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

• opposite to the CF2 moiety, which was followed by the recyclization of the intermediate diradical (Scheme 42). The activation energy for the rearrangement of 90 was lower by 9.4 kcal/mol than for the parent hydrocarbon system 92. The activation energy of the trans-isomer 91 was greater than that of cis

• rearrangement of 1,1-difluoro-2-methylenecyclopropane (96) (Scheme 45) [92]. At 210 °C the rate of cleavage of the proximal bond was only 3.8 times faster than for the analogous hydrocarbon. It was also observed that the equilibrium lay significantly in favor of the rearranged product 97, which was by 1.9 kcal

• /mol more stable. The thermal ring opening of the tosyl-substituted 1,1-difluoro-2,2-dimethyl-3-methylenecyclopropane 98 led to the thermodynamically more stable products 99 and 100, respectively (Scheme 46) [93]. Spiropentane rearrangements: Gajewsky found that the rearrangement of the hydrocarbon

Vicinal difluorination as a C=C surrogate: an analog of piperine with enhanced solubility, photostability, and acetylcholinesterase inhibitory activity

• Yuvixza Lizarme-Salas,
• Alexandra Daryl Ariawan,
• Ranjala Ratnayake,
• Hendrik Luesch,
• Angela Finch and
• Luke Hunter

Beilstein J. Org. Chem. 2020, 16, 2663–2670, doi:10.3762/bjoc.16.216

• compound for medicinal chemistry. However, piperine has some problematic physicochemical properties including poor aqueous solubility and a susceptibility to UV-induced degradation. In this work, we designed an analog of piperine in which the central conjugated hydrocarbon chain is replaced with a vicinal

A new method for the synthesis of diamantane by hydroisomerization of binor-S on treatment with sulfuric acid

• Rishat I. Aminov and
• Ravil I. Khusnutdinov

Beilstein J. Org. Chem. 2020, 16, 2534–2539, doi:10.3762/bjoc.16.205

• be emphasized that the reaction selectively gives only one of the possible isomers, hydrocarbon 3с, which is confirmed by 1H and 13C NMR spectral data. The 13C NMR spectrum of compound 3с shows five characteristic carbon signals at 33.44, 35.64, 37.84, 38.30, and 40.49 ppm, coinciding with the

• starting binor-S (2) being recovered unchanged. The reaction of hydrocarbon 2 with hydrochloric acid proceeds with the addition of HCl to the cyclopropane ring and results in the formation of a mixture of mono- and dichloro derivatives, the synthesis of which has been reported [13][14]. When sulfuric acid

Design and synthesis of a bis-macrocyclic host and guests as building blocks for small molecular knots

• Elizabeth A. Margolis,
• Rebecca J. Keyes,
• Stephen D. Lockey IV and
• Edward E. Fenlon

Beilstein J. Org. Chem. 2020, 16, 2314–2321, doi:10.3762/bjoc.16.192

• trefoil knots have been prepared with an all-hydrocarbon example by the Itami group [7] and the synthesis of a single enantiomer by Leigh’s group [8]. Complexity has also been achieved with recent work showing that eight-crossing knots [9][10][11] and a nine-crossing composite knot can be synthesized [12

Synthetic approaches to bowl-shaped π-conjugated sumanene and its congeners

• Shakeel Alvi and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 2212–2259, doi:10.3762/bjoc.16.186

• ’ “Suman”, which means “Sunflower”), a beautifully simple yet much effective bowl-shaped C3-symmetric polycyclic aromatic hydrocarbon having three benzylic positions clipped between three phenyl rings in the triphenylene framework has attracted a tremendous attention of researchers worldwide. Therefore

Photosensitized direct C–H fluorination and trifluoromethylation in organic synthesis

• Shahboz Yakubov and
• Joshua P. Barham

Beilstein J. Org. Chem. 2020, 16, 2151–2192, doi:10.3762/bjoc.16.183

• another, paving the synthetic roadmap to many natural and unnatural compounds. While C–H bonds are not normally considered as functional groups, these are, however, ubiquitous, for example, in hydrocarbon fuels and in alkyl groups of countless organic molecules. The modification of unactivated C–H

• (especially C(sp3)–H) bonds into other functional groups would not only enormously expand the synthetic maneuverability but would also intensify the use of hydrocarbon feedstocks in organic synthesis. In this context, the advantage of direct C–H fluorination over traditional fluorination methods is that it

Automated high-content imaging for cellular uptake, from the Schmuck cation to the latest cyclic oligochalcogenides

• Rémi Martinent,
• Javier López-Andarias,
• Dimitri Moreau,
• Yangyang Cheng,
• Naomi Sakai and
• Stefan Matile

