Influence of the cation in hypophosphite-mediated catalyst-free reductive amination

• Natalia Lebedeva,
• Fedor Kliuev,
• Olesya Zvereva,
• Klim Biriukov,
• Evgeniya Podyacheva,
• Maria Godovikova,
• Oleg I. Afanasyev and
• Denis Chusov

Beilstein J. Org. Chem. 2025, 21, 1661–1670, doi:10.3762/bjoc.21.130

• Chemical Technology of Russia, Miusskaya sq. 9, Moscow, 125047, Russia National Research University Higher School of Economics, Myasnitskaya St. 20, Moscow, 101000, Russia 10.3762/bjoc.21.130 Abstract Reducing agents with phosphorus–hydrogen bond, such as sodium hypophosphite, phosphite, and

• confirmed by D-experiments. The whole sequence of transformations was finished by the reduction of the charged iminium cation with the hypophosphite anion forming N,N,N-dimethylbenzylammonium phosphite in exergonic manner with a total Gibbs free energy gain of −26.8 kcal/mol (Step_5). Noteworthy, the target

Chemical synthesis of glycan motifs from the antitumor agent PI-88 through an orthogonal one-pot glycosylation strategy

• Shaokang Yang,
• Xingchun Sun,
• Hanyingzi Fan and
• Guozhi Xiao

Beilstein J. Org. Chem. 2025, 21, 1587–1594, doi:10.3762/bjoc.21.122

• desired phosphite, which was further oxidized by 3-chloroperoxybenzoic aicd (mCPBA) at −78 °C to 0 °C, producing the desired phosphorylated fully protected trisaccharide 12 in 79% overall yield over three steps. Removal of all protecting groups in trisaccharide 12 is a challenging task due to the presence

• over the following steps: 1) deprotection of the TBDPS group, 2) phosphitylation of the free alcohol with phosphoramidite 11 in the presence of 1H-tetrazole and 4 Å MS, and 3) oxidation of the phosphite by mCPBA. Hydrogenolysis of Bn and Cbz groups in 14 with Pd(OH)2/C and subsequent saponification of

Synthesis of β-ketophosphonates through aerobic copper(II)-mediated phosphorylation of enol acetates

• Alexander S. Budnikov,
• Igor B. Krylov,
• Fedor K. Monin,
• Valentina M. Merkulova,
• Alexey I. Ilovaisky,
• Liu Yan,
• Bing Yu and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2025, 21, 1192–1200, doi:10.3762/bjoc.21.96

• stirred for 3 hours at 70 °C under air (air condenser) and then cooled to room temperature, and rotary-evaporated under reduced pressure. An additional evaporation step using a rotary vane pump (0.5 mmHg) at 80 °C was made for the evaporation of phosphite excess. The residue was isolated by column

Recent advances in controllable/divergent synthesis

• Jilei Cao,
• Leiyang Bai and
• Xuefeng Jiang

Beilstein J. Org. Chem. 2025, 21, 890–914, doi:10.3762/bjoc.21.73

• in steering catalytic selectivity. In 2016, the Jiang group achieved regioselective control in the gold-catalyzed intramolecular hydroarylation of alkynes by modulating the electronic and steric effects of ligands (Scheme 2) [20]. Mechanistically, the electron-deficient phosphite ligand L1 and the

Recent advances in the electrochemical synthesis of organophosphorus compounds

• Babak Kaboudin,
• Milad Behroozi,
• Sepideh Sadighi and
• Fatemeh Asgharzadeh

Beilstein J. Org. Chem. 2025, 21, 770–797, doi:10.3762/bjoc.21.61

• the electricity passed improved the reaction yield. The use of commercial acetonitrile without additional drying reduced the yield of the target product due to the formation of byproducts (RO)3PO and (RO)2P(O)H. It suggested that the reaction proceeded via anodic oxidation of trialkyl phosphite

• arylphosphonates via carbon–phosphorus bond formation. In 2021, Xu et al. [52] reported an electrochemical process for synthesizing arylphosphonates through the hetero-coupling reaction of CH of arenes with a trialkyl phosphite. They have prepared 45 arene phosphonates with good to excellent yields and reported

