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

• Pharmaceutical Sciences, Osaka University, Yamadaoka 1-6, Suita, Osaka 565-0871, Japan 10.3762/bjoc.19.67 Abstract Although nitrocyclopropanedicarboxylic acid esters are widely used in organic syntheses, nitrocyclopropanes with an acyl group have not yet been synthesized. When adducts of β-nitrostyrene and 1,3

• esters 1a have recently attracted considerable attention from synthetic organic chemists. In addition to their polyfunctionality, their ring strain and electron deficiency lead to a wide variety of reactivities. Based on their electron-deficient nature, these compounds have been used as substrates in the

• example, when esters 1a are subjected to Lewis acid-induced denitration, highly electron-deficient enones (reaction b) [4] are obtained. The latter compounds are highly reactive and undergo reaction with, e.g., mercaptoacetaldehyde affording thiophenes (reaction c) [5] or with activated (hetero)aromatic

Asymmetric tandem conjugate addition and reaction with carbocations on acylimidazole Michael acceptors

• Brigita Mudráková,
• Renata Marcia de Figueiredo,
• Jean-Marc Campagne and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 881–888, doi:10.3762/bjoc.19.65

• organoboron reagents were realized [12]. Also, in terms of suitable Michael acceptors as substrates, unsaturated ketones, aldehydes, esters, thioesters, amides, alkenyl heterocycles and enoyl heterocycles became viable for conjugate additions. The maturity and robustness of this methodology is documented by

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

• organoboron coupling partners, Wu and co-workers [91] reported a protocol for the Cu-catalyzed C–H arylation of pyridine N-oxides 9 with arylboronic esters 114 and prepared C2-arylated pyridines 115 in moderate to good yields (Scheme 22). By using an inexpensive Cu catalyst, the method allows for the simple

Eschenmoser coupling reactions starting from primary thioamides. When do they work and when not?

• Lukáš Marek,
• Jiří Váňa,
• Jan Svoboda and
• Jiří Hanusek

Beilstein J. Org. Chem. 2023, 19, 808–819, doi:10.3762/bjoc.19.61

• thiobenzamides [26][27]. The latter authors concluded that the relative occurrence of 1,2,4-thiadiazoles (XV) during the Hantzsch reaction probably depends on the steric demands of the starting α-haloketones/esters II, but the real explanation is probably more complicated. Therefore, we have decided to examine

• theory in N,N-dimethylformamide (SMD). Extended version of Figure 2 involving energies of final products can be found in Supporting Information File 1. Eschenmoser coupling reaction between 3-substituted oxindoles and thioamides. Possible reactions of α-haloketones, esters and amides with primary

Facile access to 3-sulfonylquinolines via Knoevenagel condensation/aza-Wittig reaction cascade involving ortho-azidobenzaldehydes and β-ketosulfonamides and sulfones

• Ksenia Malkova,
• Andrey Bubyrev,
• Stanislav Kalinin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2023, 19, 800–807, doi:10.3762/bjoc.19.60

• was predominantly applied for the preparation of the corresponding esters. Inspired by this study, we became interested to utilize o-azidobenzaldehydes 1 in combination with ketosulfonamides/ketosulfones 2 as precursors in a new convenient synthetic procedure leading towards 3-sulfonyl-substituted

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

• array of organic synthetic transformations. Enolates are usually formed by deprotonation of the corresponding organic compound. However, other synthetic approaches for their generation exist, such as cleavage of enol ethers and esters, halogen–metal exchange, transmetalations, and conjugate additions to

• addition with Grignard reagents Feringa and co-workers realized the tandem conjugate addition of Grignard reagents to 4-chlorocrotonates 46 [42]. The enolate 47, which was formed in this process, underwent an intramolecular nucleophilic substitution to form cyclopropane derivatives. Thioesters, esters as

