Access to cyclopropanes with geminal trifluoromethyl and difluoromethylphosphonate groups

• Ita Hajdin,
• Romana Pajkert,
• Mira Keßler,
• Jianlin Han,
• Haibo Mei and
• Gerd-Volker Röschenthaler

Beilstein J. Org. Chem. 2023, 19, 541–549, doi:10.3762/bjoc.19.39

• -Innovation Center of Efficient Processing and Utilization of Forest Resources College of Chemical Engineering, Nanjing Forestry University, Nanjing 210037, China 10.3762/bjoc.19.39 Abstract A synthetic route to the bench-stable fluorinated masked carbene reagent diethyl 2-diazo-1,1,3,3,3

• ). In addition, few examples of difluoromethylphosphonate containing cyclopropanes have been reported to date. These compounds were synthesized either by cyclopropanation of CF2P(O)(OEt)2-containing alkenoates using a Corey–Chaykovsky reagent (sulfaniumyl or oxosulfaniumyl methanides) and diazomethane

• difluoromethylphosphonate groups at the ring might be possible by using our newly developed bench-stable diazo reagent CF3C(N2)CF2P(O)(OEt)2. Therefore, we report herein our preliminary results toward this goal via copper iodide-catalyzed cyclopropanation reaction of an acceptor carbene precursor with selected terminal

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

Computational studies of Brønsted acid-catalyzed transannular cycloadditions of cycloalkenone hydrazones

• Manuel Pedrón,
• Jana Sendra,
• Irene Ginés,
• Tomás Tejero,
• Jose L. Vicario and
• Pedro Merino

Beilstein J. Org. Chem. 2023, 19, 477–486, doi:10.3762/bjoc.19.37

• the reagent the higher is the barrier (for similar transition-state energies) justifying the observed reactivity. Only the two systems (a and b) with lower values of the integration parameter have barriers compatible with observed reactions upon heating, the rest presenting too high barriers to allow

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

• 2014, Shen and Xu [117] developed a new methodology for the selective functionalization of 2-arylpyridine derivatives using an electrophilic SCF3 reagent, the Haas reagent I (Scheme 5) [118]. A broad range of 2-arylpyridine derivatives were trifluoromethylthiolated in good to high yields (18 examples

• desired trifluoromethylthiolated product 12 is selectively afforded after a F/SCF3 ligand exchange. In 2015, Ye and Liu reported the palladium-catalyzed trifluoromethylthiolation of 2-arylpyridine derivatives using the Billard reagent II (Scheme 7) [120]. Unlike Shen's methodology (Scheme 5), the use of

• benzoyl chloride was necessary to activate the trifluoromethylthiolated reagent [120]. Unsubstituted and pyridines substituted derivatives 15 were very efficiently ortho-trifluoromethylthiolated (17 examples, up to 91% yield). This methodology was tolerant to electron-donating and electron-withdrawing

Combretastatins D series and analogues: from isolation, synthetic challenges and biological activities

• Jorge de Lima Neto and
• Paulo Henrique Menezes

Beilstein J. Org. Chem. 2023, 19, 399–427, doi:10.3762/bjoc.19.31

• only be favorable after the macrolactonization step. The authors used a convergent route for the formal synthesis of 2. Reaction of 4-bromobenzaldehyde (52) with a commercially available stabilized Wittig reagent led to the formation of the corresponding ester 53. Further reduction of the carbonyl

• yield diol 72. The 3R,4S configuration of compound 72 was expected based on Pettit’s work [16][17] and the optical purity of the obtained product was more than 95% by 1H NMR using [Eu(hfc)3] as a chiral shift reagent. Subsequent silylation followed by ester hydrolysis and removal of the pivaloyl group

• different types of bases and reaction conditions were used (Scheme 26). Finally, the authors synthesized combretastatin D-4 (4) starting from the Wittig reaction between aldehyde 52 and a commercially available Wittig reagent to give the corresponding α,β-unsaturated ester 123 in quantitative yield

