Design and synthesis of an erdafitinib-based selective FGFR2 degrader

• Yumeng Jin,
• Shidong Wang,
• Sihan Pan,
• Shuqi Huang,
• Weichen Zhou,
• Xiaohao Huang,
• Lei Zheng and
• Lingfeng Chen

Beilstein J. Org. Chem. 2026, 22, 583–591, doi:10.3762/bjoc.22.44

• . Synthesis of PROTACs towards FGFR2. Reagents and conditions: (a) K2CO3, Pd (dppf)Cl2, 1,4-dioxane/H2O 4:1, 100 °C, 5 h; (b) 3,5-dimethoxyaniline, Pd2(dba)3, BINAP, Cs2CO3, toluene, 100 °C, 12 h; (c) (2-bromoethoxy)-tert-butyldimethylsilane, NaH, DMF, rt, 12 h; (d) tetrabutylammonium fluoride, THF rt, 12 h

Screwing the helical chirality through terminal peri-functionalization

• Devesh Chandra,
• Sachin and
• Upendra Sharma

Beilstein J. Org. Chem. 2026, 22, 205–212, doi:10.3762/bjoc.22.14

• another important type of chirality, where the chirality is controlled by restricted rotation among an axis. These types of molecules play an important role as chiral ligands in organic synthesis, i.e., BINOL, BINAP, etc. [9][10][11]. Another form of chirality, where chirality depends on a constrained

Pd-catalyzed dehydrogenative arylation of arylhydrazines to access non-symmetric azobenzenes, including tetra-ortho derivatives

• Loris Geminiani,
• Kathrin Junge,
• Matthias Beller and
• Jean-François Soulé

Beilstein J. Org. Chem. 2025, 21, 2234–2242, doi:10.3762/bjoc.21.170

• (OAc)₂/BINAP catalytic system [51], which enabled selective C–N coupling at the terminal nitrogen and suppressed denitrogenative by-products [52][53][54]. Although the general strategy is similar, our method uses the [PdCl(C3H5)]2/t-BuXPhos catalytic system, which provided higher yields and broader

Preparation of a furfural-derived enantioenriched vinyloxazoline building block and exploring its reactivity

• Madara Darzina,
• Anna Lielpetere and
• Aigars Jirgensons

Beilstein J. Org. Chem. 2025, 21, 1737–1741, doi:10.3762/bjoc.21.136

• material S-3d but provided a mixture of cis- and trans-amides cis-S-5 and trans-S-5 (Scheme 3). The use of PdCl2(S-BINAP) complex as a precatalyst resulted in a longer reaction time and an exclusive formation of amide trans-S-5 with isomerized double bond (Scheme 4). The amide trans-R-5 was prepared

• . Cleavage of the N-Alloc group leading to a mixture of isomers cis-S-5 and trans-S-5. Cleavage of the N-Alloc group with PdCl2(S-BINAP) leading to trans-S-5 and trans-R-5. Cyclization of amides trans-S-5 and trans-R-5 to oxazolines S-6 and R-6. aza-Diels–Alder reaction of vinyloxazoline S-6 with TsNCO. The

Synthetic approach to borrelidin fragments: focus on key intermediates

• Yudhi Dwi Kurniawan,
• Zetryana Puteri Tachrim,
• Teni Ernawati,
• Faris Hermawan,
• Ima Nurasiyah and
• Muhammad Alfin Sulmantara

Beilstein J. Org. Chem. 2025, 21, 1135–1160, doi:10.3762/bjoc.21.91

• hydrogenation of 104, employing (R)-[(RuCl(Tol-BINAP))2(μ-Cl)3[NH2Me2], yielded the product in 90% yield with nearly complete diastereoselectivity (de >99%). Finally, the secondary alcohol was protected as a TBS ether, and the ester group was hydrolyzed to deliver Ōmura’s C1–C11 fragment 61 in 85% yield. The

• synthesis of part 62b began with the asymmetric hydrogenation of 93 to yield β-hydroxy ester 106 (Scheme 17). Initial experiments, following the procedure of Noyori et al. [51] and using [RuCl2(p-cymene)]2 metal complex with BINAP as the chiral ligand, produced 106 in 92% yield (92% ee, 99:1 dr). Optimized

• conditions were achieved by employing [RuI2(p-cymene)]2 with the chiral ligand 3,5-xylyl-BINAP, resulting in 106 with an improved yield of 98% (97% ee, 99:1 dr). The secondary alcohol of 106 was protected as a THP ether, and the ester group was reduced to a primary alcohol 107 in 89% yield. This primary

