The synthesis of functionalized bridged polycycles via C–H bond insertion

• Jiun-Le Shih,
• Po-An Chen and
• Jeremy A. May

Beilstein J. Org. Chem. 2016, 12, 985–999, doi:10.3762/bjoc.12.97

• , even when the exocyclic oxygen was acetylated. This is likely related to the effects observed by Lee (Scheme 4). The Adams group also looked for a deuterium kinetic isotope effect for insertion in both 34 (Y = D, X = OMe) and 37 (Y = D, R = H). Only a small difference in relative rates between C–H and

• deuterium kinetic isotope effect of 2.34 was seen for C–H insertion with gold catalysis. Hashmi demonstrated the viability of dual gold catalysis for carbene/alkyne cascades with diynes like 109, which gave products from either a 1,2-methyl shift (not shown) or a C–H bond insertion to form enone 112 (Scheme

Cupreines and cupreidines: an established class of bifunctional cinchona organocatalysts

• Laura A. Bryant,
• Rossana Fanelli and
• Alexander J. A. Cobb

Beilstein J. Org. Chem. 2016, 12, 429–443, doi:10.3762/bjoc.12.46

• organocatalyst with comparable results. More recently, Johnson and co-worker used the o-toluoyl derived organocatalyst CPD-33 to effect a dynamic kinetic asymmetric transformation of racemic β-bromo-α-keto esters 32 (Scheme 9a) [35]. The mechanism, deduced from deuterium labeling studies, proposes that one of

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

• are conceivable for explaining these conversions. Deuterium labelling experiments exclude the [1,4]-hydride shift as the first step. A computational study scrutinized the reaction channels of these tandem conversions starting by [1,5]-, [1,7]- and [1,9]-H shifts, revealing that this first step is the

• from those starting by [1,5]-, [1,7]- or [1,9]-H shifts, represented in Scheme 4, by deuterium labelling experiments. Thus, if the conversion of the deuterated acetal-fulvene 14, in which deuterium replaces the proton at the acetalic carbon of 3a, was actually initiated by a [1,4]-deuteride shift, the

• transformation of the dihydrobenzo[f]indenic species 15, which should form in first instance, would yield the final benz[f]indenes via intermediates 16 and 17. These are labelled with deuterium at C4 of the major product 18 and at C9 of the minor one 19 as well as probably at additional positions of the fused

Base metal-catalyzed benzylic oxidation of (aryl)(heteroaryl)methanes with molecular oxygen

• Hans Sterckx,
• Johan De Houwer,
• Carl Mensch,
• Wouter Herrebout,
• Kourosch Abbaspour Tehrani and
• Bert U. W. Maes

Beilstein J. Org. Chem. 2016, 12, 144–153, doi:10.3762/bjoc.12.16

• deuterium incorporation in the benzylic position of 16 and 3h through acid-catalyzed imine–enamine tautomerization is dependent on the strength of the acid used (Figure 1). The rate of deuterium incorporation in 2-benzylpyridine (16, pKa ≈ 5.2) is much faster when using TFA-d1 than with AcOH-d4 [34][35

• ]. With the less basic 2-benzyl-5-chloropyridine (3h, pKa ≈ 3.0) the difference is even more pronounced: Almost no deuterium incorporation could be detected using AcOH-d4 while the reaction ran smoothly using the stronger acid TFA-d1. From this we conclude that when the pyridine nitrogen becomes less

• also reflected in the chemoselectivity studies where DMSO is the only solvent in which oxidation of a (di)azinylmethyl is possible. Hydrogen–deuterium exchange through acid-catalyzed imine–enamine tautomerization of 3h (0.5 M) and 16 (0.5 M) using AcOH-d4 (0.5 M) or TFA-d1 (0.5 M). 1H NMR spectroscopy

Synthesis and reactivity of aliphatic sulfur pentafluorides from substituted (pentafluorosulfanyl)benzenes

