Synthetic applications of the Cannizzaro reaction

• Bhaskar Chatterjee,
• Dhananjoy Mondal and
• Smritilekha Bera

Beilstein J. Org. Chem. 2024, 20, 1376–1395, doi:10.3762/bjoc.20.120

• potentially useful molecules. Keywords: Cannizzaro reaction; crossed-Cannizzaro; desymmetrization; Lewis acid catalyst; natural products; Introduction The synthesis of functionalized molecules with structural complexity has always been a challenge to synthetic chemists. The Cannizzaro reaction, in its

Competing electrophilic substitution and oxidative polymerization of arylamines with selenium dioxide

• Vishnu Selladurai and
• Selvakumar Karuthapandi

Beilstein J. Org. Chem. 2024, 20, 1221–1235, doi:10.3762/bjoc.20.105

• generally attributed of diaryl selenoxides such as compound 8 [39]. Despite the complexity, we could confirm the [M + H]+ ions of the isomeric monoselenides 4 and 5 from HRMS data (Figure S10, Supporting Information File 1). In addition to the above mentioned (possible) organoselenium compounds, the oxamide

The Ugi4CR as effective tool to access promising anticancer isatin-based α-acetamide carboxamide oxindole hybrids

• Carolina S. Marques,
• Aday González-Bakker and
• José M. Padrón

Beilstein J. Org. Chem. 2024, 20, 1213–1220, doi:10.3762/bjoc.20.104

• chemists regarding process formation of new bonds and synthesis of new scaffolds. In drug discovery and development, medicinal chemists struggle everyday towards the creation of new synthetic methods, driven by the increasing complexity of the molecules and taking into consideration economic and social

Stability trends in carbocation intermediates stemming from germacrene A and hedycaryol

• Naziha Tarannam,
• Prashant Kumar Gupta,
• Shani Zev and
• Dan Thomas Major

Beilstein J. Org. Chem. 2024, 20, 1189–1197, doi:10.3762/bjoc.20.101

• (GPP, FPP, GGPP) undergo highly complex cyclisation cascades forming terpenes and terpenoids that often have great structural complexity. For class I terpene synthases this multistep process is initiated by a heterolytic C–O bond cleavage, separating the diphosphate and isoprenoid ion pairs [3][4]. The

Innovative synthesis of drug-like molecules using tetrazole as core building blocks

• Jingyao Li,
• Ajay L. Chandgude,
• Qiang Zheng and
• Alexander Dömling

Beilstein J. Org. Chem. 2024, 20, 950–958, doi:10.3762/bjoc.20.85

• efficient synthetic accessibility of drug-like molecules is of key importance. Interestingly, over the years the complexity of molecules entering the market is steadily increasing, supposedly due to the increasing complexity of contemporary molecular targets. A major Swiss API CRO reported that the

• complexity of chemical synthesis towards novel drugs has almost doubled from eight chemical steps to an average of 14 in 2021 [1]. Therefore, the need for robust reactions compatible with many functional groups in complex molecules is an integral part in contemporary medicinal chemistry and drug development

• of the de novo approach and furthermore provides an extra efficiency, complexity and diversity in the same number of steps (Figure S1, Supporting Information File 1). Also, it offers a flexibility of placement of the tetrazole moiety in the scaffold and enables additional facile post-modifications

Enantioselective synthesis of β-aryl-γ-lactam derivatives via Heck–Matsuda desymmetrization of N-protected 2,5-dihydro-1H-pyrroles

• Arnaldo G. de Oliveira Jr.,
• Martí F. Wang,
• Rafaela C. Carmona,
• Danilo M. Lustosa,
• Sergei A. Gorbatov and
• Carlos R. D. Correia

Beilstein J. Org. Chem. 2024, 20, 940–949, doi:10.3762/bjoc.20.84

• complexity in a synthetic route. The palladium-catalyzed coupling of arenediazonium salts with olefins, the Heck–Matsuda reaction, has been instrumental in this strategy involving the desymmetrization of cyclic systems [3], especially five-membered substrates [4][5][6][7]. As we have demonstrated previously

Confirmation of the stereochemistry of spiroviolene

• Yao Kong,
• Yuanning Liu,
• Kaibiao Wang,
• Tao Wang,
• Chen Wang,
• Ben Ai,
• Hongli Jia,
• Guohui Pan,
• Min Yin and
• Zhengren Xu

Beilstein J. Org. Chem. 2024, 20, 852–858, doi:10.3762/bjoc.20.77

• cyclization mechanism of spiroviolene. Keywords: boron migration; diterpene; spiroviolene; stereochemistry; Introduction Terpenes represent one of the most fascinating families of natural products due to their structural complexity and diversity, as well as their indispensable biological functions that

Chemoenzymatic synthesis of macrocyclic peptides and polyketides via thioesterase-catalyzed macrocyclization