• phosphite in an undivided cell. The C–P product was selectively produced using n-Bu4NClO4 as electrolyte and carbon and platinum electrodes as the anode and cathode at a constant current for 4 h. Using n-Bu4NI instead of KI resulted in a similar outcome, but KBr was less effective (Table 4). The desired C2

Formaldehyde surrogates in multicomponent reactions

• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Bernhard Westermann

Beilstein J. Org. Chem. 2025, 21, 564–595, doi:10.3762/bjoc.21.45

• for obtaining propargylamines. Synthesis of α-aminophosphonates One of the most robust methods for the synthesis of α-aminophosphonates is the Pudovik reaction, along with its multicomponent version, the Kabachnik–Fields reaction (Scheme 25) [72][73]. In the Pudovik reaction, a dialkyl phosphite 31

• containing a PH bond adds to the C=N bond of a preformed imine 30, while in the three-component Kabachnik–Fields reaction, the imine, which is generated in situ from a carbonyl compound and an amine, reacts with the dialkyl phosphite to produce the desired α-aminophosphonates 32 (Scheme 25) [72][74]. This

• colorless crystals from the reaction between Et3N and CH2Cl2 at 100 °C in DMF. Subsequently, the corresponding α-aminophosphonate 35a was obtained by heating 36a with an equal amount of diethyl phosphite (Scheme 28b). Furthermore, when the reaction was carried out with CD2Cl2, the corresponding deuterated

Nickel-catalyzed cross-coupling of 2-fluorobenzofurans with arylboronic acids via aromatic C–F bond activation

• Takeshi Fujita,
• Haruna Yabuki,
• Ryutaro Morioka,
• Kohei Fuchibe and
• Junji Ichikawa

Beilstein J. Org. Chem. 2025, 21, 146–154, doi:10.3762/bjoc.21.8

• phosphite were ineffective (Table 1, entry 5), the inclusion of chelating dienes improved the yield of 3bb (Table 1, entries 6–8). Among these, 5 mol % of 1,5-cyclooctadiene (cod) proved to be the most effective additive, affording 3bb in 95% yield (Table 1, entry 8). Additionally, by reducing the

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

• Pd-catalyzed cross-coupling reactions, allowing the formation of C–C and C–N bonds in the o-position of the aryl chalcogen compounds. α-Aminophosphonates 14 were the result of a one-pot condensation of an aldehyde, a primary amine and phosphite P(OMe)3 with copper triflate acting as Lewis acid

Synthesis, structure and π-expansion of tris(4,5-dehydro-2,3:6,7-dibenzotropone)

• Yongming Xiong,
• Xue Lin Ma,
• Shilong Su and
• Qian Miao

Beilstein J. Org. Chem. 2025, 21, 1–7, doi:10.3762/bjoc.21.1

• synthesized according to the procedures detailed in Supporting Information File 1. In this reaction, the first step of diazo–thioketone coupling occurred at 50 °C in THF, and the second step of desulfurization with triisopropyl phosphite occurred in refluxed toluene, giving diene 10 in a yield of 47%. The

• Barton–Kellogg reaction with 8b under similar conditions gave the episulfide intermediate, which, however, could not be desulfurized with triisopropyl phosphite, trimethyl phosphite or triphenylphosphine to give the corresponding triene. The subsequent Scholl reaction of 10 with DDQ and triflic acid at

Multicomponent syntheses of pyrazoles via (3 + 2)-cyclocondensation and (3 + 2)-cycloaddition key steps

• Ignaz Betcke,
• Alissa C. Götzinger,
• Maryna M. Kornet and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2024, 20, 2024–2077, doi:10.3762/bjoc.20.178

• . An advantage of this method for preparing 1,3,5-substituted pyrazoles is its tolerance towards a wide range of substituents. Trimethyl phosphite can be added to acetylene dicarboxylates 95 to generate a zwitterion that readily reacts with electrophiles. This zwitterion undergoes a rearrangement

New triazinephosphonate dopants for Nafion proton exchange membranes (PEM)

• Fátima C. Teixeira,
• António P. S. Teixeira and
• C. M. Rangel

Beilstein J. Org. Chem. 2024, 20, 1623–1634, doi:10.3762/bjoc.20.145

• commercially available and were prepared from 4-hydroxyphenyl- or 4-aminophenyl-based derivatives. The first nucleophile to be synthesized was diethyl (4-hydroxyphenyl)phosphonate (2) [51], starting from 4-bromophenol (3) and triethyl phosphite. When this reaction was carried out in the presence of nickel(II

