(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

• (±)-30. In a related strategy, Procter and co-workers prepared 1,2-BCHs (±)-33a–e from BCBs 32 via a SmI2-catalysed radical relay alkene insertion (Scheme 3C) [35]. This approach relied on single-electron reduction of the ketone moiety and ring-expansion from the ketyl radical anion. Electron-deficient

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

• carbene (NHC)-catalyzed radical relay, and (iv) mechanisms under electrochemical activation. By discussing selected literature examples, we illustrate how the activation mode of NHPI esters, and the reactivity of the resulting radical species, can vary depending upon the choice of catalytic or

• mechanism discussed in Scheme 7B. Lastly, radical–radical coupling between 64 and 147, accompanied by elimination of the NHC catalyst, yields ketone product 149. In subsequent studies, this NHC-catalyzed radical relay activation mode has been extended to the alkylation of aliphatic aldehydes [107] and to

Synthesis of ether lipids: natural compounds and analogues

• Marco Antônio G. B. Gomes,
• Alicia Bauduin,
• Chloé Le Roux,
• Romain Fouinneteau,
• Wilfried Berthe,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2023, 19, 1299–1369, doi:10.3762/bjoc.19.96

Photoredox catalysis harvesting multiple photon or electrochemical energies

• Mattia Lepori,
• Simon Schmid and
• Joshua P. Barham

Beilstein J. Org. Chem. 2023, 19, 1055–1145, doi:10.3762/bjoc.19.81

Photocatalytic sequential C–H functionalization expediting acetoxymalonylation of imidazo heterocycles

• Deepak Singh,
• Shyamal Pramanik and
• Soumitra Maity

Beilstein J. Org. Chem. 2023, 19, 666–673, doi:10.3762/bjoc.19.48

• from academia and industry. Herein, we report a direct C-3 acetoxymalonylation of imidazo heterocycles using relay C–H functionalization enabled by organophotocatalysis starring zinc acetate in the triple role of an activator, ion scavenger as well as an acetylating reagent. The mechanistic

• products with excellent yields and regioselectivity, thus confirming excellent functional group tolerability. Keywords: C–H functionalization; imidazo heterocycles; photoredox; regioselective; relay catalysis; Introduction Among all N-fused heterocycles, imidazo[1,2-a]pyridines (IPs) are the prevalent

• using air as the sole oxygen source. Keeping in mind the progress in photochemical relay catalysis [24] and the attention paid to photocatalytic carbon-bond functionalization in the past several years [25], here we developed an organophotoredox-catalyzed C–H functionalization of imidazo[1,2-a]pyridines

Total synthesis of grayanane natural products

• Nicolas Fay,
• Rémi Blieck,
• Cyrille Kouklovsky and
• Aurélien de la Torre

Beilstein J. Org. Chem. 2022, 18, 1707–1719, doi:10.3762/bjoc.18.181

• earliest synthetic efforts from 1971 to the latest in 2022. In a last part we will present unfinished syntheses. Review Early syntheses by Matsumoto and Shirahama The first synthetic approach towards a grayanane natural product was reported by Matsumoto in the 70s, using a relay approach. The authors first

• had previously reported a similar rearrangement for the synthesis of a grayanane-type skeleton [21]. Further methylation and protecting group interconversions lead to an advanced tricyclic structure 5, which could be further elaborated into relay intermediate 1. Although Matsumoto’s approach does not

• known to date. Thus, we anticipate that in the future, organic chemists will keep focusing on highly enantioselective, efficient and flexible synthetic strategies towards grayanane natural products. General structure of grayanane natural products. Grayanane biosynthesis. Matsumoto’s relay approach

Electrocatalytic C(sp³)–H/C(sp)–H cross-coupling in continuous flow through TEMPO/copper relay catalysis

• Bin Guo and
• Hai-Chao Xu

Beilstein J. Org. Chem. 2021, 17, 2650–2656, doi:10.3762/bjoc.17.178

• terminal alkynes has been achieved in a continuous-flow microreactor through 2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO)/copper relay catalysis. The reaction is easily scalable and requires low concentration of supporting electrolyte and no external chemical oxidants or ligands, providing straightforward

• electrocatalytic dehydrogenative cross-coupling reaction of tetrahydroisoquinolines with terminal alkynes in continuous flow (Scheme 1D). These reactions require low loadings of supporting electrolyte and proceed through Cu/TEMPO relay catalysis without need for additional ligands. Results and Discussion The