• alkenyl heteroarenes [61]. The aza-enolates were trapped with various Michael acceptors such as unsaturated ketones, esters, and amides (Scheme 25) [62]. The authors noted a strong substrate dependence of this process. The trapping reaction worked best with benzoxazole-derived substrate, while thiazole

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

• phenanthridinones produced, the authors were able to quickly afford novel fagaronine 117j and nitidine 117k derivatives. Rhodium-catalyzed reactions In 2002, the Lautens laboratory reported a tandem cyclization of arylboronate esters 118 with a variety of bicyclic alkenes 15 using a water-soluble Rh-catalytic

• system (Scheme 22) [65]. The authors reported the reaction proceeded smoothly with a limited variety of substituted norbornenes and boronate esters. In 2004, the same group expanded this Rh-catalyzed cyclization to heterobicyclic alkenes 1 with arylboronate esters 118 for the synthesis of a variety of

• significant steric interactions between the –COR group on the pendant alkene and the bridging group of the bicyclic alkene in 123. In 2006, the Lautens lab continued to extend this reaction to include dienylboronate esters 125 and found that an unexpected vinylcyclopropane product 126 was generated (Scheme 23

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

• 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

• the standard reactions for catalytic hydrogenations with copper(I)/NHC complexes [4]. In this vein, we tested complex 5 from solid and liquid phase synthesis in the catalytic hydrogenation of esters, carbonyl compounds and in the semihydrogenation of alkynes. In the catalytic hydrogenation of ethyl

Dipeptide analogues of fluorinated aminophosphonic acid sodium salts as moderate competitive inhibitors of cathepsin C

• Karolina Wątroba,
• Małgorzata Pawełczak and
• Marcin Kaźmierczak

Beilstein J. Org. Chem. 2023, 19, 434–439, doi:10.3762/bjoc.19.33

• literature data of the starting esters 5 and 7 literature data [23][24]. A very good correlation of chemical shifts was also observed in the 13C NMR spectra for the key signals from the C1 and C2 atoms (Table 1). Each sample was pure; no byproducts were present. Kinetic studies Due to the homology and

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

• secured by the NMR analysis of Mosher's esters made from (R)-(+)- and (S)-(−)-α-methoxy-α-trifluoromethylphenylacetic acid (MTPA) (see Supporting Information File 1) [23][24][25], confirming the installation of the C-11 stereocenter of latrunculins. The next steps consisted in the functionalization of 12

• relied on the comparative NMR analysis of Mosher's esters [23]. Despite clear 1H NMR spectra, irregular values of ΔδS–R precluded the unambiguous determination of the C-15 stereocenter [24]. These difficulties were attributed to the hindered character of this secondary alcohol, substituted by the

• %). This compound results from the transposition of the para-nitrobenzoyl (PNBz) group onto the 13-OH, which could be favoured by the steric hindrance of C-15 and a possible π–π stacking with the OPMB group. These PNBz esters were readily hydrolyzed to furnished diol 24 in 97% yield. The oxydation of the

Discrimination of β-cyclodextrin/hazelnut (Corylus avellana L.) oil/flavonoid glycoside and flavonolignan ternary complexes by Fourier-transform infrared spectroscopy coupled with principal component analysis

• Nicoleta G. Hădărugă,
• Gabriela Popescu,
• Dina Gligor (Pane),
• Cristina L. Mitroi,
• Sorin M. Stanciu and
• Daniel Ioan Hădărugă

Beilstein J. Org. Chem. 2023, 19, 380–398, doi:10.3762/bjoc.19.30

• (Phaseolus vulgaris L.) oil contains 55.7–58.8% of polyunsaturated FAs (relative content as methyl esters), with an important fraction of omega-3 α-linolenic acid (ALA) of 14.1–18.9%. It was stabilized by β-CD complexation, with an increased content of the omega-3 FAs into the nanoencapsulated oil of >14