• ] was also prepared, using the same reaction conditions, by the reaction between 1-bromo-4-nitrobenzene (5) and diethyl phosphonate, in the presence of Pd(PPh3)4 as catalyst and triethylamine, since the use of triethyl phosphite in the presence on nickel(II) bromide do not allow the formation of the

• nucleophilic substitution using hydrobromic acid, as a 33% solution in acetic acid, to afford the corresponding bromide derivative 9 [54] (Scheme 2). Subsequently 1-(benzyloxy)-4-(bromomethyl)benzene (9) underwent Michaelis–Arbuzov reaction with triethyl phosphite to afford diethyl [4-(benzyloxy)phenyl

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

• this also with L = (t-Bu)2P(o-biphenyl). When the more reactive urea alkene 1a is examined, the reaction with 4a is efficient enough that reaction completion occurs prior to noticeable decomposition. In contrast, when a LAuNTf2 catalyst was prepared where L = tris(2,4-di-tert-butylphenyl)phosphite (6b

Optimizations of lipid II synthesis: an essential glycolipid precursor in bacterial cell wall synthesis and a validated antibiotic target

• Milandip Karak,
• Cian R. Cloonan,
• Brad R. Baker,
• Rachel V. K. Cochrane and
• Stephen A. Cochrane

Beilstein J. Org. Chem. 2024, 20, 220–227, doi:10.3762/bjoc.20.22

• ]. The ratio of α/β-anomers in compound 5 was found to be influenced by the reaction conditions, consistently favoring the β-anomer. Further transformation of compound 5 involved α-selective phosphite formation using dibenzyl N,N-diisopropylphosphoramidite and 5-(ethylthio)-1H-tetrazole. The resulting α

• -phosphite intermediate was then oxidized with hydrogen peroxide to yield dibenzyl α-phosphate 6, achieving an overall yield of 89% for these two steps. Removal of the 2-(phenylsulfonyl)ethanol protecting group in compound 6 was successfully achieved through treatment with 1,8-diazabicyclo[5.4.0]undec-7-ene

Multi-redox indenofluorene chromophores incorporating dithiafulvene donor and ene/enediyne acceptor units

• Christina Schøttler,
• Kasper Lund-Rasmussen,
• Line Broløs,
• Philip Vinterberg,
• Ema Bazikova,
• Viktor B. R. Pedersen and
• Mogens Brøndsted Nielsen

Beilstein J. Org. Chem. 2024, 20, 59–73, doi:10.3762/bjoc.20.8

• variety of reactions; that are, phosphite- or Lawesson’s reagent-mediated olefination reactions (to introduce DTF motifs), Ramirez/Corey–Fuchs dibromo-olefinations followed by Sonogashira couplings (to introduce enediynes motifs), and Knoevenagel condensations (to introduce the vinylic diester motif). By

• explore further annellation of dihydropyrrole and pyrrole units at the DTF moiety of an IF-DTF. A phosphite-mediated coupling of either 1,3-dithiole-2-thione 2, 7, or 8 with IF dione 1 afforded IF-DTFs 9–11, as shown in Scheme 1. Compound 11 was also obtained from building block 4 via the pyrrolo

• reduction (generation of 14πz-aromatic ring) or oxidation (generation of 1,3-dithiolium ring). Synthetically, the work relies on using indenofluorene diones as key building blocks for performing olefination reactions, such as phosphite- or Lawesson’s reagent-mediated couplings, Ramirez/Corey–Fuchs dibromo

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

• 1H-tetrazole to produce the trialkyl phosphite 8.3 that was oxidized with tert-butyl hydroperoxide to produce phosphate 8.4. Then, β-elimination of the cyanoethyl protecting group produced PAF with a global yield of 70%. The limit of this method arises from the instability of the precursor 8.1 for

• ) myo-inositol (20.6). The oxidation of the phosphite intermediate with m-CPBA followed by the catalytic hydrogenolysis of the benzyl protecting groups produced PIP3-PAF (20.7). 2 Edelfosine and diether analogues PAF and PAF-analogues that feature an acyl or more generally an ester group in sn-2

• 22.10. However, the last step features the lower yield (54%) of this 8-step synthesis. In 1994, Bittman et al. reported an alternative strategy to introduce the phosphocholine moiety by the preparation of a cyclic phosphite as a key intermediate [119]. This one-pot three-step sequence starts with the

Eschenmoser coupling reactions starting from primary thioamides. When do they work and when not?