• through reversible reaction with this cationic species. Conclusion In summary, we have achieved the electrochemical dehydrogenation cross-coupling of tetrahydroisoquinolines with terminal alkynes in continuous flow through Cu/TEMPO relay catalysis. This work demonstrates that continuous-flow

Recent advances in organocatalytic asymmetric aza-Michael reactions of amines and amides

• Pratibha Sharma,
• Raakhi Gupta and
• Raj K. Bansal

Beilstein J. Org. Chem. 2021, 17, 2585–2610, doi:10.3762/bjoc.17.173

• high enantioselectivities (up to 65–91%) [40]. Rajasekar et al. developed an efficient one-pot tandem rhodium(II)/chiral squaramide relay catalysis for the enantioselective construction of dihydro-β-carbolines 37 from the Michael reaction of suitably substituted indole derivatives 34 with N-sulfonyl

Molecular basis for protein–protein interactions

• Brandon Charles Seychell and
• Tobias Beck

Beilstein J. Org. Chem. 2021, 17, 1–10, doi:10.3762/bjoc.17.1

• interactions; Introduction From signalling over transport to catalysis, the broad functionality of proteins is essential in the cellular machinery. To this effect, proteins can be seen as the workforce of the cell. Proteins relay some of their functionality via interactions between protein nodes called

Recent developments in enantioselective photocatalysis

• Callum Prentice,
• James Morrisson,
• Andrew D. Smith and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2020, 16, 2363–2441, doi:10.3762/bjoc.16.197

Clustering and curation of electropherograms: an efficient method for analyzing large cohorts of capillary electrophoresis glycomic profiles for bioprocessing operations

• Ian Walsh,
• Matthew S. F. Choo,
• Sim Lyn Chiin,
• Amelia Mak,
• Shi Jie Tay,
• Pauline M. Rudd,
• Yang Yuansheng,
• Andre Choo,
• Ho Ying Swan and
• Terry Nguyen-Khuong

Beilstein J. Org. Chem. 2020, 16, 2087–2099, doi:10.3762/bjoc.16.176

• (CQA) of most biologics. This necessitates control of glycosylation processing during a drug process development stage to ultimately relay a consistent glycosylation of the biologic product during manufacturing [6]. This is difficult because glycosylation during fermentation occurs with a high degree

An overview on disulfide-catalyzed and -cocatalyzed photoreactions

• Yeersen Patehebieke

Beilstein J. Org. Chem. 2020, 16, 1418–1435, doi:10.3762/bjoc.16.118

• nonpolar solvent, PhSSPh accelerates the [4 + 2] cycloaddition of the radical cation 19, but the electron-relay catalyst promotes the [2 + 2] cycloaddition. The radical cation 19 can undergo two different types of cyclizations, subject to the relative reactivity of its radical and cation center. The α

Combining enyne metathesis with long-established organic transformations: a powerful strategy for the sustainable synthesis of bioactive molecules

• Valerian Dragutan,
• Ileana Dragutan,
• Albert Demonceau and
• Lionel Delaude

Beilstein J. Org. Chem. 2020, 16, 738–755, doi:10.3762/bjoc.16.68

• related to the trinorsesquiterpene (−)‐clavukerin A, was also communicated by Metz et al. [79] using an enyne metathesis reaction as a key step. The authors performed a relay metathesis of the trienyne or diene–diyne precursors in the presence of the second-generation Grubbs catalyst (Scheme 14). The

• . Securinega alkaloids The total synthesis of the Securinega alkaloids, (−)-flueggine A (18) and (+)-virosaine B (19), which are potent anticancer agents, was proposed by Wei et al. [90] via a relay ring-closing metathesis (RRCM) associated with a 1,3-dipolar cycloaddition. The enyne precursors bearing a

• dienic relay unit, were prepared from Weinreb amide by an asymmetric pathway, were reacted with either the Grubbs second-generation catalyst, the Hoveyda–Grubbs second-generation catalyst, or the Zhan catalyst, the latter giving under the optimized conditions the highest yield of the expected

An efficient synthesis of the guaiane sesquiterpene (−)-isoguaiene by domino metathesis

