Advancements in hydrochlorination of alkenes

• Daniel S. Müller

Beilstein J. Org. Chem. 2024, 20, 787–814, doi:10.3762/bjoc.20.72

• deuterium incorporation. However, when D2O-saturated nitromethane was used >95% D-incorporation took place. Hence the small (500–2000 ppm) content of water in commercially available nitromethane was at the origin of the hydrochlorination reaction (Scheme 16). As a result, the reaction of 104 with water

• the alkene to the corresponding chloride 123 (Scheme 18B). A deuterium label experiment demonstrated the rapid H/D exchange with the deuterated solvent (Scheme 18C). This reaction is synthetically interesting due to the significantly lower cost of AcOD-d4 compared to deuterium-enriched methanesulfonic

• the higher-substituted carbon atom to furnish intermediate species C. The irreversibility of the hydride addition and the regioselectivity thereof were supported by a deuterium labelling study with PhSiD3. The next steps involve homolytic cleavage of the cobalt–carbon bond to yield a carbon-centered

Palladium-catalyzed three-component radical-polar crossover carboamination of 1,3-dienes or allenes with diazo esters and amines

• Geng-Xin Liu,
• Xiao-Ting Jie,
• Ge-Jun Niu,
• Li-Sheng Yang,
• Xing-Lin Li,
• Jian Luo and
• Wen-Hao Hu

Beilstein J. Org. Chem. 2024, 20, 661–671, doi:10.3762/bjoc.20.59

• )2 and Xantphos (Scheme 4e). In addition, deuterium labeling experiments were conducted to investigate the H-source of this transformation (for more details, see Supporting Information Information File 1). The isotopic-labeling experiments suggested that both types of protons from the N–H bond of the

Ligand effects, solvent cooperation, and large kinetic solvent deuterium isotope effects in gold(I)-catalyzed intramolecular alkene hydroamination

• Ruichen Lan,
• Brock Yager,
• Yoonsun Jee,
• Cynthia S. Day and
• Amanda C. Jones

Beilstein J. Org. Chem. 2024, 20, 479–496, doi:10.3762/bjoc.20.43

• faster with more Lewis basic urea substrates, (3) mixed solvents are uniquely able to enhance rates, with protic methanol and DCM identified as the best combination, and (4) kinetic isotope effects are variable depending on the concentration of protons in solution with small deuterium KIE’s at low

• undetermined deactivation pathways. A similar 31P spectrum was obtained for the bisphoshine complex of Jackiephos, but in contrast no symmetrical singlet was observed (see Supporting Information File 1, Figure S23). Kinetic deuterium isotope effect Monodeuterated methanol (CH3OD) was tested as an additive on

• exchange (t < 5 minutes) reduced the N–CH2 doublet (δ 3.84 ppm in CD2Cl2) to a singlet, indicating high incorporation of deuterium into the substrate and corresponding in situ generation of CH3OH. Furthermore, both NH signals appear absent in the 1H NMR spectrum (δ 3.93/3.66). Comparing the rates of

Synthesis of the 3’-O-sulfated TF antigen with a TEG-N₃ linker for glycodendrimersomes preparation to study lectin binding

• Mark Reihill,
• Hanyue Ma,
• Dennis Bengtsson and
• Stefan Oscarson

Beilstein J. Org. Chem. 2024, 20, 173–180, doi:10.3762/bjoc.20.17

• , Reveleris® silica cartiges 40 μm, Büchi Labortechnik AG®) and Biotage® SP4 HPFC (UV 200–500 nm, Biotage® SNAP KP-Sil 50 μm irregular silica, Biotage® AB). Instrumentation 1H NMR and 13C NMR spectra were recorded on Varian Inova spectrometers at 25 °C in chloroform-d (CDCl3), methanol-d4 (CD3OD), deuterium