• Norbert Vida,
• Jiří Václavík and
• Petr Beier

Beilstein J. Org. Chem. 2016, 12, 110–116, doi:10.3762/bjoc.12.12

• the synthesis of selectively deuterium labelled acrylic acid derivative 23. Indeed, when maleic acid 4 was evaporated twice with D2O to exchange acidic protons and heated in DMSO-d6, deuterated 23 was observed by NMR spectroscopy (Scheme 10). Conclusion In conclusion, similar to 4-(pentafluorosulfanyl

• . Synthesis of maleic anhydride 20 and Diels–Alder adducts 21. Reaction of maleic acid 4 with diazomethane. Decarboxylation of maleic acid 4 to acrylic acid 23 in DMSO and the preparation of deuterium labelled 23. Calculated reaction coordinates of Diels–Alder reaction of 12 with cyclopentadiene.a Supporting

Recent highlights in biosynthesis research using stable isotopes

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2015, 11, 2493–2508, doi:10.3762/bjoc.11.271

• the product of a polyketide biosynthetic gene cluster [24]. To test whether N-acetylcysteine could be a biosynthetic precursor of the unusual 1,5-oxathiocane structure, feeding experiments using both (2S)- and (2R)-N-((2H3)acetyl)cysteine were performed. The deuterium atoms of both precursors were

• -[2H5,15N]threonine were fed to P. luminescens. The loss of one deuterium atom for an incorporated labeled amino acid (from Cα) directly supports an epimerase function within the corresponding NRPS module, and the incorporated building block can be assigned as D-configured. In this example, epimerization

• EIMS-fragmentation reactions of 34 by comparison of the 13C-including fragments. Singly labeled FPP isotopomers also proved valuable to investigate reprotonation steps in sesquiterpene cyclization mechanisms by incubation in deuterium oxide. The biosynthesis of the recently discovered corvol ethers A

Copper-catalyzed stereoselective conjugate addition of alkylboranes to alkynoates

• Takamichi Wakamatsu,
• Kazunori Nagao,
• Hirohisa Ohmiya and
• Masaya Sawamura

Beilstein J. Org. Chem. 2015, 11, 2444–2450, doi:10.3762/bjoc.11.265

• the α-position of the carbonyl group (93% D). The syn selectivity was slightly decreased due to the deuterium isotope effect: Slower D-trap caused isomerization of organocopper intermediates (vide infra). This experimental result indicates that t-BuOH acts as a proton source. A possible mechanism for

• selectivity. Possible mechanism. Isomerization of the alkenylcopper intermediates. Conjugate addition of alkylborane 2a to alkynoate 3a. Synthesis of five membered carbocycle. Deuterium-labeling experiment. Ligand effects. Copper-catalyzed conjugate addition of alkylboranes 2 to alkynoates 3.a Supporting

New aryloxybenzylidene ruthenium chelates – synthesis, reactivity and catalytic performance in ROMP

• Patrycja Żak,
• Szymon Rogalski,
• Mariusz Majchrzak,
• Maciej Kubicki and
• Cezary Pietraszuk

Beilstein J. Org. Chem. 2015, 11, 1910–1916, doi:10.3762/bjoc.11.206

• signal that could be assigned to the hydroxy group. It is most probably a consequence of high lability of this proton and its suitability for exchange with deuterium coming from the NMR solvent (CD2Cl2) as it was observed for activated complex 1a [9]. Complex 17 was proved to exhibit high catalytic

Preparative semiconductor photoredox catalysis: An emerging theme in organic synthesis

• David W. Manley and
• John C. Walton

Beilstein J. Org. Chem. 2015, 11, 1570–1582, doi:10.3762/bjoc.11.173

• transfer of an electron to the TiO2 will compete with the loss of CO2, thus reducing yields. An intriguing aspect of the process is the source of the H atoms gained during the formation of adducts 22 and 29. This was not the proton lost from the aromatic ring in forming 31. Deuterium labelling experiments

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

• established that the hydrogen atom in the product comes exclusively from THF and not from pyridine or MeCN (Table 4). The observed deuterium enrichment using THF-d8 was around 80%. Thermal decomposition of aryldiazonium salts prepared from immobilized triazene precursors and the formation of deuterated