• Senze Qiao,
• Zhongyu Cheng and
• Fuzhuo Li

Beilstein J. Org. Chem. 2024, 20, 721–733, doi:10.3762/bjoc.20.66

• pikromycin and the aglycones in this family, 10-deoxymethynolide (24) and norbonolide (25), using asymmetric aldol reaction, Yamaguchi esterification, and ring-closing metathesis as key steps [65][66]. Nevertheless, the inherent complexity of these natural products demands high step counts, leading to low

Genome mining of labdane-related diterpenoids: Discovery of the two-enzyme pathway leading to (−)-sandaracopimaradiene in the fungus Arthrinium sacchari

• Fumito Sato,
• Terutaka Sonohara,
• Shunta Fujiki,
• Akihiro Sugawara,
• Yohei Morishita,
• Taro Ozaki and
• Teigo Asai

Beilstein J. Org. Chem. 2024, 20, 714–720, doi:10.3762/bjoc.20.65

• complexity. TCs are generally classified into two main classes, class I and class II. Class I TCs initiate the cyclization by heterolytic cleavage of substrates to generate a diphosphate anion and an allylic carbocation, and class II enzymes start cyclization by protonating a double bond or an epoxide

SOMOphilic alkyne vs radical-polar crossover approaches: The full story of the azido-alkynylation of alkenes

• Julien Borrel and
• Jerome Waser

Beilstein J. Org. Chem. 2024, 20, 701–713, doi:10.3762/bjoc.20.64

• , greatly increasing the molecular complexity of the starting substrate. Using radical chemistry would lead to a regioselective addition of azide radicals to the alkene, forming selectively the most stabilized C-centered radical. A prominent method for the generation of azide radicals relies on hypervalent

Production of non-natural 5-methylorsellinate-derived meroterpenoids in Aspergillus oryzae

• Jia Tang,
• Yixiang Zhang and
• Yudai Matsuda

Beilstein J. Org. Chem. 2024, 20, 638–644, doi:10.3762/bjoc.20.56

• strong inosine 5-monophosphate dehydrogenase inhibitor [6]. The biosynthesis of fungal meroterpenoids has garnered interest in the organic chemistry field due to their structural complexity and associated intriguing enzymatic reactions and has thus been extensively researched for over a decade, providing

Introduction of a human- and keyboard-friendly N-glycan nomenclature

• Friedrich Altmann,
• Johannes Helm,
• Martin Pabst and
• Johannes Stadlmann

Beilstein J. Org. Chem. 2024, 20, 607–620, doi:10.3762/bjoc.20.53

• an ultimate solution to this dilemma as we think it is not yet time to impose another layer of complexity onto the herein proposed model. On top, automatic converters will encounter difficulties with such side rules. Nevertheless, for “domestic needs” shall four options be presented (Scheme 1

Switchable molecular tweezers: design and applications

• Pablo Msellem,
• Maksym Dekthiarenko,
• Nihal Hadj Seyd and
• Guillaume Vives

Beilstein J. Org. Chem. 2024, 20, 504–539, doi:10.3762/bjoc.20.45

• that no new atoms are introduced into the molecule, thus ensuring first-order kinetics of the process without complexity. One of the possible mechanisms of redox-induced switching involves an intramolecular bond formation that introduces non-covalent interactions between tweezers endpoints leading to a

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

• solvent and anion effects add complexity to mechanistic interpretation, and the reluctance of alkylgold complexes to undergo protodeauration under similar conditions give us pause [28]. While computational studies support protodeauration, the significantly lower reactivity of alkenes compared to alkynes

Mechanisms for radical reactions initiating from N-hydroxyphthalimide esters

• Carlos R. Azpilcueta-Nicolas and
• Jean-Philip Lumb

Beilstein J. Org. Chem. 2024, 20, 346–378, doi:10.3762/bjoc.20.35

• reaction classes, we discuss the utility of the NHPI esters, with an eye towards their continued development in complexity-generating transformations. Keywords: decarboxylative couplings; mechanisms; NHPI-esters; radical reactions; Introduction The historical challenges of using radicals in synthetic

• stoichiometric electron donors, the presence of a TM catalyst, the formation of a charge-transfer complex, and the overall reaction conditions. While we hope that this discussion will spur the continued development of NHPI esters in complexity-generating transformations, it is not comprehensive, and we refer

Catalytic multi-step domino and one-pot reactions

• Svetlana B. Tsogoeva

Beilstein J. Org. Chem. 2024, 20, 254–256, doi:10.3762/bjoc.20.25

• atom efficiency, step and pot economies, decreased number of purification steps, or protecting-group-free synthesis. Multi-step domino [1][2] and one-pot [3] reactions represent a new powerful toolbox in organic synthesis to install molecular complexity economically and sustainably, starting from

Photochromic derivatives of indigo: historical overview of development, challenges and applications

