Using the phospha-Michael reaction for making phosphonium phenolate zwitterions

• Matthias R. Steiner,
• Max Schmallegger,
• Larissa Donner,
• Johann A. Hlina,
• Christoph Marschner,
• Judith Baumgartner and
• Christian Slugovc

Beilstein J. Org. Chem. 2024, 20, 41–51, doi:10.3762/bjoc.20.6

• similar phosphonium salt 2,4-di-tert-butyl-6-(triphenylphosphonium)phenolate features this particular signal at 6.27 ppm (4JHH = 2.7 Hz, 3JPH = 14.4 Hz [30]). In the 13C NMR spectra, the chemical shifts of the carbon atoms in positions 1 and 6 of the phenolate unit are particularly noteworthy. In the

• phosphonium phenolates are largely unaffected by changing a phenyl group for an alkyl group like in 2a–i. Also other similarly substituted phosphonium salt species give the phosphorus signal in the range of 26–19 ppm [28][37][38]. For comparison, the phosphine 1 exhibits a 31P NMR shift of −29.7 ppm [35]. In

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

• formation of compound 92, which was reduced to the corresponding alcohol and then converted into the bromide 94. Ozonolysis followed by reaction with triphenylphosphine gave the corresponding phosphonium salt 96, which was subjected to different conditions for the intramolecular Wittig reaction. The best

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

• ; electrochemical properties; phosphacyclopentadienide anion; phosphaferrocene; phosphonium salt; phosphorus heterocycle; Introduction Among the various heterometallocenes reported to date, phosphaferrocenes are by far the most investigated because of their structural and electronic features [1][2] and remain the

Asymmetric organocatalyzed synthesis of coumarin derivatives

• Natália M. Moreira,
• Lorena S. R. Martelli and
• Arlene G. Corrêa

Beilstein J. Org. Chem. 2021, 17, 1952–1980, doi:10.3762/bjoc.17.128

• recently, the strategy via introducing secondary interactions for the design of the bifunctional catalysts achieved wide application in asymmetric reactions [74]. Wu et al. described a Mannich asymmetric addition of cyanocoumarins 39 to isatin imines 112 catalyzed by an amide-phosphonium salt 114. This

• %) providing excellent results, besides the use of only 0.1 mol % of amide-phosphonium salt for the synthesis of coumarin derivatives. Some methodologies have also proven to be highly efficient in one-pot and gram-scale procedures, which turns to be more environmentally benign. Nevertheless, studies are still

• of 2-hydroxycinnamaldehydes 109 with 4-hydroxycoumarins 1. Mannich asymmetric addition of cyanocoumarins 39 to isatin imines 112 catalyzed by the amide-phosphonium salt 114. Enantioselective total synthesis of (+)-scuteflorin A (119). Funding The authors gratefully acknowledge FAPESP (grants 2013

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

• reduction of dibromodifluoromethane was also used for the approach of Burton and Naae (Scheme 4), which is again suitable for electron-rich alkenes [19]. Dibromodifluoromethane reacted with triphenylphosphine to give a phosphonium salt, which then decomposed to difluorocarbene. The yields from this method

Facile synthesis of 7-alkyl-1,2,3,4-tetrahydro-1,8-naphthyridines as arginine mimetics using a Horner–Wadsworth–Emmons-based approach

• Rhys A. Lippa,
• John A. Murphy and
• Tim N. Barrett

Beilstein J. Org. Chem. 2020, 16, 1617–1626, doi:10.3762/bjoc.16.134

• , GlaxoSmithKline disclosed a route to a fluoropyrrolidine 6 using a Wittig reaction between phosphonium salt 4 and aldehyde 5 [2]. The synthesis of phosphonium salt 4 (itself requiring 6 steps including partial saturation of a 1,8-naphthyridine moiety) and the formation of the triphenylphosphine oxide byproduct in

Azidophosphonium salt-directed chemoselective synthesis of (E)/(Z)-cinnamyl-1H-triazoles and regiospecific access to bromomethylcoumarins from Morita–Baylis–Hillman adducts

• Soundararajan Karthikeyan,
• Radha Krishnan Shobana,
• Kamarajapurathu Raju Subimol,
• J. Helen Ratna Monica and
• Ayyanoth Karthik Krishna Kumar