• Lukáš Marek,
• Jiří Váňa,
• Jan Svoboda and
• Jiří Hanusek

Beilstein J. Org. Chem. 2023, 19, 808–819, doi:10.3762/bjoc.19.61

• desirable ECR product 9a in 62% or 55% yield (entries 3 and 7 in Table 1) together with other decomposition products from which only thiobenzamide and benzonitrile were identified. In pure trimethyl phosphite (Table 1, entry 8) that acts simultaneously as polar solvent and mild thiophile, the parallel

• formation of products 8a and 8a-Me was observed, but their combined yield was lower than in DMF or MeCN. The introduction of the N-methyl group coming from trimethyl phosphite must occur prior to the dehydration step of the intermediary thiazole 7a because heating of independently prepared 8a with trimethyl

• phosphite does not give 8a-Me at all. The combined yield of 8a and 8a-Me can be increased when trifluoroacetic acid is added (Table 1, entry 9). Its role probably involves an acid-catalyzed elimination of a water molecule from 7a or 7a-Me. On the other hand, the addition of a stronger base (triethylamine

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

• (phosphite/phosphine-pyridine amide, phosphine-sulfoxide, phosphoramidite, MINBOL, see Figure 1) and they usually showed excellent diastereoselectivity (dr >20:1). The catalytic systems even with low catalyst loadings tolerated both electron-donating and withdrawing groups on the aromatic substituents

• (Scheme 16). Within the framework of these domino reactions, we have mainly employed ferrocenyl phosphane ligands such as Taniaphos or Josiphos. In collaboration with Prof. Schmalz from Cologne University, we have also tested phosphite-phosphine ligands (e.g., L15) from their lab. The advantage of these

Combretastatins D series and analogues: from isolation, synthetic challenges and biological activities

• Jorge de Lima Neto and
• Paulo Henrique Menezes

Beilstein J. Org. Chem. 2023, 19, 399–427, doi:10.3762/bjoc.19.31

• to improve the water solubility of combretastatin D-2 (2) by converting it into a series of phosphate salts and other prodrugs. Thus, phosphorylation of combretastatin D-2 (2) using dibenzyl phosphite gave derivative 183. Further cleavage of the benzyl groups using TMSBr followed by the reaction of

Identification and determination of the absolute configuration of amorph-4-en-10β-ol, a cadinol-type sesquiterpene from the scent glands of the African reed frog Hyperolius cinnamomeoventris

• Angelique Ladwig,
• Markus Kroll and
• Stefan Schulz

Beilstein J. Org. Chem. 2023, 19, 167–175, doi:10.3762/bjoc.19.16

• cleanly obtained in 75% yield from triethyl phosphite and 3-chloro-2-methylpropene by addition of NaI [14]. Subsequent reduction of the ester with LiAlH4 and oxidation with IBX gave aldehyde 7 in 95% yield. Grignard addition of vinylmagnesium bromide afforded the alcohol 8, which comprised the desired

Redox-active molecules as organocatalysts for selective oxidative transformations – an unperceived organocatalysis field

• Elena R. Lopat’eva,
• Igor B. Krylov,
• Dmitry A. Lapshin and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2022, 18, 1672–1695, doi:10.3762/bjoc.18.179

• ][72]. A recent achievement of the enantioselective hydroxylation of α‑aryl-δ-lactams by O2 is shown in Scheme 5 [73] as an example of such organocatalyzed reaction type. Triethyl phosphite is added to reduce a hydroperoxide, which is initially formed by the enolate oxidation with O2. In summary

An alternative C–P cross-coupling route for the synthesis of novel V-shaped aryldiphosphonic acids

• Stephen J. I. Shearan,
• Enrico Andreoli and
• Marco Taddei

Beilstein J. Org. Chem. 2022, 18, 1518–1523, doi:10.3762/bjoc.18.160

• order of addition of reactants to perform the transition-metal-catalyzed C–P cross-coupling reaction, often referred to as the Tavs reaction, employing NiCl2 as a pre-catalyst in the phosphonylation of aryl bromide substrates using triisopropyl phosphite. This new method was employed in the synthesis of

