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

• similar to a Michaelis–Arbuzov reaction, yielding an α,β-unsaturated ketone 97. The domino sequence concludes by cyclocondensation of intermediate 97 with phenylhydrazine, ultimately affording fully substituted pyrazoles 96 after the elimination of dimethyl phosphonate (Scheme 34) [117]. β-Thioalkyl-α,β

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

• 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

• ]phosphonate (14) (Scheme 4). With the starting compound 15, the Michaelis-Arbuzov reaction did not afford the tetraethyl bisphosphonate derivative. To reach the star-shaped s-triazine derivatives bearing a phosphonate group, it was considered that the best strategy was to carry out the substitution of

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

• and co-workers also demonstrated the synthesis of pyrrolo[1,2-a]quinolines (12) and ullazines (13) from N-arylpyrroles (10) with arylalkynes (11) using Rh-6G (Figure 6) [46]. Additionally, the König group also used Rh-6G as a catalyst for a photo-Arbuzov reaction to generate arylphosphonates (15) from

• ][63][64]. Arylphosphonates 15 were obtained in a photo-Arbuzov reaction by trapping with trimethylphosphite in good to excellent yields (62–88%) (Figure 12B). Additionally, intramolecular trapping via dearomative hydroarylation gave access to spirocyclic cyclohexadienes bearing dihydrobenzofuran and

Organophosphorus chemistry: from model to application

• György Keglevich

Beilstein J. Org. Chem. 2023, 19, 89–90, doi:10.3762/bjoc.19.8

• ” topics of the discipline under discussion. Cross-coupling reactions are also of importance in organophosphorus chemistry. Taddei and co-workers applied an alternative method to the classical Hirao reaction [1]. They utilized the Ni-catalyzed double Michaelis–Arbuzov reaction of bis(bromoaryl) species and

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

• ][25][26]. These catalytic cross-coupling reactions tend to follow similar pathways to the Michaelis–Arbuzov reaction, with the inclusion of a catalytic intermediate step. A number of suitable catalysts have been identified, ranging from nickel(II) bromide and nickel(II) chloride, to palladium(II

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

• ethyl esters and diethyl chlorophosphite (83a, R = EtO) or ethyl N,N-diethylchlorophosphamidite (83b, R = NEt2) followed by an intramolecular cyclization via an intramolecular Arbuzov reaction under heating [35]. The obtained γ-phosphonolactams 85 were further hydrolyzed into 2-(3-phosphonopropyl

• derivatives 83 followed by an intramolecular cyclization via the intramolecular Arbuzov reaction under heating generated 1,2-azaphospholidine 2-oxides 89. Compounds 89 were further transformed into N-phosphoryl- and N-thiophosphoryl-1,2-azaphospholidine 2-oxides 90/2-sulfides 91 via oxidation with hydrogen

1,2,3-Triazoles as leaving groups in S_NAr–Arbuzov reactions: synthesis of C6-phosphonated purine derivatives

• Kārlis-Ēriks Kriķis,
• Irina Novosjolova,
• Anatoly Mishnev and
• Māris Turks

Beilstein J. Org. Chem. 2021, 17, 193–202, doi:10.3762/bjoc.17.19

• event. The SNAr–Arbuzov reaction of 2,6-bistriazolylpurines follows the general regioselectivity pattern of the C6-position being more reactive towards substitution, which was unambiguously proved by X-ray analysis of diethyl (9-heptyl-2-(4-phenyl-1H-1,2,3-triazol-1-yl)-9H-purin-6-yl)phosphonate

• . Keywords: Arbuzov reaction; 2,6-bistriazolylpurines; nucleophilic aromatic substitution; purinylphosphonates; Introduction Acyclic nucleoside phosphonates (ANPs) are an important compound class due to their biological activity profile [1][2][3][4][5][6]. Compounds bearing a phosphonate moiety in their N9

• development of this topic [8][9][10][11]. On the contrary, only a few examples can be found in the literature where a phosphorus-containing substituent is directly attached to the purine ring [12][13]. In 2008, an SNAr–Arbuzov reaction was developed for 6-chloropurine derivatives under microwave irradiation

Selective preparation of tetrasubstituted fluoroalkenes by fluorine-directed oxetane ring-opening reactions

• Clément Q. Fontenelle,
• Thibault Thierry,
• Romain Laporte,
• Emmanuel Pfund and
• Thierry Lequeux

Beilstein J. Org. Chem. 2020, 16, 1936–1946, doi:10.3762/bjoc.16.160

• corresponding chloride (not shown). An Arbuzov reaction was performed directly on the allylic bromide obtained by treatment of 27 with LiBr (5 equiv), to give the phosphonate 29 in 76% overall yield. Finally, azide 28 was obtained in 89% yield in two steps from the non-isolated intermediate mesylate 27. After

