Regioselective alkylation of a versatile indazole: Electrophile scope and mechanistic insights from density functional theory calculations

• Pengcheng Lu,
• Luis Juarez,
• Paul A. Wiget,
• Weihe Zhang,
• Krishnan Raman and
• Pravin L. Kotian

Beilstein J. Org. Chem. 2024, 20, 1940–1954, doi:10.3762/bjoc.20.170

• character of TsO− and triphenylphosphine oxide, precluding any thermodynamic versus kinetic arguments for regioselectivity. Conclusion We have established highly regioselective N1- and N2-alkylations of methyl 5-bromo-1H-indazole-3-carboxylate from diverse commercially available alcohols with excellent

Harnessing unprotected deactivated amines and arylglyoxals in the Ugi reaction for the synthesis of fused complex nitrogen heterocycles

• Javier Gómez-Ayuso,
• Pablo Pertejo,
• Tomás Hermosilla,
• Israel Carreira-Barral,
• Roberto Quesada and
• María García-Valverde

Beilstein J. Org. Chem. 2024, 20, 1758–1766, doi:10.3762/bjoc.20.154

• methodology has several drawbacks, as the need to synthesise the 2-azidobenzoic acid from anthranilic acid and sodium azide, the requirement of anhydrous conditions to perform the Staudinger/aza-Wittig sequence or the generation of large quantities of triphenylphosphine oxide which needs to be removed by

Generation of alkyl and acyl radicals by visible-light photoredox catalysis: direct activation of C–O bonds in organic transformations

• Mithu Roy,
• Bitan Sardar,
• Itu Mallick and
• Dipankar Srimani

Beilstein J. Org. Chem. 2024, 20, 1348–1375, doi:10.3762/bjoc.20.119

• benzoate. This benzoate then reacts with the triphenylphosphine radical cation, resulting in the formation of the phosphoranyl radical intermediate, which undergoes β-scission, leading to the formation of a benzoyl radical, accompanied by the liberation of a triphenylphosphine oxide molecule. After this

• phosphoranyl radical intermediate then undergoes β-cleavage, giving rise to a benzylic radical and triphenylphosphine oxide. A terminal hydrogen atom transfer (HAT), facilitated by an aryl thiol, results in the formation of the desired product with concurrent formation of the thiyl radical. The reduction of

Skeletal rearrangement of 6,8-dioxabicyclo[3.2.1]octan-4-ols promoted by thionyl chloride or Appel conditions

• Martyn Jevric,
• Julian Klepp,
• Johannes Puschnig,
• Oscar Lamb,
• Christopher J. Sumby and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2024, 20, 823–829, doi:10.3762/bjoc.20.74

• alkoxytriphenylphosphonium chloride (26, R = Bn), which then slowly rearranged over 24 hours at 83 °C in DCE, eliminating triphenylphosphine oxide (Figure 2). A single ion was observed in the ESI mass spectrum for the intermediate at m/z 571.1 corresponding to the [M + PPh3 − H]+, and in the 1H NMR, the H4 adjacent to the

• the byproduct triphenylphosphine oxide, necessitating chromatography which resulted in some hydrolysis. There are a number of catalytic activation strategies for Appel or Mitsunobu reactions such as those described by the Denton group [30], and Rutjes and co-workers [31], and while these may prove

• chlorosulfite 25 or the alkoxytriphenylphosphonium chloride 26, respectively. With heating, SO2 or triphenylphosphine oxide is extruded with a concerted migration of the neighbouring O8 leading to an oxocarbenium ion 27, which is then trapped with chloride giving the observed products. The crystal structure for

Continuous flow synthesis of 6-monoamino-6-monodeoxy-β-cyclodextrin

• János Máté Orosz,
• Dóra Ujj,
• Petr Kasal,
• Gábor Benkovics and
• Erika Bálint

Beilstein J. Org. Chem. 2023, 19, 294–302, doi:10.3762/bjoc.19.25

• Staudinger reduction using triphenylphosphine (PPh3) and N3-β-CD (3) in DMF has been the most popular method for the synthesis of NH2-β-CD (4) since its first publication by Bonnet et al. [46]. This is despite the fact, that PPh3 and its oxidized product (triphenylphosphine oxide) form complexes with β-CD

