(Bio)isosteres of ortho- and meta-substituted benzenes

• H. Erik Diepers and
• Johannes C. L. Walker

Beilstein J. Org. Chem. 2024, 20, 859–890, doi:10.3762/bjoc.20.78

• , respectively (Scheme 12B) [58]. Saponification of the ester moieties in these species followed by Curtius rearrangements then led to amines 114 and 116. Non-natural amino acid derivatives 113 and 117 are intermediates prepared using these methods that could be of interest to medicinal chemistry. Alcohol 111

Skeletal rearrangement of 6,8-dioxabicyclo[3.2.1]octan-4-ols promoted by thionyl chloride or Appel conditions

• Martyn Jevric,
• Julian Klepp,
• Johannes Puschnig,
• Oscar Lamb,
• Christopher J. Sumby and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2024, 20, 823–829, doi:10.3762/bjoc.20.74

• -cleavage reactions and rearrangements when modified at the 4-position [15][16][17]. Baillargeon and Reddy first reported rearrangements of 6,8-dioxabicyclo[3.2.1]octane derivatives promoted by diethylaminosulfur trifluoride (DAST) [18], and later Karban and co-workers reported a migration of oxygen from

• angle of 176°, explaining the preference for the different skeletal rearrangements in the two possible configurations at C4 in these rigid ring systems [19][21]. The involvement of the ring-oxygen in nucleophilic displacement reactions in 1,6-anhydroglucose derivatives has also been invoked to explain

Ligand effects, solvent cooperation, and large kinetic solvent deuterium isotope effects in gold(I)-catalyzed intramolecular alkene hydroamination

• Ruichen Lan,
• Brock Yager,
• Yoonsun Jee,
• Cynthia S. Day and
• Amanda C. Jones

Beilstein J. Org. Chem. 2024, 20, 479–496, doi:10.3762/bjoc.20.43

• are apparent from others’ HOTf control studies. First, a “simple” Bronsted acid-catalyzed mechanism that is possible with sulfonamides (i.e., with HOTf catalyst) is not operating here. Second, more complex acid-mediated rearrangements observed with ureas (authors propose a hetero-ene mechanism with

Green and sustainable approaches for the Friedel–Crafts reaction between aldehydes and indoles

• Periklis X. Kolagkis,
• Eirini M. Galathri and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2024, 20, 379–426, doi:10.3762/bjoc.20.36

Electron-beam-promoted fullerene dimerization in nanotubes: insights from DFT computations

• Laura Abella,
• Gerard Novell-Leruth,
• Josep M. Ricart,
• Josep M. Poblet and
• Antonio Rodríguez-Fortea

Beilstein J. Org. Chem. 2024, 20, 92–100, doi:10.3762/bjoc.20.10

• with irreversible C–C fusions [7]. In phase 1, a [2 + 2] cycloadduct C120 dimer is formed, which was initially proposed to be with Cs symmetry, in contrast to the X-ray structure for the C120 dimer that shows D2h symmetry [3][9]. In phase 2, irreversible structural rearrangements occur leading to a

Functional characterisation of twelve terpene synthases from actinobacteria

• Anuj K. Chhalodia,
• Houchao Xu,
• Georges B. Tabekoueng,
• Binbin Gu,
• Kizerbo A. Taizoumbe,
• Lukas Lauterbach and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2023, 19, 1386–1398, doi:10.3762/bjoc.19.100

• rearrangements. During the past decades numerous enzymes have been characterised from all branches of life. Only considering type I terpene synthases, after the identification of the 5-epi-aristolochene (1) synthase from Nicotiana tabacum [1] and the casbene (2) synthase from Ricinus communis [2] (Figure 1

