Synthesis of ethoxy dibenzooxaphosphorin oxides through palladium-catalyzed C(sp²)–H activation/C–O formation

• Seohyun Shin,
• Dongjin Kang,
• Woo Hyung Jeon and
• Phil Ho Lee

Beilstein J. Org. Chem. 2014, 10, 1220–1227, doi:10.3762/bjoc.10.120

• ranging from 50% and 63%. We carried out kinetic isotope effect (KIE) studies to prove the reaction mechanism (see Scheme 8). The required deuterium-labeled 2-(phenyl)phenylphosphonic acid monoethyl ester 1a-[D5] was efficiently prepared by a Suzuki reaction of deuterated bromobenzene (6) with 2

• -bromophenylboronic acid (5), a lithium bromide exchange reaction of 2-bromo deuterated biphenyl 7 followed by diethylphosphinylation with diethyl chlorophosphate, and C–O cleavage of diethyl 2-(phenyl)phenylphosphonate by using L-Selectride (Scheme 6). In addition, the deuterium-labeled 2-(phenyl)phenylphosphonic

cis–trans Isomerization of silybins A and B

• Michaela Novotná,
• Radek Gažák,
• David Biedermann,
• Florent Di Meo,
• Petr Marhol,
• Marek Kuzma,
• Lucie Bednárová,
• Kateřina Fuksová,
• Patrick Trouillas and
• Vladimír Křen

Beilstein J. Org. Chem. 2014, 10, 1047–1063, doi:10.3762/bjoc.10.105

• of taxifolin isomerization [34]. A deuterium incorporation NMR study supported by quantum chemical calculations showed that the intermediate of taxifolin with an open benzopyranone ring (α-hydroxychalcone related to IIc in our study) is very short-lived and the energy barrier for its formation is

Staudinger ligation towards cyclodextrin dimers in aqueous/organic media. Synthesis, conformations and guest-encapsulation ability

• Malamatenia D. Manouilidou,
• Yannis G. Lazarou,
• Irene M. Mavridis and
• Konstantina Yannakopoulou

Beilstein J. Org. Chem. 2014, 10, 774–783, doi:10.3762/bjoc.10.73

• proceed. Addition of deuterium oxide resulted in hydrolysis of the intermediate and disappearance of the 19.8 ppm peak within ~4 h while the emergence of a peak at 35.4 ppm validated the formation of dimer 6. The above confirmed DMF as the optimal solvent. In DMSO and CH3CN, numerous 31P signals upon

Zirconoarylation of alkynes through p-chloranil-promoted reductive elimination of arylzirconates

• Xiaoyu Yan,
• Chao Chen and
• Chanjuan Xi

Beilstein J. Org. Chem. 2014, 10, 528–534, doi:10.3762/bjoc.10.48

• isolated in 60% yield with >95% of deuterium incorporation (Scheme 4). The deuterium experiment revealed the formation of triphenylvinylzirconocene 4a as intermediate. Under similar reaction conditions, a study on the substrate scope was carried out, and the results are summarized in Table 1. When

• , Me4Si) δ 6.93 (s, 1H), 6.99–7.30 (m, 15H); 13C NMR (75 MHz, CDCl3, Me4Si) δ 126.6, 126.8, 127.5, 127.6, 127.7, 128.1, 128.3, 128.7, 129.7, 130.5, 137.5, 140.5, 142.7, 143.5; GC–MS m/z: 256. 2-Deuterium-1,1,2-triphenylethene (3a-D) [59]: The reaction mixture containing 4a was quenched with DCl, and 3a-D

A catalyst-free multicomponent domino sequence for the diastereoselective synthesis of (E)-3-[2-arylcarbonyl-3-(arylamino)allyl]chromen-4-ones

• Pitchaimani Prasanna,
• Pethaiah Gunasekaran,
• Subbu Perumal and
• J. Carlos Menéndez

Beilstein J. Org. Chem. 2014, 10, 459–465, doi:10.3762/bjoc.10.43

• tautomeric equilibrium. However, this reaction failed to show any incorporation of deuterium into 5, and therefore we had to abandon the hydride-transfer hypothesis. We came up with an alternative explanation based on the well-known fact that DMF decomposes into dimethylamine and carbon monoxide at its

Carbenoid-mediated nucleophilic “hydrolysis” of 2-(dichloromethylidene)-1,1,3,3-tetramethylindane with DMSO participation, affording access to one-sidedly overcrowded ketone and bromoalkene descendants^§

