Assembly strategy for thieno[3,2-b]thiophenes via a disulfide intermediate derived from 3-nitrothiophene-2,5-dicarboxylate

• Roman A. Irgashev

Beilstein J. Org. Chem. 2025, 21, 2489–2497, doi:10.3762/bjoc.21.191

• LiH and Mg(OMe)2 chosen for the cyclization are convenient from the point of view of availability and work safety. Indeed, LiH is not a pyrophoric hydride compared to other alkali metal hydrides, NaH or KH, while Mg(OMe)2 is easily prepared by dissolving I2-activated Mg metal in dry methanol

Recent advances in Norrish–Yang cyclization and dicarbonyl photoredox reactions for natural product synthesis

• Peng-Xi Luo,
• Jin-Xuan Yang,
• Shao-Min Fu and
• Bo Liu

Beilstein J. Org. Chem. 2025, 21, 2315–2333, doi:10.3762/bjoc.21.177

• moderate diastereoselectivity; this was followed by Mn(III)-catalyzed metal-hydride hydrogen atom (MHAT) transfer to reduce the endocyclic olefin, forming 41 as a single diastereomer. Subsequent transformations – including a Wittig reaction, demethylation, and oxidation of the resulting phenol to a p

Enantioselective radical chemistry: a bright future ahead

• Anna C. Renner,
• Sagar S. Thorat,
• Hariharaputhiran Subramanian and
• Mukund P. Sibi

Beilstein J. Org. Chem. 2025, 21, 2283–2296, doi:10.3762/bjoc.21.174

• excess of radical precursor, (d) use of toxic H-atom sources such as tin hydride, and (e) limited variation in the nature of the radicals (mostly nucleophilic). Organocatalyzed radical reactions Chiral secondary amine-based catalytic systems have been used in several asymmetric transformations [41][42

Pathway economy in cyclization of 1,n-enynes

• Hezhen Han,
• Wenjie Mao,
• Bin Lin,
• Maosheng Cheng,
• Lu Yang and
• Yongxiang Liu

Beilstein J. Org. Chem. 2025, 21, 2260–2282, doi:10.3762/bjoc.21.173

• addition happened to generate the spiroindoleninium intermediate. This transient species was subsequently trapped by water physisorbed in the silica gel, forming hemiaminal adduct 132. A 1,5-hydride shift was then mediated by Al2O3, ultimately affording the spiro[indoline-3,3'-pyrrolidin]-2-one derivatives

Aryl iodane-induced cascade arylation–1,2-silyl shift–heterocyclization of propargylsilanes under copper catalysis

• Rasma Kroņkalne,
• Rūdolfs Beļaunieks,
• Armands Sebris,
• Anatoly Mishnev and
• Māris Turks

Beilstein J. Org. Chem. 2025, 21, 1984–1994, doi:10.3762/bjoc.21.154

• species are limited to aryl- [7][8][10] or heteroaryl groups [7][8]. In one example methyl ethers were used [9]. Under [Pd]-catalyzed conditions a syn-type addition is observed [8][11], while [Cu] catalysts promote anti-addition [7][10]. In substrates prone to cationic rearrangements (or hydride shifts

Photochemical reduction of acylimidazolium salts

• Michael Jakob,
• Nick Bechler,
• Hassan Abdelwahab,
• Fabian Weber,
• Janos Wasternack,
• Leonardo Kleebauer,
• Jan P. Götze and
• Matthew N. Hopkinson

Beilstein J. Org. Chem. 2025, 21, 1973–1983, doi:10.3762/bjoc.21.153

• electron and a hydrogen atom from the amine to the excited carbonyl species, and analysis of the computed charge distributions indicates that these processes occur simultaneously in what can be best described as a formal hydride ion transfer. Addition/elimination of E into the carbonyl group of a second

Enantioselective desymmetrization strategy of prochiral 1,3-diols in natural product synthesis

• Lihua Wei,
• Rui Yang,
• Zhifeng Shi and
• Zhiqiang Ma

Beilstein J. Org. Chem. 2025, 21, 1932–1963, doi:10.3762/bjoc.21.151

• bromide 71 in two steps. Lipase PS-mediated desymmetrization of 72 with vinyl butanoate provided monoester 73 in 90% yield with 97% ee. To obtain (S)-Rosaphen (74), monoester 73 was converted via mesylation followed by hydride reduction. In contrast, the synthesis of (R)-Rosaphen (75) required a four-step

