Oxime radicals: generation, properties and application in organic synthesis

• Igor B. Krylov,
• Stanislav A. Paveliev,
• Alexander S. Budnikov and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2020, 16, 1234–1276, doi:10.3762/bjoc.16.107

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

• trapping of the ensuing C(sp3) radical with the deuterated or tritiated thiol results in the incorporation of deuterium or tritium in multiple positions within the product 9.3. C(sp2) radicals Aryl radicals Considering the importance of arylation reactions in organic synthesis [61], aryl radicals are

Aldehydes as powerful initiators for photochemical transformations

• Maria A. Theodoropoulou,
• Nikolaos F. Nikitas and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2020, 16, 833–857, doi:10.3762/bjoc.16.76

• (116) decomposition, initiating the radical chain reaction. Other substituted benzaldehydes were also investigated. Finally, experiments employing benzaldehyde-α-d1, showing no hydrogen/deuterium exchange, indicated no formation of a benzoyl radical (10) in this reaction. In 2019, Hashmi and co-workers

Current understanding and biotechnological application of the bacterial diterpene synthase CotB2

• Ronja Driller,
• Daniel Garbe,
• Norbert Mehlmer,
• Monika Fuchs,
• Keren Raz,
• Dan Thomas Major,
• Thomas Brück and
• Bernhard Loll

Beilstein J. Org. Chem. 2019, 15, 2355–2368, doi:10.3762/bjoc.15.228

• rearrangement. Hong and Tantillo performed the first theoretical study of the reaction mechanism in CotB2 via gas phase density functional theory (DFT) calculations [33]. Simultaneously, Sato et al. also studied the CotB2 reaction mechanism in the gas phase using DFT, combined with experimental deuterium

• deuterium labeling [33][34][35], to form the carbocation located at position C8 of dolabellatrienyl (B). By ring closure and formation of a novel C–C bond the tricyclic 5–8–5 ring system (C) is established. F107, F149, and the pyrophosphate moiety stabilize the carbocation at position C3 (Scheme 2 and

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

• period. In recovered starting material 9d-D deuterium incorporation (about 60% calculated from the NMR resonance of 5-H) was detected exclusively at C-5, clearly indicating the regioselectivity of this metalation (Scheme 2). Probably, the metalation rate is even higher than 60% (compare the 71% yield for

Analysis of sesquiterpene hydrocarbons in grape berry exocarp (Vitis vinifera L.) using in vivo-labeling and comprehensive two-dimensional gas chromatography–mass spectrometry (GC×GC–MS)

• Philipp P. Könen and
• Matthias Wüst

Beilstein J. Org. Chem. 2019, 15, 1945–1961, doi:10.3762/bjoc.15.190

• -copaene, β-copaene, α-cubebene, β-cubebene and the bicyclic δ-cadinene were biosynthesized via (S)-(−)-germacrene D rather than via (R)-(+)-germacrene D as intermediate. Keywords: biosynthesis; deuterium labeling; germacrene; HS-SPME; terpenes; TOF–MS; Introduction The aroma profile of grape berries at

• , clone 1Gm, isolated exocarp) showed the presence of several hundred components. Twenty-five of these compounds were unequivocally identified as sesquiterpene hydrocarbons (Figure 1). Deuterium-labeled compounds eluted earlier than the unlabeled analogues (Figure 3). This is due to the inverse isotope

• effect described by Matucha et al. which results in the gas chromatographic separation of isotopologic substances [28]. In the following, the fully deuterium-labeled compounds are examined and their possible biosynthesis pathways described. However, it was also possible to detect the peaks of the

Mechanistic investigations on multiproduct β-himachalene synthase from Cryptosporangium arvum

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2019, 15, 1008–1019, doi:10.3762/bjoc.15.99

• labelled 1 with incorporation of deuterium into diastereotopic hydrogen positions. Together with the relative configuration of the targeted methylene group as deduced by NOESY, the stereochemical outcome of these experiments, which can be easily monitored by sensitive HSQC, infers the absolute

• HcS (Figure 7). The selective incorporation of deuterium into the diastereotopic positions of 7 is explainable by a 1Si,11Re-cyclisation of (R)-NPP. Given the absolute configuration of NPP and its formation via a 1,3-syn-allylic rearrangement from FPP, this ring closure represents an example of a

• of the commercial available products (Table S4–S8, Supporting Information File 1) clearly obeys the anti-SN2’ case (Figures S12–S14, Supporting Information File 1). The observation that 15 was obtained as a nearly racemic mixture contrasts the far more selective incorporation of deuterium into the