Revisiting the bromination of 3β-hydroxycholest-5-ene with CBr₄/PPh₃ and the subsequent azidolysis of the resulting bromide, disparity in stereochemical behavior

• Christian Schumacher,
• Jas S. Ward,
• Kari Rissanen,
• Carsten Bolm and
• Mohamed Ramadan El Sayed Aly

Beilstein J. Org. Chem. 2023, 19, 91–99, doi:10.3762/bjoc.19.9

• C3 hydroxy of 1 is activated. Deprotonation of 10 at C2 with bromide as base provides diene 9 as the minor product. Bromide 4 is formed via cyclopropyl cation 11, which is generated from 10 by loss of triphenylphosphine oxide being supported by involvement of the Δ5 π-bond electrons from the α-face

Improving the accuracy of ³¹P NMR chemical shift calculations by use of scaling methods

• William H. Hersh and
• Tsz-Yeung Chan

Beilstein J. Org. Chem. 2023, 19, 36–56, doi:10.3762/bjoc.19.4

• use of the locally dense basis set approach, in which the larger pcS-3 basis set was used on phosphorus and the smaller pcS-2 basis set was then used on all the other atoms, allowed the computation of chemical shifts for a variety of benchmark compounds up to 35-atom triphenylphosphine oxide

Synthesis and late stage modifications of Cyl derivatives

• Phil Servatius and
• Uli Kazmaier

Beilstein J. Org. Chem. 2022, 18, 174–181, doi:10.3762/bjoc.18.19

• ozonide formed during the reaction [57]. Consequently, no PPh3 or Me2S was required to obtain the crude aldehyde. Subsequent addition of a Wittig ylide gave access to a cyclopeptide with an α,β-unsaturated ester side chain as a (E/Z) mixture. Unfortunately, this compound contained triphenylphosphine oxide

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

• ascertained a gradual decrease in the yield of 3a (Table 1, entries 5 and 6). The outcome of this analysis might have been due to the formation of large amounts of the byproduct triphenylphosphine oxide, which impeded the purification process and decreased the yield of 3a. Alternative Cu(I) catalysts, CuCl

• outcome of this process was the phosphonium-protected MBH moiety Ib and hydrazoic acid. The counter ion bromine facilitated the nucleophilic attack at the vinylic centre of Ib and the spontaneous removal of triphenylphosphine oxide to yield IIb. A consecutive intramolecular nucleophilic attack of the

Mechanistic studies of an L-proline-catalyzed pyridazine formation involving a Diels–Alder reaction with inverse electron demand

• Anne Schnell,
• J. Alexander Willms,
• S. Nozinovic and
• Marianne Engeser

Beilstein J. Org. Chem. 2019, 15, 30–43, doi:10.3762/bjoc.15.3

• and the organic layer was washed six times with a 2:1 mixture of deionized water/methanol (6 × 40 mL). The aqueous layer was evaporated to yield 17 mg of a light pink solid. The 1H NMR, 31P NMR and ESIMS spectra show an impurity of triphenylphosphine oxide in the product, which does not interfere with

• ), 130.4 or 130.3 (C-15), 129.4 (C-3), 128.7 (C-10), 128.6 (C-11), 128.1 (C-4), 128.1 (C-9), 128.1, 118.3 (C-2), 117.6 (C-2), 31.0 or 30.6 (C-1). Signals not allocated to 4∙Br: 132.9, 132.7, 132.3, 132.2, 132.1, 131.7, 131.7, 131.6; 31P{1H} NMR (162 MHz, CDCl3, 298 K) δ [ppm] 29.22 (triphenylphosphine

• oxide), 23.72 (P-12). The numbering of the atoms in the molecule can be found in Supporting Information File 1. The allocation of NMR signals was accomplished with H,H-COSY, HMBC and HSQC spectra. UV–vis: local maximum ≈240 nm, local maximum ≈300 nm, local maximum 548.5 nm. Fluorescence (excitation 302

Recent advances on organic blue thermally activated delayed fluorescence (TADF) emitters for organic light-emitting diodes (OLEDs)

• Thanh-Tuân Bui,
• Fabrice Goubard,
• Malika Ibrahim-Ouali,
• Didier Gigmes and
• Frédéric Dumur

