Recent advances in allylation of chiral secondary alkylcopper species

• Minjae Kim,
• Gwanggyun Kim,
• Doyoon Kim,
• Jun Hee Lee and
• Seung Hwan Cho

Beilstein J. Org. Chem. 2025, 21, 639–658, doi:10.3762/bjoc.21.51

• conditions render this method attractive for constructing complex chiral molecular architectures. A plausible mechanistic pathway for this cascade asymmetric hydroboration and hydroallylation of alkynes was proposed based on a series of control experiments, including deuterium-labeling experiments and DFT

• operative, deuterium-labeling studies were conducted using an enantioenriched, isotopically labeled allylic bromide (S)-54 (61:39 er) and 1,1-diborylethane 52a under optimized reaction conditions (Scheme 19a). The resulting product 55 formed with 39:61 E/Z selectivity, indicating an anti-SN2' oxidative

Copper-catalyzed yne-allylic substitutions: concept and recent developments

• Shuang Yang and
• Xinqiang Fang

Beilstein J. Org. Chem. 2024, 20, 2739–2775, doi:10.3762/bjoc.20.232

• , 50a–l) axial chirality in remarkable enantiopurities. Mechanistic studies and deuterium labeling experiments have revealed that the reaction proceeds in a stepwise manner without involving a 1,5-H migration process. Based on these findings, the authors have proposed a mechanism wherein the

Transition-metal-catalyst-free electroreductive alkene hydroarylation with aryl halides under visible-light irradiation

• Kosuke Yamamoto,
• Kazuhisa Arita,
• Masami Kuriyama and
• Osamu Onomura

Beilstein J. Org. Chem. 2024, 20, 1327–1333, doi:10.3762/bjoc.20.116

• hydroarylation product was not observed (Scheme 3b). This result strongly supported the involvement of radical intermediates in the present transformation. Next, a deuterium-labeling experiment was conducted to elucidate the H-source of this reaction (Scheme 3c). The reaction of 1a and 2e in MeCN with D2O

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

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

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

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

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

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

• 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

• 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

• labeling [34]. Another important step towards a deeper understanding of the cyclization mechanism was the availability of crystal structures (Table 1) revealing structural snapshots along the reaction trajectory commencing with the open, inactive conformation completing with the closed, active conformation

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

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

Polyketide stereocontrol: a study in chemical biology

• Kira J. Weissman

Beilstein J. Org. Chem. 2017, 13, 348–371, doi:10.3762/bjoc.13.39

Enantioconvergent catalysis

• Justin T. Mohr,
• Jared T. Moore and
• Brian M. Stoltz

Beilstein J. Org. Chem. 2016, 12, 2038–2045, doi:10.3762/bjoc.12.192

• . Deuterium labeling experiments have shown that the hydrogenation reaction occurs only on the chiral keto tautomer, and therefore the catalyst selects one enantiomer of the substrate when the reduction takes place. Enantioconvergent methods are not limited to carbon stereocenters. An exceptional example of

Conjugate addition–enantioselective protonation reactions

• James P. Phelan and
• Jonathan A. Ellman

Beilstein J. Org. Chem. 2016, 12, 1203–1228, doi:10.3762/bjoc.12.116

• mechanism of their reaction through a combination of DFT calculations, deuterium labeling studies, and control experiments (Scheme 13) [34]. The authors proposed that after migratory insertion of the rhodium–aryl bond across the acrylate, 58 undergoes β-hydride elimination of the enamide proton to generate

• rhodium catalyst binding to the benzoxazole nitrogen 68. Deuterium labeling studies were performed on the system and based on their results a mechanism was proposed in which the stereodetermining step is a rhodium-hydride transfer instead of protonation of an oxo-π-allylrhodium species (Scheme 17

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

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

• from carbon numbers of GGPP (44). Proposed mechanism of the cyclooctat-9-en-7-ol (52) biosynthesis catalysed by CotB2. Annotated hydrogen atoms (a–c) were investigated by deuterium labeling. Asterisks are used to follow the rearrangement of C-8 and C-9 (carbon numbers as for GGPP). Cyclization

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

• 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 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

• 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

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

• cyclopentenone 4e. The deuterium labeling experiment of the d1-1a→d1-4a transformation (Scheme 2, reaction 1) indicates that one methylene proton of 4a is derived from the original acetal group. Accordingly, we postulate a 1,4-hydride shift [21][22] for the intermediate transformation B→C. We excluded an

• % yields. Conclusion In summary, we report a gold-catalyzed transformation of allenyl acetals 1 into 5-alkylidenecyclopent-2-en-1-ones 4. Our deuterium labeling experiments support a 1,4-hydride shift for the resulting allyl cation because of a complete deuterium transfer. This observation excludes the

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

• 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

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

• strain of DSS-3. The incorporation rates of the deuterium labeling into the MeSH-derived volatiles were reduced (64% for 1) in comparison to the wild type strain (95%) and the ratio of the cleavage pathway increased to 35% (Figure 4B). The incorporation of isotopic labeling from [2H6]DMSP by the dmdA

• the deuterium labeling into 1 (85% incorporation rate, Figure S1 of Supporting Information File 1) and other MeSH-derived volatiles. Selenium volatiles from marine alphaproteobacteria Agar-plate cultures of P. gallaeciensis grown on half-strength MB2216 medium, plain or amended with different selenium

Caryolene-forming carbocation rearrangements

• Quynh Nhu N. Nguyen and
• Dean J. Tantillo

Beilstein J. Org. Chem. 2013, 9, 323–331, doi:10.3762/bjoc.9.37

• positioned on opposite sides of the hydrocarbon substrate due to the steric congestion at its core (note the position of NH3 throughout Figure 7), a scenario that could be probed by deuterium labeling of farnesyl diphosphate if a suitable caryolene synthase were isolated. The energetics for both pathways

Radical zinc-atom-transfer-based carbozincation of haloalkynes with dialkylzincs

• Fabrice Chemla,
• Florian Dulong,
• Franck Ferreira and
• Alejandro Pérez-Luna

Beilstein J. Org. Chem. 2013, 9, 236–245, doi:10.3762/bjoc.9.28

• warming, the zinc carbenoid is stereochemically labile and isomerizes to its more stable form. In the absence of added air, no decomposition of the carbenoid intermediate is observed at room temperature for at least 24 h. Deuterium labeling and iodolysis experiments evidence that the zinc carbenoids

Recent advances in the gold-catalyzed additions to C–C multiple bonds

• He Huang,
• Yu Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2011, 7, 897–936, doi:10.3762/bjoc.7.103

• sp3-hybridized C–H bond can be achieved by undergoing 1,3-addition to a vinyl–carbenoid intermediate [142]. The bicyclo[3.2.1]oct-6-en-2-ones 265 and 267 could be synthesized stereoselectively by this method. Deuterium labeling experiments indicated the cyclization involved an unprecedented 1,3

• via oxidative gold catalysis and provided expedient access to various substituted N- or O-heterocycles (344–351) (Scheme 57). Deuterium labeling experiments were carried out to unveil the reaction mechanism. The results established the anti nature of the alkene functionalization and the indispensable

Gold-catalyzed heterocyclizations in alkynyl- and allenyl-β-lactams

• Benito Alcaide and
• Pedro Almendros

Beilstein J. Org. Chem. 2011, 7, 622–630, doi:10.3762/bjoc.7.73

• reveal, 5-exo oxyauration via 16 is restricted by the steric hindrance between the (methoxymethyl)oxy group and the substituents at the quaternary stereocenter. With the aim of trapping the organo–gold intermediate to confirm the mechanism of this reaction, deuterium labeling studies with deuterium oxide