Stereochemical investigations on the biosynthesis of achiral (Z)-γ-bisabolene in Cryptosporangium arvum

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2019, 15, 789–794, doi:10.3762/bjoc.15.75

• terpinyl cation has been investigated using deuterium labelling, demonstrating different stereochemical courses in the plant Salvia officinalis [8][9] and in the bacterium Streptomyces clavuligerus [10]. Also the highly unusual methylated sesquiterpene sodorifen (4) possesses a mirror plane [11] making any

Selective benzylic C–H monooxygenation mediated by iodine oxides

• Kelsey B. LaMartina,
• Haley K. Kuck,
• Linda S. Oglesbee,
• Asma Al-Odaini and
• Nicholas C. Boaz

Beilstein J. Org. Chem. 2019, 15, 602–609, doi:10.3762/bjoc.15.55

• via a similar mechanism we examined several aspects of the NHPI-iodate system. A substrate deuterium kinetic isotope effect (KIE) study indicated that the benzylic C–H bond is broken more rapidly than the C–D bond of the deuterated substrate. Catalytic oxidation of a stoichiometric mixture of proteo

• and perdeutero ethylbenzene (8a,b) afforded a deuterium KIE of 3.21 ± 0.08 (Figure 5). The magnitude of this value indicates a primary KIE, which is observed with other reported deuterium KIE values of benzylic C–H scission via PINO radicals. Deuterium KIE values for hydrogen atom abstraction by the

• PINO radical vary based upon conditions such as temperature and solvent [63][64][65]. Ishii and co-workers have shown that catalytic oxidation of ethylbenzene in acetic acid solvent via PINO radical catalysis yields a competitive deuterium KIE of 3.8, similar to the system described herein [60]. The

Syntheses and chemical properties of β-nicotinamide riboside and its analogues and derivatives

• Mikhail V. Makarov and
• Marie E. Migaud

Beilstein J. Org. Chem. 2019, 15, 401–430, doi:10.3762/bjoc.15.36

Synthesis of nonracemic hydroxyglutamic acids

• Dorota G. Piotrowska,
• Iwona E. Głowacka,
• Andrzej E. Wróblewski and
• Liwia Lubowiecka

Beilstein J. Org. Chem. 2019, 15, 236–255, doi:10.3762/bjoc.15.22

• methods they are available from 3- or 4-hydroxyglutamic acids by direct hydroxy to fluoride displacement [91][123][124]. Deuterium- [72] and tritium-labelled [125] glutamic acids have also been prepared from 4-hydroxyglutamic acids via 4-mesyloxy derivatives. And finally reduction of the ethoxycarbonyl

Volatiles from the hypoxylaceous fungi Hypoxylon griseobrunneum and Hypoxylon macrocarpum

• Jan Rinkel,
• Alexander Babczyk,
• Tao Wang,
• Marc Stadler and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2018, 14, 2974–2990, doi:10.3762/bjoc.14.277

• of Scheme 2. Note that because of an isotope effect the isotopomers of 24 can be separated by gas chromatography depending on their deuterium content [34][35], which makes the usage of (methyl-2H3)methionine superior to the usage of 13C-labelled methionine that would not have led to chromatographic

Cobalt- and rhodium-catalyzed carboxylation using carbon dioxide as the C1 source

• Tetsuaki Fujihara and
• Yasushi Tsuji

Beilstein J. Org. Chem. 2018, 14, 2435–2460, doi:10.3762/bjoc.14.221

• CoI2(dppf) (10 mol %), Zn(OAc)2 (10 mol %), and Et4NI (10 mol %) in a mixture of CH3CN and DMF (v/v = 10:1) under an atmospheric pressure of CO2 at 40 °C. When the reaction mixture was quenched with D2O (>99% D), deuterated 17a-D was obtained in a 1H NMR yield of 80% with excellent deuterium

Synthesis of a water-soluble 2,2′-biphen[4]arene and its efficient complexation and sensitive fluorescence enhancement towards palmatine and berberine

• Xiayang Huang,
• Xinghua Zhang,
• Tianxin Qian,
• Junwei Ma,
• Lei Cui and
• Chunju Li

Beilstein J. Org. Chem. 2018, 14, 2236–2241, doi:10.3762/bjoc.14.198

• spectra were determined with a SHIMADZU RF5301 spectrometer. Deuterated phosphate buffer solutions (20 mM) of pD 7.4 for 1H NMR experiments were prepared by mixing K2DPO4 deuterium oxide solution (20 mM) and KD2PO4 deuterium oxide solution (20 mM) according to the calculated volume ratios. The pH/pD

