The trans-influence in gold chemistry from a catalytic perspective

• Manfred Bochmann

Beilstein J. Org. Chem. 2026, 22, 838–856, doi:10.3762/bjoc.22.66

• trialkylphosphines, anionic carbon and hydride ligands. N- and O-lone pair donors (pyridine, water) are weak ligands. The following indicative series is typical for Pt(II), although there may be slight variations in the specific ordering depending on the complex type under investigation: CO, CN−, C2H4 > P(alkyl)3

• (II) congener, K[PtCl3(ethylene)] [28], as well as the first examples of gold(III) alkyne [29], CO [30], hydride [31] and σ-complexes [32] (Scheme 3). The olefin complexes were isolated as microcrystalline powders which as dry solids are fairly stable in air at room temperature. The olefin bonding is

• , the hydride ligand is an ideal system for assessing the influence of a trans-ligand. Likewise, 1H NMR chemical shifts are amenable to high-level computations, which provide evidence for the molecular orbital changes that underly the observed chemical shifts. Kaupp and co-workers employed quasi

Synthesis and structural elucidation of a novel bis-spirooxindole from isatin and ethylenediamine

• Irene Moreno-Gutiérrez,
• Josefa L. López-Martínez,
• Sonia Berenguel-Gómez,
• Irene Torres-García,
• Duane Choquesillo-Lazarte,
• Manuel Muñoz-Dorado,
• Miriam Álvarez-Corral and
• Ignacio Rodríguez-García

Beilstein J. Org. Chem. 2026, 22, 813–820, doi:10.3762/bjoc.22.63

• NaBH4 or by the ethylenediamine acting as a hydride donor. In addition, if the formation of 28 by addition of the enol of 27 to the imine were reversible (and the reduction step irreversible), then the more stable, dipole-opposed C2-symmetric structure for 28 should be dominant, thus explaining the

Design, synthesis, and biological evaluation of FXR/ASK1 dual-target modulators

• Xi Zhang,
• Jingyan Wang,
• Ziqiang Zhao,
• Caiyi Wang,
• Zenghui Ye,
• Wei-Yuan Ma,
• Jian-Xing Xu and
• Fengzhi Zhang

Beilstein J. Org. Chem. 2026, 22, 771–781, doi:10.3762/bjoc.22.59

• II with NCS, followed by cyclization with methyl 3-cyclopropyl-3-oxopropionate, furnished isoxazole IV. Reduction of IV with lithium aluminum hydride gave alcohol V, which was then brominated with phosphorus tribromide to yield the desired isoxazole intermediate 2 in five steps (Scheme 4) [31]. The

• LiOH or lithium aluminum hydride to obtain compounds Z4–7. The synthesis of compounds Z8–15 followed a similar preparation procedure as for Z1–7. The synthesis of target compounds Z16–29 is illustrated in Scheme 7. Intermediates 8 and 10 were synthesized by the Suzuki cross-coupling reaction using

• dioxaborolane 7 or boronic acid 9 and IXa–c. Next, Z16–18 and Z23–25 were obtained by Williamson ether synthesis from the intermediates 8, 10 and isoxazole intermediates 2. Finally, hydrolysis in the presence of LiOH and reduction in the presence of lithium aluminum hydride provided target compounds Z19–22 and

Rongalite addition to dienones: diastereoselectivity in cyclic sulfone synthesis; stereochemical rationalization and prospects as a general conjugate nucleophile

• Melina Goga,
• Hao Zong,
• James Franco,
• Jazmine Prana,
• Rudolph Michel,
• Antonia Muro,
• Elana Rubin,
• Janet Brenya,
• Henk Eshuis and
• Magnus W. P. Bebbington

Beilstein J. Org. Chem. 2026, 22, 742–752, doi:10.3762/bjoc.22.56

• 1b was provided by derivatization of both molecules in ways that confirmed their relative stereochemistry by taking advantage of the different symmetry elements present in each case. Thus, both reductive amination and hydride reduction of C2-symmetric 1a led to the isolation of the only possible

• (chiral) diastereomer of the products 3 and 4 in each case – reaction of the nucleophile with either face of the iminium ion or ketone gives the same diastereomer, as illustrated. By contrast, hydride reduction of 1b gave an approx. 9:1 mixture of products 5 and 6, as judged by the crude 1H NMR spectrum

• . The major product was isolated and assigned as 5 (from axial attack of a small hydride reagent) [24]. From analysis of the NMR spectra of 5, it was clear that the molecule retained symmetry following reduction, reflected in the reduced number of signals in both 1H and 13C spectra compared to alcohol 4