Using the phospha-Michael reaction for making phosphonium phenolate zwitterions

• Matthias R. Steiner,
• Max Schmallegger,
• Larissa Donner,
• Johann A. Hlina,
• Christoph Marschner,
• Judith Baumgartner and
• Christian Slugovc

Beilstein J. Org. Chem. 2024, 20, 41–51, doi:10.3762/bjoc.20.6

• of 0.7 equiv of deuterium in the α-position to the cyano group. However, this experiment does not allow for a conclusive distinction between the two postulated hydrogen transfer pathways as the phenolic hydrogen is quickly exchanged for deuterium under these conditions. The evenly strong Michael

Aromatic systems with two and three pyridine-2,6-dicarbazolyl-3,5-dicarbonitrile fragments as electron-transporting organic semiconductors exhibiting long-lived emissions

• Karolis Leitonas,
• Brigita Vigante,
• Dmytro Volyniuk,
• Audrius Bucinskas,
• Pavels Dimitrijevs,
• Sindija Lapcinska,
• Pavel Arsenyan and
• Juozas Vidas Grazulevicius

Beilstein J. Org. Chem. 2023, 19, 1867–1880, doi:10.3762/bjoc.19.139

• . Photoelectrical and charge-transporting properties The ionization potentials (IPPE) of thin films were obtained by photoelectron emission (PE) spectroscopy in air (Figure 7 and Table 1). To generate photoelectrons detectable by a counter electrode within the PE experiments, a low-power deuterium UV lamp was used

• , a negative voltage of 300 V was applied to the sample substrate, promoting electron emission from the surface. The photoelectron emission spectra were recorded using a Spectral Products© 30 W deep UV deuterium light source (180–400 nm) ASBN-D130-CM, coupled with the CM110 1/8 m monochromator, which

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

• . Product 25a is formed on addition of an iPr radical generated by I-atom transfer from iPrI to the Et radical, and is diagnostic for the formation of the latter in the reaction medium. Deuterium labeling experiments were then performed to substantiate the formation of a zinc enolate following radical

• addition (Scheme 7, bottom). Much to our surprise however, no deuterium incorporation is observed on quenching with ND4Cl/D2O the reaction between 8a and Et2Zn. By contrast, a significant deuterium incorporation is obtained when deuterated starting material (8a-d) is engaged. The combination of these two

• results is in agreement with the formation of a zinc enolate that undergoes proto- (or deuterio)demetalation with the N–H (or N–D) as proton (or deuterium) source. To further analyze the influence of the presence of an N–H function, we performed other reactions with N-benzyl enoate 10 which proved highly

Photoredox catalysis enabling decarboxylative radical cyclization of γ,γ-dimethylallyltryptophan (DMAT) derivatives: formal synthesis of 6,7-secoagroclavine

• Alessio Regni,
• Francesca Bartoccini and
• Giovanni Piersanti

Beilstein J. Org. Chem. 2023, 19, 918–927, doi:10.3762/bjoc.19.70

• tested the reaction in N,N-dimethylformamide-d7 (DMF-d7), which showed almost quantitative deuterium incorporation. While this result was surprising, further studies into this complex mechanism are ongoing and will be reported in due course. The synthetic potential and utility of this method was further

Intermediates and shunt products of massiliachelin biosynthesis in Massilia sp. NR 4-1

• Till Steinmetz,
• Blaise Kimbadi Lombe and
• Markus Nett

Beilstein J. Org. Chem. 2023, 19, 909–917, doi:10.3762/bjoc.19.69

• molecular formula of C15H18N2O2S (calcd. for C15H19N2O2S, 291.1173) and corresponds to eight degrees of unsaturation. In comparison to the other five molecules compound 6 must contain an even number of nitrogen atoms. The NMR data is comparable to compound 3, but includes a deuterium exchangeable proton

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

• containing bioactive molecules (Scheme 10). To attain enantioselectivity a chiral phosphine oxide (43)-ligated Ni–Al bimetallic catalyst was used that was critical in improving the reactivity and controlling the selectivity of the reaction. Further, based on deuterium labelling experiments, KIE studies, and

