Organophosphorus chemistry: from model to application

• György Keglevich

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

• Gyorgy Keglevich Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, 1521 Budapest, Hungary 10.3762/bjoc.19.8 Keywords: organophosphorus chemistry; The thematic issue “Organophosphorus chemistry: from model to application” shows a number of “hot

• ” 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

• related N-heterocycles to prepare the respective bisphosphonate derivatives that were transformed to the corresponding diphosphonic acids. The Pudovik addition is still an evergreen reaction as it leads to α-hydroxyphosphonates that are versatile intermediates in organophosphorus chemistry. Yang et al

Dienophilic reactivity of 2-phosphaindolizines: a conceptual DFT investigation

• Nosheen Beig,
• Aarti Peswani and
• Raj Kumar Bansal

Beilstein J. Org. Chem. 2022, 18, 1217–1224, doi:10.3762/bjoc.18.127

• organophosphorus compounds. Computational Methods All calculations were done using the Gaussian 16 program [29]. We found that almost without exception, hybrid of Becke 3 and LYP correlation functional [30][31] has been used for determining reactivity descriptors [32][33][34][35] and the results were found to be

Fritsch–Buttenberg–Wiechell rearrangement of magnesium alkylidene carbenoids leading to the formation of alkynes

• Tsutomu Kimura,
• Koto Sekiguchi,
• Akane Ando and
• Aki Imafuji

Beilstein J. Org. Chem. 2021, 17, 1352–1359, doi:10.3762/bjoc.17.94

• –Wadsworth–Emmons (HWE) reaction of carbonyl compounds with organophosphorus reagents containing carbene sources and the 1,2-rearrangement of alkylidene carbenes and related species, referred to as Fritsch–Buttenberg–Wiechell (FBW) rearrangement [8][9]. While alkynes are synthesized from carbonyl compounds

Highly regio- and stereoselective phosphinylphosphination of terminal alkynes with tetraphenyldiphosphine monoxide under radical conditions

• Dat Phuc Tran,
• Yuki Sato,
• Yuki Yamamoto,
• Shin-ichi Kawaguchi,
• Shintaro Kodama,
• Akihiro Nomoto and
• Akiya Ogawa

Beilstein J. Org. Chem. 2021, 17, 866–872, doi:10.3762/bjoc.17.72

• variety of terminal alkynes including both alkyl- and arylalkynes. Keywords: (E)-1,2-bis(diphenylphosphino)ethylene derivative; radical addition; stereoselective phosphinylphosphination; terminal alkyne; tetraphenyldiphosphine monoxide; Introduction Organophosphorus compounds are an essential class of

• compounds in catalytic technologies, biochemistry, and materials [1][2][3][4][5][6]. In particular, in coordination chemistry and catalyst chemistry, organophosphorus compounds such as triorganylphosphines are widely used as typical monodentate ligands for many metals [7][8]. In addition, diphosphines such

Metal-free synthesis of phosphinoylchroman-4-ones via a radical phosphinoylation–cyclization cascade mediated by K₂S₂O₈

• Qiang Liu,
• Weibang Lu,
• Guanqun Xie and
• Xiaoxia Wang

Beilstein J. Org. Chem. 2020, 16, 1974–1982, doi:10.3762/bjoc.16.164

• appropriate radical precursors through visible-light promoted systems [15][16], transition-metal-catalyzed systems [17][18], or transition-metal-free systems [19][20], have emerged as a powerful strategy for the synthesis of diversely functionalized chroman-4-one derivatives. Organophosphorus compounds are

• for a huge number of organic reactions [21][22][23][24][25][26]. Due to the importance of the chroman-4-one scaffold on one hand and that of organophosphorus compounds on the other, the development of concise and efficient approaches for the synthesis of chroman-4-one derivatives decorated with

The McKenna reaction – avoiding side reactions in phosphonate deprotection

• Katarzyna Justyna,
• Joanna Małolepsza,
• Damian Kusy,
• Waldemar Maniukiewicz and
• Katarzyna M. Błażewska