Hydrogen production from formic acid catalyzed by NHC–Cu complexes

• Orlando Santoro and
• Catherine S. J. Cazin

Beilstein J. Org. Chem. 2026, 22, 620–627, doi:10.3762/bjoc.22.48

• equimolar mixture of H2 and CO2. The efficiency of the catalysis showed to be strongly dependent on the nature of the amine. Keywords: copper N-heterocyclic carbene; formic acid dehydrogenation; hydrogen storage; metal hydride; silanes; Introduction The discovery and utilization of alternative and

• )] (1a) with formic acid provides the formato species [Cu{OC(O)H}(IPr)] (1b) [52][53]. It was hypothesized that the thermal decarboxylation of 1b would generate in situ a highly reactive hydride species. The reaction of the latter with formic acid would regenerate the formato complex and release H2

• decomposition of its corresponding hydride species with respect to the IPr-based analogues. Remarkably, catalyst loadings as low as 1 mol % with complex 1a proved to promote the reaction, albeit at a slower rate (Figure 2d). Finally, at 40 °C and with only 0.1 mol % of 1a and 1 equivalent of PhSiH3 (Figure 2e

Computational prediction of C–H hydricities and their use in predicting the regioselectivity of electron-rich C–H functionalisation reactions

• Rasmus M. Borup,
• Nicolai Ree and
• Jan H. Jensen

Beilstein J. Org. Chem. 2026, 22, 603–610, doi:10.3762/bjoc.22.46

• of 3278 C–H sites across 740 molecules to train a machine learning (ML) model based on CM5 atomic charge descriptors, achieving an MAE of 2.30 kcal/mol and an RMSE of 3.74 kcal/mol relative to QM-computed hydricities. The method was further applied to 250 hydride transfer-like reactions, including C

• host of other reactivity predictors. Keywords: bond dissociation energy; hydricity; hydride affinity; hydride-transfer reactions; machine learning (ML); quantum chemistry (QM); Introduction Bond dissociation energies (BDEs) and pKa values for C–H bonds are often used to rationalise and predict the

• train ML models. Quantum chemistry-based workflow Following our previous work [3][8][9][10][11], we present a fully automated QM-based workflow that computes C–H hydricities. DMSO was chosen as solvent as most compounds (26/35) were experimentally measured in that medium. Hydride abstraction is carried

Modern synthetic pathways towards eribulin and its subunits

• Sebastian Dominik Graf

Beilstein J. Org. Chem. 2026, 22, 495–526, doi:10.3762/bjoc.22.37

• -moiety and reprotection with (iPr)2SiHCl afforded 75. The addition of BF3·OEt2 at low temperatures induced the fluorination of the silane protecting group and a follow-up intramolecular hydride transfer (via 76). Afterwards, the introduced fluoride was substituted with Mg(OMe)2 in MeOH and the

• known procedure [79]. Acidic treatment in MeOH and subsequent addition of MeLi furnished full acetal 301 (Scheme 35). Treatment with Tf2NPh yielded an intermediate enol triflate, which underwent a β-hydride elimination towards allene 302 upon addition of Pd2(dba)3. Next, ring opening of the full acetal

Dialkylaminoalkylation of β-ketosulfones via ring-opening of 3-sulfonylpyrrolidines

• Evgeny M. Buev,
• Alexander V. Pavlushin,
• Vladimir S. Moshkin and
• Vyacheslav Y. Sosnovskikh

Beilstein J. Org. Chem. 2026, 22, 383–389, doi:10.3762/bjoc.22.26

• of the pyrrolidines 2. In this way, the hydride anion was formally added to the list of possible nucleophiles (H-, N-, O-, S-). Conclusion In conclusion, we developed a practical route to the novel skeleton of N,N-dialkyl-3-(sulfonyl)butan-1-amines from β-ketosulfones. The proposed approach exploits

Ring contraction and ring expansion reactions in terpenoid biosynthesis and their application to total synthesis

• Nicolas Kratena,
• Nicolas Heinzig and
• Peter Gärtner

Beilstein J. Org. Chem. 2026, 22, 289–343, doi:10.3762/bjoc.22.21

• . Alkyl and hydride shifts, stepwise or dyotropic rearrangements have been described to occur during terpene cyclisation, including multiple ring-size modifications. The CYP450s play a central role for the oxidative functionalisation of terpenes, enabling the rich diversity of secondary metabolites [40