• of the alkene provides the intermediate 57 which on subsequent reductive elimination furnishes the C4-alkylated products 55. Based on the deuterium exchange experiment, the author suggested that the steps involved in the catalytic cycle from 56A to 57 are reversible in nature, which may activate the

• with various tethered alkenes, such as 1,1-disubstituted alkenes, styrene, diene, trisubstituted alkene and enamines. To get insights into the mechanism the authors conducted additional experiments including deuterium labelling reactions and proposed the mechanism depicted in Scheme 37b. Initially, the

Preparation of β-cyclodextrin-based dimers with selectively methylated rims and their use for solubilization of tetracene

• Konstantin Lebedinskiy,
• Volodymyr Lobaz and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2022, 18, 1596–1606, doi:10.3762/bjoc.18.170

• with Thermo Scientific Helios γ with wolfram and deuterium lamp. The wavelength range is 190–800 nm. 1H, 13C, and 2D NMR spectra were measured on Bruker Avance III HD 400 spectrometer. For TLC detection of CDs, we charred a TLC plate with 50% sulfuric acid water solution at 250 °C. UV measurements The

Synthesis of the biologically important dideuterium-labelled adenosine triphosphate analogue ApppI(d₂)

• Petri A. Turhanen

Beilstein J. Org. Chem. 2022, 18, 1466–1470, doi:10.3762/bjoc.18.153

• spectrometry. Keywords: ApppI; ATP; deuterium labelling; HPCCC; mevalonate pathway; NMR; synthesis; Introduction It has become clear and evident that phosphonate chemistry plays a crucial role in drug research and development [1][2][3][4]. There are several phosphonate-containing compounds under research or

• , which was finally confirmed after the tosylation step and purification of compound 4. The signal at 68 ppm with clear carbon–deuterium coupling (1JCD = 22.9 Hz) in the 13C NMR spectrum was unambiguous proof of the doubly deuterated product 4. ApppI(d2) was isolated using two different amounts of TBA

• deuterium-labelled highly important ATP analogue ApppI(d2) has been described in detail. This leaves the possibility to develop a quantitative MS method for the determination of ApppI in biological samples by using ApppI(d2) as internal standard. Samples of ApppI(d2) are available from the author upon

Characterization of a new fusicoccane-type diterpene synthase and an associated P450 enzyme

• Jia-Hua Huang,
• Jian-Ming Lv,
• Liang-Yan Xiao,
• Qian Xu,
• Fu-Long Lin,
• Gao-Qian Wang,
• Guo-Dong Chen,
• Sheng-Ying Qin,
• Dan Hu and
• Hao Gao

Beilstein J. Org. Chem. 2022, 18, 1396–1402, doi:10.3762/bjoc.18.144

• with or without addition of deuterated water (D2O). GC–MS analysis showed that when the reaction mixture was supplemented with D2O, the ion peak at m/z 273 was observed, indicating that exogenous deuterium was incorporated into 1 (Supporting Information File 1, Figure S19). This suggests that TadA

Cyclodextrin-based Schiff base pro-fragrances: Synthesis and release studies

• Attila Palágyi,
• Jindřich Jindřich,
• Juraj Dian and
• Sophie Fourmentin

Beilstein J. Org. Chem. 2022, 18, 1346–1354, doi:10.3762/bjoc.18.140

• phosphate buffer solutions of pH 1.08, 2.00, 3.00, 4.00, 5.00, 6.00, 7.00, 8.00, 9.00, 10.00 11.00, 12.00, and 12.80 were prepared (see Experimental section) using deuterium oxide instead of water to facilitate NMR spectroscopy experiments. Because of the low solubility of the pro-fragrance in water, it had

• , 7.00, 8.00, 9.00, 10.00 11.00, 12.00, and 12.80 were prepared by mixing 0.1 M solutions of H3PO4, KH2PO4, K2HPO4, and K3PO4 in ratios given in Table 2 using deuterium oxide instead of distilled water to facilitate NMR spectroscopy experiments. The exact pH value was tuned with titration with the help