• Gökhan Kaplan,
• Zeynel Seferoğlu and
• Daria V. Berdnikova

Beilstein J. Org. Chem. 2024, 20, 228–242, doi:10.3762/bjoc.20.23

• new level of complexity and promise. The photochromic indigos represent a relatively rare type of visible-light-responsive T-type photoswitches demonstrating negative photochromism. The absorption of the photoswitchable indigos covers the spectral range from green to NIR light (≈550–700 nm) making

Synthesis of the 3’-O-sulfated TF antigen with a TEG-N₃ linker for glycodendrimersomes preparation to study lectin binding

• Mark Reihill,
• Hanyue Ma,
• Dennis Bengtsson and
• Stefan Oscarson

Beilstein J. Org. Chem. 2024, 20, 173–180, doi:10.3762/bjoc.20.17

• to analyse when data were recorded in CDCl3. Changing the NMR solvent to CD3OD greatly reduced the complexity of the spectra [21][22][23]. Since 7 possessed an azido group as part of the linker, removal of the Troc group under reductive conditions was ruled out due to probable chemoselectivity issues

Perspectives on push–pull chromophores derived from click-type [2 + 2] cycloaddition–retroelectrocyclization reactions of electron-rich alkynes and electron-deficient alkenes

• Michio Yamada

Beilstein J. Org. Chem. 2024, 20, 125–154, doi:10.3762/bjoc.20.13

• multiple chromophore units induces complexity in the interpretation of the resulting circular dichroism (CD) spectra because of the overlap of several exciton couplets. Thus, exciton coupling CD signals were not discernible for 51–55. Further, regarding 56, the exciton coupling CD signal in the ICT region

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

• singlet state [10]. Although only a few analyses of the reaction mechanisms have been studied due to the complexity of the system, several intermediates inside the CNT have been proposed [3][11][12], which may be different from those proposed to take place in the gas phase or in the solid state at high

Optimizing reaction conditions for the light-driven hydrogen evolution in a loop photoreactor

• Pengcheng Li,
• Daniel Kowalczyk,
• Johannes Liessem,
• Mohamed M. Elnagar,
• Dariusz Mitoraj,
• Radim Beranek and
• Dirk Ziegenbalg

Beilstein J. Org. Chem. 2024, 20, 74–91, doi:10.3762/bjoc.20.9

• nitride; solar energy storage; Introduction The world is in the midst of the first truly global energy crisis with unprecedented breadth and complexity [1]. Meanwhile, the rise of the world’s population and economic growth demands more energy. Of all energy sources, fossil fuels have been dominating over

Studying specificity in protein–glycosaminoglycan recognition with umbrella sampling

• Mateusz Marcisz,
• Sebastian Anila,
• Margrethe Gaardløs,
• Martin Zacharias and
• Sergey A. Samsonov

Beilstein J. Org. Chem. 2023, 19, 1933–1946, doi:10.3762/bjoc.19.144

• complexity in decoding their sulfation pattern. Their charged nature necessitates the application of appropriate methods for electrostatics, ions, and solvent, particularly given their abundance in protein–GAG interfaces compared to complexes involving other classes of biomolecules. The periodicity can lead

• reflect the system's state under particular conditions with explicitly defined reaction coordinate values, the visualization of these continuous data potentially offers a more comprehensive insight into the complexity of the system related to its dynamic behavior within each window. Basic FGF Ligand 1

• potential of non-purely electrostatics dominance in the protein–GAG interactions. The more detailed analysis of the GAG recognition in this system in near-native states points out to the complexity of free energy landscape but at the same identifies the key charged H-bonding contributors to the GAG binding

Biphenylene-containing polycyclic conjugated compounds

• Cagatay Dengiz

Beilstein J. Org. Chem. 2023, 19, 1895–1911, doi:10.3762/bjoc.19.141

• ) [46]. This complexity arises from factors such as limited substrate versatility and the difficulty in incorporating solubilizing groups into the symmetric azaacene framework. In the initial stage, the condensation reactions between biphenylene-2,3-dione (52) and diaminothiadiazoles 55a,b resulted in

Active-metal template clipping synthesis of novel [2]rotaxanes

• Cătălin C. Anghel,
• Teodor A. Cucuiet,
• Niculina D. Hădade and
• Ion Grosu

Beilstein J. Org. Chem. 2023, 19, 1776–1784, doi:10.3762/bjoc.19.130

• , reported by Sauvage in 1983 [14], the synthetic strategies employed to access MIMs, including catenanes, rotaxanes and molecular knots, have grown in number and complexity of the obtained structures [15]. Thus, currently, synthesis of rotaxanes is usually performed through clipping, capping, snaping or

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

• ; biosynthesis; enzymes; NMR spectroscopy; terpenes; Introduction Terpene synthases are remarkable enzymes that can convert acyclic and achiral oligoprenyl pyrophosphates into terpene hydrocarbons or alcohols of high structural complexity. These enzymatic reactions are initiated by ionisation of the substrate