• Yuzhou Wang,
• Ahmed F. Darweesh,
• Patrick Zimdars and
• Peter Metz

Beilstein J. Org. Chem. 2019, 15, 858–862, doi:10.3762/bjoc.15.83

• feature a domino metathesis event and an organocatalytic Michael addition as the key steps. In closer analogy to our improved synthesis of clavukerin A (2) [8], a relay metathesis [9] of trienyne 3 was expected to lead to the hydroazulene 1 selectively. Trienyne 3 was envisioned to result from a

• [11][12][13][14] of compound 7 or its relay surrogate 8 might give rise to the conjugated triene 6, chemoselective hydrogenation [15] of which would generate the target molecule 1. Similar to the disconnection of trienyne 3, the metathesis substrates 7 and 8 can be derived from aldehyde 9, which is

• finally also traced back to (S)-citronellal (5). Scheme 2 illustrates the synthesis of (−)-isoguaiene (1) by relay metathesis of trienyne 3. The unsaturated aldehyde 4 required for the organocatalytic Michael addition was readily prepared in five steps commencing with (S)-citronellal (5). After protection

Synthesis of the polyketide section of seragamide A and related cyclodepsipeptides via Negishi cross coupling

• Jan Hendrik Lang and
• Thomas Lindel

Beilstein J. Org. Chem. 2019, 15, 577–583, doi:10.3762/bjoc.15.53

• Suberites japonicus (Thiele) has been synthesized only once, with relay ring-closing metathesis being the key step [9]. Characteristically, seragamides A–E exhibit a L-threonine unit at the C-terminus of the peptide moiety. There is a considerable body of work on the synthesis of the C12 polyketide section

Local energy decomposition analysis of hydrogen-bonded dimers within a domain-based pair natural orbital coupled cluster study

• Ahmet Altun,
• Frank Neese and
• Giovanni Bistoni

Beilstein J. Org. Chem. 2018, 14, 919–929, doi:10.3762/bjoc.14.79

• importance for regulating molecular properties like polarizability [1] and in various biochemical processes, including protein folding [2] and stability [3], replication of DNA and RNA [4], enzyme catalysis [5], proton relay mechanism [6], and drug delivery [7]. Energy decomposition analysis (EDA) schemes

A mechanochemical approach to access the proline–proline diketopiperazine framework

• Nicolas Pétry,
• Hafid Benakki,
• Eric Clot,
• Pascal Retailleau,
• Farhate Guenoun,
• Fatima Asserar,
• Chakib Sekkat,
• Thomas-Xavier Métro,
• Jean Martinez and
• Frédéric Lamaty

Beilstein J. Org. Chem. 2017, 13, 2169–2178, doi:10.3762/bjoc.13.217

• bond distances associated to the transformation. In the transition state, the C–OMe bond cleavage was well advanced and the C–N bond formation was also almost complete. This indicated that the transformation was concerted and that the explicit methanol molecule only acted as a relay to accept the

The chemistry and biology of mycolactones

• Matthias Gehringer and
• Karl-Heinz Altmann

Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159

Total syntheses of the archazolids: an emerging class of novel anticancer drugs

• Stephan Scheeff and
• Dirk Menche

Beilstein J. Org. Chem. 2017, 13, 1085–1098, doi:10.3762/bjoc.13.108

• could successfully couple the three main fragments 39, 40 and 6 by first a Stille reaction, followed by a Kita esterification. Notably, this esterification was critical to avoid unfavorable isomerizations. For closing of the macrolide core they planned a challenging Hoye relay ring closing metathesis

• -catalysis to get the final fragment 54 in 32% yield [85][86]. The envisioned Hoye relay RCM was catalyzed by Grubbs’ second generation catalyst to close the macrocycle in 27% yield. The final acid-mediated deprotection liberated finally archazolid B (2). Notably, no cyclization was observed in an analogous

• RCM reaction with a substrate without the relay tether, which underscores the usefulness of this relay tactic. It is important to mention, that the three main fragments were coupled in only four steps, showing the highly modular approach from Trauner and co-workers. With this strategy it was possible

Modular synthesis of the pyrimidine core of the manzacidins by divergent Tsuji–Trost coupling

• Sebastian Bretzke,
• Stephan Scheeff,
• Felicitas Vollmeyer,
• Friederike Eberhagen,
• Frank Rominger and
• Dirk Menche