Synthetic strategies for the preparation of γ-phostams: 1,2-azaphospholidine 2-oxides and 1,2-azaphospholine 2-oxides

• Jiaxi Xu

Beilstein J. Org. Chem. 2022, 18, 889–915, doi:10.3762/bjoc.18.90

• diphenyl-N-benzyl-N-methylphosphinamide (107) in the presence of sec-butyllithium followed by treatment with methanol, deuterium oxide, methyl iodide, and benzaldehyde, affording a series of cyclohexadiene-fused γ-phosphinolactams 108–112 in low regio- and stereoselectivies (Scheme 21) [46]. They further

Mechanistic studies of the solvolysis of alkanesulfonyl and arenesulfonyl halides

• Malcolm J. D’Souza and
• Dennis N. Kevill

Beilstein J. Org. Chem. 2022, 18, 120–132, doi:10.3762/bjoc.18.13

• considerable interest because, if the solvolysis is carried out in a deuterated solvent of type ROD in the presence of the conjugate base (OR−), it is found that there is deuterium uptake into the product. This is believed to be excellent evidence for the intermediacy of a sulfene formed by an elimination

• reaction promoted by the OR− species, with the sulfene then rapidly adding a solvent molecule to give a final product which is identical to the direct substitution product, except that, with the deuterated solvent, deuterium uptake can easily be detected [72][73][74] (Equation 4). This reaction was found

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

• contradicts the retainment of this hydrogen as reported by Croteau [9]. Further support for Akhila’s mechanism was provided by Ekramzadeh et al., who observed the uptake of two deuterium atoms at C3 and C12 in an incubation of FPP with PTS in deuterium oxide buffer that explain the reprotonations of the

• migration from C to D in Scheme 1A), and a Wagner–Meerwein rearrangement to G. The final steps are identical to those in Akhila’s mechanism (Scheme 2A). This work also reported on a labelling experiment with (2-2H)FPP that was enzymatically converted with PTS with incorporation of deuterium at C2 of 3

• reported, which was explained by an unusual intramolecular deuterium transfer. Herein, the deuteron is released from (2-2H)-J in the deprotonation step to 5 (or other enzyme products losing the same hydrogen in the terminal deprotonation). Deprotonation of (2-2H)-H was suggested to produce the unknown

Targeting active site residues and structural anchoring positions in terpene synthases

• Anwei Hou and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2021, 17, 2441–2449, doi:10.3762/bjoc.17.161

• to incorporation of deuterium into diastereotopic hydrogen positions that can be distinguished by NMR spectroscopy. Herein, the additional 13C-labellings allow for a sensitive analysis by HSQC spectroscopy (Figure 7). Conversion of both substrates (R)- and (S)-(1-13C,1-2H)GGPP with the SmTS1 A222M

• variant showed the incorporation of deuterium into only one of the diastereotopic hydrogens, indicating that (R)-9 is formed in an enantiomerically pure form, while for 8 from (R)-(1-13C,1-2H)GGPP an enantiomeric ratio of 1.00:0.68 (19% ee) and from (S)-(1-13C,1-2H)GGPP an enantiomeric ratio of 0.77:1.00

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

Methodologies for the synthesis of quaternary carbon centers via hydroalkylation of unactivated olefins: twenty years of advances

• Thiago S. Silva and
• Fernando Coelho

Beilstein J. Org. Chem. 2021, 17, 1565–1590, doi:10.3762/bjoc.17.112

• -substituted β-diketones 2a and 2b (61 and 70% yield, respectively). Notably, the unsaturated carbocycles expected from palladium β-hydride elimination were not observed, indicating that an oxidant was not required in the reaction medium to regenerate the Pd(II) species. Later, deuterium-labeling experiments