Preparation of 2-phospholene oxides by the isomerization of 3-phospholene oxides

• Péter Bagi,
• Réka Herbay,
• Nikolett Péczka,
• Zoltán Mucsi,
• István Timári and
• György Keglevich

Beilstein J. Org. Chem. 2020, 16, 818–832, doi:10.3762/bjoc.16.75

• butadiene derivative and P-reagent used [36][48][49][50]. However, the long reaction times, as well as the moderate or low yields make this approach less appealing. More recent syntheses of the phospholene oxides involve either a ring-closing metathesis [35][51][52][53][54], or a double Arbuzov reaction of

Non-metal-templated approaches to bis(borane) derivatives of macrocyclic dibridgehead diphosphines via alkene metathesis

• Tobias Fiedler,
• Michał Barbasiewicz,
• Michael Stollenz and
• John A. Gladysz

Beilstein J. Org. Chem. 2018, 14, 2354–2365, doi:10.3762/bjoc.14.211

• (in,in/out,out)-2·2BH3 (2%). Four of these structures are verified by independent syntheses. Second, 1,14-tetradecanedioic acid is converted (reduction, bromination, Arbuzov reaction, LiAlH4) to H2P((CH2)14)PH2 (10; 76% overall yield). The reaction with H3B·SMe2 gives 10·2BH3, which is treated with n

• -dibromotetradecane (8) [38][39][40][41][42][43]. An Arbuzov reaction then afforded the diphosphonate (EtO)2(O=)P((CH2)14)P(=O)(OEt)2 (9) [44]. Subsequent reduction with LiAlH4 gave the diprimary diphosphine H2P((CH2)14)PH2 (10) in 76% yield from 7 as a foul smelling white powder. It has been shown that borane

Phosphonic acid: preparation and applications

• Charlotte M. Sevrain,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2017, 13, 2186–2213, doi:10.3762/bjoc.13.219

• are methyl, ethyl, isopropyl or, occasionally, n-butyl [127]. This observation is likely explained by the synthetic methods employed to prepare phosphonates that frequently made use of the Arbuzov reaction [128] involving the commercially available trimethyl, triethyl or triisopropyl phosphite [129

• Arbuzov reaction to produce the intermediate II [158]. The repetition of this mechanism produced de disilylated intermediate III. The hydrolysis of this intermediate III produced phosphonic acid, trimethylsilanol and hexamethyldisiloxane that are two volatile side products. The methanolysis of 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

First DMAP-mediated direct conversion of Morita–Baylis–Hillman alcohols into γ-ketoallylphosphonates: Synthesis of γ-aminoallylphosphonates

• Marwa Ayadi,
• Haitham Elleuch,
• Emmanuel Vrancken and
• Farhat Rezgui

Beilstein J. Org. Chem. 2016, 12, 2906–2915, doi:10.3762/bjoc.12.290

• step protocol involves firstly the mesylation of corresponding alcohols and then the conversion of the intermediate mesylates into their halides. Further an Arbuzov reaction of alkyl phosphites with such halides affords the phosphonates. Interestingly, a direct conversion of common allyl alcohols into

• corresponding SN2-type products 6a–d in 63 to 70% isolated yields. Alternatively, the alcohol 5 produced the corresponding acetate 7 which, mediated by Ce(III), was successfully converted into the corresponding γ-aminoallylphosphonates 8a–d. Keywords: allylic substitution; γ-aminoallylphosphonate; Arbuzov

• reaction; γ-ketoallylphosphonate; organophosphorus chemistry; Introduction Phosphonates and their derivatives are an important class of substances that have a wide range of applications in numerous areas such as medicinal [1][2][3] and agricultural chemistry [4][5]. Among them, multifunctional derivatives

Synthesis of dinucleoside acylphosphonites by phosphonodiamidite chemistry and investigation of phosphorus epimerization

• William H. Hersh

Beilstein J. Org. Chem. 2015, 11, 184–191, doi:10.3762/bjoc.11.19

• shortly. The straightforward route for the synthesis of 3 involves the Arbuzov reaction of a trialkyl phosphite ester with an acid chloride [40], necessarily giving the dialkyl acylphosphonate with identical alkoxy groups. Thus, no comparable synthesis of 1 could be carried out since the dinucleoside

Synthesis and biological evaluation of novel N-α-haloacylated homoserine lactones as quorum sensing modulators

• Michail Syrpas,
• Ewout Ruysbergh,
• Christian V. Stevens,
• Norbert De Kimpe and
• Sven Mangelinckx

Beilstein J. Org. Chem. 2014, 10, 2539–2549, doi:10.3762/bjoc.10.265

• chromatography. Chlorinated AHL analogues 11a–f were prepared via a one pot procedure (Scheme 3). In this route the acylphosphonates 9a–f were prepared by an Arbuzov reaction and were subsequently chlorinated via reaction with sulfuryl chloride [29][30]. The phosphonate function is used as a strong activating