Pd-Catalyzed asymmetric allylic amination with isatin using a P,olefin-type chiral ligand with C–N bond axial chirality

• Natsume Akimoto,
• Kaho Takaya,
• Yoshio Kasashima,
• Kohei Watanabe,
• Yasushi Yoshida and
• Takashi Mino

Beilstein J. Org. Chem. 2025, 21, 1018–1023, doi:10.3762/bjoc.21.83

• amination of allyl esters using isatin as a nucleophile. In this reaction, bisphosphine-type ligands such as BINAP and SEGPHOS derivatives, as well as P,N-type ligands like oxazoline-type ligands, were utilized as chiral ligands [26]. On the other hand, several groups have recently reported new chiral

Recent advances in organocatalytic atroposelective reactions

• Henrich Szabados and
• Radovan Šebesta

Beilstein J. Org. Chem. 2025, 21, 55–121, doi:10.3762/bjoc.21.6

• compounds comprising a stereogenic plane or axis is much less developed. Axially chiral compounds are well known as chiral ligands in asymmetric catalysis, with notable examples of binaphthyl-based derivatives such as BINAP, SEGPHOS, or binaphthyl-based phosphoric acid derivatives, which are among the

C–C Coupling in sterically demanding porphyrin environments

• Liam Cribbin,
• Brendan Twamley,
• Nicolae Buga,
• John E. O’ Brien,
• Raphael Bühler,
• Roland A. Fischer and
• Mathias O. Senge

Beilstein J. Org. Chem. 2024, 20, 2784–2798, doi:10.3762/bjoc.20.234

• compared to the 85 °C used in the synthesis of the para-equivalent 26 gave no conversion and was accompanied by the formation of palladium black [49]. No reactivity was observed by either TLC or mass spectrometry when switching back to Pd2(dba)3 with three different ligands SPhos, XantPhos, and Rac-Binap

Access to optically active tetrafluoroethylenated amines based on [1,3]-proton shift reaction

• Yuta Kabumoto,
• Eiichiro Yoshimoto,
• Bing Xiaohuan,
• Masato Morita,
• Motohiro Yasui,
• Shigeyuki Yamada and
• Tsutomu Konno

Beilstein J. Org. Chem. 2024, 20, 2776–2783, doi:10.3762/bjoc.20.233

• published that the asymmetric conjugate addition of 4-methylphenylboronic acid towards (E)-5-bromo-4,4,5,5-tetrafluoro-1-phenyl-2-penten-1-one (8) in the presence of a rhodium catalyst coordinated with (S)-BINAP gave the corresponding Michael adduct 9 in 94% enantiomeric excess (reaction 2, Scheme 1) [22

Palladium-catalyzed three-component radical-polar crossover carboamination of 1,3-dienes or allenes with diazo esters and amines

• Geng-Xin Liu,
• Xiao-Ting Jie,
• Ge-Jun Niu,
• Li-Sheng Yang,
• Xing-Lin Li,
• Jian Luo and
• Wen-Hao Hu

Beilstein J. Org. Chem. 2024, 20, 661–671, doi:10.3762/bjoc.20.59

• of the hybrid α-ester alkylpalladium radical generated from the diazo ester (Table 1, entry 10) [53]. Replacing Xantphos with rac-BINAP or DPEphos gave very low product formation, indicating that the type of ligand was crucial for this transformation (Table 1, entries 11 and 12). Changing the

Unveiling the regioselectivity of rhodium(I)-catalyzed [2 + 2 + 2] cycloaddition reactions for open-cage C₇₀ production

• Cristina Castanyer,
• Anna Pla-Quintana,
• Anna Roglans,
• Albert Artigas and
• Miquel Solà

Beilstein J. Org. Chem. 2024, 20, 272–279, doi:10.3762/bjoc.20.28

• and Discussion We started our study by testing the cycloaddition of N-tosyl-tethered bisalkyne 1a and C70 (Scheme 2) using our previously optimized reaction conditions for the C60 derivative [33]: that is, using 10 mol % of a mixture of [Rh(cod)2]BF4 and Tol-BINAP in o-dichlorobenzene (o-DCB) and

• group was substituted by a mesyl substituent and BIPHEP was used as a model phosphine ligand instead of Tol-BINAP to reduce the computational cost. The calculations, conducted at the B3LYP-D3/cc-pVTZ-PP(SMD=o-DCB)//B3LYP-D3/cc-pVDZ-PP level (see full computational details in Supporting Information File

Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles

• Péter Kisszékelyi and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44

• addition of organozirconium reagent 227 to enone 1. In the presence of the (R)-BINAP ligand, the Michael adduct 228 could be isolated in 97% ee. Finally, the Zr enolate was trapped by aldehyde 229 prepared from ᴅ-ribose. The aldol adduct 230 was isolated in 80% yield and excellent diastereoselectivity (>20

Derivatives of benzo-1,4-thiazine-3-carboxylic acid and the corresponding amino acid conjugates

• Péter Kisszékelyi,
• Tibor Peňaška,
• Klára Stankovianska,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2022, 18, 1195–1202, doi:10.3762/bjoc.18.124

• (BINAP)-assisted hydrogenation with H2 pressure up to 50 bar was also found to be ineffective. By changing the metal complex to Rh(COD)2BF4, we successfully realized the saturation of the double bond. Chiral ligands (R)-BINAP (L1) and (R,R)-phenyl-BPE (L4) gave unsatisfactory selectivity (Table 2

Organocatalytic asymmetric nitroso aldol reaction of α-substituted malonamates

• Ekta Gupta,
• Narendra Kumar Vaishanv,
• Sandeep Kumar,
• Raja Krishnan Purshottam,
• Ruchir Kant and
• Kishor Mohanan

Beilstein J. Org. Chem. 2022, 18, 217–224, doi:10.3762/bjoc.18.25

• using a silver-BINAP catalyst combination [25]. Later, the same group could successfully tune the catalytic system to control the regioselectivity in the addition of metal enolate to nitrosoarenes to achieve an α-hydroxyamination [26]. Since then, several groups have shown the use of metal-catalyzed

Recent advances in the asymmetric phosphoric acid-catalyzed synthesis of axially chiral compounds

• Alemayehu Gashaw Woldegiorgis and
• Xufeng Lin

Beilstein J. Org. Chem. 2021, 17, 2729–2764, doi:10.3762/bjoc.17.185

• ][21] (Figure 2), and chiral building blocks in modern organic synthesis [5]. During the past decades, both C2 and non-C2 symmetric axially chiral biaryl compounds such as BINAP, BINAM, NOBIN and their derivatives BINOL have played a crucial role as ligands in the development of transition-metal

Visible-light-mediated copper photocatalysis for organic syntheses

• Yajing Zhang,
• Qian Wang,
• Zongsheng Yan,
• Donglai Ma and
• Yuguang Zheng

Beilstein J. Org. Chem. 2021, 17, 2520–2542, doi:10.3762/bjoc.17.169

• alkyl halides 14, olefins, and trifluoromethylthiolate 15. Mechanistic studies demonstrated that the photoexcited CuI/binap/SCF3 complex generated in situ engages in electron transfer with the alkyl halides, thereby providing an alkyl radical and the CuII/binap/SCF3 species. Subsequently, the alkyl

• radical reacts with the olefin generating a new alkyl radical, which is trapped by CuII/binap/SCF3 to provide the coupling product (Scheme 10). In 2019, Zhang and co-workers [58] reported the photoinduced copper-catalyzed carboamination of alkenes that involved organic halides 16, alkenes, and amines 17

Total synthesis of pyrrolo[2,3-c]quinoline alkaloid: trigonoine B

• Takashi Nishiyama,
• Erina Hamada,
• Daishi Ishii,
• Yuuto Kihara,
• Nanase Choshi,
• Natsumi Nakanishi,
• Mari Murakami,
• Kimiko Taninaka,
• Noriyuki Hatae and
• Tominari Choshi

Beilstein J. Org. Chem. 2021, 17, 730–736, doi:10.3762/bjoc.17.62

• synthesis of the 2,3-dihydroquinolin-4-one moiety of trigonoine B (1) by cycloamination of 22c (Scheme 4). The Buchwald–Hartwig amination of 22c was conducted in the presence of t-BuONa, BINAP, and Pd2(dba)3·CHCl3; however, the desired tetrahydroquinoline 23 was not obtained and only 22c was recovered. We

Amino- and polyaminophthalazin-1(2H)-ones: synthesis, coordination properties, and biological activity

• Zbigniew Malinowski,
• Emilia Fornal,
• Agata Sumara,
• Renata Kontek,
• Karol Bukowski,
• Beata Pasternak,
• Dariusz Sroczyński,
• Joachim Kusz,
• Magdalena Małecka and
• Monika Nowak