• because of the less enolizable character of these compounds. Deuterium incorporation at the olefin terminal carbon was obtained when the deuterated substrate α-13-d2 was subjected to the reaction conditions, indicating the participation of an internal proton source in the putative protodemetalation step

• cyclization of internal alkenes, such as 19c, were not generated by this methodology. Additional experiments in the presence of deuterated water corroborated the authors’ proposal of an involvement of gold catalysis in the enolization of the substrates (a hydrogen–deuterium [H–D] exchange in saturated

Icilio Guareschi and his amazing “1897 reaction”

• Gian Cesare Tron,
• Alberto Minassi,
• Giovanni Sorba,
• Mara Fausone and
• Giovanni Appendino

Beilstein J. Org. Chem. 2021, 17, 1335–1351, doi:10.3762/bjoc.17.93

• irreversible one-electron oxidation at 0.80 V, in accordance with the involvement of oxygen in the reaction. Remarkably, when the glutarimide was labeled with deuterium in position 3, the deuterium labeling was transferred to the hydrocarbon liberated in the reaction, showing that hydrogen abstraction was

α,γ-Dioxygenated amides via tandem Brook rearrangement/radical oxygenation reactions and their application to syntheses of γ-lactams

• Mikhail K. Klychnikov,
• Radek Pohl,
• Ivana Císařová and
• Ullrich Jahn

Beilstein J. Org. Chem. 2021, 17, 688–704, doi:10.3762/bjoc.17.58

• enolate formation from 8h,i with s-BuLi, a deuterium quenching experiment with D2O was performed. Analysis by 1H NMR spectroscopy revealed 87 and 91% deuterium incorporation, respectively, indicating that a deprotonation occurred, but the epoxide opening was hampered by the combination of a sterically

• diastereomeric ratios. To confirm enolate formation, lactam 12f was deprotonated by LDA at −78 °C and quenched with D2O, resulting in lactam 12f with 86% deuterium incorporation, but no change in the diastereomeric ratio. Spirolactams 12m,n were also subjected to epimerization (Scheme 4). The change of the

Identification of volatiles from six marine Celeribacter strains

• Anuj Kumar Chhalodia,
• Jan Rinkel,
• Dorota Konvalinkova,
• Jörn Petersen and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2021, 17, 420–430, doi:10.3762/bjoc.17.38

• -deuterated analogs by gas chromatography [61]). The base peak appears at m/z = 168, demonstrating its formation with participation of one deuterium from the S-methyl group. Analogous results were obtained by feeding of (methyl-13C)methionine, showing incorporation into 37 (74%, Figure S1C in Supporting

• 2.1L (deuterium lamp, 190–700 nm) and a YMC ChiralART Cellulose-SC column (5 μm; 250 × 20 mm) with a guard column of the same type (30 × 20 mm). The elution was performed with hexane/propanol 60:40 (isocratic) at a flow rate of 10 mL min−1 (36 bar). The UV–vis absorption was monitored at 275 nm

CF₃-substituted carbocations: underexploited intermediates with great potential in modern synthetic chemistry

• Anthony J. Fernandes,
• Armen Panossian,
• Bastien Michelet,
• Agnès Martin-Mingot,
• Frédéric R. Leroux and
• Sébastien Thibaudeau

Beilstein J. Org. Chem. 2021, 17, 343–378, doi:10.3762/bjoc.17.32

• free-energy relationship between the solvolysis rate and YOTs was obtained, suggesting an important solvent participation in these cases. Further investigations on 22f showed deuterium isotope effects in agreement with the transient formation of a carbenium ion. A solvent dependence of the kH/kD ratio

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

• spiropentane to form methylenecyclobutane occurred with the cleavage of the C1–C2 bond [94]. Dolbier then used deuterium labeling to study the analogous reaction of 1,1-difluorospiropentane (101) (Scheme 47) [95]. The cleavage of the C1–C2 bond that is proximal to the fluorine resulted in the formation of two