• Rudolf Knorr,
• Thomas Menke,
• Johannes Freudenreich and
• Claudio Pires

Beilstein J. Org. Chem. 2014, 10, 307–315, doi:10.3762/bjoc.10.28

• , assigned as above in accord with the deuterium-induced shifts 2Δ = –0.068 for C-2, 3Δ = −0.021 for C-3, and 3Δ = −0.045 ppm for C-1 as caused by the =CαD–S(O)–CD3 group incorporated during a run in [D6]DMSO; IR (KBr) ν: 2971, 2959, 2920, 2860, 1627 (w), 1484, 1363, 1032, 1022, 968, 748, 677, 505 cm−1; anal

[²H₂₆]-1-epi-Cubenol, a completely deuterated natural product from Streptomyces griseus

• Christian A. Citron and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2013, 9, 2841–2845, doi:10.3762/bjoc.9.319

• Streptomyces griseus. This compound represents the first completely deuterated terpene obtained by fermentation. Despite a few previous reports in the literature the operability of this approach to fully deuterated compounds is still surprising, because the strong kinetic isotope effect of deuterium is known

• to slow down all metabolic processes in living organisms. Potential applications of completely labelled compounds from natural sources in structure elucidation, biosynthetic or pharmacokinetic investigations are discussed. Keywords: biosynthesis; deuterium; labelling; natural products; Streptomyces

• incorporation can be detected by 13C NMR spectroscopy. As we have recently shown the sensitivity of modern 13C NMR spectrometers is even good enough for analysis of microgram amounts of isotopically enriched material in complex headspace extracts [8][9]. Deuterium is very powerful, particularly when hydrogen

N,N'-(Hexane-1,6-diyl)bis(4-methyl-N-(oxiran-2-ylmethyl)benzenesulfonamide): Synthesis via cyclodextrin mediated N-alkylation in aqueous solution and further Prilezhaev epoxidation

• Julian Fischer,
• Simon Millan and
• Helmut Ritter

Beilstein J. Org. Chem. 2013, 9, 2834–2840, doi:10.3762/bjoc.9.318

• (99+%) were purchased from Acros Organics, bisphenol A diglycidyl ether and deuterium oxide (99.9%) were provided from Sigma Aldrich, chloroform-d (99.80%) was obtained from Euriso-Top and dimethyl sulfoxide-d6 (99.9%) was purchased from Deutero. 1H NMR, 13C NMR and 2D ROESY spectra were recorded on a

• Bruker Avance DRX 300 and a Bruker Avance III – 600 by using deuterium oxide, dimethyl sulfoxide-d6 or chloroform-d as solvents. The chemical shifts (δ) are given in parts per million (ppm) using the solvent peak as an internal standard. FTIR spectra were recorded on a Nicolet 6700 FTIR spectrometer

Oligomeric epoxide–amine adducts based on 2-amino-N-isopropylacetamide and α-amino-ε-caprolactam: Solubility in presence of cyclodextrin and curing properties

• Julian Fischer and
• Helmut Ritter

Beilstein J. Org. Chem. 2013, 9, 2803–2811, doi:10.3762/bjoc.9.315

• oil pump over P4O10. Glycine methyl ester hydrochloride (98%) and L(+)-lysine monohydrochloride (99+%) were purchased from Acros Organics, di-tert-butyl dicarbonate (97+%) and isopropylamine (99+%) were obtained from Alfa Aesar, glycerol diglycidyl ether and deuterium oxide (D2O, 99.9% D) were

• purchased from Sigma Aldrich and chloroform-d (CDCl3, 99.80% D) was obtained from Euriso-Top. 1H NMR, 13C NMR and 1H-1H-ROESY spectra were recorded on a Bruker Avance DRX 300 by using deuterium oxide or chloroform-d as solvents. The chemical shifts (δ) are given in parts per million (ppm) using the solvent

Advancements in the mechanistic understanding of the copper-catalyzed azide–alkyne cycloaddition