Beilstein J. Org. Chem. 2020, 16, 1579–1587, doi:10.3762/bjoc.16.130

• powerful synthetic tools. Keywords: halomethylcoumarin; Morita–Baylis–Hillman adducts; organocatalyst; phosphonium salt; triazolation; Introduction The presence of versatile functional groups in close proximity classifies Morita–Baylis–Hillman adducts as privileged key scaffolds for synthetic organic

• protection and elimination of the allylic hydroxy group. We believe that this crucial strategy could be primarily resolved by a quaternary phosphonium salt. After the initial screening of various quaternary phosphonium salts, the azidophosphonium salt [Ph3P+CBr3]N3−, reported by Blanco and co-workers, was

• hydroxy moiety at the carbonyl carbon of IIIb further drove the cyclisation to afford the bromomethylcoumarin 4a. Conclusion In summary, we reported the first protocol on the quaternary phosphonium salt-mediated direct synthesis of cinnamyltriazoles and 3-(bromomethyl)coumarins from Morita–Baylis–Hillman

N-(1-Phenylethyl)aziridine-2-carboxylate esters in the synthesis of biologically relevant compounds

• Iwona E. Głowacka,
• Aleksandra Trocha,
• Andrzej E. Wróblewski and
• Dorota G. Piotrowska

Beilstein J. Org. Chem. 2019, 15, 1722–1757, doi:10.3762/bjoc.15.168

• moiety (Scheme 13) [51]. Before conversion of the chloromethyl group into a phosphonium salt the chiral auxiliary was removed. The reaction of the ylide (R)-45 prepared from the chloride (R)-44 with benzaldehyde afforded (E)-alkene (S)-46 which after hydrogenation and basic hydrolysis gave ʟ

Introduction of an isoxazoline unit to the β-position of porphyrin via regioselective 1,3-dipolar cycloaddition reaction

• Xiujun Liu,
• Xiang Ma and
• Yaqing Feng

Beilstein J. Org. Chem. 2019, 15, 1434–1440, doi:10.3762/bjoc.15.143

• derivative TPP-CH2Cl. Notably, this intermediate was labile on silica-gel column to give the precursor hydroxymethylporphyrin. Hence recrystallization was employed to purify it. Later, refluxing of the solution of TPP-CH2Cl and PPh3 in toluene gave the phosphonium salt 1 [44]. To introduce the vinyl group at

• the β-position, a Wittig reaction was performed, in which the porphyrin phosphonium salt 1 reacted with 4-MeCO2-benzaldehyde in the presence of DBU to furnish the double bond, followed by insertion of Zn ions into the porphyrin cavity to give compound 2. Nitrile oxides [45] as one of the most reactive

• enantiomers of 3a is present, which assembled to a dimeric structure with the fifth chelation of a Zn2+ ion by the carbonyl group of the other molecule. The self-dimerization property of 3a may be utilized in supramolecular chemistry [50][51][52][53]. Experimental 1: Porphyrin phosphonium salt 1 was prepared

Liquid-assisted grinding and ion pairing regulates percentage conversion and diastereoselectivity of the Wittig reaction under mechanochemical conditions

• Kendra Leahy Denlinger,
• Lianna Ortiz-Trankina,
• Preston Carr,
• Kingsley Benson,
• Daniel C. Waddell and
• James Mack

Beilstein J. Org. Chem. 2018, 14, 688–696, doi:10.3762/bjoc.14.57

• , and 5 indicates that the carbonate bases deprotonated the phosphonium salt to form the ylide which then subsequently added to the benzaldehyde. However, the oxygen anion could not bind to the phosphorus cation to produce the stilbene product, presumably due to the mismatched counter ion pair. After

• reacted and is bound to the polymer and thus less production of the desired phosphonium salt. As expected, only 8.5% unreacted 4-nitrobenzyl bromide was recovered when ethanol was used as a LAG solvent, demonstrating that ethanol is an effective LAG solvent for the production of the phosphonium salt

• (Table 5). Because the formation of the phosphonium salt is the first step of the Wittig reaction, the question arose whether performing the reaction stepwise could influence our ability to select for both percent conversion and diastereoselectivity. Using a stepwise reaction approach with ethanol as the

Vinylphosphonium and 2-aminovinylphosphonium salts – preparation and applications in organic synthesis