Cationic cobalt-catalyzed [1,3]-rearrangement of N-alkoxycarbonyloxyanilines

• Itaru Nakamura,
• Mao Owada,
• Takeru Jo and
• Masahiro Terada

Beilstein J. Org. Chem. 2018, 14, 1972–1979, doi:10.3762/bjoc.14.172

• made the reaction much milder than the thermally-induced reaction but also changed the rearrangement mode to an unprecedented [1,3]-manner. In addition, intermolecular and intramolecular competitive experiments using deuterium-labelled substrates resulted in no kinetic effect (Scheme 4). These results

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

• for 2,3-benzotropone (12) are condensation reactions with active methylenic compounds, resulting in the formation of benzoheptafulvenoids (Figure 6). For example, Machiguchi reported that the condensation reaction of deuterium tracer 2,3-benzotropone 177 with malononitrile to yield 8,8-dicyano-2,3

Hypervalent iodine-guided electrophilic substitution: para-selective substitution across aryl iodonium compounds with benzyl groups

• Cyrus Mowdawalla,
• Faiz Ahmed,
• Tian Li,
• Kiet Pham,
• Loma Dave,
• Grace Kim and
• I. F. Dempsey Hyatt

Beilstein J. Org. Chem. 2018, 14, 1039–1045, doi:10.3762/bjoc.14.91

• -Claisen rearrangement (RICR) to describe the product selectivity they encountered [8]. More recently, exceptional progress has been made in investigating the RICR’s substrate scope (electron-donating versus electron-withdrawing substituents on PhI(OAc)2 (1a)), mechanism (deuterium labelling studies

• ] compelling evidence was shown by deuterium labelling studies supporting a concerted intramolecular mechanism (RICR) occurring rather than a stepwise intermolecular one. To corroborate their findings with our own, we investigated the HIGES reaction through crossover experiments which appear to conclude a

Chlorination of phenylallene derivatives with 1-chloro-1,2-benziodoxol-3-one: synthesis of vicinal-dichlorides and chlorodienes

• Zhensheng Zhao and
• Graham K. Murphy

Beilstein J. Org. Chem. 2018, 14, 796–802, doi:10.3762/bjoc.14.67

• processes that might not be elucidated through product analysis alone, deuterated biphenylallene [D2]-2b was subjected to the standard reaction conditions, and [D2]-3b (E/Z = 1:2) was obtained in 79% yield (Scheme 6 top, also see Supporting Information File 1). As there was no indication of deuterium

Stereochemical outcomes of C–F activation reactions of benzyl fluoride

• Neil S. Keddie,
• Pier Alexandre Champagne,
• Justine Desroches,
• Jean-François Paquin and
• David O'Hagan

Beilstein J. Org. Chem. 2018, 14, 106–113, doi:10.3762/bjoc.14.6

• explore the stereointegrity of the aforementioned reactions using enantiopure 7-[2H1]-(R)-benzyl fluoride ((R)-1, Figure 2) as a primary, yet chiral electrophile [10]. Substitution reactions of benzyl fluoride (1) will generate substituted products that retain the deuterium atom, and the degree of

• reduced under Noyori’s conditions [12] using (S,S)-Ru(DPEN)2 as catalyst and [2H2]-formic acid as the deuterium source. This afforded the corresponding 7-[2H1]-(S)-benzyl alcohol ((S)-3) in moderate yield (81%) and high ee (95%), as evidenced by 2H-PBLG-NMR. Benzyl alcohol 3 was converted to the

Hydrolysis, polarity, and conformational impact of C-terminal partially fluorinated ethyl esters in peptide models

• Vladimir Kubyshkin and
• Nediljko Budisa

Beilstein J. Org. Chem. 2017, 13, 2442–2457, doi:10.3762/bjoc.13.241

• AcGlyGlyProGlyGlyNH2 [71] and AcGlyProOMe [68] compounds when measured in deuterium oxide. For 1–5, we found the trans/cis ratios ≈ 5 for all five esters when measured in aqueous medium; the kinetic parameters of the amide rotation were also nearly identical (Table 2). We then noticed that the trans/cis ratios

• in compound 1 [74]. We examined the values of Jαβ for compounds 1–5 in a polar (deuterium oxide) and nonpolar (benzene-d6) solvents. The observed Jαβ values are consistent with those reported previously [74][83], and the value differences likely reflect a change of only a few percent due to the

• applied a simple set of equations for estimation of the diffusion coefficients of an oligomeric hydrophobic polyproline-II helix [71]. Here, we combined these equations in order to derive Equation 5, which describes diffusion as a function of molecular weight assuming pure deuterium oxide solution at 298

