Development and mechanistic studies of calcium–BINOL phosphate-catalyzed hydrocyanation of hydrazones

• Carola Tortora,
• Christian A. Fischer,
• Sascha Kohlbauer,
• Alexandru Zamfir,
• Gerd M. Ballmann,
• Jürgen Pahl,
• Sjoerd Harder and
• Svetlana B. Tsogoeva

Beilstein J. Org. Chem. 2025, 21, 755–765, doi:10.3762/bjoc.21.59

• rearrangement under mild conditions [6], and the Nazarov-type electrocyclization of alkenyl aryl carbinols [7]. Exploiting the ease with which calcium forms hydrides, hydrogenation of aldimines, transfer hydrogenation of alkenes, and even deuteration of benzene by an SNAr mechanism, have been recently achieved

Synthesis of tricarbonylated propargylamine and conversion to 2,5-disubstituted oxazole-4-carboxylates

• Kento Iwai,
• Akari Hikasa,
• Kotaro Yoshioka,
• Shinki Tani,
• Kazuto Umezu and
• Nagatoshi Nishiwaki

Beilstein J. Org. Chem. 2024, 20, 2827–2833, doi:10.3762/bjoc.20.238

• experiments were conducted in the same way. In the deuteration experiment, the reaction was quenched with deuterium oxide (0.2 mL) instead of acetic acid. The decrease of the integral of the signal of the benzyl proton was confirmed by 1H NMR analysis. Synthesis of polyfunctionalized methane derivatives

A review of recent advances in electrochemical and photoelectrochemical late-stage functionalization classified by anodic oxidation, cathodic reduction, and paired electrolysis

• Nian Li,
• Ruzal Sitdikov,
• Ajit Prabhakar Kale,
• Joost Steverlynck,
• Bo Li and
• Magnus Rueping

Beilstein J. Org. Chem. 2024, 20, 2500–2566, doi:10.3762/bjoc.20.214

Facile preparation of fluorine-containing 2,3-epoxypropanoates and their epoxy ring-opening reactions with various nucleophiles

• Yutaro Miyashita,
• Sae Someya,
• Tomoko Kawasaki-Takasuka,
• Tomohiro Agou and
• Takashi Yamazaki

Beilstein J. Org. Chem. 2024, 20, 2421–2433, doi:10.3762/bjoc.20.206

• corresponding intermediate by D2O proved that no deuteration occurred. This result clearly indicated that hydride was released from the t-Bu group of the Cu(III) species formed after the nucleophilic attack of the epoxy ring. In our case, since the strongly electron-withdrawing CF3 group would render the rate

Deuterated reagents in multicomponent reactions to afford deuterium-labeled products

• Kevin Schofield,
• Shayna Maddern,
• Yueteng Zhang,
• Grace E. Mastin,
• Rachel Knight,
• Wei Wang,
• James Galligan and
• Christopher Hulme

Beilstein J. Org. Chem. 2024, 20, 2270–2279, doi:10.3762/bjoc.20.195

• deuteration of formamide product while increasing formamide equivalents increases the yield at the cost of deuterated %. Excess reaction time increases side product formation and thermal degradation of the aldehyde starting material. To combat this, microwave irradiation was employed which dramatically

• increased the overall yield of the reaction (Table 1, entry 5). In summary, minimal formamide (1–2 equiv), excess [D2]-formic acid, and heating to 170 °C in a microwave reactor for 5 minutes is expected to give excellent yields in good deuteration %. A tentative mechanism to [D3]-formamides is shown in

• selective deuteration of often metabolically soft benzylic C–H sites. Lastly and most importantly, preliminary surrogate metabolic stability studies on site selective [D1]-DHPs suggest these novel deuterated analogs may afford increased exposure in an in vivo setting. The methodology is likely to have wide

Multicomponent syntheses of pyrazoles via (3 + 2)-cyclocondensation and (3 + 2)-cycloaddition key steps

• Ignaz Betcke,
• Alissa C. Götzinger,
• Maryna M. Kornet and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2024, 20, 2024–2077, doi:10.3762/bjoc.20.178

• with electrophiles, such as deuteration or electrophilic chlorination using N-chlorosuccinimide, in this consecutive three-component synthesis to give persubstituted pyrazoles 165 (Scheme 55) [162]. (3 + 2)-Cycloaddition – C2 building blocks as substrates 1,3-Dipolar cycloadditions are important