• sequence comprising TBS protection, ester hydrolysis, mesylation, and hydride reduction. In 2014, Tokuyama and co-workers accomplished the total synthesis of (−)-petrosin and (+)-petrosin, two marine-derived bisquinolizidine alkaloids [45]. They first completed the synthesis of (−)-petrosin (84) (Scheme

• . Epoxidation of 131 followed by methylation generated epoxide 132. Construction of the lactone moiety commenced with the oxidative cleavage of the double bond, and the resulting carboxylic acid underwent intramolecular cyclization in the presence of BF3·Et2O to give lactone 133. Subsequent hydride reduction

Convenient alternative synthesis of the Malassezia-derived virulence factor malassezione and related compounds

• Karu Ramesh and
• Stephen L. Bearne

Beilstein J. Org. Chem. 2025, 21, 1730–1736, doi:10.3762/bjoc.21.135

• -protected malassezione, which upon deprotection yields malassezione in an overall yield of ca. 20%. This is an improvement over the preparation of the isonitrile followed by an Fe hydride initiated isonitrile–olefin intramolecular coupling reaction, which generated malassezione with an overall yield of ca

• [20], or, more recently, (iii) prepared via an Fe hydride initiated isonitrile–olefin intramolecular coupling reaction (Scheme 1A) [18]. The reported synthetic route relies on an initial 4-step preparation of the isonitrile precursor, which was accomplished in an overall yield of ca. 14%. The

• . 20% (4 steps) relative to an overall yield of ca. 5% via the preparation of the isonitrile followed by the Fe hydride initiated isonitrile–olefin intramolecular coupling reaction [18]. Protection of the indole nitrogens with the Boc group was preferable to the use of benzyl protecting groups since

Heterologous biosynthesis of cotylenol and concise synthesis of fusicoccane diterpenoids

• Ye Yuan,
• Zhenhua Guan,
• Xue-Jie Zhang,
• Nanyu Yao,
• Wenling Yuan,
• Yonghui Zhang,
• Ying Ye and
• Zheng Xiang

Beilstein J. Org. Chem. 2025, 21, 1489–1495, doi:10.3762/bjoc.21.111

• Nozaki–Hiyama–Kishi reaction and a one-pot Prins cyclization/transannular hydride transfer to construct the 5-8-5 tricyclic scaffold. Enzymatic oxidations were used to install the hydroxy group at the C-3 position. Ten fusicoccanes were synthesized in 8–13 steps each. Despite these efforts, a strategy

Copper catalysis: a constantly evolving field

• Elena Fernández and
• Jaesook Yun

Beilstein J. Org. Chem. 2025, 21, 1477–1479, doi:10.3762/bjoc.21.109

• hydride catalysis, and enantiotopic group-selective allylations of 1,1-diborylalkanes as core strategies. At the same time, the authors provide detailed mechanistic insights into the stereocontrol and provide a perspective on currently unresolved challenges in the field. Concerning Full Research Papers

• allenes with diisobutylaluminum hydride, which is followed by the allylation with p-toluenesulfonyl cyanide in a regio- and stereoselective manner. They propose a new way to access accessing acyclic β,γ-unsaturated nitriles with α-all-carbon quaternary centers. In the process, they managed to achieve a

Oxetanes: formation, reactivity and total syntheses of natural products

• Peter Gabko,
• Martin Kalník and
• Maroš Bella

Beilstein J. Org. Chem. 2025, 21, 1324–1373, doi:10.3762/bjoc.21.101

• homoallylic alcohols 18/19 via metal hydride atom transfer/radical polar crossover (MHAT/RPC) method (Scheme 6) [41]. This mild and high-yielding protocol displays good functional group tolerance and has a broad substrate scope, even providing access to medicinally relevant spirooxetanes. The proposed MHAT

• /RPC mechanism starts with a single-electron oxidation of the cobalt catalyst followed by a reaction with the siloxane to generate a cobalt–hydride complex. Subsequent hydride transfer to the alkene produces radical pair 23 which collapses to alkylcobalt intermediate 24. Another single-electron