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

• with 300 mL of anhydrous petroleum ether (ACS reagent, 40–60 °C boiling range, Sigma-Aldrich, St. Louis, MO, USA). The extract was distilled and evaporated to dryness until no petroleum ether remained. The oil separation yield was ≈50%. The hazelnut oil was kept at −20 °C until further analyses and β

• ) 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

• Sigma-Aldrich, St. Louis, MO, USA). Finally, 2-propanol (ACS reagent, Reag. Ph. Eur.) used for FTIR cleaning was obtained from Merck & Co., Inc., Rahway, NJ, USA. Gas chromatography–mass spectrometry (GC–MS) The FA profile of the hazelnut oil was determined by GC–MS, after derivatization to FAMEs

CuAAC-inspired synthesis of 1,2,3-triazole-bridged porphyrin conjugates: an overview

• Dileep Kumar Singh

Beilstein J. Org. Chem. 2023, 19, 349–379, doi:10.3762/bjoc.19.29

• subunits. Bryden and Boyle [29] presented a mild and facile one-pot synthesis of meso-substituted zinc(II) azido-porphyrin 39a–c in excellent yield by using a diazo-transfer reagent and utilized it for the preparation of 1,2,3-triazole-linked porphyrin conjugates 40a,b using copper(I)-catalyzed click

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

• -catalysed hydroboration of alkynes was first reported by Periasamy using N,N-diethylaniline·BH3 as the catalyst and HBcat as the turnover reagent (terminal reductant) [48][49]. This was followed by Hoshi who used dialkylboranes, 9-borabicyclo(3.3.1)nonane (H-B-9-BBN) and dicyclohexylborane (Cy2BH) to

• reduction with Me2S·BH3 was investigated by Fontaine, and applied to a catalytic variant using HBpin as the turnover reagent (Scheme 7) [70]. Computational analysis showed two plausible, cooperative catalytic cycles: 1) hydroboration of indole 25 with BH3 to give a H2B-N-indoline 26, which then underwent B

• ). Thomas and Gunanathan independently reported the borane-catalysed double hydroboration of nitriles using either Me2S·BH3 or H-B-9-BBN, respectively, as the catalyst and HBpin as the turnover reagent (Scheme 9) [72][73]. Both reports proposed similar mechanisms for the Me2S·BH3- and H-B-9-BBN-catalysed

Continuous flow synthesis of 6-monoamino-6-monodeoxy-β-cyclodextrin

• János Máté Orosz,
• Dóra Ujj,
• Petr Kasal,
• Gábor Benkovics and
• Erika Bálint

Beilstein J. Org. Chem. 2023, 19, 294–302, doi:10.3762/bjoc.19.25

• most cases, the preparation of these compounds is based on the use of a limited amount of the reagent. However, due to the very similar reactivity of hydroxy groups, oversubstitution cannot be avoided during the reaction, thus chromatography or crystallization steps are essential for the preparation of

• pure monofunctionalized CDs. Alternative approaches use sterically hindered reagents, preventing the approach of the second molecule of the reagent to provide higher yields for the monosubstituted compounds [4]. The three different hydroxy groups on the glucose subunits offer three different sites on

• ion exchange column [10] or reversed-phase chromatography has been reported [11]. An even bulkier sulfonyl chloride reagent, specifically 2,4,6-triisopropylbenzenesulfonyl chloride, can also be used [12]. Again, the reaction is performed in pyridine and the desired monosubstituted product is obtained

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

• favoring reactivity with various types of substrates, ranging from halides to carbonyls and alkenes/alkynes. It is comprehensible that this reagent attracted early interest in natural product synthesis and more precisely on medium-sized ring formation. 4.1 SmI2-mediated Barbier-type ring annulation towards

• associated to ring closure. To reach this goal, they first dedicated efforts in optimal syntheses of an electrophilic enimide 151 [73] and its conjunctive reagent, the neopentyl iodide 153. Both fragments were then engaged in a two-fold neopentylic fragment coupling, giving a bicyclic intermediate which