• ) of the FA glycerides to the corresponding FA methyl esters (FAMEs) [11][13]. The derivatization involved methanol–boron trifluoride (20% BF3), hexane (GC grade) and anhydrous sodium sulfate, all purchased from Merck & Co., Inc., Rahway, NJ, USA. Sodium chloride (reagent grade) used for the separation

• 2096.4. The other important FAs, as methyl esters, were palmitoleic, palmitic, linoleic, elaidic/vaccenic, and stearic acids with concentrations of 0.13, 7.54, 15.51, 2.85 and 2.73%, respectively (a total of 98.68% identified FAMEs in the hazelnut oil). Synthesis of ternary complexes by the kneading

Group 13 exchange and transborylation in catalysis

• Dominic R. Willcox and
• Stephen P. Thomas

Beilstein J. Org. Chem. 2023, 19, 325–348, doi:10.3762/bjoc.19.28

• catalyse the hydroboration of alkynes with HBcat [50]. Hoshi later reported that Cy2BH [51] and in situ generated bis(pentafluorophenyl)borane, Piers’ borane [52], catalysed the hydroboration of alkynes with HBpin, to give alkenyl pinacol boronic esters. Tris(2,4,6-trifluorophenyl)borane [53], tris(3,4,5

• esters, lactones, and carbonates with HBpin under microwave irradiation (Scheme 13) [57]. When HBpin and boric acid were reacted together, BH3-coordinated HBpin and O(Bpin)2 were detected by 11B NMR spectroscopy. Supported by computational analysis and single-turnover experiments, the reaction was

• reaction of enones and esters or lactones (Scheme 14) [77]. Through a series of single-turnover reactions, a mechanism was proposed (Scheme 14): H-B-9-BBN underwent 1,4-hydroboration with the enone 29, followed by B‒O/B‒H transborylation with HBpin to give an O-Bpin enolate 52 and regenerate H-B-9-BBN

Sequential hydrozirconation/Pd-catalyzed cross coupling of acyl chlorides towards conjugated (2E,4E)-dienones

• Benedikt Kolb,
• Daniela Silva dos Santos,
• Sanja Krause,
• Anna Zens and
• Sabine Laschat

Beilstein J. Org. Chem. 2023, 19, 176–185, doi:10.3762/bjoc.19.17

• ; hydrozirconation; palladium catalysis; Schwartz's reagent; terpenes; Introduction Conjugated dienones are recurring structural motifs in natural products. Several biologically relevant compounds carry (2Ε,4E)-unsaturated ketones or the corresponding esters or amides. Selected examples are clifednamide H (1) which

Catalytic aza-Nazarov cyclization reactions to access α-methylene-γ-lactam heterocycles

• Bilge Banu Yagci,
• Selin Ezgi Donmez,
• Onur Şahin and
• Yunus Emre Türkmen

Beilstein J. Org. Chem. 2023, 19, 66–77, doi:10.3762/bjoc.19.6

• suitable mobile phase for the column chromatographic separation of the diastereomeric esters 16a and 16b. With the successful isolation of these esters in pure form, both were converted to the corresponding acyl chlorides 6ba and 6bb via an initial basic hydrolysis followed by treatment with oxalyl

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

• Dan Liu Yue Zhao Frederic W. Patureau Institute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, 52074 Aachen, Germany 10.3762/bjoc.19.5 Abstract A practical NaI/PPh3-catalyzed decarboxylative radical cascade cyclization of N-arylacrylamides with redox-active esters is described, which

• reported a Ru(bpy)3Cl2-catalyzed synthesis of N-Boc proline oxindole derivatives under visible-light assistance [47]. Therein, N-hydroxyphthalimide (NPhth) esters were utilized as alkyl radical precursors, which can be readily prepared from highly available carboxylic acids. In 2015, Cheng and co-workers