Radical ligand transfer: a general strategy for radical functionalization

• David T. Nemoto Jr,
• Kang-Jie Bian,
• Shih-Chieh Kao and
• Julian G. West

Beilstein J. Org. Chem. 2023, 19, 1225–1233, doi:10.3762/bjoc.19.90

• azides for a wide range of both activated (benzylic) and unactivated carboxylic acids. Control reactions support the intermediacy of alkyl radicals and the absence of carbocation rearrangements in a variety of probe substrates disfavor the reaction proceeding via RPC. Intriguingly, no additional oxidant

Synthesis of imidazo[4,5-e][1,3]thiazino[2,3-c][1,2,4]triazines via a base-induced rearrangement of functionalized imidazo[4,5-e]thiazolo[2,3-c][1,2,4]triazines

• Dmitry B. Vinogradov,
• Alexei N. Izmest’ev,
• Angelina N. Kravchenko,
• Yuri A. Strelenko and
• Galina A. Gazieva

Beilstein J. Org. Chem. 2023, 19, 1047–1054, doi:10.3762/bjoc.19.80

• closely related hybrid compounds including fragments of 1,3-thiazine and imidazo-1,2,4-triazine is still highly relevant. Earlier we have demonstrated that imidazo[4,5-e]thiazolo[3,2-b]-1,2,4-triazines and their derivatives functionalized at position 6 are capable of undergoing skeletal rearrangements and

• spectra of compounds 4a and 5a in DMSO-d6 in the region of 4.3–9.0 ppm. 13C NMR GATED spectra of compounds 4a and 5a in DMSO-d6 in the region of 156.0–168.0 ppm. General view of 5a in the crystal in thermal ellipsoid representation (p = 80%). Base-induced transformations and rearrangements of

Copper-catalyzed N-arylation of amines with aryliodonium ylides in water

• Kasturi U. Nabar,
• Bhalchandra M. Bhanage and
• Sudam G. Dawande

Beilstein J. Org. Chem. 2023, 19, 1008–1014, doi:10.3762/bjoc.19.76

• in oxidation, C–C, C–X bond formation, rearrangements, and halogenation reactions [23][24][25]. Due to the nontoxic nature, easier preparation, and handling of the hypervalent iodine reagents, many researchers are attracted to unravel the chemistry and reactivity of these reagents. Amongst different

Bromination of endo-7-norbornene derivatives revisited: failure of a computational NMR method in elucidating the configuration of an organic structure

• Demet Demirci Gültekin,
• Arif Daştan,
• Yavuz Taşkesenligil,
• Cavit Kazaz,
• Yunus Zorlu and
• Metin Balci

Beilstein J. Org. Chem. 2023, 19, 764–770, doi:10.3762/bjoc.19.56

• rearrangements, as postulated by Novitskiy and Kutateladze do not occur spontaneously from neutral compounds without the intermediacy of carbocations. As it turns out, compound 3 in the authors’ scheme is one of the products we described in our original manuscript and is perfectly stable thermally and does not

Strategies in the synthesis of dibenzo[b,f]heteropines

• David I. H. Maier,
• Barend C. B. Bezuidenhoudt and
• Charlene Marais

Beilstein J. Org. Chem. 2023, 19, 700–718, doi:10.3762/bjoc.19.51

• authors postulated an intramolecular electrophilic substitution via a carbocation intermediate 42 (Scheme 9). Elliott et al. [47] investigated several methods to synthesise substituted dibenzo[b,f]azepines, which included the ring expansion of N-arylindoles 41 to synthesise 43 and the rearrangements of 9

Germacrene B – a central intermediate in sesquiterpene biosynthesis

• Houchao Xu and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2023, 19, 186–203, doi:10.3762/bjoc.19.18

• this multistep process is initiated by the abstraction of diphosphate to produce an allyl cation that subsequently undergoes typical cation reactions such as cyclisations by intramolecular attack of an olefin to the cationic centre, Wagner–Meerwein rearrangements, hydride or proton shifts. The process

Revisiting the bromination of 3β-hydroxycholest-5-ene with CBr₄/PPh₃ and the subsequent azidolysis of the resulting bromide, disparity in stereochemical behavior