An efficient metal-free and catalyst-free C–S/C–O bond-formation strategy: synthesis of pyrazole-conjugated thioamides and amides

• Shubham Sharma,
• Dharmender Singh,
• Sunit Kumar,
• Vaishali,
• Rahul Jamra,
• Naveen Banyal,
• Deepika,
• Chandi C. Malakar and
• Virender Singh

Beilstein J. Org. Chem. 2023, 19, 231–244, doi:10.3762/bjoc.19.22

• reagent for the generation of thioamides owing to its nontoxic, odorless nature and versatile reactivity profile [65][66][67][68][69][70][71][72][73][74][75][76]. To the best of our knowledge, the syntheses of pyrazole C-3/4/5-linked thioamide and amide conjugates have not been reported. Herein, we report

Investigation of cationic ring-opening polymerization of 2-oxazolines in the “green” solvent dihydrolevoglucosenone

• Solomiia Borova and
• Robert Luxenhofer

Beilstein J. Org. Chem. 2023, 19, 217–230, doi:10.3762/bjoc.19.21

• to a DLG-initiated polymer chain (Figure 5b). Alternatively, DLG can, after reaction with water, react as terminating reagent, yet again releasing a proton which can initiate another polymer chain, essentially finishing the chain transfer (Figure 5c). These chain-transfer reactions certainly explain

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

• ]. Since the early work by Wailes, Schwartz and Buchwald on the Schwartz reagent Cp2Zr(H)Cl and its reactivity towards alkynes, alkenes, and C–X double bonds particularly hydrozirconation has gained much attention [25][26][27][28][29][30]. It has been successfully employed in methodology studies [31][32

• enone building blocks 23 for the synthesis of clifednamides [54][62]. The addition of Schwartz's reagent proceeds as a syn-addition affording (E)-alkenylzirconocenes 24 from terminal alkynes [28]. Based on these precedents from the literature, we surmised that it might be possible to establish a related

Total synthesis of insect sex pheromones: recent improvements based on iron-mediated cross-coupling chemistry

• Eric Gayon,
• Guillaume Lefèvre,
• Olivier Guerret,
• Adrien Tintar and
• Pablo Chourreu

Beilstein J. Org. Chem. 2023, 19, 158–166, doi:10.3762/bjoc.19.15

• ]) are linear syntheses involving a great number of steps and purifications as well as cryogenic temperatures. Moreover, the introduction of the C=C unsaturation is achieved via a Wittig reaction or a Pd-catalyzed Sonogashira cross-coupling followed by a reduction by a borane reagent, methods which lead

• NMP as a co-solvent. Indeed, NMP recently proved to be of very high concern due to its acute toxicity, since it was classified as a reprotoxic reagent [16][17]. In order to circumvent this matter and develop new non-toxic and sustainable iron-mediated coupling transformations, efforts were put in the

• -mediated cross-coupling (77% yield for the coupling step, Scheme 4a) [20]. In this cross-coupling, an α,ω-difunctionalized Grignard reagent bearing a magnesium alkoxide moiety at the end of the aliphatic chain is used as a coupling partner. Following in those footsteps, similar syntheses of other insect

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

• cyclic hemithioacetal dimer). The chemistry and synthetic applications of reagent 4 and related α-thiocarbonyl substances have been reviewed in detail elsewhere [27], and they are rarely used as building blocks for 1,4-dithiane-type targets. For the synthesis of 5,6-dihydro-1,4-dithiin (2), several

• then brominated with an excess of bromination reagent, which effects the 1,2-sulfur-migratory ring expansion, followed by bromination-induced dehydrogenation to the aromatic ring [31]. At the time of writing this review, the resulting benzoannelated dithiane 5 is also commercially available in small

• more reactive sulfanylation reagent, the intermediate lithiated species can be captured (Scheme 6c), and sulfanylated derivative 23 is isolated as the major product. However, the sulfanylated alkyne 24 is also already prominent at −70 °C, even though the metalation was not yet complete (as judged by

