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

Glycoscience@Synchrotron: Synchrotron radiation applied to structural glycoscience

• Serge Pérez and
• Daniele de Sanctis

Beilstein J. Org. Chem. 2017, 13, 1145–1167, doi:10.3762/bjoc.13.114

• allomorphism, the elucidation of the structure of cellulose I, awaited the mature developments of large scale facilities of synchroton and neutron sources, and the mastering of deuteration methods of the intra-crystalline regions of the native cellulose samples without altering the overall structural integrity

Aggregation behaviour of a single-chain, phenylene-modified bolalipid and its miscibility with classical phospholipids

• Simon Drescher,
• Vasil M. Garamus,
• Christopher J. Garvey,
• Annette Meister and
• Alfred Blume

Beilstein J. Org. Chem. 2017, 13, 995–1007, doi:10.3762/bjoc.13.99

• ) was followed. The deuteration of alkyl chains in phospholipids usually causes a shift of the main transition by about 5 K to lower temperatures, as shown by Petersen et al. [57]. At T = 10.9 °C, the frequency of νs(CH2) is at 2850.8 cm−1, which is comparable to the frequency of νs(CH2) of the pure PC

New approach toward the synthesis of deuterated pyrazolo[1,5-a]pyridines and 1,2,4-triazolo[1,5-a]pyridines

• Aleksey Yu. Vorob’ev,
• Vyacheslav I. Supranovich,
• Gennady I. Borodkin and
• Vyacheslav G. Shubin

Beilstein J. Org. Chem. 2017, 13, 800–805, doi:10.3762/bjoc.13.80

• and a high degree of deuterium incorporation were achieved. The procedure was applied for several 4-R-1-aminopyridinium cations (R = H, Me, OMe). Keywords: deuteration; 1,3-dipolar cycloaddition; pyrazolo[1,5-a]pyridine; 1,2,4-triazolo[1,5-a]pyridine; Introduction Isotopically labeled compounds find

• years deuteration became also an efficient tool in drug design [6]. Pyrazolo[1,5-a]pyridine and 1,2,4-triazolo[1,5-a]pyridine scaffolds attracted significant attention to the medicinal chemistry community during the past decade. For example, pyrazolo[1,5-a]pyridine derivatives were used in the design of

• dimethyl acetylenedicarboxylate (2a, DMAD) in MeCN D-labeled pyrazolo[1,5-a]pyridine 3 was obtained in 70% yield (Table 1). The deuteration at room temperature even for 24 h led to a significantly lower degree of deuteration (DD, 20%). Salt 1b gave the corresponding 5-CD3-7-D-pyrazolopyridine 5 along with

Cp₂TiCl/D₂O/Mn, a formidable reagent for the deuteration of organic compounds

• Antonio Rosales and
• Ignacio Rodríguez-García

Beilstein J. Org. Chem. 2016, 12, 1585–1589, doi:10.3762/bjoc.12.154

• experimental conditions and with great economic advantages. Keywords: deuteration; deuterium atom transfer; radical and/or organometallic chemistry; titanocene; Introduction Deuterium is a stable isotope of hydrogen with 0.015% natural abundance broadly used in organic chemistry, pharmacology, organometallic

• develop efficient procedures for the preparation of deuterated compounds, several methodologies of deuteration have been reported [5]. One of the first procedures reported was the acid- or base-catalyzed exchange of enolizable protons for deuterium. However, in order to achieve high isotopic purities

• for deuteration [7]. The principal disadvantage of the use of reducing agents labelled with deuterium is the high cost of these reagents and the handling of highly flammable substances. The use of palladium metal and D2O is a useful and efficient methodology for H/D exchange in aliphatic and benzylic

Tandem processes promoted by a hydrogen shift in 6-arylfulvenes bearing acetalic units at ortho position: a combined experimental and computational study

• Mateo Alajarin,
• Marta Marin-Luna,
• Pilar Sanchez-Andrada and
• Angel Vidal

Beilstein J. Org. Chem. 2016, 12, 260–270, doi:10.3762/bjoc.12.28

• monodeuterated acetal-fulvene 20 bearing the deuterium atom at C4. This species converted into a 2:1 mixture of the monodeuterated regioisomers 21 and 22 as the only isolated reaction products (Scheme 6). In both compounds, the deuteration percentage at their respective C4 and C9 positions was determined, by 1H

Pyridine-promoted dediazoniation of aryldiazonium tetrafluoroborates: Application to the synthesis of SF₅-substituted phenylboronic esters and iodobenzenes

• George Iakobson,
• Junyi Du,
• Alexandra M. Z. Slawin and
• Petr Beier

Beilstein J. Org. Chem. 2015, 11, 1494–1502, doi:10.3762/bjoc.11.162

• tributyltin hydride or THF was tested and THF proved to be a more efficient hydrogen atom donor. The addition of excess pyridine to MeCN/THF solution of diazonium tetrafluoroborates 3a or 3b led to an efficient hydrodediazoniation and the formation of (pentafluorosulfanyl)benzene (6). Deuteration experiments

Why base-catalyzed isomerization of N-propargyl amides yields mostly allenamides rather than ynamides

• Armando Navarro-Vázquez

Beilstein J. Org. Chem. 2015, 11, 1441–1446, doi:10.3762/bjoc.11.156

• ). Nonetheless, the above results suggest that varying the reaction conditions (perhaps solvent polarity) could eventually lead to the observation of the allenimides. NMR deuteration studies could be of help to experimentally eliminate possible kinetic effects in the observed lack of reactivity [19]. Having

Superoxide chemistry revisited: synthesis of tetrachloro-substituted methylenenortricyclenes

• Basavaraj M. Budanur and
• Faiz Ahmed Khan

Beilstein J. Org. Chem. 2014, 10, 2531–2538, doi:10.3762/bjoc.10.264

• . Absence of the peak at δ 4.26 (singlet) in 1H NMR suggest the incorporation of deuterium and a triplet at δ 71.0, arising from C–D coupling, instead of sharp peak at δ 71.3 in 13C NMR further confirmed the deuteration at the chlorine-attached carbon atom in 5n (Scheme 3). Further, in order to understand