Fluorination of some highly functionalized cycloalkanes: chemoselectivity and substrate dependence

• Attila Márió Remete,
• Melinda Nonn,
• Santos Fustero,
• Matti Haukka,
• Ferenc Fülöp and
• Loránd Kiss

Beilstein J. Org. Chem. 2017, 13, 2364–2371, doi:10.3762/bjoc.13.233

• 60 F254 was purchased from Merck. The NMR spectra were acquired at room temperature on a Bruker Avance 400 spectrometer with 11.75 T magnetic field strength (1H frequency: 400.13 MHz, 19F frequency: 376.50 MHz, 13C frequency: 100.76 MHz, respectively) in CDCl3 or DMSO-d6 solution, using the deuterium

Structural diversity in the host–guest complexes of the antifolate pemetrexed with native cyclodextrins: gas phase, solution and solid state studies

• Magdalena Ceborska,
• Magdalena Zimnicka,
• Aneta Aniela Kowalska,
• Kajetan Dąbrowa and
• Barbara Repeć

Beilstein J. Org. Chem. 2017, 13, 2252–2263, doi:10.3762/bjoc.13.222

• signals of acidic protons are not visible in D2O due to the fast substitution by deuterium atoms we performed 1D NMR measurements in DMSO-d6 (see Figures S15–S17, S18, S23 and Tables S5 and S6 in Supporting Information File 1). From these experiments it can be clearly seen that pyrrolic proton PTX#H4

Remarkable functions of sn-3 hydroxy and phosphocholine groups in 1,2-diacyl-sn-glycerolipids to induce clockwise (+)-helicity around the 1,2-diacyl moiety: Evidence from conformation analysis by ¹H NMR spectroscopy

• Yoshihiro Nishida,
• Mengfei Yuan,
• Kazuo Fukuda,
• Kaito Fujisawa,
• Hirofumi Dohi and
• Hirotaka Uzawa

Beilstein J. Org. Chem. 2017, 13, 1999–2009, doi:10.3762/bjoc.13.196

• ; deuterium labeling; sn-glycerol; glycerolipids; glycerophospholipids; helicity; Karplus equation; proton NMR spectroscopy; staggered conformers; Introduction Glycerophospholipids, constituting the basic elements of cytoplasm bilayer membranes, are responsible for several cell functions [1][2][3]. These

• storage in CDCl3 solution. Acquisition of the 1H NMR spectral data of H1proR and H1proS signals Each of the four glycerolipids 1–4 is dissolved in either CDCl3 or the mixed solvents containing methanol-d4 in CDCl3 (deuterium content > 99.5%) at ca. 10 mM concentrations. 1H NMR spectroscopy is measured on

18-Hydroxydolabella-3,7-diene synthase – a diterpene synthase from Chitinophaga pinensis

• Jeroen S. Dickschat,
• Jan Rinkel,
• Patrick Rabe,
• Arman Beyraghdar Kashkooli and
• Harro J. Bouwmeester

Beilstein J. Org. Chem. 2017, 13, 1770–1780, doi:10.3762/bjoc.13.171

• analysis of the obtained terpene products. Incubation of (R)-(1-13C,1-2H)GGPP with HdS resulted in the specific incorporation of the deuterium labelling into the 2α position as indicated by a deminished crosspeak in the HSQC spectrum, while the crosspeak for H2β was strongly enhanced because of the 13C

• labelling of C2 (Figure 2). Consistently, the substrate (S)-(1-13C,1-2H)GGPP gave a product with specific incorporation of the deuterium label into the 2β position. Assuming inversion of configuration at C1 for the cyclisation of GGPP to 3 as reported for several other terpene synthases [13][20][21][22

• gave a stereospecific incorporation of the deuterium labelling into H10α from (R)-(1-13C,1-2H)GPP and into H10β from (S)-(1-13C,1-2H)GPP (Figure 3), which pointed to the same absolute configuration for 3 as deduced from the experiments with the two enantiomers of (1-13C,1-2H)GGPP. Similar incubation

Theoretical simulation of the infrared signature of mechanically stressed polymer solids

• Matthew S. Sammon,
• Milan Ončák and
• Martin K. Beyer

Beilstein J. Org. Chem. 2017, 13, 1710–1716, doi:10.3762/bjoc.13.165

• modes specific to the polymer ends would be very weak. Therefore, hydrogen atoms from the terminal methyl groups were substituted with deuterium. The spectral lines originating from these CD3 groups were removed from the simulated spectra. To simulate the intensities of infrared bands in the fingerprint