• between a primary alkyl halide and a trialkyl phosphite, first reported in the late 1890s, the general scheme for which can be seen in Supporting Information File 1, Scheme S1 [22]. It should be noted that this reaction is not suitable for use with aryl halide substrates due to the poor reactivity between

• ) acetate and palladium(II) chloride [23][27][28]. Reactions involving these catalysts are most often carried out at high temperatures, usually in excess of 160 °C, and involve slow dropwise addition of the trialkyl phosphite to the substrate [23]. In the search for milder reaction conditions, a new

Synthesis and electrochemical properties of 3,4,5-tris(chlorophenyl)-1,2-diphosphaferrocenes

• Almaz A. Zagidullin,
• Farida F. Akhmatkhanova,
• Mikhail N. Khrizanforov,
• Robert R. Fayzullin,
• Tatiana P. Gerasimova,
• Ilya A. Bezkishko and
• Vasili A. Miluykov

Beilstein J. Org. Chem. 2022, 18, 1338–1345, doi:10.3762/bjoc.18.139

• bromides from one starting aryl aldehyde. Diethyl phosphite was allowed to react with appropriately substituted benzaldehydes in THF for 48 hours at 25 °C to afford diethyl (hydroxy(aryl)methyl)phosphonates 1, which were detected by 31P NMR spectroscopy in THF (21.4 ppm for 1a, 21.0 ppm for 1b, and 21.5

Modular synthesis of 2-furyl carbinols from 3-benzyldimethylsilylfurfural platforms relying on oxygen-assisted C–Si bond functionalization

• Sebastien Curpanen,
• Per Reichert,
• Gabriele Lupidi,
• Giovanni Poli,
• Julie Oble and
• Alejandro Perez-Luna

Beilstein J. Org. Chem. 2022, 18, 1256–1263, doi:10.3762/bjoc.18.131

• , but the yield of product 21 remained the same (Table 1, entry 4). In spite of the satisfactory yield of 21, these conditions were synthetically impractical as we were unable to conveniently separate the final product from the phosphite ligand. The use of a ligand for copper revealed to be necessary

Mechanochemical bottom-up synthesis of phosphorus-linked, heptazine-based carbon nitrides using sodium phosphide

• Blaine G. Fiss,
• Georgia Douglas,
• Michael Ferguson,
• Jorge Becerra,
• Jesus Valdez,
• Trong-On Do,
• Tomislav Friščić and
• Audrey Moores

Beilstein J. Org. Chem. 2022, 18, 1203–1209, doi:10.3762/bjoc.18.125

• group as well as others, suggest that the broad resonance corresponds to a largely amorphous phase with predominately phosphate and phosphite-like environments, with the broad resonance at −8.9 ppm possibly corresponding to hydrated sodium phosphate byproducts [43][44]. The NMR spectrum of the g-h

Synthetic strategies for the preparation of γ-phostams: 1,2-azaphospholidine 2-oxides and 1,2-azaphospholine 2-oxides

• Jiaxi Xu

Beilstein J. Org. Chem. 2022, 18, 889–915, doi:10.3762/bjoc.18.90

• ) from the reaction of dimethyl 2-(methylamino)benzoylphosphonate (70) and trimethyl phosphite at 105 °C through an ylide intermediate D. The ylide D was generated via deoxygenation of benzoylphosphonate 70 with trimethyl phosphite to form a carbene intermediate B, and trimethyl phosphite nucleophilic

• complex showed 23% enantiomeric excess in the asymmetric borane reduction of acetophenone in THF at room temperature (Scheme 33) [58]. The reaction of 3-(phenylaminomethylene)-2-phenylamino-6-methyl-2,3-dihydro-4H-chromen-4-one (213) and diethyl phosphite at 90–100 °C generated 2-ethoxy-6-methyl-2-oxo-1

• reaction of 2-imino-2H-chromene-3-carboxamide (228) and diethyl phosphite at 80–90 °C under the catalysis of boron trifluoride, afforded 4-amino-1-ethoxy-9b-hydrochromeno[4,3-c][1,2]azaphosphol-3(2H)-one 1-oxide (229) in 40% yield through the Michael addition and subsequent tautomerization and