• Anna Kuźnik,
• Roman Mazurkiewicz and
• Beata Fryczkowska

Beilstein J. Org. Chem. 2017, 13, 2710–2738, doi:10.3762/bjoc.13.269

• triphenylphosphine with 1-bromoethylbenzene. The resulting phosphonium salt 11 was then deprotonated to the corresponding ylide 12, which in the last step was subjected to bromination to give the expected α-bromoethylphosphonium bromide 13 [10]. 1.3. Peterson olefination of α-trimethylsilylphosphonium ylides with

• -propynyltriphenylphosphonium bromide (24) involved propadienylphosphonium bromide (25) – the tautomeric form of the starting phosphonium salt. The same authors carried out a series of nucleophilic additions of amines and hydrazine derivatives to 24 to obtain products with the proposed structure of 2-aminovinylphosphonium

• triphenylphosphine to a triple bond of acetylenedicarboxylate followed by protonation of the adduct by the NH-acid gave the expected vinylphosphonium salt 92. The attack of the carbanion on the β-position of the phosphonium salt followed by two competitive intramolecular Wittig reactions of the intermediate ylide 93

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

• benzophosphole-fused indole derivative and its various functionalized analogs such as the corresponding phosphine oxide, phosphonium salt, and borane–phosphine complex. Results and Discussion The synthesis of the parent tetracyclic molecule 10-phenyl-[1]benzophospholo[3,2-b]-N-methylindole (3), is shown in

Chiral phase-transfer catalysis in the asymmetric α-heterofunctionalization of prochiral nucleophiles

• Johannes Schörgenhumer,
• Maximilian Tiffner and
• Mario Waser

Beilstein J. Org. Chem. 2017, 13, 1753–1769, doi:10.3762/bjoc.13.170

• substrate scope when using just 2 mol % of phosphonium salt F1 under liquid/liquid biphasic conditions (Scheme 3). As already stated before, the use of chiral anionic PTCs became increasingly important over the last years and especially asymmetric fluorine-transfer reactions have been very extensively

• conditions [90]. Key to success in this spectacular report was the use of the systematically optimized sulfonamide-containing phosphonium salt J1. With this catalyst, they were able to achieve high selectivities in the α-chlorination of 1 with N-chlorophthalimide (13) as the Cl-source under H2O-rich

• group then described the use of the bifunctional phosphonium salt-based catalyst J2 for the α-sulfanylation of β-ketoesters 1 [90]. Very impressively, only 0.1 mol % of the catalyst were sufficient to achieve high yields and high enantioselectivities for this transformation under base-free water-rich

1-Imidoalkylphosphonium salts with modulated C_α–P⁺ bond strength: synthesis and application as new active α-imidoalkylating agents

• Jakub Adamek,
• Roman Mazurkiewicz,
• Anna Węgrzyk and
• Karol Erfurt

Beilstein J. Org. Chem. 2017, 13, 1446–1455, doi:10.3762/bjoc.13.142

• was isolated in 73% yield accompanied by only trace amounts of the expected phosphonium salt 5o (Table 2, last entry). It is assumed that both the extraordinary effective resonance stabilization of the imide anion and the excessive steric congestion in the transition state make the splitting of the Cα

• conditions, the reaction had already started at about 130 °C (Table 3, entry 9). Again, the reaction of the same phosphonium salt with the much more reactive 1,3-dimethoxybenzene started at the same temperature (150 °C; Table 3, entry 20). This observation suggests that the generation of a 1-imidocarbenium

• (Table 3, entry 18). All attempts to carry out the imidoalkylation of 1,3,5-trimethoxybenzene with phosphonium salt 5e failed. In this case 1-(2,4,6-trimethoxyphenyl)ethyltris(4-trifluoromethylphenyl)phosphonium tetrafluoroborate (10) was isolated from the reaction mixture in 73% yield as the only

Catalytic Wittig and aza-Wittig reactions

• Zhiqi Lao and
• Patrick H. Toy

Beilstein J. Org. Chem. 2016, 12, 2577–2587, doi:10.3762/bjoc.12.253

• -catalysts. Prototypical Wittig reaction involving in situ phosphonium salt and phosphonium ylide formation. Bu3As-catalyzed Wittig-type reactions. Ph3As-catalyzed Wittig-type reactions using Fe(TCP)Cl and ethyl diazoacetate for arsonium ylide generation. Bu2Te-catalyzed Wittig-type reactions. Polymer