Beilstein J. Org. Chem. 2020, 16, 1436–1446, doi:10.3762/bjoc.16.119

• University of Technology, Zeromskiego St. 116, 90-924 Lodz, Poland 10.3762/bjoc.16.119 Abstract The McKenna reaction is a well-known and popular method for the efficient and mild synthesis of organophosphorus acids. Bromotrimethylsilane (BTMS) is the main reagent in this reaction, which transforms dialkyl

• . Keywords: bromotrimethylsilane; McKenna reaction; organophosphorus acid; oxazole; phosphonate ester; Introduction The McKenna reaction is a tool for the synthesis of organophosphorus acids from their esters and known for over 40 years [1][2]. The importance of this class of compounds is widely recognized

• reagent of choice for phosphonate ester cleavage, compared with its more and less reactive analogs, iodotrimethylsilane (ITMS) [11][12] and chlorotrimethylsilane (CTMS) [13], respectively. While being one of the most popular methods for the deprotection of organophosphorus esters, the McKenna reaction may

Synthesis, antiinflammatory activity, and molecular docking studies of bisphosphonic esters as potential MMP-8 and MMP-9 inhibitors

• Abimelek Cortes-Pacheco,
• María Adelina Jiménez-Arellanes,
• Francisco José Palacios-Can,
• José Antonio Valcarcel-Gamiño,
• Rodrigo Said Razo-Hernández,
• María del Carmen Juárez-Vázquez,
• Adolfo López-Torres and
• Oscar Abelardo Ramírez-Marroquín

Beilstein J. Org. Chem. 2020, 16, 1277–1287, doi:10.3762/bjoc.16.108

• docking; organophosphorus compounds; Introduction Bisphosphonic acids (or bisphosphonates) are organophosphorus compounds characterized by a P–C–P moiety. These organic compounds are valuable drugs for the treatment of bone diseases as osteoporosis, Paget’s disease, and malignant hypercalcemia [1][2][3

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

• double bond migration pathways were elucidated by quantum chemical calculations. Keywords: chlorophosphonium salts; isomerization; 2-phospholene oxides; 3-phospholene oxides; quantum chemistry; Introduction P-Heterocyclic derivatives are valuable targets in synthetic organophosphorus chemistry [1][2][3

Copper-catalyzed O-alkenylation of phosphonates

• Nuria Vázquez-Galiñanes,
• Mariña Andón-Rodríguez,
• Patricia Gómez-Roibás and
• Martín Fañanás-Mastral

Beilstein J. Org. Chem. 2020, 16, 611–615, doi:10.3762/bjoc.16.56

• valuable enol phosphonates in very good yields. Keywords: alkenylation; copper; C(sp2)–O bond formation; hypervalent iodine; phosphonates; Introduction Organophosphorus compounds represent an important class of products with a wide range of applications in biology, agriculture and synthetic organic

[1,3]/[1,4]-Sulfur atom migration in β-hydroxyalkylphosphine sulfides

• Katarzyna Włodarczyk,
• Piotr Borowski and
• Marek Stankevič

Beilstein J. Org. Chem. 2020, 16, 88–105, doi:10.3762/bjoc.16.11

• many others. In organophosphorus chemistry, rearrangements are less developed transformations, however, some examples can be found in the literature (Scheme 1). These include the famous Arbuzov rearrangement [29][30][31][32] as well as phospha-Fries ([1,3]-rearrangements) [33][34][35][36][37], phospha

• phosphonate–phosphinate rearrangement of dimethyl phosphonates [50]. Other [1,3]-rearrangements of organophosphorus compounds include phosphoenolpyruvate formation from phosphonopyruvate [51], benzylphosphonium salt formation from the corresponding o-methylaryl-substituted precursors [52], or the formation of

• -hydroxyalkylphosphine sulfides, and therefore, an alternative methodology had to be developed for the synthesis of chiral organophosphorus compounds possessing either phosphaindane or benzophosphorinane skeletons. As such, it was decided to test the ability of Lewis acids to catalyze the cyclization of β

Synthesis and photophysical properties of novel benzophospholo[3,2-b]indole derivatives