Beilstein J. Org. Chem. 2018, 14, 282–308, doi:10.3762/bjoc.14.18

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

• of triphenylphosphine oxide and the formation of a new C–C bond between the carbon atom at the α-position of the phosphonium salt and the carbon atom of the carbonyl group of the carboxylate anion. The obtained enone 123 was then trapped by reaction with alkyl isocyanide, which finally led to ring

Strategies toward protecting group-free glycosylation through selective activation of the anomeric center

• A. Michael Downey and
• Michal Hocek

Beilstein J. Org. Chem. 2017, 13, 1239–1279, doi:10.3762/bjoc.13.123

Exploring endoperoxides as a new entry for the synthesis of branched azasugars

• Svenja Domeyer,
• Mark Bjerregaard,
• Henrik Johansson and
• Daniel Sejer Pedersen

Beilstein J. Org. Chem. 2017, 13, 644–647, doi:10.3762/bjoc.13.63

• was a Wittig reaction with methyltriphenylphosphonium iodide to provide 14–16. Compound 14 was found to be volatile and thus was only isolated in a poor yield. For diene 15 the low yield was largely due to complications with removing the triphenylphosphine oxide side product. However, at this stage

New syntheses of (±)-tashiromine and (±)-epitashiromine via enaminone intermediates

• Darren L. Riley,
• Joseph P. Michael and
• Charles B. de Koning

Beilstein J. Org. Chem. 2016, 12, 2609–2613, doi:10.3762/bjoc.12.256

• . We reverted to using the original procedure, but adjusted the purification protocol by first separating both the products and triphenylphosphine oxide residues from the baseline impurities by column chromatography, then removing most of the remaining triphenylphosphine residues by simple

TMSBr-mediated solvent- and work-up-free synthesis of α-2-deoxyglycosides from glycals

• Mei-Yuan Hsu,
• Yi-Pei Liu,
• Sarah Lam,
• Su-Ching Lin and
• Cheng-Chung Wang

Beilstein J. Org. Chem. 2016, 12, 1758–1764, doi:10.3762/bjoc.12.164

• conditions in good to excellent yields. In addition, with triphenylphosphine oxide as an additive, the TMSBr-mediated direct glycosylations of glycals with a large range of alcohols were highly α-selective. Keywords: 2-deoxyglycosides; glycals; trimethylsilyl bromide (TMSBr); triphenylphosphine oxide (TPPO

Pyridylidene ligand facilitates gold-catalyzed oxidative C–H arylation of heterocycles

• Kazuhiro Hata,
• Hideto Ito,
• Yasutomo Segawa and
• Kenichiro Itami

Beilstein J. Org. Chem. 2015, 11, 2737–2746, doi:10.3762/bjoc.11.295

• such oxidative reaction conditions. For example, triphenylphosphine is easily oxidized to triphenylphosphine oxide by a hypervalent iodine reagent that has been used as an oxidant for gold-catalyzed C–H arylation [69]. Appropriate ligands that are tolerant to the oxidative conditions would offer

• reactions, we hypothesize that the highly electron-donating PyC ligand facilitates the oxidation of gold(I) to gold(III). As triphenylphosphine is known to be easily oxidized to triphenylphosphine oxide under the current oxidative conditions, the ligand-free gold(III) species is thought to be an active

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

• ; polymer-supported reagent; rasta resin; triphenylphosphine oxide; Introduction One of the major drawbacks of the Wittig [1] and Mitsunobu [2][3] reactions is that they result in the formation of a stoichiometric quantity of triphenylphosphine oxide (1) as a byproduct. From an atom economy perspective

• ), which bears both triphenylphosphine oxide and tertiary amine moieties, in order to increase the efficiency and appeal of our method. We have extensive experience in preparing functionalized resins with two different catalytic groups [35][36][37][38], and prepared 18 by oxidation of 19, which we

• rasta resin-supported triphenylphosphine oxide 16, and have applied it as a phosphonium halide salt precursor in a wide range of halogenation reactions from which it is readily recovered and reused. The reusability of this polymer was demonstrated by the fact that all of the reactions reported herein

