A recent overview on the synthesis of 1,4,5-trisubstituted 1,2,3-triazoles

• Pezhman Shiri,
• Ali Mohammad Amani and
• Thomas Mayer-Gall

Beilstein J. Org. Chem. 2021, 17, 1600–1628, doi:10.3762/bjoc.17.114

• . This method was then extended to ketone, tosyl, and phthalimide groups on alkyl azides to produce the desired triazole derivatives. The ethylene glycol-, phenylalanine-, and glucose-derived azides were also good candidates to furnish the triazole derivatives. This protocol provides access to various

Synthetic reactions driven by electron-donor–acceptor (EDA) complexes

• Zhonglie Yang,
• Yutong Liu,
• Kun Cao,
• Xiaobin Zhang,
• Hezhong Jiang and
• Jiahong Li

Beilstein J. Org. Chem. 2021, 17, 771–799, doi:10.3762/bjoc.17.67

• Katritzky alkylpyridinium salt 149 and B2cat2 as substrates as well as DMA as coordination solvent under blue-light irradiation, followed by subsequent reaction with pinacol to afford boration product 151 (Scheme 52). A number of secondary alkylamines, even those that have carbamate- or phthalimide

Metal-free visible-light-enabled vicinal trifluoromethyl dithiolation of unactivated alkenes

• Xiaojuan Li,
• Qiang Zhang,
• Weigang Zhang,
• Jinzhu Ma,
• Yi Wang and
• Yi Pan

Beilstein J. Org. Chem. 2021, 17, 551–557, doi:10.3762/bjoc.17.49

• of blue LEDs, allyl boronate 1a (0.1 mmol), disulfide 2a (1.0 equiv) and N-(trifluoromethylthio)phthalimide (Phth-SCF3, 3, 1.5 equiv), the desired trifluoromethylthiolated product 4a was obtained in 71% yield with 1,2,3,5-tetrakis(carbazol-9-yl)-4,6-dicyanobenzene (4CzIPN, 2 mol %) as the

• complexation of the intermediate I with K2HPO4 provides the intermediate II. Then, 4CzIPN* (4CzIPN+/4CzIPN*: E1/2red = −1.04 V vs SCE) [51] reduces the intermediate II to generate a phthalimide anion (Phth− [50]) and a trifluoromethylthio radical under irradiation. The SCF3 radical readily reacts with the

Synthesis of imidazo[1,5-a]pyridines via cyclocondensation of 2-(aminomethyl)pyridines with electrophilically activated nitroalkanes

• Dmitrii A. Aksenov,
• Nikolai A. Arutiunov,
• Vladimir V. Maliuga,
• Alexander V. Aksenov and
• Michael Rubin

Beilstein J. Org. Chem. 2020, 16, 2903–2910, doi:10.3762/bjoc.16.239

• (3.01 g, 10 mmol) in DMF (16 mL) was added potassium phthalimide (1.85 g, 10 mmol) in portions. The mixture was stirred at room temperature for 5 h. Then, water (30 mL) was added, and the formed precipitate was collected by filtration and washed with water. Recrystallization from ethanol afforded

Optical detection of di- and triphosphate anions with mixed monolayer-protected gold nanoparticles containing zinc(II)–dipicolylamine complexes

• Lena Reinke,
• Julia Bartl,
• Marcus Koch and
• Stefan Kubik

Beilstein J. Org. Chem. 2020, 16, 2687–2700, doi:10.3762/bjoc.16.219

• nanoparticle surface after immobilization. Compound 2 was prepared by starting from potassium phthalimide and 1,12-dibromododecane (Scheme 2). The product resulting from this step was treated with bis(2-pyridylmethyl)amine to give a DPA derivative that was coupled to (R)-lipoic acid after deprotection to

• . Conditions: i) potassium phthalimide, DMF, 25 °C, 18 h, 67%; ii) 2,2'-dipicolylamine, K2CO3, KI, acetone, reflux 14 h, 50%; iii) N2H4⋅H2O, ethanol, 25 °C, 16 h, 56%; iv) (R)-lipoic acid, EDC⋅HCl, DMAP, CH2Cl2, 25 °C, 18 h, 52%. Minimum salt concentrations required to precipitate and to subsequently