• Mio Matsumura,
• Mizuki Yamada,
• Atsuya Muranaka,
• Misae Kanai,
• Naoki Kakusawa,
• Daisuke Hashizume,
• Masanobu Uchiyama and
• Shuji Yasuike

Beilstein J. Org. Chem. 2017, 13, 2304–2309, doi:10.3762/bjoc.13.226

• may be associated with the low fluorescence quantum yields. Conclusion A series of novel indole-fused phospholes were synthesized by simple chemical modifications at the trivalent phosphorus center. These organophosphorus compounds generated a whole series of derivatives from only one precursor. The X

Mechanochemical synthesis of small organic molecules

• Tapas Kumar Achar,
• Anima Bose and
• Prasenjit Mal

Beilstein J. Org. Chem. 2017, 13, 1907–1931, doi:10.3762/bjoc.13.186

• synthesis under mechanochemical conditions. Phosphonylation of benzothiazole and thiazole derivatives were done with organophosphorus compounds using 3 equiv of Mn(OAc)3·2H2O in a mixer mill for 1.5 h. Benzothiazole or thiazole rings having electron-donating or -withdrawing groups worked efficiently under

• this protocol. Different organophosphorus compounds including phosphine oxides, phosphinate ester, and phosphonate diester underwent C–P bond formation to give 22–94% of yield (Scheme 42). This method was also found to be applicable in gram scale synthesis with excellent yield. Mechanistically they

Structure–efficiency relationships of cyclodextrin scavengers in the hydrolytic degradation of organophosphorus compounds

• Sophie Letort,
• Michaël Bosco,
• Benedetta Cornelio,
• Frédérique Brégier,
• Sébastien Daulon,
• Géraldine Gouhier and
• François Estour

Beilstein J. Org. Chem. 2017, 13, 417–427, doi:10.3762/bjoc.13.45

• , France 10.3762/bjoc.13.45 Abstract New derivatives of cyclodextrins were prepared in order to determine the relative importance of the structural key elements involved in the degradation of organophosphorus nerve agents. To avoid a competitive inclusion between the organophosphorus substrate and the

• of the agents. The degradation efficiency was found to be dependent on the relative position of the heterocycle towards the reactive group as well as on the nature of the organophosphorus derivative. Keywords: cyclodextrin; decontamination; enzyme mimic; nerve agents; organophosphorus pesticides

• ; Introduction Originally employed as pesticides, organophosphorus compounds were further developed as chemical warfare agents during the Second World War. These compounds act as potent irreversible inhibitors of cholinesterases [1][2][3][4][5][6] and are able to cause lethal intoxications [3]. Despite the

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

• 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

Multicomponent reactions: A simple and efficient route to heterocyclic phosphonates

• Mohammad Haji

Beilstein J. Org. Chem. 2016, 12, 1269–1301, doi:10.3762/bjoc.12.121

• . As shown in this review, they play an important role in organophosphorus chemistry where phosphorus reagents are used as substrates for the synthesis of a wide range of phosphorylated heterocycles. In this article, an overview about multicomponent reactions used for the synthesis of heterocyclic

• compounds bearing a phosphonate group on the ring is given. Keywords: multicomponent reactions; organophosphorus chemistry; phosphorus reagents; phosphorylated heterocycles; Introduction Heterocyclic rings are found in many naturally occurring compounds and they compose the core structures of many

• an important class of organophosphorus compounds that has attracted the attention of both industrial and medicinal chemists [5][6][7][8][9][10][11][12]. Many efforts have been made to prepare these bioactive compounds over the last 60 years [13]. There are two general approaches to the synthesis of

One-pot synthesis of enantiomerically pure N-protected allylic amines from N-protected α-amino esters

• Gastón Silveira-Dorta,
• Sergio J. Álvarez-Méndez,
• Víctor S. Martín and
• José M. Padrón

Beilstein J. Org. Chem. 2016, 12, 957–962, doi:10.3762/bjoc.12.94

• subsequent in situ addition of organophosphorus reagents yielded the corresponding allylic amines without the need to isolate the intermediate aldehyde. This circumvents the problem of instability of the aldehydes. The method tolerates well both Wittig and Horner–Wadsworth–Emmons organophosphorus reagents. A