Beilstein J. Org. Chem. 2016, 12, 1111–1121, doi:10.3762/bjoc.12.107

• , variously substituted 6-membered heterocycles of type 9 may be obtained in a general and concise fashion. Notably, this anionic relay process may directly generate up to four new stereogenic centers and thus demonstrates a high increase in structural complexity from readily available starting materials

Opportunities and challenges for direct C–H functionalization of piperazines

• Zhishi Ye,
• Kristen E. Gettys and
• Mingji Dai

Beilstein J. Org. Chem. 2016, 12, 702–715, doi:10.3762/bjoc.12.70

• method, despite its relatively low yield and selectivity, does offer a rapid way to access potential drug metabolites or analogs for further biological evaluations. Free radical approach In 1994, Undheim and co-workers developed a radical relay strategy, using a progression from an aryl radical to an α

Interactions of cyclodextrins and their derivatives with toxic organophosphorus compounds

• Sophie Letort,
• Sébastien Balieu,
• William Erb,
• Géraldine Gouhier and
• François Estour

Beilstein J. Org. Chem. 2016, 12, 204–228, doi:10.3762/bjoc.12.23

• appears that the size of the cavity is not the only parameter to take into account. Indeed, the ability of CDs to relay radicals towards the phosphorus atom might be tuned by the geometrical disposition of the hydroxy groups of CDs. The origin of the higher efficiency of β-CD on the photodegradation might

• be due to the presence of a strong hydrogen bond network between the secondary hydroxy groups, which restricts their degree of liberty, and lets them to relay the active radicals toward the phosphorus atom. Hydrolysis of chemical warfare agents Accelerating nerve agent’s hydrolysis, CDs are

Profluorescent substrates for the screening of olefin metathesis catalysts

• Raphael Reuter and
• Thomas R. Ward

Beilstein J. Org. Chem. 2015, 11, 1886–1892, doi:10.3762/bjoc.11.203

• -methoxynaphthalene-1-sulfonamide moiety that is connected by an internal double bond to a 2,4-dinitroaniline core, acting as a fluorescence quencher [17]. Both the sulfonamide of the fluorophore and the aniline group of the quencher bear another allyl group. Upon relay ring-closing metathesis, the fluorophore and

Fe(II)/Et₃N-Relay-catalyzed domino reaction of isoxazoles with imidazolium salts in the synthesis of methyl 4-imidazolylpyrrole-2-carboxylates, its ylide and betaine derivatives

• Ekaterina E. Galenko,
• Olesya A. Tomashenko,
• Alexander F. Khlebnikov,
• Mikhail S. Novikov and
• Taras L. Panikorovskii

Beilstein J. Org. Chem. 2015, 11, 1732–1740, doi:10.3762/bjoc.11.189

• Emb. 7/9, 199034, St. Petersburg, Russia 10.3762/bjoc.11.189 Abstract A simple approach was developed for the synthesis of methyl 4-imidazolylpyrrole-2-carboxylates from easily available compounds, 5-methoxyisoxazoles and phenacylimidazolium salts under hybrid Fe(II)/Et3N relay catalysis. The

• reaction with sulfur affording the corresponding imidazolethiones under very mild conditions. Keywords: imidazole; isoxazole; NHC carbene; pyrrole-2-carboxylate; relay catalysis; Introduction Pyrrole-2-carboxyate and imidazole units are present in bioactive pyrrole-imidazole alkaloids and pyrrole

• -dicarbonyl compounds under relay catalysis [31]. Taking into account the facts discussed above, we envisioned that the synthesis of 5-alkoxycarbonylpyrrol-3-ylimidazolium salts 1 could be carried out starting from easily available 5-alkoxyisoxazoles 7 [32][33] and 1-alkyl-3-phenacyl-1H-imidazolium bromides 9

Active site diversification of P450cam with indole generates catalysts for benzylic oxidation reactions

• Paul P. Kelly,
• Anja Eichler,
• Susanne Herter,
• David C. Kranz,
• Nicholas J. Turner and
• Sabine L. Flitsch

Beilstein J. Org. Chem. 2015, 11, 1713–1720, doi:10.3762/bjoc.11.186

• . Threonines in libraries II and III were often substituted for Phe, Gly or aliphatic side chains. The OH group was also frequently preserved by substitution with Ser, which in library V was always the case. Thr252 (library V) is involved in a proton relay network that promotes O–O bond scission during