• -membered ring structure 3ra could be successfully isolated with a good yield (66%). A number of alkyl radical precursors were then synthesized and evaluated in the reaction (Scheme 3). We found that redox-active esters derived from primary, secondary, and tertiary aliphatic carboxylic acids were all

Combining the best of both worlds: radical-based divergent total synthesis

• Kyriaki Gennaiou,
• Antonios Kelesidis,
• Maria Kourgiantaki and
• Alexandros L. Zografos

Beilstein J. Org. Chem. 2023, 19, 1–26, doi:10.3762/bjoc.19.1

• nickel-mediated decarboxylative Giese reactions and decarboxylative radical zinc-mediated cross-coupling reactions of redox-active esters, established from previous works of the group [27][28], for the key C–C bonds of the diverse congeners. To this end, a hypothetical intermediate 3 was envisioned for

• A (52) as the radical cross-coupling employing redox-active esters of carboxylic acid 46 proved unsuccessful. The coupling was followed by an acid-catalyzed cyclization to yield the pyrone core of the natural products. The divergent plan described provided various meroterpenoids in 7–12 steps

Rhodium-catalyzed intramolecular reductive aldol-type cyclization: Application for the synthesis of a chiral necic acid lactone

• Motoyuki Isoda,
• Kazuyuki Sato,
• Kenta Kameda,
• Kana Wakabayashi,
• Ryota Sato,
• Hideki Minami,
• Yukiko Karuo,
• Atsushi Tarui,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2022, 18, 1642–1648, doi:10.3762/bjoc.18.176

• aldol-type reactions, and reductive Mannich-type reactions using RhCl(PPh3)3 with Et2Zn [41][42][43][44][45][46][47]. The rhodium-catalyzed reductive aldol reaction of α,β-unsaturated esters with aldehydes or ketones gives aldol-type products in good to excellent yields (Scheme 1) [43][44]. In addition

One-pot double annulations to confer diastereoselective spirooxindolepyrrolothiazoles

• Juan Lu,
• Bin Yao,
• Desheng Zhan,
• Zhuo Sun,
• Yun Ji and
• Xiaofeng Zhang

Beilstein J. Org. Chem. 2022, 18, 1607–1616, doi:10.3762/bjoc.18.171

• one-pot reactions were also developed by Zhang using the 4-aminoquinoline synthesis, for example, in amino acids(esters)-based [3 + 2] cycloadditions [38][39][40][41][42][43][44][45][46][47][48] and in the synthesis of pyrrolidine-containing systems [49][50][51][52][53][54][55][56][57][58][59

Simple synthesis of multi-halogenated alkenes from 2-bromo-2-chloro-1,1,1-trifluoroethane (halothane)

• Yukiko Karuo,
• Atsushi Tarui,
• Kazuyuki Sato,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2022, 18, 1567–1574, doi:10.3762/bjoc.18.167

• detected (Table 2, entry 11). An aldehyde group was found to be incompatible with this method (Table 2, entry 12). Esters, which are susceptible to hydrolysis, can be used in the reaction under controlled conditions, i.e., with the temperature kept below 60 °C and THF as the solvent. However, the yield of

Efficient synthesis of aziridinecyclooctanediol and 3-aminocyclooctanetriol

• Emine Salamci and
• Ayse Kilic Lafzi

Beilstein J. Org. Chem. 2022, 18, 1539–1543, doi:10.3762/bjoc.18.163

• antibiotic activities. Therefore, synthetic methodologies for the preparation of the aziridinyl system have attracted attention in recent decades. Opening of the aziridine ring by using different nucleophiles gives the corresponding amino alcohols, amino esters, azido amines, amines, and other derivatives [9

New triazole-substituted triterpene derivatives exhibiting anti-RSV activity: synthesis, biological evaluation, and molecular modeling

• Elenilson F. da Silva,
• Krist Helen Antunes Fernandes,
• Denise Diedrich,
• Jessica Gotardi,
• Marcia Silvana Freire Franco,
• Carlos Henrique Tomich de Paula da Silva,
• Ana Paula Duarte de Souza and
• Simone Cristina Baggio Gnoatto

