Hypervalent iodine-mediated intramolecular alkene halocyclisation

• Charu Bansal,
• Oliver Ruggles,
• Albert C. Rowett and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 3113–3133, doi:10.3762/bjoc.20.258

• , deuterium labelling, rearrangements on stereodefined substrates, and structural analyses (NMR and X-ray) of the reaction products. RT-NMR-derived data strongly supported a pathway of alkene activation by the iodane, as opposed to the formation of an N-I(III) adduct. The presence of 5-exo-products, with

• support of a deuterium labelling experiment, also ruled out the possibility of an N-activation pathway. Therefore, the proposed mechanism involves BF3-coordinated I(III) iodane forming iodiranium(III) ions with the alkene, followed by diastereo-determining 5-exo-cyclisation. These transiently formed

A facile three-component route to powerful 5-aryldeazaalloxazine photocatalysts

• Ivana Weisheitelová,
• Radek Cibulka,
• Marek Sikorski and
• Tetiana Pavlovska

Beilstein J. Org. Chem. 2024, 20, 1831–1838, doi:10.3762/bjoc.20.161

• source in this reaction, a deuterium labelling experiment was conducted (Scheme 2C). Indeed, the deazaalloxazine derivative 6-d with quantitative incorporation of deuterium in C(5) position, was isolated and confirmed by 1H NMR analysis and mass spectrometry (for more details on possible reaction

Manganese-catalyzed C–C and C–N bond formation with alcohols via borrowing hydrogen or hydrogen auto-transfer

• Mohd Farhan Ansari,
• Atul Kumar Maurya,
• Abhishek Kumar and
• Saravanakumar Elangovan

Beilstein J. Org. Chem. 2024, 20, 1111–1166, doi:10.3762/bjoc.20.98

• condensation with ketones, yielding an α,β-unsaturated compound, which was hydrogenated by the manganese hydride species, resulting in the final alkylated product (Scheme 25). A set of deuterium labelling tests and additional control studies determined that the alcohol dehydrogenation was aided by an

• substituted primary alcohols gave moderate to good yields (50–82%). Deuterium-labelling experiments with deuterated 1-phenylethanol-α-d1 and benzyl alcohol-α,α-d2 suggested a hydrogen auto-transfer and dehydrogenation process. The amido species Mn18-a generated from Mn18 by the base is responsible for the

Advancements in hydrochlorination of alkenes

• Daniel S. Müller

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

• 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

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

• 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

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

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

• -labelled substrates were used in conjunction with deuterium labelling. These substrates have the advantage that the incorporation of labelling can be detected and localised through 13C NMR spectroscopy with very high sensitivity, but no hints for critical steps such as 1,3- or 1,4-hydride shifts or

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

On the mass spectrometric fragmentations of the bacterial sesterterpenes sestermobaraenes A–C

• Anwei Hou and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2020, 16, 2807–2819, doi:10.3762/bjoc.16.231

• knowledge allows for structural predictions based on GC–MS data [17]. The deuterium labelling technique was also applied to other compound classes such as alkylbenzenes and ketones [18][19][20][21]. For terpenes, structural proposals can only be made based on the mass spectra for structurally less

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

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

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

• 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

• experiments were performed with (R)- and (S)-(1-13C,1-2H)FPP, IPP, GGPPS and HdS, resulting in the stereospecific incorporation of deuterium labelling into the hydrogens at C6 of 3 (Figure 4). These experiments could not be used to confirm the absolute configuration of the diterpene, because the signals for

The reductive decyanation reaction: an overview and recent developments

• Jean-Marc R. Mattalia

Beilstein J. Org. Chem. 2017, 13, 267–284, doi:10.3762/bjoc.13.30

• treatment with NaBH4 in 2-propanol by using both basic and nucleophilic properties of the hydride ion. The proposed mechanism involves a double-bond isomerization to the α-aminonitrile intermediate which is then reduced by the hydride ion in a classical way (Scheme 7). Interestingly, deuterium-labelling

• reduction of radical probes (no rearranged products formed from 25d,l,m) and deuterium-labelling experiments (no deuterium incorporation using THF-d8 and quenching with D2O) discard the possibility of a single-electron transfer pathway. Other reductions suggest a hydride addition with formation of an iminyl

Synthesis of a deuterated probe for the confocal Raman microscopy imaging of squalenoyl nanomedicines

• Eric Buchy,
• Branko Vukosavljevic,
• Maike Windbergs,
• Dunja Sobot,
• Camille Dejean,
• Simona Mura,
• Patrick Couvreur and
• Didier Desmaële

Beilstein J. Org. Chem. 2016, 12, 1127–1135, doi:10.3762/bjoc.12.109

• : deuterium labelling; nanomedicine; Raman spectroscopy; Shapiro reaction; squalene; Introduction Application of nanotechnology to medicine holds promises to profoundly impact healthcare especially to treat severe diseases such as cancer, intracellular infections, neurodegenerative diseases, etc. Indeed, the

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

• conceivable for explaining these cascade transformations leading to benz[f]indenes. The results of deuterium labelling experiments excluded a [1,4]-hydride shift as the initial step. The reaction of the unsubstituted 1,3-dioxolane-fulvene has been computationally studied by DFT methods. The results of this

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

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

• 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

• reaction was derived through a controlled experiment with BHT which improved the yields of nortricyclenes and a deuterium labelling experiment using DMSO-d6. Further, acylation reactions of the synthesized methylenenortricyclens afforded the 2-propanone-substituted pentachloronorbornenes in good yields

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

[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

• 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

Novel fatty acid methyl esters from the actinomycete Micromonospora aurantiaca

• Jeroen S. Dickschat,
• Hilke Bruns and
• Ramona Riclea

Beilstein J. Org. Chem. 2011, 7, 1697–1712, doi:10.3762/bjoc.7.200

• isopropyl group (m/z = 43 and m/z =143) shifted to m/z = 50 and m/z = 145 in agreement with the deuterium labelling of this portion of the molecule. The labelling was also introduced into the iso-odd FAMEs 102 and 103 (Figures S3C to S3F of Supporting Information File 1) and the higher homologue methyl 15

• instance visible by an increase of the molecular ion from m/z = 242 to m/z = 245, whereas the McLafferty rearrangement and β-cleavage fragment ions were detected at m/z = 74 and m/z = 87, as for the unlabelled compound. The deuterium labelling of the γ-methyl group was indicated by a shift of the fragment

Isotopic labelling studies for a gold-catalysed skeletal rearrangement of alkynyl aziridines

• Paul W. Davies,
• Nicolas Martin and
• Neil Spencer

Beilstein J. Org. Chem. 2011, 7, 839–846, doi:10.3762/bjoc.7.96

• the deuterium labelling study using Ph3PAuCl/AgOTf. Supporting Information Supporting Information contains full experimental details for the preparation of the cyclisation precursors and their subsequent reactions. NMR spectra for the labelling studies are provided. Supporting Information File 74