• Wittig and Horner–Wadsworth–Emmons (HWE) organophosphorus reagents (Table 2). When considering phosphonium ylides (Table 2, entries 1 and 2), better Z-(dia)stereoselectivity was observed when compared to the previous one-pot method. The olefination with the semistable ylide obtained by the addition of KN

• , entry 3 vs 4) in order to increase the yield of the reaction. We speculate that the free hydroxy group coordinates to the DIBAL-H, making compulsory the additional amount of reducing agent. As shown in Table 4, this modification of the one-pot protocol is compatible with the use of HWE organophosphorus

Superstructures with cyclodextrins: chemistry and applications III

• Gerhard Wenz and
• Eric Monflier

Beilstein J. Org. Chem. 2016, 12, 937–938, doi:10.3762/bjoc.12.91

• , the group of F. Estour has published an update on the current application of CDs for the detoxification of organophosphorus compounds [14]. In fact, the bowl-shaped structure of cyclodextrins is ideally suited for the design of new chemical scavengers for organophosphorus compounds, allowing these

Aluminacyclopentanes in the synthesis of 3-substituted phospholanes and α,ω-bisphospholanes

• Vladimir A. D’yakonov,
• Alevtina L. Makhamatkhanova,
• Rina A. Agliullina,
• Leisan K. Dilmukhametova,
• Tat’yana V. Tyumkina and
• Usein M. Dzhemilev

Beilstein J. Org. Chem. 2016, 12, 406–412, doi:10.3762/bjoc.12.43

• organophosphorus compounds (OPC) is the direct transformation of five-membered metallacarbocycles based on transition metals to phosphacarbocycles on treatment with phosphorus dihalides. For example, a method for the direct conversion of zirconacyclopentenes [1][2][3][4] and zirconacyclopentadienes [5] to

• , in our opinion, the development of these reactions would give rise to practically promising one-pot methods for the preparation of a broad range of cyclic and acyclic organophosphorus compounds of specified structure (phospholanes, phospholenes, phospholes and 1,2- and 1,4-diphosphorus compounds

• cyclic organophosphorus compounds. Results and Discussion First, we studied the effect of the structure of substituent in position 3 of the initial aluminacyclopentanes on the yield of target phospholanes. Under the selected conditions (toluene, 20–22 °С, 30 min), 3-alkyl-substituted aluminacyclopentanes

Interactions of cyclodextrins and their derivatives with toxic organophosphorus compounds

• Sophie Letort,
• Sébastien Balieu,
• William Erb,
• Géraldine Gouhier and
• François Estour

Beilstein J. Org. Chem. 2016, 12, 204–228, doi:10.3762/bjoc.12.23

• on the current use of cyclodextrins against organophosphorus compound intoxications. Organophosphorus pesticides and nerve agents play a determinant role in the inhibition of cholinesterases. The cyclic structure of cyclodextrins and their toroidal shape are perfectly suitable to design new chemical

• scavengers able to trap and hydrolyze the organophosphorus compounds before they reach their biological target. Keywords: cyclodextrin; enzyme mimic; nerve agents; organophosphorus compounds; pesticides; Introduction Due to their biological activities, organophosphorus compounds have had considerable

• commercial impacts during the last decades, phosphates, phosphonates, phosphinates, or phosphines being prominent in several fields. As an example, drugs bearing an organophosphorus moiety hold a significant place in chemotherapy for the treatment of various diseases. Nevertheless, the high polarity of these

Aerobic addition of secondary phosphine oxides to vinyl sulfides: a shortcut to 1-hydroxy-2-(organosulfanyl)ethyl(diorganyl)phosphine oxides

• Svetlana F. Malysheva,
• Alexander V. Artem’ev,
• Nina K. Gusarova,
• Nataliya A. Belogorlova,
• Alexander I. Albanov,
• C. W. Liu and
• Boris A. Trofimov

Beilstein J. Org. Chem. 2015, 11, 1985–1990, doi:10.3762/bjoc.11.214

• )phosphine oxides in 70–93% yields. Keywords: addition; green method; phosphine oxides; regioselectivity; vinyl sulfides; Findings Tertiary phosphines and phosphine chalcogenides are important organophosphorus compounds that are widely used in industry, organic synthesis, polymer science, medicinal and