Recent advances in oxidative radical difunctionalization of N-arylacrylamides enabled by carbon radical reagents

• Jiangfei Chen,
• Yi-Lin Qu,
• Ming Yuan,
• Xiang-Mei Wu,
• Heng-Pei Jiang,
• Ying Fu and
• Shengrong Guo

Beilstein J. Org. Chem. 2025, 21, 1207–1271, doi:10.3762/bjoc.21.98

• either a 1,5-hydride shift to give D or a direct cyclization with the aryl ring via intermediate E, which upon deprotonation lead to the final products 16 and 17. In a 2016 study by Van der Eycken’s group (Scheme 9), an innovative copper-catalyzed alkylarylation of activated alkenes using isocyanides as

• alkyl chloride and generating an alkyl–PdI–Cl radical hybrid species III. The alkyl radical then adds to the acrylamide double bond, forming a quaternary carbon radical intermediate IV. This intermediate undergoes intramolecular radical cyclization onto the aromatic ring, followed by either β-hydride

A versatile route towards 6-arylpipecolic acids

• Erich Gebel,
• Cornelia Göcke,
• Carolin Gruner and
• Norbert Sewald

Beilstein J. Org. Chem. 2025, 21, 1104–1115, doi:10.3762/bjoc.21.88

• , heterogeneous catalytic hydrogenation of the enamine with palladium on carbon was chosen. While the hydride reduction of the acyliminium intermediate gave a nearly 1:1 diastereomer ratio, a 9:1 ratio was obtained for the catalytic hydrogenation (Scheme 4). While the hydride reduction of the N-acyliminium

Recent advances in synthetic approaches for bioactive cinnamic acid derivatives

• Betty A. Kustiana,
• Galuh Widiyarti and
• Teni Ernawati

Beilstein J. Org. Chem. 2025, 21, 1031–1086, doi:10.3762/bjoc.21.85

• intermediate 168 formed through hydride transfer from 167 (Scheme 54A) [95]. Similarly, Huang and co-workers (2020) employed the same NHC catalyst but used ambient air as the external oxidant for acyl azolium intermediate formation (Scheme 54B) [96]. On the other hand, Ohshima and co-workers (2020) directly

• been successfully done for this method. Similarly, Hou and co-workers (2022) also used CO2 to carry out an auto-tandem Cu-catalyzed carboxylation of styrenes via β-hydride elimination (208) (Scheme 60B) [104]. Impressively, several natural product-like compounds (e.g., 207) were successfully prepared

• -branched (L/B) selectivity of >20:1. The reaction involves the formation of palladium hydride (Pd–H) 270 as the key species followed by alkyne and CO insertion reactions via 271 and 272 (Scheme 68A) [116]. On the one hand, Jia and co-workers (2021) utilized environmentally benign water as the hydrogen

A convergent synthetic approach to the tetracyclic core framework of khayanolide-type limonoids

• Zhiyang Zhang,
• Jialei Hu,
• Hanfeng Ding,
• Li Zhang and
• Peirong Rao

Beilstein J. Org. Chem. 2025, 21, 926–934, doi:10.3762/bjoc.21.75

• at C10 was then introduced via a Michael addition (MeMgBr, CuI) to afford 22 in a yield of 65% (4:1 dr at C10). Initial attempts on the carbonyl 1,2-transposition protocol reported by Dong and co-workers were ineffective [45], leading to premature hydride termination and the formation of alkene 23

Regioselective formal hydrocyanation of allenes: synthesis of β,γ-unsaturated nitriles with α-all-carbon quaternary centers

• Seeun Lim,
• Teresa Kim and
• Yunmi Lee

Beilstein J. Org. Chem. 2025, 21, 800–806, doi:10.3762/bjoc.21.63

• Seeun Lim Teresa Kim Yunmi Lee Department of Chemistry, Kwangwoon University, Seoul 01897, Republic of Korea 10.3762/bjoc.21.63 Abstract This study introduces a highly selective hydrocyanation method based on copper-catalyzed hydroalumination of allenes with diisobutylaluminum hydride, followed