Beilstein J. Org. Chem. 2020, 16, 2007–2016, doi:10.3762/bjoc.16.167

• library of 259 molecular tweezers through an ethidium bromide (EB) displacement assay, show a negligible DNA transfection efficiency (Figure 3). However, the derivative 15, with two lipophilic hydrocarbon chains, results in a remarkable DNA delivery and transfection [35]. These two hydrocarbon chains

Polarity effects in 4-fluoro- and 4-(trifluoromethyl)prolines

• Vladimir Kubyshkin

Beilstein J. Org. Chem. 2020, 16, 1837–1852, doi:10.3762/bjoc.16.151

• additional polarity drop associated with partial mutual compensation of the CF3 and the amide dipoles (Figure 7). Indeed, this occurs experimentally. In fact, the lipophilicity contribution from the CF3 group in 3 and 4 (ΔlogPH/CF3 +0.7) is notably larger compared to an isolated CF3 group in a hydrocarbon

One-pot synthesis of isosorbide from cellulose or lignocellulosic biomass: a challenge?

• Isaline Bonnin,
• Raphaël Mereau,
• Thierry Tassaing and
• Karine De Oliveira Vigier

Beilstein J. Org. Chem. 2020, 16, 1713–1721, doi:10.3762/bjoc.16.143

• showed that the acidity is important in the conversion of lignocellulosic biomass to isosorbide and that the acid can react with the metal-supported catalyst. Another study was devoted to the use of boron phosphate for the conversion of cellulose into liquid hydrocarbon C1–C6 over Ru/C [23]. A mixture of

Heterogeneous photocatalysis in flow chemical reactors

• Christopher G. Thomson,
• Ai-Lan Lee and
• Filipe Vilela

Beilstein J. Org. Chem. 2020, 16, 1495–1549, doi:10.3762/bjoc.16.125

• (PDI) aggregates have become a popular choice of heterogeneous photocatalyst. As PDI is a large, planar, polyaromatic hydrocarbon molecule, it spontaneously forms ordered 1D supramolecular assemblies through efficient π–π stacking and side chain interactions [192]. Despite the PDI units having only non

Fluorinated phenylalanines: synthesis and pharmaceutical applications

• Laila F. Awad and
• Mohammed Salah Ayoup

Beilstein J. Org. Chem. 2020, 16, 1022–1050, doi:10.3762/bjoc.16.91

• improve protein stability, natural hydrocarbon amino acids were replaced with Pff 77a. The effect of enhanced protein stability upon this replacement is referred as to ‘fluoro-stabilization effect’ [56]. 1.7. Knoevenagel condensation of methyl isocyanoacetate Three isomers of fluorinated phenylalanines

Photocatalytic deaminative benzylation and alkylation of tetrahydroisoquinolines with N-alkylpyrydinium salts

• David Schönbauer,
• Carlo Sambiagio,
• Timothy Noël and
• Michael Schnürch

Beilstein J. Org. Chem. 2020, 16, 809–817, doi:10.3762/bjoc.16.74

• interest [27]. In our continuing quest to develop methods for the introduction of pure hydrocarbon residues avoiding volatile reagents [28][29], our attention was drawn to stable N-alkyl-(2,4,6-triphenyl)pyridinium salts (Katritzky salts) as alkylation reagents in the context of non-directed C–H

Six-fold C–H borylation of hexa-peri-hexabenzocoronene

• Mai Nagase,
• Kenta Kato,
• Akiko Yagi,
• Yasutomo Segawa and
• Kenichiro Itami

Beilstein J. Org. Chem. 2020, 16, 391–397, doi:10.3762/bjoc.16.37

• , Nagoya, 464-8602, Japan 10.3762/bjoc.16.37 Abstract Hexa-peri-hexabenzocoronene (HBC) is known to be a poorly soluble polycyclic aromatic hydrocarbon for which direct functionalization methods have been very limited. Herein, the synthesis of hexaborylated HBC from unsubstituted HBC is described. Iridium

Synthesis, liquid crystalline behaviour and structure–property relationships of 1,3-bis(5-substituted-1,3,4-oxadiazol-2-yl)benzenes

• Afef Mabrouki,
• Malek Fouzai,
• Armand Soldera,
• Abdelkader Kriaa and
• Ahmed Hedhli

Beilstein J. Org. Chem. 2020, 16, 149–158, doi:10.3762/bjoc.16.17

• , while their hydrocarbon counterparts are non-mesomorphic [20]. On the other hand, many heterocyclic-based liquid crystals have been designed and then synthesised due to their large scope of applications [21]. In this context, the 1,3,4-oxadiazole group was of a particular interest from a synthetic