• exclusively the anti-Markovnikov adducts (Scheme 2). On the other hand, vinyl ethers and vinyl selenides (congeners of vinyl sulfides) were found to react with phosphine oxide 1a at 80 °C for about 30 and 20 h, respectively, to deliver difficult-to-separate mixtures of organophosphorus compounds (31P NMR). To

Synthesis of γ-hydroxypropyl P-chirogenic (±)-phosphorus oxide derivatives by regioselective ring-opening of oxaphospholane 2-oxide precursors

• Iris Binyamin,
• Shoval Meidan-Shani and
• Nissan Ashkenazi

Beilstein J. Org. Chem. 2015, 11, 1332–1339, doi:10.3762/bjoc.11.143

• ; oxaphospholanes; phosphinates; phosphine oxides; Introduction Organophosphorus compounds containing phosphorus to carbon bond(s) are widely used in organic transformations. Textbook examples are the Wittig and the Horner–Wadsworth–Emmons reactions. Moreover, the vast majority of ligands used in organometallic

• catalysis possess this bond(s). Among which organophosphorus compounds bearing three different alkyl (or aryl) ligands are of a great interest, as such compounds possess the essential backbone for P-chirogenic derivatives [1][2][3]. The formation of P–C bonds [4][5][6] may be classified into two main types

• TBP phosphorane intermediate is formed, which could not undergo pseudorotation due to a high energetic barrier. The endocyclic P–O bond is cleaved almost exclusively (Scheme 4) to form the respective phosphinates and phosphine oxides in high yields. Propargyl organophosphorus compounds present a

Enhancing the reactivity of 1,2-diphospholes in cycloaddition reactions

• Almaz Zagidullin,
• Vasili Miluykov,
• Elena Oshchepkova,
• Artem Tufatullin,
• Olga Kataeva and
• Oleg Sinyashin

Beilstein J. Org. Chem. 2015, 11, 169–173, doi:10.3762/bjoc.11.17

• of electron-withdrawing groups (EWGs) at the phosphorus atom or (b) the introduction of EWGs to the carbon atoms of aryl substituents. This work will provide access to new polycyclic, organophosphorus compounds having significant potential as weak, bulky ligands in homogeneous catalysis [12][13][14

Encapsulation of biocides by cyclodextrins: toward synergistic effects against pathogens

• Véronique Nardello-Rataj and
• Loïc Leclercq

Beilstein J. Org. Chem. 2014, 10, 2603–2622, doi:10.3762/bjoc.10.273

• −1 from UV–vis spectrophotometry. The degradation rate of chloramidophos in 14 days incubation was slowed down by a factor of 3.6 when complexed with β-CD. The authors reported that the biocidal mechanism is not affected by the organophosphorus complexation. Indeed, the formation of chloramidophos–β

A modular phosphate tether-mediated divergent strategy to complex polyols

• Paul R. Hanson,
• Susanthi Jayasinghe,
• Soma Maitra,
• Cornelius N. Ndi and
• Rambabu Chegondi

Beilstein J. Org. Chem. 2014, 10, 2332–2337, doi:10.3762/bjoc.10.242

• five polyol fragments. Each of the product polyols bears a central 1,3-anti-diol subunit with differential olefinic geometries at the periphery. Keywords: phosphate-tether; one-pot; sequential processes; organophosphorus; polyol; stereodivergent; Introduction 1,3-anti-Diol subunits are a central

Chiral phosphines in nucleophilic organocatalysis

• Yumei Xiao,
• Zhanhu Sun,
• Hongchao Guo and
• Ohyun Kwon

Beilstein J. Org. Chem. 2014, 10, 2089–2121, doi:10.3762/bjoc.10.218

• carbonates, Michael additions, γ-umpolung additions, and acylations of alcohols. Keywords: asymmetric catalysis; chiral phosphine; nucleophilic; organocatalysis; organophosphorus; synthesis; Introduction During the past two decades, tertiary phosphine catalysts have been applied extensively in a wide range