• cyanating reagents, such as p-toluenesulfonyl cyanide (TsCN) and N-cyano-N-phenyl-p-toluenesulfonamide [29]. The hydroboration of allenes with 9-BBN (9-borabicyclo[3.3.1]nonane) as the hydride source, followed by regioselective cyanation with allylic boranes, provided nitrile-substituted quaternary carbon

• -catalyzed regioselective hydroalumination of allenes using diisobutylaluminum hydride (DIBAL-H), we envisioned that the nucleophilic attack of allylaluminum reagents on electrophilic cyanating reagents could provide a regioselective pathway for the synthesis of alkyl nitriles bearing quaternary carbon

Asymmetric synthesis of fluorinated derivatives of aromatic and γ-branched amino acids via a chiral Ni(II) complex

• Maurizio Iannuzzi,
• Thomas Hohmann,
• Michael Dyrks,
• Kilian Haoues,
• Katarzyna Salamon-Krokosz and
• Beate Koksch

Beilstein J. Org. Chem. 2025, 21, 659–669, doi:10.3762/bjoc.21.52

• (II) complex of bisTfMePhe have differed significantly. Here, sodium hydride (NaH) was identified as optimal base leading to a yield of 85% when using DMF as solvent at 0 °C to room temperature (Table 2, entry 4). Testing different base equivalents, solvents, solvent mixtures and temperatures didn’t

• ) complex 1 was synthesized according the procedure described by Romoff et al. [16]. Sodium hydride was used as a 60% dispersion in mineral oil. Triethylamine was dried over CaH2 and distilled freshly before use. Perfluorobutanesulfonyl fluoride was dried over CaCl2 and freshly distilled before use. Other

Recent advances in allylation of chiral secondary alkylcopper species

• Minjae Kim,
• Gwanggyun Kim,
• Doyoon Kim,
• Jun Hee Lee and
• Seung Hwan Cho

Beilstein J. Org. Chem. 2025, 21, 639–658, doi:10.3762/bjoc.21.51

• transmetalation of organolithium and organoboron compounds, copper hydride catalysis, and enantiotopic-group-selective transformations of 1,1-diborylalkanes. Detailed mechanistic insights into stereochemical control and current challenges in this field are also discussed. Keywords: allylic substitution; chiral

• transfer (TS2). The structural features of the tert-butyl group allow more efficient pyramidalization compared to the rigid adamantyl framework, suggesting that the flexibility of the transferring group plays a crucial role in facilitating transmetalation. Copper hydride chemistry for enantioselective

• allylic substitution reactions Among the various approaches in copper-catalyzed asymmetric allylic substitution, copper hydride (CuH) catalysis has received significant attention due to its unique ability to generate configurationally well-defined chiral organocopper species 28 under mild conditions

Total synthesis of (±)-simonsol C using dearomatization as key reaction under acidic conditions

• Xiao-Yang Bi,
• Xiao-Shuai Yang,
• Shan-Shan Chen,
• Jia-Jun Sui,
• Zhao-Nan Cai,
• Yong-Ming Chuan and
• Hong-Bo Qin

Beilstein J. Org. Chem. 2025, 21, 601–606, doi:10.3762/bjoc.21.47

• DIPEA, affording compound 17 with an 89% yield [11]. For the following alkylation step with tert-butyl bromoacetate, three bases were tested: potassium carbonate, cesium carbonate, and sodium hydride. Considering the targeted alkylation of a phenolic hydroxy group and the pKa requirements of this

• consumption of the starting material. Subsequently, when the base was changed to the stronger base sodium hydride [12], the reaction proceeded much better. Within 2 hours, the starting material was completely converted, yielding compound 18 with 95% isolated yield. Proton abstraction of the hydrogen in the α

Dioxazolones as electrophilic amide sources in copper-catalyzed and -mediated transformations

• Seungmin Lee,
• Minsuk Kim,
• Hyewon Han and
• Jongwoo Son

Beilstein J. Org. Chem. 2025, 21, 200–216, doi:10.3762/bjoc.21.12

• motifs such as a benzofuran, indazole, and quinoline were also shown to undergo the desired Markovnikov amidation with high efficiency (23j–l). Several mechanistic experiments were performed to rationalize the reaction pathways. As shown in Figure 7, copper hydride, generated from a copper precatalyst