Concise, stereodivergent and highly stereoselective synthesis of cis- and trans-2-substituted 3-hydroxypiperidines – development of a phosphite-driven cyclodehydration

• Peter H. Huy,
• Julia C. Westphal and
• Ari M. P. Koskinen

Beilstein J. Org. Chem. 2014, 10, 369–383, doi:10.3762/bjoc.10.35

• overcoming separation difficulties usually associated to triphenylphosphine oxide. Keywords: amino acids; asymmetric synthesis; cyclodehydration; hydroxypiperidines; natural products; one-pot; Introduction 1,2-Amino alcohols of the type A (Figure 1) represent a frequent core motif of many pharmacologically

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

• TMSCF2Cl was used, TMSCl is not reactive enough to trap the betaine 3, thus the oxaphosphetane 5 could be formed to give olefins and triphenylphosphine oxide (Scheme 4). Finally, the olefination of aldehyde 1b with TMSCF3 as the difluoromethylene source was tested. The results showed that no desired

Diversity-oriented synthesis of dihydrobenzoxazepinones by coupling the Ugi multicomponent reaction with a Mitsunobu cyclization

• Lisa Moni,
• Luca Banfi,
• Andrea Basso,
• Alice Brambilla and
• Renata Riva

Beilstein J. Org. Chem. 2014, 10, 209–212, doi:10.3762/bjoc.10.16

• triphenylphosphine oxide. We eventually found that the easiest and most efficient protocol involved reduction with Me3P, followed by evaporation of the solvent and by subsequent Ugi reaction on the crude. With Me3P, phosphazene hydrolysis was much faster and the phosphine oxide was much more easily separated by

• –d were straightforwardly prepared in excellent yields from low cost starting materials 1, 3, 4, and 7, in all cases passing through the benzyl alcohols (Scheme 1). Apart from 2a [11], they are all new compounds. Initially we reduced azide 2a with PPh3 and separated the amine from triphenylphosphine

• oxide by extracting it into acidic water. However, the amine recovery, after basification and a second extraction with an organic solvent, was never complete and the yields were poorly reproducible. This can be due to the sluggish and unpredictable hydrolysis of the intermediate phosphazene, and to the

Advancements in the mechanistic understanding of the copper-catalyzed azide–alkyne cycloaddition

• Regina Berg and
• Bernd F. Straub

Beilstein J. Org. Chem. 2013, 9, 2715–2750, doi:10.3762/bjoc.9.308

• Cu(I) (similar to TCEP as reducing agent in biological applications [45][46][47][48][49][50][51][52][53][54][55]). However, Staudinger side reactions between the azide and the phosphine may take place as well, leading to the formation of the corresponding amine and triphenylphosphine oxide as

One-pot sequential synthesis of isocyanates and urea derivatives via a microwave-assisted Staudinger–aza-Wittig reaction

• Diego Carnaroglio,
• Katia Martina,
• Giovanni Palmisano,
• Andrea Penoni,
• Claudia Domini and
• Giancarlo Cravotto

Beilstein J. Org. Chem. 2013, 9, 2378–2386, doi:10.3762/bjoc.9.274

• versatile and can be used for the synthesis of many products. However, the byproduct of this reaction is triphenylphosphine oxide, which is difficult to remove. It is known that this reaction can be performed in a heterogeneous system using PS-PPh2. Despite the higher costs for the reagent, the use of PS

The application of a monolithic triphenylphosphine reagent for conducting Ramirez gem-dibromoolefination reactions in flow

• Kimberley A. Roper,
• Malcolm B. Berry and
• Steven V. Ley

Beilstein J. Org. Chem. 2013, 9, 1781–1790, doi:10.3762/bjoc.9.207

• -dibromovinyl)benzene (3) in 84% yield. Triphenylphosphine oxide (4) was also isolated from the reaction as a byproduct. These gem-dibromoolefin products are particularly important intermediates in the one carbon homologation of an aldehyde into the corresponding terminal alkyne, known as the Corey–Fuchs

• reaction [42], and more recently stereospecific hydrogenolysis, Stille and Suzuki reactions have been used to further elaborate these useful products [43][44][45]. The triphenylphosphine oxide byproduct can often be difficult to remove from the reaction mixture, requiring extensive, time-consuming