1,2-Difluoroethylene (HFO-1132): synthesis and chemistry

• Liubov V. Sokolenko,
• Taras M. Sokolenko and
• Yurii L. Yagupolskii

Beilstein J. Org. Chem. 2024, 20, 1955–1966, doi:10.3762/bjoc.20.171

• cis-isomer decreases, i.e., the cis-isomer of 1,2-difluoroethylene is thermodynamically favored [47]. Deuteration The stereospecific reaction of (E/Z)-1,2-difluoroethylene with a 1–2 M solution of NaOD in D2O (90–120 °C, 2 d) led to the formation of CDF=CDF with high isotopic purity (Scheme 8) [76][77

• -Difluoroethylene synthesis from perfluoropropyl vinyl ether. Deuteration reaction of 1,2-difluoroethylene. Halogen addition to 1,2-difluoroethylene. Hypohalite addition to 1,2-difluoroethylene. N-Bromobis(trifluoromethyl)amine addition to 1,2-difluoroethylene. N-Chloroimidobis(sulfonyl fluoride) addition to 1,2

Electrocatalytic hydrogenation of cyanoarenes, nitroarenes, quinolines, and pyridines under mild conditions with a proton-exchange membrane reactor

• Koichi Mitsudo,
• Atsushi Osaki,
• Haruka Inoue,
• Eisuke Sato,
• Naoki Shida,
• Mahito Atobe and
• Seiji Suga

Beilstein J. Org. Chem. 2024, 20, 1560–1571, doi:10.3762/bjoc.20.139

• semihydrogenation of alkynes to form Z-alkenes using a PEM reactor [31]. The Pd/C catalyst was essential for the reaction. They recently found that a PEM reactor with a Rh/C catalyst was effective for the stereoselective reduction of cyclic ketones [40]. Nagaki et al. reported the electrochemical deuteration of

Cathodic generation of reactive (phenylthio)difluoromethyl species and its reactions: mechanistic aspects and synthetic applications

• Sadanobu Iwase,
• Shinsuke Inagi and
• Toshio Fuchigami

Beilstein J. Org. Chem. 2022, 18, 872–880, doi:10.3762/bjoc.18.88

• resulted in much lower product yields. The detailed reaction mechanism was clarified based on the cathodic reduction of 1 in the presence of deuterated acetonitrile, CD3CN. Keywords: bis(phenylthio)difluoromethane; cathodic reduction; deuteration; o-phthalonitrile mediator; (phenylthio)difluoromethylation

• determine the hydrogen source of the products 2 and 4, indirect cathodic reduction of 1 was carried out in deuterated acetonitrile, CD3CN (Scheme 9). As shown in Scheme 9, deuterated products 2 and 4 were formed. In the case of product 2, almost complete deuteration was observed, which clearly indicates

The enzyme mechanism of patchoulol synthase

• Houchao Xu,
• Bernd Goldfuss,
• Gregor Schnakenburg and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2022, 18, 13–24, doi:10.3762/bjoc.18.2

• in the structure of 3 with the absolute configuration as shown in Figure 2. The absolute configuration of 3 was furthermore independently confirmed through a stereoselective deuteration strategy (Scheme 4; all labelling experiments of this study are summarised in Supporting Information File 1, Table

• the target compound (2-2H)FPP with some (2,15-2H2)FPP, seems to be the more likely explanation for the deuteration of 3 at C15 observed by Faraldos et al. [14]. This can also much better explain the deuterium content observed by GC–MS in the PTS products that were proposed to transfer deuterium to 3

Copper-catalyzed monoselective C–H amination of ferrocenes with alkylamines

• Zhen-Sheng Jia,
• Qiang Yue,
• Ya Li,
• Xue-Tao Xu,
• Kun Zhang and
• Bing-Feng Shi

Beilstein J. Org. Chem. 2021, 17, 2488–2495, doi:10.3762/bjoc.17.165

• in 50% yield (Scheme 4b, 1.32 g). For synthetic utility, the directing group was conveniently removed by refluxing with KOH in EtOH and the benzyl-protected ester 5 was obtained in 75% yield. We also conducted several deuteration experiments to shed a preliminary insight into the mechanism. No H/D