Total synthesis of leopolic acid A, a natural 2,3-pyrrolidinedione with antimicrobial activity

• Atul A. Dhavan,
• Rahul D. Kaduskar,
• Loana Musso,
• Leonardo Scaglioni,
• Piera Anna Martino and
• Sabrina Dallavalle

Beilstein J. Org. Chem. 2016, 12, 1624–1628, doi:10.3762/bjoc.12.159

• DIBAL-H gave the corresponding primary alcohol, which was converted into bromide 5 by Appel reaction with PPh3 and CBr4. The phosphonium salt obtained from this bromide was subjected to a Wittig reaction with nonanal, to afford compound 6 [12]. Attempts to remove the PMB protecting group (CAN, DDQ, TFA

Synthesis of a deuterated probe for the confocal Raman microscopy imaging of squalenoyl nanomedicines

• Eric Buchy,
• Branko Vukosavljevic,
• Maike Windbergs,
• Dunja Sobot,
• Camille Dejean,
• Simona Mura,
• Patrick Couvreur and
• Didier Desmaële

Beilstein J. Org. Chem. 2016, 12, 1127–1135, doi:10.3762/bjoc.12.109

• from the monoproduct, potassium carbonate treatment gave the expected diepoxide 7. Oxidative cleavage with periodic acid provided the corresponding dialdehyde 5 in 17% overall yield from squalene. The perdeuterated phosphonium salt 9 was obtained by simple condensation of commercially available 2

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

• -membered ring lactams [20]. Finally, a one-pot reduction-olefination involving an α-amino β-hydroxy ester and a phosphonium salt, both bearing free hydroxy groups, has been used in the synthesis of (−)-α-conhydrine [21]. In this work, our aim was to study in more detail this one-pot strategy. Similarly to

Hydroquinone–pyrrole dyads with varied linkers

• Hao Huang,
• Christoffer Karlsson,
• Maria Strømme,
• Martin Sjödin and
• Adolf Gogoll

Beilstein J. Org. Chem. 2016, 12, 89–96, doi:10.3762/bjoc.12.10

• material, a Wittig reaction was chosen as an alternative. The Wittig reaction approach is shown in Scheme 2. In this reaction, phosphonium salt 7 was prepared in quantitative yield from 5 and triphenylphosphine by reflux in toluene, according to a procedure reported for dimethoxybenzyl chloride [21]. The

• work-up involved simple filtration and washing with toluene. Use of t-BuOK as a base to deprotonate the phosphonium salt resulted in a dark red phosphorous ylide, to which 1-(triisopropylsilyl)-1H-pyrrole-3-carbaldehyde was added, followed by heating at 80 °C. The desired product 4c was obtained in 40

A new method for the synthesis of α-aminoalkylidenebisphosphonates and their asymmetric phosphonyl-phosphinyl and phosphonyl-phosphinoyl analogues

• Anna Kuźnik,
• Roman Mazurkiewicz,
• Mirosława Grymel,
• Katarzyna Zielińska,
• Jakub Adamek,
• Ewa Chmielewska,
• Marta Bochno and
• Sonia Kubica

Beilstein J. Org. Chem. 2015, 11, 1418–1424, doi:10.3762/bjoc.11.153

• -methoxyalkylphosphonic acid derivatives, their methoxy group was successfully displaced by the triphenylphosphonium group. Thus, heating the homogeneous mixture of diethyl 1-(N-acetylamino)-1-methoxymethylphosphonate (6a) with triphenylphosphonium tetrafluoroborate at 50 °C gave hitherto unknown phosphonium salt 7a as a

• resin-like compound stable at room temperature (Scheme 2). In the case of 1-(N-acetylamino)-1-methoxyethylphosphonate (6b), the analogous reaction with triphenylphosphonium tetrafluoroborate proceeded very quickly, without heating, but the resulting phosphonium salt 7b underwent slow decomposition even

Palladium-catalysed cyclisation of alkenols: Synthesis of oxaheterocycles as core intermediates of natural compounds