• Regina Berg and
• Bernd F. Straub

Beilstein J. Org. Chem. 2013, 9, 2715–2750, doi:10.3762/bjoc.9.308

New developments in gold-catalyzed manipulation of inactivated alkenes

• Michel Chiarucci and
• Marco Bandini

Beilstein J. Org. Chem. 2013, 9, 2586–2614, doi:10.3762/bjoc.9.294

• is woth mentioning, that a 1:1 mixture of AuCl3 and AgOTf promoted the ring-closing processes of arenes 68, delivering the corresponding dihydrobenzopyrans, tetralins and tetrahydroquinolines 69 in good yields (Scheme 19a). Experimental controls with deuterium labelled compounds suggested the step

• substituted N- or O-heterocycles in high yields (Scheme 33) [76]. Deuterium labeling experiments unambiguously demonstrated the anti-functionalization of the double bond and the use of neutral gold complexes suggested that [Au(I)] oxidation took place prior of C–X bond formation. The same team also reported

Oxidative 3,3,3-trifluoropropylation of arylaldehydes

• Akari Ikeda,
• Masaaki Omote,
• Shiho Nomura,
• Miyuu Tanaka,
• Atsushi Tarui,
• Kazuyuki Sato and
• Akira Ando

Beilstein J. Org. Chem. 2013, 9, 2417–2421, doi:10.3762/bjoc.9.279

• product in which deuterium was inserted on the α- and β-carbons of the carbonyl group with rates of 22% and 53%, respectively (Scheme 1, (1)). This result suggests that deuterium on the β-carbon should be incorporated by a 1,3-proton shift. In contrast, deuterium on the α-carbon should be inserted when

• the enolate intermediate, which is generated during the reaction, intermolecularly extracted the benzylic deuterium of 4. To further investigate the reaction mechanism, 4a was exposed to basic conditions to observe whether or not the isomerization of 4a to 3a would occur. Indeed, the treatment of 4a

Gold(I)-catalyzed 6-endo hydroxycyclization of 7-substituted-1,6-enynes

• Ana M. Sanjuán,
• Alberto Martínez,
• Patricia García-García,
• Manuel A. Fernández-Rodríguez and
• Roberto Sanz

Beilstein J. Org. Chem. 2013, 9, 2242–2249, doi:10.3762/bjoc.9.263

• compound [D]-7b in 75% yield (>90% deuterium incorporation at C4). The generation of that compound could be explained by deuterodemetallation of the vinylgold species B generated by an attack of the nucleophile on intermediate 4b or 4b’ (Scheme 8). Conclusion We described an efficient gold(I)-catalyzed 6

Regioselective carbon–carbon bond formation of 5,5,5-trifluoro-1-phenylpent-3-en-1-yne

• Motoki Naka,
• Tomoko Kawasaki-Takasuka and
• Takashi Yamazaki

Beilstein J. Org. Chem. 2013, 9, 2182–2188, doi:10.3762/bjoc.9.256

• using 5,5,5-trifluoro-1-phenylpent-3-en-1-yne as a model substrate, and predominant acceptance of electrophiles β to a CF3 group as well as a deuterium trap experiment of the lithiated species led to the conclusion that the obtained regioselectivity is kinetically determined for the reactions with

• regioisomeric 5 and 6 would give us a hint for solving this puzzling question. Moreover, we also expected that such data as well as the additional deuterium trap experiment would offer deeper insight to the actual mechanism. Results and Discussion Investigation of reaction conditions was initially carried out

• constant of 2.3 Hz, which is close to the 4JH-F coupling value of 4 shown above. Moreover, disappearance of the large 3JH-H constant typical for (E)-alkenes suggested that a deuterium atom should be incorporated at the site where Ha was originally situated and that 4-d2 was actually produced. It is also

Gold-catalyzed cyclization of allenyl acetal derivatives

• Dhananjayan Vasu,
• Samir Kundlik Pawar and
• Rai-Shung Liu

Beilstein J. Org. Chem. 2013, 9, 1751–1756, doi:10.3762/bjoc.9.202

• deuterium labeling experiments supports a 1,4-hydride shift of the resulting allyl cationic intermediates because a complete deuterium transfer is observed. We tested the reaction on various acetal substrates bearing a propargyl acetate, giving 4-methoxy-5-alkylidenecyclopent-2-en-1-ones 4 via a degradation

• bond of the acetal group. We prepared d1-1a bearing a deuterium (>98%, Scheme 2, reaction 1) at its acetal group. The resulting product d1-4a has almost one full deuterium (X = 0.98 D) at one of the methylene protons according to DEPT 13C NMR analysis. In the presence of added D2O, undeuterated 1a gave