• Christian Schumacher,
• Jas S. Ward,
• Kari Rissanen,
• Carsten Bolm and
• Mohamed Ramadan El Sayed Aly

Beilstein J. Org. Chem. 2023, 19, 91–99, doi:10.3762/bjoc.19.9

• ·OEt2 [12]. All of those results confirmed the involvement of regio- and stereospecific i-steroid and retro-i-steroid rearrangements. Later, tetrabutylammonium halides were used as cost effective and stable alternatives of TMS-based reagents [15]. Treatment of compound 4 (Scheme 1) with NaN3 in

Combining the best of both worlds: radical-based divergent total synthesis

• Kyriaki Gennaiou,
• Antonios Kelesidis,
• Maria Kourgiantaki and
• Alexandros L. Zografos

Beilstein J. Org. Chem. 2023, 19, 1–26, doi:10.3762/bjoc.19.1

• from ent-kaurane diterpenoids through carbocationic rearrangements [42]. Jungermatrobrunin A (89) [43] bears a highly oxidized scaffold with a unique bicyclo[3.2.1]octene backbone and an unprecedented peroxide bridge (Scheme 7). Natural product (−)-1α,6α-diacetoxyjungermannenone C (88) [43] was

Efficient synthesis of aziridinecyclooctanediol and 3-aminocyclooctanetriol

• Emine Salamci and
• Ayse Kilic Lafzi

Beilstein J. Org. Chem. 2022, 18, 1539–1543, doi:10.3762/bjoc.18.163

• versatility in numerous regio- and stereoselective ring opening and/or expansion reactions, as well as rearrangements [5]. The aziridine structural motif is present in natural products such as mitomycins and azinomycins (Figure 1) [1][5], which exhibit potent biological activities such as antitumor and

Cytochrome P450 monooxygenase-mediated tailoring of triterpenoids and steroids in plants

• Karan Malhotra and
• Jakob Franke

Beilstein J. Org. Chem. 2022, 18, 1289–1310, doi:10.3762/bjoc.18.135

• cycle can also lead to different reaction outcomes, e.g., rearrangements, desaturations or epoxidations. Multiple oxidation rounds, leading to aldehydes/ketones or carboxylic acids, are also commonly observed. Together, this versatile oxidative chemistry makes CYPs key enzymes in specialised metabolism

Understanding the competing pathways leading to hydropyrene and isoelisabethatriene

• Shani Zev,
• Marion Ringel,
• Ronja Driller,
• Bernhard Loll,
• Thomas Brück and
• Dan T. Major

Beilstein J. Org. Chem. 2022, 18, 972–978, doi:10.3762/bjoc.18.97

• pyrophosphate (FPP), and geranylgeranyl pyrophosphate (GGPP), to produce mono-, sesqui-, and diterpenes, respectively. The formation of terpenes relies on an assortment of carbocation steps like cyclization, methyl migrations, rearrangements, proton or hydride transfers, hydroxylations, and epoxidations. TPS

Inductive heating and flow chemistry – a perfect synergy of emerging enabling technologies

• Conrad Kuhwald,
• Sibel Türkhan and
• Andreas Kirschning

Beilstein J. Org. Chem. 2022, 18, 688–706, doi:10.3762/bjoc.18.70

• comparable to microwave-induced heating. In continuation of these studies a two-step sequence was developed which showed that Claisen rearrangements can be accelerated in water as solvent (Scheme 8B) [51]. The phenolate salt 11 was mixed with allyl bromide in a static mixer and inductively heated to 110 °C

Anomeric 1,2,3-triazole-linked sialic acid derivatives show selective inhibition towards a bacterial neuraminidase over a trypanosome trans-sialidase

• Peterson de Andrade,
• Sanaz Ahmadipour and
• Robert A. Field

Beilstein J. Org. Chem. 2022, 18, 208–216, doi:10.3762/bjoc.18.24

• of both enzymes in complex with DANA reveals a bulky hydrophobic loop that sits over the active site of TcTS (PDB code 1MS1 – coloured red) (Figure 5A) but is absent for neuraminidase (PDB code 2VK6 – coloured green) (Figure 5B). In this case, induced structural rearrangements caused DANA to be