Application of cyclic phosphonamide reagents in the total synthesis of natural products and biologically active molecules

• Thilo Focken and
• Stephen Hanessian

Beilstein J. Org. Chem. 2014, 10, 1848–1877, doi:10.3762/bjoc.10.195

• phosphonamides: (A) Arbuzov reaction, (B) condensation of diamines with phosphonic acid dichlorides, (C) nucleophilic displacement, and (D) alkylation of 2-oxo-1,3,2-diazaphospholidine (Scheme 9). All of these methods were employed to prepare the phosphonamide reagents used in the synthesis of the natural

• products and bioactive compounds discussed in this review. Phosphonamides by Arbuzov reaction An example for the application of the Arbuzov reaction is the synthesis of phosphonamide (R,R)-28a. Thus, heating of (R,R)-N,N’-dimethyl-1,2-diaminocyclohexane (58) with hexamethylphosphorus triamide gave the

• distillable phospholane 59, which was further converted with ethanol into 60. Treatment with ethyl iodide in an Arbuzov reaction provided the desired ethyl phosphonamide 28a (Scheme 9A) [1][30]. Cyclic phosphonamides derived from C2-symmetric diamines such as 28a do not have a stereogenic P-atom and therefore

Phosphinate-containing heterocycles: A mini-review

• Olivier Berger and
• Jean-Luc Montchamp

Beilstein J. Org. Chem. 2014, 10, 732–740, doi:10.3762/bjoc.10.67

• ,b were prepared in 51% and 62% yields. The same approach was reported earlier by Mioskowski and coworkers [15][16] except the starting phosphinates 3a,b were prepared less efficiently by the sila-Arbuzov reaction of bis(trimethylsiloxy)phosphine (Me3SiO)2PH. Phosphindoles Montchamp and coworkers

• which are 1,3-azaphospholidine and 1,4-azaphosphorine derivatives 26, 29 [26]. For the 5-membered ring 26, hydroxymethyl-H-phosphinic acid (24) underwent a sila-Arbuzov reaction with the bromide 25, the crude mixture was esterified with diphenyldiazomethane, cyclized using Mitsunobu conditions and then

• McCormack reaction of conjugated dienes, the sila-Arbuzov reaction of bis(trimethylsiloxy)phosphine with dihalides, etc. continue to be useful. However, novel approaches in both the preparation of acyclic precursors and the reactions to achieve their heterocyclization, have led to more efficient synthesis

Methylidynetrisphosphonates: Promising C₁ building block for the design of phosphate mimetics

• Vadim D. Romanenko and
• Valery P. Kukhar

Beilstein J. Org. Chem. 2013, 9, 991–1001, doi:10.3762/bjoc.9.114

• ]. Review Preparation of methylidynetrisphosphonates Synthesis via a Michaelis–Arbuzov reaction Phosphonate esters are often prepared through Michaelis–Arbuzov reaction of a trialkyl phosphite with an alkyl halide [9]. However, contrary to the early patent claims, trisphosphonate esters cannot be derived

• ). Trisphosphonate 2 is also formed by the reaction of [(EtO)2P(O)]2C(Cl)NCO as well as (EtO)2P(O)CCl2NCO with 1 or 2 equiv of (EtO)3P, correspondingly [21]. An unsuccessful attempt to synthesize trisphosphonates from isocyanide dichlorides was made by the combination of Arbuzov reaction and dialkyl phosphite

• prepared in good yield by the Arbuzov reaction of trimethylsilyl esters of trivalent phosphorus acids with the easily accessible 2,6-di-tert-butyl-4-(dichloromethyl)phenol. In the next step, the bisphosphonate 16 was oxidized with K3Fe(CN)6 into quinone methide 17 in 91% yield. Further addition of diethyl

New modification of the Perkow reaction: halocarboxylate anions as leaving groups in 3-acyloxyquinoline- 2,4(1H,3H)-dione compounds

• Oldřich Paleta,
• Karel Pomeisl,
• Stanislav Kafka,
• Antonín Klásek and
• Vladislav Kubelka

Beilstein J. Org. Chem. 2005, 1, No. 17, doi:10.1186/1860-5397-1-17

• according to the Michaelis-Arbuzov reaction,[4] the α-halocarbonyl compounds react with triethylphosphite to form enol phosphites 3 as a product of the Perkow reaction (Scheme 2). [5] The reaction is otherwise known to take place in halogenated ketones, diketones, aldehydes and also in some halogenoesters

• ring. In the reaction of the fluoroiodoacetyl derivative 4, triethyl phosphite does not attack the C-I bond to form the corresponding product of Michaelis-Arbuzov reaction as is usual for the alkyl fluoroiodoacetates. [14] Instead, the phosphorus atom of triethyl phosphite attacks either the carbonyl