Beilstein J. Org. Chem. 2022, 18, 1524–1531, doi:10.3762/bjoc.18.161

• resulted in the synthesis of derivatives 3 and 4, with 90 and 83% yield, respectively (Scheme 2). The C-28-propargylated triterpene esters (5 and 6, 70% yield for both) of the acetate derivatives (3 and 4) were obtained. Finally, the reaction of derivatives 5 and 6 with meta-nitro-substituted azide (c

An alternative C–P cross-coupling route for the synthesis of novel V-shaped aryldiphosphonic acids

• Stephen J. I. Shearan,
• Enrico Andreoli and
• Marco Taddei

Beilstein J. Org. Chem. 2022, 18, 1518–1523, doi:10.3762/bjoc.18.160

• Abstract The synthesis of phosphonate esters is a topic of interest for various fields, including the preparation of phosphonic acids to be employed as organic linkers for the construction of metal phosphonate materials. We report an alternative method that requires no solvent and involves a different

• three novel aryl diphosphonate esters which were subsequently transformed to phosphonic acids through silylation and hydrolysis. Keywords: arylphosphonic acids; cross-coupling reaction; phosphonate esters; transition-metal catalysis; Introduction Phosphonates and phosphonic acids are a very

• mmol), 4.0 g (12.2 mmol) or 3.0 g (7.4 mmol) of substrate. Once the phosphonate esters had been successfully obtained and characterized by 1H, 31P, 13C NMR and mass spectrometry (see experimental section and Supporting Information File 1), they were then subjected to silylation and subsequent

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

• noted that the borohydride-catalysed reductions generally proceed at lower reaction temperatures using 5 mol % NaBHEt3 [24]. Esters undergo stoichiometric reduction by H3B·SMe2 (see Supporting Information File 1) [32]; therefore, chemoselective nitrile hydroboration highlights the benefit of this

A one-pot electrochemical synthesis of 2-aminothiazoles from active methylene ketones and thioureas mediated by NH₄I

• Shang-Feng Yang,
• Pei Li,
• Zi-Lin Fang,
• Sen Liang,
• Hong-Yu Tian,
• Bao-Guo Sun,
• Kun Xu and
• Cheng-Chu Zeng

Beilstein J. Org. Chem. 2022, 18, 1249–1255, doi:10.3762/bjoc.18.130

• 3v in 23% yield. In addition to β-keto esters, other active methylene derivatives, including β-ketoamide, β-keto nitrile and β-keto sulfone were also suitable coupling partners with relatively lower yields (3w–y) and most of the starting materials were recovered. The method could also be applied to

Vicinal ketoesters – key intermediates in the total synthesis of natural products

• Marc Paul Beller and
• Ulrich Koert

Beilstein J. Org. Chem. 2022, 18, 1236–1248, doi:10.3762/bjoc.18.129

• Marc Paul Beller Ulrich Koert Fachbereich Chemie, Philipps-Universität Marburg, Hans-Meerwein-Straße 4, 35032 Marburg, Germany 10.3762/bjoc.18.129 Abstract This review summarizes examples for the application of vicinal ketoesters such as α-ketoesters, mesoxalic esters, and α,β-diketoesters as key

• -diketo esters 2 (Scheme 1). On the other hand, two carboxylic acid functionalities adjacent to a keto group result in mesoxalic diesters 3, or mesoxalic ester amides 4. The increased electrophilicity of the keto group and the high density of these complex functional groups make such structures attractive

• intramolecular aldol addition of ketones such as 7 (Scheme 2) [5]. Brønsted-acid catalysis leads via a transition state 8 to the aldol 9, while the use of chelating Lewis acids results via 10 in the epimeric aldol 11. This review is a collection of total syntheses of natural products where vicinal keto esters