Beilstein J. Org. Chem. 2021, 17, 558–568, doi:10.3762/bjoc.17.50

• Xantphos/Pd(OAc)2/t-BuOK and our standard procedure [30][35], in which the amine is added after the lactam 3a, for the initial experiments ended with failure. In most cases, regardless of the used catalytic system (Pd source: Pd(OAc)2, Pd2(dba)3, ligand: DPEPhos, DavePhos, BINAP), solvent (1,4-dioxane

• cross-coupling reaction. To confirm this idea, we carried out an experiment in which to the in situ-generated (BINAP)Pd complex (Pd2(dba)3/rac-BINAP or (R)-BINAP; 15:15 mol %) morpholine was added prior to the addition of lactam 3a. As a result, we obtained the target 4-(morpholin-4-yl) derivative 5a in

• 77% yield. Moreover, it turned out that this amination reaction also proceeded with a reduced amount of Pd2(dba)3 from 15 mol % to 2 mol % without loss of the product yield. These results showed that the coordination of the amine to the (BINAP)Pd complex probably leads to the formation of a (BINAP)Pd

Synthesis of monophosphorylated lipid A precursors using 2-naphthylmethyl ether as a protecting group

• Jundi Xue,
• Ziyi Han,
• Gen Li,
• Khalisha A. Emmanuel,
• Cynthia L. McManus,
• Qiang Sui,
• Dongmian Ge,
• Qi Gao and
• Li Cai

Beilstein J. Org. Chem. 2020, 16, 1955–1962, doi:10.3762/bjoc.16.162

• (3) was treated with Meldrum’s acid (2,2-dimethyl-1,3-dioxane-4,6-dione) followed by decarboxylation in methanol to give methyl 3-oxotetradecanoate (4) in 77% yield. The enantioselective hydrogenation of the β-carbonyl group using (R)-Ru(OAc)2(BINAP) at 65 °C and under 1.5 MPa H2 afforded methyl (R

• )-3-hydroxytetradecanoate (5) in 98% yield. The same hydrogenation reaction was carried out using the (S)-Ru(OAc)2(BINAP) catalyst. Then both the R and S products were compared using chiral HPLC to confirm the absolute configuration and enantiomeric purity (Figure S1, Supporting Information File 1

• -protected (R)-3-hydroxytetradecanoic acid (7). Conditions: (a) Meldrum's acid, pyridine, CH2Cl2, 0 °C; (b) CH3OH, reflux, 77% over two steps; (c) (R)-Ru(OAc)2(BINAP), H2, CH3OH, 65 °C, 98%; (d) NapCHO, TMSOTf, (TMS)2O, Et3SiH, THF, 0 °C; (e) LiOH, THF, H2O, 65 °C, 78% (over two steps). Synthesis of

Rhodium-catalyzed reductive carbonylation of aryl iodides to arylaldehydes with syngas

• Zhenghui Liu,
• Peng Wang,
• Zhenzhong Yan,
• Suqing Chen,
• Dongkun Yu,
• Xinhui Zhao and
• Tiancheng Mu

Beilstein J. Org. Chem. 2020, 16, 645–656, doi:10.3762/bjoc.16.61

• , triphos, dpp-BINAP, dpp-OPh, dppb, dppe, P(PhF5)3, P(4-FPh)3, Cydpp, Bipy, DBU, Im, and PPh3 (their structures are shown in Table 2)), bases (Et3N, 1,4-diaza[2.2.2]bicyclooctane (DABCO), N,N-diisopropylethylamine (DIPEA), N,N,N',N'-tetramethylethylenediamine (TMEDA) and 1,2,2,6,6-pentamethylpiperidine

Copper-catalyzed enantioselective conjugate reduction of α,β-unsaturated esters with chiral phenol–carbene ligands

• Shohei Mimura,
• Sho Mizushima,
• Yohei Shimizu and
• Masaya Sawamura

Beilstein J. Org. Chem. 2020, 16, 537–543, doi:10.3762/bjoc.16.50

• chiral p-tol-BINAP/copper catalyst established the excellent utility of chiral bisphosphine ligands for this type of reaction [4]. Surprisingly, however, chiral ligands based on N-heterocyclic carbenes (NHCs) [12] have not been applied to the conjugate reduction of α,β-unsaturated carbonyl compounds

Recent advances in photocatalyzed reactions using well-defined copper(I) complexes