• the product without deuterium content (Scheme 2, reaction 2). The results of these labeling experiments reveal a 1,4-hydrogen shift [20][21][22] in the d1-1a→d1-4a transformation. Scheme 3 shows a plausible mechanism to rationalize the transformation of the allenyl acetal 1e into the observed

A reductive coupling strategy towards ripostatin A

• Kristin D. Schleicher and
• Timothy F. Jamison

Beilstein J. Org. Chem. 2013, 9, 1533–1550, doi:10.3762/bjoc.9.175

• product by 1H NMR revealed that no deuterium incorporation (to the sensitivity of integration) had occurred at the desired dithiane site, while approximately 80% deuterium incorporation had occurred at the allylic/benzylic site. These results indicated that the presence of the trisubstituted C18–C19

• ketone 57. Unfortunately, attempts to unite ketone 57 and bromide 56 via alkylation were unsuccessful. Although deprotection at the less-substituted site of the methyl ketone using LDA was verified in a deuterium quench experiment, the alkylation did not proceed at temperatures from −78 °C to 0 °C. While

• changes in reductive couplings of alkynes and 3-oxygenated epoxides. Enyne reductive coupling with 1,2-epoxyoctane. Synthesis of dithiane by Claisen rearrangement. Deuterium labeling reveals that the allylic/benzylic site is most acidic. Oxy-Michael addition to δ-hydroxy-α,β-enones. Synthesis of

True and masked three-coordinate T-shaped platinum(II) intermediates

• Manuel A. Ortuño,
• Salvador Conejero and
• Agustí Lledós

Beilstein J. Org. Chem. 2013, 9, 1352–1382, doi:10.3762/bjoc.9.153

• . Nevertheless, the three-coordinate intermediate 17 is not isolable and reacts further with a molecule of the starting material 7a leading to the dinuclear species 19. The inclusion of deuterium atoms in the t-Bu groups of 19 suggests that both intra- and intermolecular C–H bond activations are competitive

Study on the total synthesis of velbanamine: Chemoselective dioxygenation of alkenes with PIFA via a stop-and-flow strategy

• Huili Liu,
• Kuan Zheng,
• Xiang Lu,
• Xiaoxia Wang and
• Ran Hong

Beilstein J. Org. Chem. 2013, 9, 983–990, doi:10.3762/bjoc.9.113

• ” in a planar amide [41]. In the PIFA-promoted cyclization, lactonization was more likely to be a prominent process than lactamization. Following Tellitu’s procedure [46], we re-synthesized 13 and subjected it to the proton NMR in the presence of D2O. Three proton signals were exchanged with deuterium

Isotopically labeled sulfur compounds and synthetic selenium and tellurium analogues to study sulfur metabolism in marine bacteria

• Nelson L. Brock,
• Christian A. Citron,
• Claudia Zell,
• Martine Berger,
• Irene Wagner-Döbler,
• Jörn Petersen,
• Thorsten Brinkhoff,
• Meinhard Simon and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2013, 9, 942–950, doi:10.3762/bjoc.9.108

• , Germany 10.3762/bjoc.9.108 Abstract Members of the marine Roseobacter clade can degrade dimethylsulfoniopropionate (DMSP) via competing pathways releasing either methanethiol (MeSH) or dimethyl sulfide (DMS). Deuterium-labeled [2H6]DMSP and the synthetic DMSP analogue dimethyltelluriopropionate (DMTeP

• incorporation of a deuterium label into MeSH and DMS. Knockout of relevant genes from the known DMSP demethylation pathway to MeSH showed in both species a residual production of [2H3]MeSH, suggesting that a second demethylation pathway is active. The role of DMSP degradation pathways for MeSH and DMS formation

• substrate for dmd-gene-mediated liberation of MeSH even in the absence of an active dmdA gene, [2H6]DMSP was fed to a knockout mutant with a loss of the 262 kb plasmid [26]. This plasmid-cured strain exhibited the same reduced incorporation rates (32%) of deuterium label into the MeSH-derived volatiles. The

Superstructures of fluorescent cyclodextrin via click-reaction

• Arkadius Maciollek,
• Helmut Ritter and
• Rainer Beckert

Beilstein J. Org. Chem. 2013, 9, 827–831, doi:10.3762/bjoc.9.94

• without further purification. β-CD was obtained from Wacker Chemie GmbH, Burghausen, Germany and was used after drying overnight with a vacuum oil pump over P4O10. N,N-Dimethylformamide (DMF) was purchased from Fluka, Germany. Dimethyl sulfoxide-d6 (99.9 atom % D) and deuterium oxide, D2O, were obtained

