme 5) [26]. Subsequently, compound 33 was converted in four steps into aldehyde 34 which was engaged in a coupling reaction with bromoketone 35 according to Utimoto conditions to furnish the A-C-D adduct 36 as a single stereoisomer in high yield. Of note, the Utimoto

• . Despite the relative simplicity of substrate 99, the reaction was running in the exclusive presence of G-II catalyst and necessitated a high catalyst loading (30 mol %) to eventually furnish modest yields. The presence of two major byproducts was also noticed, namely the cross metathesis adduct resulting

• from 2 equivalents of 99 and the cross metathesis adduct resulting from 99 and a styrene unit coming from the catalyst. In addition, the corresponding RCM on the alkene analogue of 99 did not proceed either with G-II or Schrock catalysts, showcasing the substrate sensitivity of this reaction. 1.3

Germacrene B – a central intermediate in sesquiterpene biosynthesis

• Houchao Xu and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2023, 19, 186–203, doi:10.3762/bjoc.19.18

• -workers [19], through a sequence of reduction to the alcohol, acetylation and reduction with lithium in ammonia (Scheme 3A) [20], and its structure was unambiguously assigned by X-ray crystallography of a silver nitrate adduct [21]. From natural sources, the compound was first obtained from Humulus

Identification and determination of the absolute configuration of amorph-4-en-10β-ol, a cadinol-type sesquiterpene from the scent glands of the African reed frog Hyperolius cinnamomeoventris

• Angelique Ladwig,
• Markus Kroll and
• Stefan Schulz

Beilstein J. Org. Chem. 2023, 19, 167–175, doi:10.3762/bjoc.19.16

• adduct with 18 that was readily separable from the target ketones. Following the optimization of reaction conditions, a change of solvent to THF was shown to be as equally effective as toluene (Table 1, entry 10). The ketones S-9, S-10, and S-11 were obtained in a ratio of 1:6.9:5.2, indicating a higher

Nostochopcerol, a new antibacterial monoacylglycerol from the edible cyanobacterium Nostochopsis lobatus

• Naoya Oku,
• Saki Hayashi,
• Yuji Yamaguchi,
• Hiroyuki Takenaka and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2023, 19, 133–138, doi:10.3762/bjoc.19.13

• based on a sodium adduct pseudomolecular ion at m/z 349.2348 [M + Na]+ observed by high-resolution ESITOFMS (calcd for C19H34NaO4+, 349.2349). Three degrees of unsaturation, calculated from the molecular formula, were accounted for by a carboxyl group (δC 175.3) and two double bonds (δC 130.9, 130.6

1,4-Dithianes: attractive C2-building blocks for the synthesis of complex molecular architectures

• Bram Ryckaert,
• Ellen Demeyere,
• Frederick Degroote,
• Hilde Janssens and
• Johan M. Winne

Beilstein J. Org. Chem. 2023, 19, 115–132, doi:10.3762/bjoc.19.12

• at room temperature to form the expected Diels–Alder adduct 32, while non-cyclic vinyl disulfones require heating to 80 °C for 20–48 h. Deoxygenation of the epoxide and desulfonylation with sodium amalgam affords barrelene (33) in an excellent overall yield from oxepin. The chlorinated 1,4-dithiin

• -tetroxide ring gives the cyclohexa-1,4-diene intermediate 39. This intermediate can then be easily oxidized to afford the aromatic adduct 40, which is the known cycloaddition product of furan and benzyne. Although this synthetic equivalent of benzyne requires a lengthy work-around, all synthetic operations

• -adduct dithiin 42 in quantitative yield. Although 2,5-dimethylhexa-2,4-diene cannot possibly adopt a coplanar single-cis conformation, and is therefore completely unreactive in Diels–Alder reactions as a diene, its 1,4-dithiane-tethered version in 41 must show a sufficient proximity between the terminal

NaI/PPh₃-catalyzed visible-light-mediated decarboxylative radical cascade cyclization of N-arylacrylamides for the efficient synthesis of quaternary oxindoles

• Dan Liu,
• Yue Zhao and
• Frederic W. Patureau

Beilstein J. Org. Chem. 2023, 19, 57–65, doi:10.3762/bjoc.19.5

• a TEMPO-trapped adduct (4) was detected by HRMS (Scheme 4a). Moreover, the radical-mediated ring-opening product 3am could be obtained with 66% yield in a radical clock experiment when redox-active ester 5 was engaged to react with acrylamide 1a under standard conditions (Scheme 4b). Finally, it