• prepared compounds perform three kinds of conformations, A, B and C. The hydrocarbon derivatives exhibit conformation A (Figure 5a–a”), whereas the fluorocarbon analogues adopt, depending on whether they carry linking segment C2H4S or not, the conformation B (Figure 5b–b”) or C (Figure 5c–c”). In Figure 6

• standard. The oxadiazole moieties are thought to be responsible for the majority of the dipole moment in the prepared compounds. Due to the electron-donating effect of alkyl groups in combination with the electron-accepting oxadiazole [35], the prepared hydrocarbon compounds are expected to perform dipole

Bacterial terpene biosynthesis: challenges and opportunities for pathway engineering

• Eric J. N. Helfrich,
• Geng-Min Lin,
• Christopher A. Voigt and
• Jon Clardy

Beilstein J. Org. Chem. 2019, 15, 2889–2906, doi:10.3762/bjoc.15.283

• potential with molecular structure is severely restricted. The canonical terpene biosynthetic pathway uses a single enzyme to form a cyclized hydrocarbon backbone followed by modifications with a suite of tailoring enzymes that can generate dozens of different products from a single backbone. This

• a linear polyene with branching methyl groups that form the core hydrocarbon structure in a single enzyme-catalyzed step [9]. The enzyme, which is called terpene cyclase, holds the linear methyl-branched polyene in a defined conformation that initiates a series of carbocation-driven cyclizations and

• rearrangements, creating the basic hydrocarbon skeleton of a terpene [10][11]. This basic hydrocarbon skeleton is then modified to generate a large number of terpenoid structures, which can be further modified by addition of other building blocks, like sugars, amino acids, or fatty acids [12]. Terpenes are named

Emission and biosynthesis of volatile terpenoids from the plasmodial slime mold Physarum polycephalum

• Xinlu Chen,
• Tobias G. Köllner,
• Wangdan Xiong,
• Guo Wei and
• Feng Chen

Beilstein J. Org. Chem. 2019, 15, 2872–2880, doi:10.3762/bjoc.15.281

•  1B). The two unidentified are putative sesquiterpenoids. Compound 3 is a putative hydrocarbon sesquiterpene with a molecular mass of 204 (Figure 1C). In contrast, compound 4 has a molecular formula of C15H22O and a molecular mass of 218 (Figure 1C). It was predicated to be a sesquiterpene aldehyde

• specific terpene synthases. PpolyTPS4 produced α-muurolene (5) as a major product, and (E)-β-caryophyllene (2) and an unidentified sesquiterpene hydrocarbon as minor products. These three terpenes could also be found in the headspace of P. polycephalum with α-muurolene as the most abundant constituent

• repeated three times with similar results. 1, linalool; 2, (E)-β-caryophyllene; 3, unidentified sesquiterpene hydrocarbon (compound 3); 4, unidentified putative sesquiterpene aldehyde (compound 4); 5, α-muurolene. B) Structures of known terpenoids. The structure of compound 2 shows the (−)-enantiomer of (E

Photoreversible stretching of a BAPTA chelator marshalling Ca²⁺-binding in aqueous media

• Aurélien Ducrot,
• Arnaud Tron,
• Robin Bofinger,
• Ingrid Sanz Beguer,
• Jean-Luc Pozzo and
• Nathan D. McClenaghan

Beilstein J. Org. Chem. 2019, 15, 2801–2811, doi:10.3762/bjoc.15.273

• . In this regard a higher release efficiency would equally undoubtedly be required than that shown by prototype 1 described herein. To this end, shortening/rigidification of the hydrocarbon azobenzene-BAPTA linkages in 1 may be anticipated to lead to an exalted difference in trans/cis-binding affinity

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

• generate a vast number of (poly)cyclic hydrocarbon scaffolds. Remarkably, this complex chemical reaction, comprising changes in bonding, hybridization as well as the introduction of specific stereochemistry, is performed in a single reaction cascade without consumption of a cofactor [11]. In this review we

• result of heterolytic cleavage of the pyrophosphate–hydrocarbon bond or protonation of a double bond, (2) propagation of the carbocation along the forming terpene skeleton as a result of ring formations, hydride and/or methyl shifts, de- and reprotonation of intermediates, the creation of a terminal

Harnessing enzyme plasticity for the synthesis of oxygenated sesquiterpenoids

• Melodi Demiray,
• David J. Miller and
• Rudolf K. Allemann

Beilstein J. Org. Chem. 2019, 15, 2184–2190, doi:10.3762/bjoc.15.215

• -derived sesquiterpenes β-sesquiphellandrene [38][39][40] and zingiberene [40], a hydrocarbon with antifertility, antiviral and anticancer activity [41], suggested that the major compound was 12-methoxy-β-sesquiphellandrene (26), while the minor product was identified as 12-methoxyzingiberene (27). The two