• the targeted amidated product upon protonation, while simultaneously regenerating the active copper hydride species. 2.2 Hydroamidation of alkynes In 2022, Sato and co-workers introduced a copper-catalyzed hydroamidation of alkynes 25 using dioxazolones 24 as amide sources (Scheme 9) [99]. A

Recent advances in electrochemical copper catalysis for modern organic synthesis

• Yemin Kim and
• Won Jun Jang

Beilstein J. Org. Chem. 2025, 21, 155–178, doi:10.3762/bjoc.21.9

• remains a significant challenge owing to the high energy barrier required for oxidative addition and facile β-hydride elimination [12]. The development of radical approaches facilitated by transition-metal catalysis has provided a promising solution to overcome the limitations of conventional coupling

• . First, TEMPO is converted to TEMPO+ through anodic oxidation, and iminium intermediate 15 is created through hydride transfer from THIQ (13) to TEMPO+. TEMPO–H, generated during the hydrogen transfer step, then returns to TEMPO+ through anodic oxidation. Chiral acetylide species 17 is produced from the

• (Figure 15) [70]. In this catalytic system, catalytic amounts of Cu(sBOX) (L3) and Co(salen) complexes promote the formation of chiral nitriles 89 in the presence of PhSiH3 (88) as the hydride source and TMSCN (21) as the cyanide source via the effective sequential addition of a hydrogen atom and a CN

Cu(OTf)₂-catalyzed multicomponent reactions

• Sara Colombo,
• Camilla Loro,
• Egle M. Beccalli,
• Gianluigi Broggini and
• Marta Papis

Beilstein J. Org. Chem. 2025, 21, 122–145, doi:10.3762/bjoc.21.7

• intermediate XXXV. Finally, the final product 35 is yielded via a 1,3-hydride shift. The reaction between diazo derivatives, nitriles, and azodicarboxylates catalyzed by Cu(OTf)2 is an efficient synthetic method to obtain 2,3-dihydro-1,2,4-triazole derivatives 36 (Scheme 27) [45]. The reaction proceeds via a

Facile one-pot reduction of β-nitrostyrenes to phenethylamines using sodium borohydride and copper(II) chloride

• Laura D’Andrea and
• Simon Jademyr

Beilstein J. Org. Chem. 2025, 21, 39–46, doi:10.3762/bjoc.21.4

• reduction can be accomplished via catalytic hydrogenation, involving stepwise reactions and workup, use of additional reagents, and reaction time between 3 and 24 hours [11][12]. Most commonly, metal hydrides are employed, typically lithium aluminum hydride [13][14][15][16][17][18], requiring an inert

• aluminum hydride, sodium borohydride is a non-pyrophoric and easy-to-handle reducing agent. Since the first attempts in 1967, NaBH4 has been employed to reduce β-nitrostyrene scaffolds to the corresponding nitroalkanes [19][20][21]. Several catalysts have been combined with NaBH4 to facilitate full

Giese-type alkylation of dehydroalanine derivatives via silane-mediated alkyl bromide activation

• Perry van der Heide,
• Michele Retini,
• Fabiola Fanini,
• Giovanni Piersanti,
• Francesco Secci,
• Daniele Mazzarella,
• Timothy Noël and
• Alberto Luridiana

Beilstein J. Org. Chem. 2024, 20, 3274–3280, doi:10.3762/bjoc.20.271

• derivatives. Upon abstraction of a hydride from tris(trimethylsilyl)silane (TTMS) by an excited benzophenone derivative, the formed silane radical can undergo a XAT with an alkyl bromide to generate an alkyl radical. Consequently, the alkyl radical undergoes a Giese-type reaction with the Dha derivative

Synthesis of spiroindolenines through a one-pot multistep process mediated by visible light

• Francesco Gambuti,
• Jacopo Pizzorno,
• Chiara Lambruschini,
• Renata Riva and
• Lisa Moni

Beilstein J. Org. Chem. 2024, 20, 2722–2731, doi:10.3762/bjoc.20.230

• and highly reactive BrCCl3 radical anion. Anyway, the N-Ph-THIQ can undergo numerous pathways towards the iminium ion 1a (see reference [28] for details). The oxidation of compound 2d may occur according to the same mechanism. However, alternative mechanisms, such as the direct hydride transfer from