• of the bicyclo[3.1.0]hexane system present in thujane monoterpenes [56] (see Scheme 2A). Starting from geranyl pyrophosphate (6), monoterpene cyclases first build up a 6-membered ring with an exocyclic carbocation, commonly referred to as α-terpinyl cation 6a. From there, a 1,2-hydride shift gives

• 12c. From here, a second cyclisation towards 12d, 1,5-hydride shift to secondary carbocation 12e and follow-up oxidative decoration of 12f affords the pleuromutilin molecule 13. A more recently unveiled example of a specific cyclase enzyme effecting a change in ring size during polyene cyclisation was

Total synthesis of natural products based on hydrogenation of aromatic rings

• Haoxiang Wu and
• Xiangbing Qi

Beilstein J. Org. Chem. 2026, 22, 88–122, doi:10.3762/bjoc.22.4

• in quinoline to generate hexahydroquinoline using a Ru catalyst (Scheme 8) [67]. When (S,S,S)-DKP was used as a ligand, the hydrogenation of the carbon ring was highly selective. Reduction of aromatic rings via hydride or electron transfer pathways Beyond catalytic hydrogenation, aromatic rings can

• also be reduced through hydride-based or electron-transfer pathways, which provide complementary modes of reactivity that are often orthogonal to metal-catalyzed hydrogenation systems. Classical dissolving-metal reductions such as the Birch reduction convert arenes into 1,4-dihydro intermediates via

• sequential electron transfer and protonation, enabling regioselective partial dearomatization that is difficult to achieve under hydrogenation conditions. Likewise, hydride reagents – including NaBH3CN, DIBAL-H, and other aluminum or borohydride derivatives – have been widely employed for the selective

Reactivity umpolung of the cycloheptatriene core in hexa(methoxycarbonyl)cycloheptatriene

• Dmitry N. Platonov,
• Alexander Yu. Belyy,
• Rinat F. Salikov,
• Kirill S. Erokhin and
• Yury V. Tomilov

Beilstein J. Org. Chem. 2026, 22, 64–70, doi:10.3762/bjoc.22.2

• -group elimination but through intermolecular hydride-transfer reactions as well. Therefore, the expected strategy to establish a chemical bond with a cycloheptatriene core is a reaction of a tropylium ion derivative with a nucleophile. Such reactions may involve either carbon [9][10][11] or heteroatom

Synthesis and applications of alkenyl chlorides (vinyl chlorides): a review

• Daniel S. Müller

Beilstein J. Org. Chem. 2026, 22, 1–63, doi:10.3762/bjoc.22.1

One-pot synthesis of ethylmaltol from maltol

• Immanuel Plangger,
• Marcel Jenny,
• Gregor Plangger and
• Thomas Magauer

Beilstein J. Org. Chem. 2025, 21, 2755–2760, doi:10.3762/bjoc.21.212

• amounts of sodium hydride and n-butyllithium followed by trapping with methyl iodide afforded mostly recovered maltol (2, 75%) along with traces of desired ethylmaltol (1, Table 1, entry 1). We attributed the low conversion rate to the poor solubility of the in situ-generated sodium maltolate and instead

• procedure, maltol (2) was deprotonated with sodium hydride followed by treatment with TBSCl to in situ obtain silyl ether 8e, which was subsequently deprotonated with LiHMDS and C-methylated with methyl iodide at 0 °C. Addition of aqueous hydrochloric acid enabled silyl deprotection to ethylmaltol (1) in 52

Recent advancements in the synthesis of Veratrum alkaloids

• Morwenna Mögel,
• David Berger and
• Philipp Heretsch

Beilstein J. Org. Chem. 2025, 21, 2657–2693, doi:10.3762/bjoc.21.206

• substituted cyclopentenone motif 37. The authors report the reaction to favor the desired diastereomer and could further enrich the desired isomer by recrystallization. Final steps for this fragment included a 1,4-reduction of the enone motif via a copper hydride species, a Wittig reaction to install the exo

• acid, presumably through an epoxide opening, 1,2-hydride shift, and deprotonation, alcohol 69 was obtained. These two transformations were combined to achieve rearrangement of 57 to 69 in 71% in one single step. The exo-methylene group was selectively hydrogenated, the C17-alcohol eliminated, and then

• regioselectively desaturated to furnish known phenylsulfonylenamine (Scheme 23). Conversion toward the bromohydrin, treatment with potassium hydride, and subsequent addition of the crotyl-Grignard reagent 75 gave the desired isomer 76 in 22% yield over four steps. More exactly, the diastereomeric piperidine was

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