Quantification of N-acetylcysteamine activated methylmalonate incorporation into polyketide biosynthesis

• Stephan Klopries,
• Uschi Sundermann and
• Frank Schulz

Beilstein J. Org. Chem. 2013, 9, 664–674, doi:10.3762/bjoc.9.75

• deuterium. Relative incorporation of the D3-label into erythromycin (A) and rapamycin (B), depending on the fed concentration of rac-4. Color coding: green: no incorporation; blue: single; red: double; magenta: triple incorporation as detected by LC/ESI–MS. ESI–MS spectra of feeding experiments with an

Synthesis and stability study of a new major metabolite of γ-hydroxybutyric acid

• Ida Nymann Petersen,
• Jesper Langgaard Kristensen,
• Christian Tortzen,
• Torben Breindahl and
• Daniel Sejer Pedersen

Beilstein J. Org. Chem. 2013, 9, 641–646, doi:10.3762/bjoc.9.72

• glucuronidation approach that provides GHB glucuronide 2 and a deuterium-labelled analogue d4-2 of high purity suitable for analytical chemistry. In addition, we have assessed the stability of GHB glucuronide 2 by mimicking the natural pH range for urine, which is of importance in the development of new

• reported. Herein we wish to disclose the synthesis of GHB glucuronide 2 and a deuterium labelled analogue d4-2, which is required as an internal standard for chromatography. Moreover, we have assessed the stability of GHB glucuronide 2 towards aqueous hydrolysis within the pH range normally observed for

• spectrometer, respectively, by using an internal deuterium lock. Solvents were used as internal standard when assigning NMR spectra [29]. J values are given in hertz (Hz) and rounded to the nearest 0.5 Hz. Dry column vacuum chromatography (DCVC) was carried out according to the published procedure [30]. High

Kinetics and mechanism of the anilinolysis of aryl phenyl isothiocyanophosphates in acetonitrile

• Hasi Rani Barai and
• Hai Whang Lee

Beilstein J. Org. Chem. 2013, 9, 615–620, doi:10.3762/bjoc.9.68

• and with rate-limiting bond formation for less basic anilines is proposed based on the positive and negative ρXY values, respectively. The deuterium kinetic isotope effects involving deuterated anilines (XC6H4ND2) showed primary normal and secondary inverse DKIEs for more basic and less basic anilines

• . Keywords: anilinolysis; cross-interaction constant; deuterium kinetic isotope effects; phosphoryl transfer reaction; reactive intermediates; Y-aryl phenyl isothiocyanophosphates; Introduction The nucleophilic substitution reactions of tetracoordinate phosphorus have been studied extensively

• ). The kinetic results of the present work are discussed based on the selectivity parameters and deuterium kinetic isotope effects (DKIEs). The aim of this work is to gain further information on the substituent effects, DKIEs and mechanism of the phosphoryl transfer reactions. Results and Discussion

Intramolecular carbolithiation cascades as a route to a highly strained carbocyclic framework: competition between 5-exo-trig ring closure and proton transfer

• William F. Bailey and
• Justin D. Fair

Beilstein J. Org. Chem. 2013, 9, 537–543, doi:10.3762/bjoc.9.59

• % isolated yield. Quenching with MeOD afforded an authentic sample of 4 deuterated at the C(2) position (2H NMR: δ 5.84–5.75 (m, 1D)); the lack of a molecular ion in the GC–MS of triene 4 precluded accurate determination of the deuterium content. Addition at –78 °C of dry, oxygen-free N,N,N’,N

A peptidic hydrogel that may behave as a “Trojan Horse”

• Nicola Castellucci,
• Giorgio Sartor,
• Natalia Calonghi,
• Carola Parolin,
• Giuseppe Falini and
• Claudia Tomasini

Beilstein J. Org. Chem. 2013, 9, 417–424, doi:10.3762/bjoc.9.44

• , CT) equipped with a deuterium background corrector, Autosampler AS-72, graphite furnace Perkin-Elmer Mod. HGA-800. A Pt Lumina (Perkin-Elmer) hollow-cathode lamp was used. Ten microliters of sample was injected and the furnace was heated slowly to 2500 °C. The absorbance of atomized platinum was