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

• co-workers described the deuteration of several pharmaceuticals via an Fe-catalyzed C–H activation protocol (Scheme 29A and B) [161]. The site selectivity of the bulky iron catalyst was orthogonal to conventional iridium catalysts used in deuterium labelling experiments, allowing the

• functionalization of complementary positions in several molecules of medicinal importance. Using molecular deuterium gas, the deuterium exchange occurred at different positions in small molecules in different proportions and satisfactory yields. Late-stage site-selective deuteration of pharmaceuticals like

Recent advances in palladium-catalysed asymmetric 1,4–additions of arylboronic acids to conjugated enones and chromones

• Jan Bartáček,
• Jan Svoboda,
• Martin Kocúrik,
• Jaroslav Pochobradský,
• Alexander Čegan,
• Miloš Sedlák and
• Jiří Váňa

Beilstein J. Org. Chem. 2021, 17, 1048–1085, doi:10.3762/bjoc.17.84

• decrease of the enantioselectivity from 93% ee to 91% ee (entries 1 and 2, Table 17). Additional deuteration experiments demonstrated that water acted as a proton source in the catalytic cycle [48]. Furthermore, only a very low conversion was achieved without water, especially in large-scale experiments

A new method for the synthesis of diamantane by hydroisomerization of binor-S on treatment with sulfuric acid

• Rishat I. Aminov and
• Ravil I. Khusnutdinov

Beilstein J. Org. Chem. 2020, 16, 2534–2539, doi:10.3762/bjoc.16.205

• (2) acts as the hydrogen source for the isomer C14H17D3, 1-D3. Our attempt to carry out the deuteration of diamantane (1) with D2SO4 in carbon disulfide for 7 h at 20 °C was unsuccessful. Evidently, the deuterium exchange, resulting in the formation of diamantanes 1-D7 and 1-D8 containing 7 and 8

NMR Spectroscopy of supramolecular chemistry on protein surfaces

• Peter Bayer,
• Anja Matena and
• Christine Beuck

Beilstein J. Org. Chem. 2020, 16, 2505–2522, doi:10.3762/bjoc.16.203

• for many proteins, however the tolerance for co-solvents varies widely. For larger proteins (>25–30 kDa), the transverse relaxation optimized spectroscopy (TROSY) versions of the 1H,15N-HSQC [93] can increase the signal-to-noise ratio of the NMR signals. Deuteration (C–D instead of C–H, partial or

Recent developments in enantioselective photocatalysis

• Callum Prentice,
• James Morrisson,
• Andrew D. Smith and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2020, 16, 2363–2441, doi:10.3762/bjoc.16.197

• ). It is notable that pyridyl ketones do not perform well in this reaction (1 example, 70:30 er). A further extension of this methodology includes the deuteration of 128 and alkyl halides 132 using D2O to afford 133 (18 examples, up to >99:1 er) and 134 (34 examples, up to 98:2 er), respectively (Scheme

One-pot and metal-free synthesis of 3-arylated-4-nitrophenols via polyfunctionalized cyclohexanones from β-nitrostyrenes

• Haruyasu Asahara,
• Minami Hiraishi and
• Nagatoshi Nishiwaki

Beilstein J. Org. Chem. 2020, 16, 1830–1836, doi:10.3762/bjoc.16.150

• structure of nitroalkenes 1b and 1d. Synthetic scheme of the 3-arylated-4-nitrophenols 5. Conversion from 3a to 4a and one-pot synthesis of 4a. Deuteration of cyclohexanone 4a. A plausible mechanism for the formation of 5a. Optimization of the reaction conditions for the Diels–Alder reaction.a Aromatization

Facile synthesis of 7-alkyl-1,2,3,4-tetrahydro-1,8-naphthyridines as arginine mimetics using a Horner–Wadsworth–Emmons-based approach

• Rhys A. Lippa,
• John A. Murphy and
• Tim N. Barrett

Beilstein J. Org. Chem. 2020, 16, 1617–1626, doi:10.3762/bjoc.16.134

• deuteration. Conclusion In conclusion, a novel method for the assembly of 7-alkyl-1,2,3,4-tetrahydro-1,8-naphthyridine-based arginine mimetics was developed. The synthesis of phosphonate 7 was optimised, with a sequential diphosphorylation process using commercially available starting materials affording the

Photocatalysis with organic dyes: facile access to reactive intermediates for synthesis