• Mingbing Zhong,
• Xavier Pannecoucke,
• Philippe Jubault and
• Thomas Poisson

Beilstein J. Org. Chem. 2020, 16, 451–481, doi:10.3762/bjoc.16.42

• -substituted olefins (Scheme 17) [33]. The reaction was carried out using the complex [Cu(I)(dmp)(binap)]PF6, and the desired tribromomethylated products were isolated in good to excellent yields. The authors suggested a similar mechanism to the one described by Reiser and co-workers in Scheme 14. In 2018, Hu

• with the [Cu(II)] species bearing the phthalimide forms the product and regenerates the active [Cu(I)] catalyst. Collins and co-workers described the use of [Cu(I)(dq)(binap)]BF4 as an efficient catalyst for the reductive decarboxylative coupling of a NHP ester derived from cyclohexanecarboxylic acid

• avoided the presence of a Brønsted acid in the reaction media. As such, Collins and co-workers developed the catalyst [Cu(I)(pypzs)(BINAP)]BF4 where the ligand (5-(4-fluorosulfonyl)amino-3-(2pyridyl)pyrazole)) (pypzs) had an acidic proton prone to activate the carbonyl group during the pinacol coupling

Architecture and synthesis of P,N-heterocyclic phosphine ligands

• Wisdom A. Munzeiwa,
• Bernard Omondi and
• Vincent O. Nyamori

Beilstein J. Org. Chem. 2020, 16, 362–383, doi:10.3762/bjoc.16.35

• (diphenylphosphino)-1,1'-binaphthyl (BINAP) with a greater π-density and sterically demanding groups, have been extensively used in catalytic reactions [94]. Wang et al. [95] reported a copper-catalyzed phosphorylation in the synthesis of an oxazolylindolylphosphine as shown in Scheme 18. The intermediate amide 97

Copper-catalyzed enantioselective conjugate addition of organometallic reagents to challenging Michael acceptors

• Delphine Pichon,
• Jennifer Morvan,
• Christophe Crévisy and
• Marc Mauduit

Beilstein J. Org. Chem. 2020, 16, 212–232, doi:10.3762/bjoc.16.24

• reagents was reported by Alexakis and co-workers in 2010 [14]. After screening various chiral phosphine-based ligands, the combinations of either phosphoramidite L1 with Cu(OTf)2, or (R)-BINAP (L2) with copper thiophenecarboxylate (CuTC) appeared to be the most efficient for the addition of Et2Zn to a

• moderate to good yields, with ee values of up to 76%. When the conjugate addition was performed with Grignard reagents, significant amounts of 1,2-products and enols were formed, despite the use of cryogenic conditions. (R)-BINAP (L2) gave the best regio- and enantioselectivity, with 62% of the 1,4-product

• -substitution of enals [21]. By using (R)-BINAP (L2)/CuTC in combination with chiral prolinol derivatives L4–6 as organocatalysts, various α,β-functionalized aldehydes were synthesized in good isolated yields (57–74%) and remarkable enantioselectivity (99%) from diethylzinc or dimethylzinc as nucleophiles and

Palladium-catalyzed synthesis and nucleotide pyrophosphatase inhibition of benzo[4,5]furo[3,2-b]indoles

• Hoang Huy Do,
• Saif Ullah,
• Alexander Villinger,
• Joanna Lecka,
• Jean Sévigny,
• Peter Ehlers,
• Jamshed Iqbal and
• Peter Langer

Beilstein J. Org. Chem. 2019, 15, 2830–2839, doi:10.3762/bjoc.15.276

• ). Monodentate ligands, like XPhos, SPhos, DavePhos, RuPhos, or P(t-Bu)3·HBF4, were not effective in the reaction and gave product 5b in low yields. Bidentate phosphine ligands, such as BINAP, XantPhos, dppe, or dppf (Table 1), worked very well and allowed to improve the yield of 5b up to 75% (Table 1, entry 4

• ). As compared to Pd2(dba)3, the use of Pd(OAc)2 as the Pd source resulted in a decrease of the yield (52%). Performing the reaction in dioxane or DMF gave lower yields as well. In summary, up to 75% yield of 5b could be achieved using BINAP and Pd2(dba)3 as the catalytic system. Subsequently, the scope

• with amine derivatives, exemplified by the synthesis of benzo[4,5]furo[3,2-b]indoles 5a–j. Similarly as previously described [31], 1.1 equiv of amine 4 was added to a pressure tube charged with 3, Pd2(dba)3 (5 mol %), BINAP (10 mol %) and 3 equiv of NaOt-Bu under Argon. The mixture was dissolved in