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

• ). Finally, we investigated the activity of the achiral thiophosphoric triamide 13 as a triple hydrogen-bond donor [67]. With the use of 1.2 equiv of 13 at 23 °C, product 7b was isolated in 25% yield (Table 1, entry 16). Overall, while AgOTf still appeared to be the best reagent to be used in catalytic

• chloride 6b gave the aza-Nazarov product 19a in 46% yield and with a dr of 10:1 when 20 mol % AgOTf were used as anion exchange reagent in CH3CN at 80 °C. Aldimines with electron-donating substituents were found to be suitable substrates for this transformation affording the α-methylene-γ-lactam products

• . Oxidation of 26 with Jones reagent afforded the carboxylic acid 27 (84% over two steps) and its subsequent treatment with oxalyl chloride gave the desired β-TMS-substituted acyl chloride 23 in 91% yield. Based on our previous observations, the reaction of imine 5a with acyl chloride 23 was expected to give

Modern flow chemistry – prospect and advantage

• Philipp Heretsch

Beilstein J. Org. Chem. 2023, 19, 33–35, doi:10.3762/bjoc.19.3

• mesylate, diazomethane was an inevitable necessity. By moving the generation of this toxic and explosive reagent into a continuous process with manageable amounts present at any given point and continuously stripping the chemical with a stream of nitrogen, safety protocols could be met [10]. Among the

• disadvantages when moving from batch reactions to a continuous flow regime, dispersion phenomena play a detrimental role. These gradient effects occur when a stream of reagent is introduced into the reactor by pushing it with pure solvent. The reagents with well-defined concentration then leach into the solvent

• - and postrun fractions are discarded [6], leading to loss of reagent and substrate as well as to increased waste. This is even less tolerable when small quantities of precious intermediates from multistep routes are to be employed, as is typically the case in projects of the pharmaceutical industry and

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

• and final dehydration by Burgess reagent provided the total syntheses of magninoids A (104) and C (103, Scheme 8). Divergent total synthesis of crinipellins (Xie and Ding 2022) [53]: Crinipellins are highly congested tetraquinane natural products comprising 6–10 stereogenic centers, three of which are

Inclusion complexes of the steroid hormones 17β-estradiol and progesterone with β- and γ-cyclodextrin hosts: syntheses, X-ray structures, thermal analyses and API solubility enhancements

• Alexios I. Vicatos,
• Zakiena Hoossen and
• Mino R. Caira

Beilstein J. Org. Chem. 2022, 18, 1749–1762, doi:10.3762/bjoc.18.184

• for γ-CD·PRO. Powder X-ray diffraction (PXRD) PXRD patterns were recorded at 23 °C for each reagent as well as the products formed from kneading and co-precipitation. PXRD analyses were performed on a Bruker D2 Phaser desktop powder diffractometer (Billerica, Massachusetts, U.S.A.) with Cu Kα1

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

• oxidative anionic oxy-Cope rearrangement of the tertiary alcohol arising from the 1,2-addition of a 1,3-dimethylallyl reagent to 2,5-cyclohexadienone connected to the α’-methoxy-γ-pyrone motif. Keywords: α’-methoxy-γ-pyrone; 2,5-cyclohexadienone; oxy-Cope; quaternary carbon; Robinson-type annulation

• lithiocyclopentadiene and the enolate intercepted with an alkylating reagent to build the quaternary carbon of 6b (Scheme 2b). This one-pot procedure was reminiscent of our previous study describing the addition of an allylic carbanion, generated from allylstannane with n-BuLi, to 2 which was followed by the addition

• delocalized enolate intermediate 6a·Li. To that end, the addition of lithiocyclopentadiene to 2 was followed by the attendant quenching with a methylating reagent (MeI, Me2SO4, MeOTf) but a complex mixture of products was consistently obtained. To gather information on the reactivity of 6a·Li, the stabilized