Synthesis and late stage modifications of Cyl derivatives

• Phil Servatius and
• Uli Kazmaier

Beilstein J. Org. Chem. 2022, 18, 174–181, doi:10.3762/bjoc.18.19

• ][30][31], while others cyclodepsipeptides are strong actin binders [32][33]. Recently, we also became interested in the synthesis of the cyclic HDAC inhibitors. We developed syntheses for chlamydocin [34], Cyl-1 [35], and trapoxin [36] using either Claisen rearrangements [37][38] or Pd-catalyzed

• chirality transfer. With this positive results in hand, we incorporated 5 into the desired tetrapeptide 8. So far, we carried out peptide Claisen rearrangements only with small dipeptides, but never used longer peptide chains, such as tetrapeptides. We knew from previous work that the protecting groups on

• soluble and could easily be purified. Conclusion In conclusion, we could show that chelate Claisen rearrangements can be carried out in longer peptides, such as tetrapeptides, as long as acidic positions can be identified, and the amount of base can be adjusted accordingly. The formation of thiol-ene

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

• migrations via I to J would indeed be much easier. The final transformations involving two Wagner–Meerwein rearrangements through G and D can proceed smoothly. Isolation of guaia-1,11-dien-1-ol from patchouli oil Fractionation of patchouli oil by column chromatography resulted in the isolation of the new

The PIFA-initiated oxidative cyclization of 2-(3-butenyl)quinazolin-4(3H)-ones – an efficient approach to 1-(hydroxymethyl)-2,3-dihydropyrrolo[1,2-a]quinazolin-5(1H)-ones

• Alla I. Vaskevych,
• Nataliia O. Savinchuk,
• Ruslan I. Vaskevych,
• Eduard B. Rusanov,
• Oleksandr O. Grygorenko and
• Mykhailo V. Vovk

Beilstein J. Org. Chem. 2021, 17, 2787–2794, doi:10.3762/bjoc.17.189

• )-ones 7 upon action of bis(trifluoroacetoxy)iodobenzene (PIFA) (see Scheme 1D). A part from the well-known applications of hypervalent iodine compounds for oxidative rearrangements, fragmentations, halogenations and hydroxylations [37][38], they were also involved in the synthesis of N-heterocycles [39

α-Ketol and α-iminol rearrangements in synthetic organic and biosynthetic reactions

• Scott Benz and
• Andrew S. Murkin

Beilstein J. Org. Chem. 2021, 17, 2570–2584, doi:10.3762/bjoc.17.172

• features the 1,2-shift of an alkyl or aryl group. In the process, the hydroxy group is converted to a carbonyl and the aldehyde/ketone or imine is converted to an alcohol or amine. Such α-ketol/α-iminol rearrangements are used in a wide variety of synthetic applications including asymmetric synthesis

• , tandem reactions, and the total synthesis and biosynthesis of natural products. This review explores the use of α-ketol rearrangements in these contexts over the past two decades. Keywords: acyloin rearrangement; asymmetric synthesis; iminol rearrangement; ketol rearrangement; tandem reactions

• and pinacol/semipinacol rearrangements, the 1,2-shift does not require a leaving group or carbocation intermediate, as the neighboring π system is capable of accepting the migrating group. While the reaction is generally reversible, the product can be favored through four common strategies: (1) the

Targeting active site residues and structural anchoring positions in terpene synthases

• Anwei Hou and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2021, 17, 2441–2449, doi:10.3762/bjoc.17.161

• attack of an olefinic double bond to the cationic centre Wagner–Meerwein rearrangements, and proton or hydride migrations [2]. These multistep cascade reactions ultimately result in terpene hydrocarbons that are often (poly)cyclic and contain several stereogenic centres [3][4]. In some cases, water is

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90