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

• corresponding synthase as a final proof is yet missing. In the following, the sesquiterpene hydrocarbon α-cubebene is used as an example to illustrate our interpretations in more detail (Figure 4). Genuine (d0) α-cubebene has a molecular ion peak [M]+• at m/z = 204 (Figure 4, upper mass spectrum, marked red

• isopropyl group leads to the fragment with m/z = 166. At this point it becomes obvious why it can be assumed that the tricyclic sesquiterpene hydrocarbon α-cubebene is synthesized via (S)-(−)-germacrene D and not via (R)-(+)-germacrene D. Assuming the biosynthesis of α-cubebene takes place via (R

• ]. Tantillo and co-workers showed that germacrene D does not have to be involved in the formation of α-ylangene due to carbocation energetics. However, according to our results the formation of this tricyclic sesquiterpene hydrocarbon and its isomer β-ylangene occurs via the intermediate (R)-(+)-germacrene D

Halide metathesis in overdrive: mechanochemical synthesis of a heterometallic group 1 allyl complex

• Ross F. Koby,
• Nicholas R. Rightmire,
• Nathan D. Schley,
• Timothy P. Hanusa and
• William W. Brennessel

Beilstein J. Org. Chem. 2019, 15, 1856–1863, doi:10.3762/bjoc.15.181

• of [KA'] and alkali metal iodides, extracting the ground mixtures with hydrocarbon solvents, and then attempting crystallization of the extracts. This is necessarily an imperfect route to sampling the product space, as definitive characterization of any product(s) depended critically on the

Cyclobutane dication, (CH₂)₄²⁺: a model for a two-electron four-center (2e-4c) Woodward–Hoffmann frozen transition state

• G. K. Surya Prakash and
• Golam Rasul

Beilstein J. Org. Chem. 2019, 15, 1475–1479, doi:10.3762/bjoc.15.148

• G. K. Surya Prakash Golam Rasul Loker Hydrocarbon Research Institute and Department of Chemistry, University of Southern California, University Park, Los Angeles, CA 90089-1661, USA 10.3762/bjoc.15.148 Abstract The structures of the elusive cyclobutane dication, (CH2)42+, were investigated at the

• CCSD(T)/cc-pVTZ optimized Cartesian coordinates of 1–4, energies, ZPE and relative energies of 1–4 (Table S9) and calculated frequencies and IR intensities of 1 (Table S10). Acknowledgements Support of our work by Loker Hydrocarbon Research Institute is gratefully acknowledged.

Formation of an unexpected 3,3-diphenyl-3H-indazole through a facile intramolecular [2 + 3] cycloaddition of the diazo intermediate

• Andrew T. King,
• Hugh G. Hiscocks,
• Lidia Matesic,
• Mohan Bhadbhade,
• Roger Bishop and
• Alison T. Ung

Beilstein J. Org. Chem. 2019, 15, 1347–1354, doi:10.3762/bjoc.15.134

• (H···H = 2.48 Å) there is also a linear C6D–H6D···H6D–C6D close contact (H···H = 2.37 Å) around a further inversion centre. These two motifs alternate along the a axis to produce infinite hydrocarbon tapes with inversion centres separated by a/2 (Figure 6). The molecular structure of 8 precludes

• stepladder association of eight molecules (5b, lower). Crystallographic colour code: C–H···N purple), C–H···H–C (light blue), inversion centre (orange sphere), and incomplete contacts (red). Part of a hydrocarbon tape along a formed by a combination of alternating linear and cyclic C–H···H–C close contacts

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

• install C–O functionality with high selectivity into a C–H bond is a challenge to synthetic organic chemists. Importantly, this transformation allows for the creation of value-added products from hydrocarbon feedstocks. Benzylic positions are a prevalent example of a functionality whose relatively weak C

Thiol-free chemoenzymatic synthesis of β-ketosulfides

• Adrián A. Heredia,
• Martín G. López-Vidal,
• Marcela Kurina-Sanz,
• Fabricio R. Bisogno and
• Alicia B. Peñéñory

Beilstein J. Org. Chem. 2019, 15, 378–387, doi:10.3762/bjoc.15.34

• Table 2, entries 1–6) [46]. For aliphatic substituents at the α-position, a methyl group was perfectly accepted (Table 2, entries 22–24). Longer unbranched hydrocarbon was tolerated, although moderate conversion was achieved, even with higher lipase loading (Table 2, entry 12, 1l). For the latter, it