• Miroslav Palík,
• Jozef Kožíšek,
• Peter Koóš and
• Tibor Gracza

Beilstein J. Org. Chem. 2014, 10, 2077–2086, doi:10.3762/bjoc.10.216

• ]. Synthesis of alkenols 20-23 and 30. Reagents and conditions: a) lit. [31] (COCl)2, DMSO, Et3N, CH2Cl2, −78 °C to rt, 2 h; b) Phosphonium salt, BuLi, THF, 0 °C to rt, overnight, MPLC; c) lit. [32] (EtO)2POCH2CO2Et, NaH, THF, 0 °C to rt, 3 h; d) 60% AcOH, 60 °C, 3 h; e) MeMgCl, Et2O, 0 °C to rt, 1 h; f) Dess

Facile synthesis of 1-alkoxy-1H-benzo- and 7-azabenzotriazoles from peptide coupling agents, mechanistic studies, and synthetic applications

• Mahesh K. Lakshman,
• Manish K. Singh,
• Mukesh Kumar,
• Raghu Ram Chamala,
• Vijayender R. Yedulla,
• Domenick Wagner,
• Evan Leung,
• Lijia Yang,
• Asha Matin and
• Sadia Ahmad

Beilstein J. Org. Chem. 2014, 10, 1919–1932, doi:10.3762/bjoc.10.200

• demonstrated the isolation and synthetic utility of a nucleoside phosphonium salt [28]. Thus, to us the reaction of oximes with BOP was an intriguing result, leading us to query whether a benzotriazolyl intermediate, rather than a phosphonium ion, was formed en route to the cyanide. This line of reasoning

Rasta resin–triphenylphosphine oxides and their use as recyclable heterogeneous reagent precursors in halogenation reactions

• Xuanshu Xia and
• Patrick H. Toy

Beilstein J. Org. Chem. 2014, 10, 1397–1405, doi:10.3762/bjoc.10.143

• reagents and catalysts [27][28][29][30][31][32][33], and have used easily synthesized rasta resin–Ph3P (14) in various Wittig reactions that required only filtration and solvent removal for product purification (Figure 1) [27][28][29]. Additionally, 14 was converted into phosphonium salt 15, which proved

Deoxygenative gem-difluoroolefination of carbonyl compounds with (chlorodifluoromethyl)trimethylsilane and triphenylphosphine

• Fei Wang,
• Lingchun Li,
• Chuanfa Ni and
• Jinbo Hu

Beilstein J. Org. Chem. 2014, 10, 344–351, doi:10.3762/bjoc.10.32

• difluoromethylene phosphonium ylide, which can be generated in situ either by the transformation of a difluorinated phosphonium salt or by the reaction between difluorocarbene (:CF2) and a phosphine (Scheme 1) [19][20][21][22][23][24][25][26]. In 1964, Fuqua and co-workers first reported the difluoromethylenation

• of aldehydes by using ClCF2CO2Na/PPh3 [19]. In 1967, Burton and Herkes suggested that the ylide intermediate involved in the olefination process was more likely to be formed by the decarboxylation of a difluorinated phosphonium salt rather than the combination of :CF2 and a phosphine (Scheme 1

• ). As determined by 19F NMR, besides the side product (difluoromethyl)triphenylphosponium bromide (δ −127.9, dd, 3JP-F = 80 Hz, 2JF-H = 47 Hz) as reported in the Wittig olefination with FSO2CF2CO2Me [25], a new product which was assigned as difluorinated phosphonium salt 4 (δ −88.8, ddd, 2JF-F = 298 Hz

Cyclic phosphonium ionic liquids

• Sharon I. Lall-Ramnarine,
• Joshua A. Mukhlall,
• James F. Wishart,
• Robert R. Engel,
• Alicia R. Romeo,
• Masao Gohdo,
• Sharon Ramati,
• Marc Berman and
• Sophia N. Suarez

Beilstein J. Org. Chem. 2014, 10, 271–275, doi:10.3762/bjoc.10.22

• thermal properties of the phosphonium ILs 5a–d and their ammonium congeners are given in Table 1. Comparison of the five-membered cyclic cation ILs C4mPphol NTf2 5a and C4mPyrr NTf2 (butylmethylpyrrolidinium NTf2) reveals that the viscosity of the phosphonium salt is one third higher than that of the