• Stephanie G. E. Amos,
• Marion Garreau,
• Luca Buzzetti and
• Jerome Waser

Beilstein J. Org. Chem. 2020, 16, 1163–1187, doi:10.3762/bjoc.16.103

• excited state of the photocatalyst engages in SET or energy transfer events with suitable cocatalysts for hydrogen shuttling, such as thiols. This results in the formation of active species that promote the H abstraction from the substrates. MacMillan exploited this strategy for the deuteration and

Synthesis of 3-alkenylindoles through regioselective C–H alkenylation of indoles by a ruthenium nanocatalyst

• Abhijit Paul,
• Debnath Chatterjee,
• Srirupa Banerjee and
• Somnath Yadav

Beilstein J. Org. Chem. 2020, 16, 140–148, doi:10.3762/bjoc.16.16

• , there are few reports. For example, the supported Ru-catalysed regiospecific C(sp2)–H arylation of benzo[h]quinolines and the addition of vinylsilanes to the C–H bonds of α-tetralones were reported by Inoue and co-workers [41][42]. Pieters et al. reported the Ru nanoparticle-catalysed C–H deuteration

• . for C–H deuteration reactions occurring α to the nitrogen atom [43][44]. The synergistic effect of the surface oxides in promoting the efficiency of zerovalent Ru nanoparticles is also documented through experimental as well as computational results in a study of the C–H selenylation of indoles where

Functionalization of 4-bromobenzo[c][2,7]naphthyridine via regioselective direct ring metalation. A novel approach to analogues of pyridoacridine alkaloids

• Benedikt C. Melzer,
• Alois Plodek and
• Franz Bracher

Beilstein J. Org. Chem. 2019, 15, 2304–2310, doi:10.3762/bjoc.15.222

• the iodine quenching product 13), as D2O quenching of metalated arenes obtained with amide bases do not necessarily give complete deuteration. A hydrogen-bonded complex between the metalated species and TMP is postulated to undergo partial H/D exchange reactions with D2O before quenching takes place

Generation of 1,2-oxathiolium ions from (arysulfonyl)- and (arylsulfinyl)allenes in Brønsted acids. NMR and DFT study of these cations and their reactions

• Stanislav V. Lozovskiy,
• Alexander Yu. Ivanov,
• Olesya V. Khoroshilova and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2018, 14, 2897–2906, doi:10.3762/bjoc.14.268

• , including 1H, 13C, DEPT, COSY, and HSQC spectra (see Supporting Information File 1), demonstrated unambiguously that compounds 1a,b and 2a–h underwent cyclization into the corresponding ions Aa,b and Ba–h via protonation (deuteration for D2SO4, Bd-d) of the central carbon allenic triad followed by

[3 + 2]-Cycloaddition reaction of sydnones with alkynes

• Veronika Hladíková,
• Jiří Váňa and
• Jiří Hanusek

Beilstein J. Org. Chem. 2018, 14, 1317–1348, doi:10.3762/bjoc.14.113

• formation followed by Cu–N dissociation and C–N bond formation. Experiments performed in t-BuOD/D2O [119] also showed almost exclusive (>98:2) deuteration of position 3 in the final pyrazole ring. This finding supports the idea of Cu(I)-acetylide addition to give 3-metalated pyrazole (Cu-pyrazolide) that is

One hundred years of benzotropone chemistry

• Arif Dastan,
• Haydar Kilic and
• Nurullah Saracoglu

Beilstein J. Org. Chem. 2018, 14, 1120–1180, doi:10.3762/bjoc.14.98

• ) and monosubstituted tetrahydro-7H-benzo[7]annulenone, St-Jacques' group benefited extensively from the use of dynamic nuclear magnetic resonance (DNMR) techniques [126][127]. A catalytic deuterogenation of 4,5-benzotropone (11) followed by deuteration led to deuterated 5,6,8,9-tetrahydro-7H-benzo[7

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation. Part 1: Use of CF₃SO₂Na

• Hélène Guyon,
• Hélène Chachignon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2764–2799, doi:10.3762/bjoc.13.272

• were compatible with the reaction conditions. A series of control experiments that included the inhibition of the reaction in the presence of TEMPO, deuteration and isotope effect experiments were carried out and led the authors to propose the single-electron transfer mechanism presented in Scheme 44