• from intermolecular competition experiment using 3b and a 1:1 mixture of THF and THF-d8 giving KIE = 5.5 (6:6-D ratio determined by GC–MS) and combined yield of 62%. This means that the hydrogen abstraction is much faster than the deuterium abstraction and suggests the C-H(D) bond formation as the rate

Gold-catalyzed formation of pyrrolo- and indolo-oxazin-1-one derivatives: The key structure of some marine natural products

• Sultan Taskaya,
• Nurettin Menges and
• Metin Balci

Beilstein J. Org. Chem. 2015, 11, 897–905, doi:10.3762/bjoc.11.101

• products we carried out two different reactions. First, 15 was reacted with CD3OD under the same reaction conditions. The 1H NMR spectral analysis indicated the formation of 49 and 50 in 65% and 35% yields, respectively. Furthermore, the amount of deuterium atoms in 49 and 50 attached to the methylene

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

• -di-tert-butyl-4-methylphenol) improved the yields of methylenenortricyclenes. A complete deuterium incorporation was observed in the superoxide-mediated reaction in DMSO-d6. Friedel–Crafts acylation reactions of 3-methylenenorticyclenes yielded 2-propanone-substituted pentachloronorbornenes

• did not yield any product which suggested that there is a unique and exceptional degree of reactivity of the superoxide ion species which triggered this kind of reaction. To elucidate the reaction mechanism, we have performed a deuterium labelling experiment by treating 3c with KO2 in DMSO-d6 at rt

• . 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

Photochemical approach to functionalized benzobicyclo[3.2.1]octene structures via fused oxazoline derivatives from 4- and 5-(o-vinylstyryl)oxazoles

• Ivana Šagud,
• Simona Božić,
• Željko Marinić and
• Marija Šindler-Kulyk

Beilstein J. Org. Chem. 2014, 10, 2222–2229, doi:10.3762/bjoc.10.230

• the incorporation of deuterium in the bicyclo[3.2.1]octadiene moiety and a methoxy group on the N=C oxazoline bond by 1,4-addition or more likely by addition to the N=C bond followed by keto–enol tautomerization giving 14. The adducts are spectroscopically completely identified (see Supporting

Visible light photoredox-catalyzed deoxygenation of alcohols

• Daniel Rackl,
• Viktor Kais,
• Peter Kreitmeier and
• Oliver Reiser

Beilstein J. Org. Chem. 2014, 10, 2157–2165, doi:10.3762/bjoc.10.223

• from a substitution process with acetonitrile as the methyl source, the reaction was carried out in deuterated acetonitrile. No deuterium incorporation was observed which proved that acetonitrile is not responsible for the presence of the methyl group in 12. Performing the reaction in the presence of

Pyrrolidine nucleotide analogs with a tunable conformation

• Lenka Poštová Slavětínská,
• Dominik Rejman and
• Radek Pohl

Beilstein J. Org. Chem. 2014, 10, 1967–1980, doi:10.3762/bjoc.10.205

• agreement with the data reported [16][17], adenine becomes deuterated predominantly on N-1 at pD ~ 3 while thymine releases its deuterium at N-3 at pD ~ 10.5 and becomes negatively charged. Typically, a pD value of 5.7–6.9 was reached when 50 mM solutions of 7–10 in D2O were prepared for the NMR measurement

• provide NOE contacts to protons on both sides of the pyrrolidine ring, suggesting an exchange of deuterium connected to the pyrrolidine nitrogen. NMR study of phosphonoformyl derivatives In contrast to 7–10, an amidic pyrrolidine nitrogen atom in phosphonoformyl derivatives 11–14 is not involved in

Supercritical carbon dioxide: a solvent like no other

• Jocelyn Peach and
• Julian Eastoe

Beilstein J. Org. Chem. 2014, 10, 1878–1895, doi:10.3762/bjoc.10.196

• to contrast individual components in a multicomponent mixture through selective isotropic (hydrogen/deuterium) labelling. Research around a group of tri-chain surfactants has been carried out through the addition of a third extensively methylated tail in hope to both enhance CO2 compatibility and to

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