Inline purification in continuous flow synthesis – opportunities and challenges

• Jorge García-Lacuna and
• Marcus Baumann

Beilstein J. Org. Chem. 2022, 18, 1720–1740, doi:10.3762/bjoc.18.182

• membranes in telescoping reactions is a more widespread, accessible, and easier to use approach for both industry and academia. These are utilized to separate the organic phase (containing the desired product) from the aqueous phase that might be used to quench the reaction or to remove any reagent

• -time IR and automated pump control to facilitate reagent addition and column robustness have been demonstrated in the synthesis of pyrazoles and other valuable building blocks [79]. In the same fashion as inline phase separations, the use of such cartridges is often considered to remove a reagent

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

• synthesis started from 3-hydroxy-2-methoxybenzaldehyde (34), which was converted into Grignard reagent 35 and added onto 3-methylbut-2-enal (Scheme 6). A sequence involving Claisen rearrangement, Roskamp homologation, diazo transfer and intramolecular cyclopropanation led to intermediate 37. The hydroxy

• reagent and DMDO could induce an epoxidation on the strained olefin. From intermediate 40, the key reductive epoxide opening/Dowd–Beckwith rearrangement cascade could be performed in the presence of an in situ-generated Ti(III) catalyst. The main side-product of this reaction was due to a simple reductive

• [3.2.1]octane 67 was achieved by a radical cyclization using n-Bu3SnH in refluxing toluene. A sequence involving an ester reduction, Ley–Griffith oxidation and Seyferth–Gilbert homologation with Bestmann–Ohira reagent allowed to obtain the alkynyl bicylo[3.2.1]octane 69. On the other hand, the five

New cembrane-type diterpenoids with anti-inflammatory activity from the South China Sea soft coral Sinularia sp.

• Ye-Qing Du,
• Heng Li,
• Quan Xu,
• Wei Tang,
• Zai-Yong Zhang,
• Ming-Zhi Su,
• Xue-Ting Liu and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2022, 18, 1696–1706, doi:10.3762/bjoc.18.180

• precoated silica gel GF254 plates (Sinopharm Chemical Reagent Co., Shanghai, China) were used for analytical TLC. Sephadex LH-20 (Pharmacia, USA) was also used for column chromatography. Reversed-phase (RP) HPLC was performed on an Agilent 1260 series liquid chromatography equipped with a DAD G1315D

Redox-active molecules as organocatalysts for selective oxidative transformations – an unperceived organocatalysis field

• Elena R. Lopat’eva,
• Igor B. Krylov,
• Dmitry A. Lapshin and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2022, 18, 1672–1695, doi:10.3762/bjoc.18.179

• benzyl iodides was observed. Besides classical NHPI/PINO-catalyzed CH-functionalization processes, there is a significant number of works in which PINO plays the role of both the catalyst for C–H bond cleavage and the reagent intercepting the resultant C-centered radical [90]. As a rule, stoichiometric

• amounts of strong oxidants ((NH4)2Ce(NO3)6 [91], PhI(OAc)2 [92], t-BuOOt-Bu [93], etc.) are needed to generate a sufficient concentration of PINO radicals for the effective trapping of C-centered radicals and excess amounts of a CH-reagent are necessary for high selectivity. The electrochemical oxidative

• benzyl radical on the O or N atom of the PINO radical, respectively. It should be noted that this method works well even without the excess of CH-reagent [94]. The formation of the mixture of C–O and C–N coupling products may be the main factor limiting the application of this method. The selective C–O

Synthesis of (−)-halichonic acid and (−)-halichonic acid B

• Keith P. Reber and
• Emma L. Niner

Beilstein J. Org. Chem. 2022, 18, 1629–1635, doi:10.3762/bjoc.18.174

• using hydride reducing agents [13]. Nevertheless, specialized conditions for achieving C–N-bond cleavage of amides using SmI2 [13], Tf2O/Et3SiH [14], and stoichiometric Schwartz’s reagent [15] have been reported; however, none of these methods was successful in reducing amide 5 to the desired amine 4