Recent developments in enantioselective photocatalysis

• Callum Prentice,
• James Morrisson,
• Andrew D. Smith and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2020, 16, 2363–2441, doi:10.3762/bjoc.16.197

• quenching cycle, generating [Ir]•−, which reduces the phthalimide ester 117 to give α-amino radicals 117• after decarboxylation. The CPA then activates the azaarene 118 through protonation and brings the two reactive species together in a hydrogen bonded complex 119, which facilitates radical addition

• separately developed a Minisci-type reaction using phthalimide esters 123; however, their system did not extend past isoquinoline substrates 124 (Scheme 17b) [62]. Zheng and Studer expanded the scope of this type of reactivity to a three-component cascade reaction with alkyl bromides 125 and enamides 126

Design and synthesis of a bis-macrocyclic host and guests as building blocks for small molecular knots

• Elizabeth A. Margolis,
• Rebecca J. Keyes,
• Stephen D. Lockey IV and
• Edward E. Fenlon

Beilstein J. Org. Chem. 2020, 16, 2314–2321, doi:10.3762/bjoc.16.192

• bromide in 1-bromo-4-chlorobutane (16) with sodium azide to give azide 17 in 52% yield (Scheme 5). Treatment of 17 with potassium phthalimide and catalytic potassium iodide was followed by hydrazine unmasking to give the desired aminoazide 18 in 37% over the two steps. Reductive amination of 18 with dial

Photosensitized direct C–H fluorination and trifluoromethylation in organic synthesis

• Shahboz Yakubov and
• Joshua P. Barham

Beilstein J. Org. Chem. 2020, 16, 2151–2192, doi:10.3762/bjoc.16.183

• with Selectfluor® [153]. The authors justified the use of protecting groups due to their extensive use in peptide synthesis. Of all the PGs tested, phthalimide (Phth)- and trifluoroacetate (TFA)-protected substrates underwent photosensitized C–H fluorination to give the highest yield of 80% and 71% of

Syntheses of spliceostatins and thailanstatins: a review

• William A. Donaldson

Beilstein J. Org. Chem. 2020, 16, 1991–2006, doi:10.3762/bjoc.16.166

• utilized the sequential application of a cross-metathesis and a Suzuki–Miyaura coupling in the syntheses of thailanstatin A and B (7 and 5) and spliceostatin D (9, Scheme 24) [24][25]. To this end, the methylhydrazinolysis of the phthalimide 39 and the amide formation with 12c yielded 121. The cross

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

• bromide ion despite the presence of bulky substituents (phthalimido and alkyl groups), a comparative study was initiated using non-fluorinated alkylidene oxetanes as substrates. Since the oxetane ring was attacked from the side of the bulky phthalimide or alkyl chain, it appeared plausible that the

Fluorohydration of alkynes via I(I)/I(III) catalysis

• Jessica Neufeld,
• Constantin G. Daniliuc and
• Ryan Gilmour

Beilstein J. Org. Chem. 2020, 16, 1627–1635, doi:10.3762/bjoc.16.135

• exposure of a model internal alkyne to the standard conditions proved also successful affording 6 in 46% yield. Finally, replacement of the benzoate unit by a phthalimide moiety was possible and led to the protected amine derivative 7 (64% yield). The structure of α-fluoroketone 2 was unequivocally

• spectroscopy. This contrasts sharply with the phthalimide derivative 7 (64%). Doping a representative reaction (14 → 9) with methyl benzoate (15) (Figure 3B) to explore for potential activator effects also proved unsuccessful. Finally, a stoichiometric reaction of alkynyl phthalimide 16 with freshly prepared p

• Lewis base upon ligand exchange (Figure 5) [56]. This working hypothesis may also rationalise the deletion experiment (10), the recalcitrance of acetyl derivatives, and the striking reactivity disparity between amides (12/13) and the phthalimide derivative 16. Finally, to investigate the fate of water

[3 + 2] Cycloaddition with photogenerated azomethine ylides in β-cyclodextrin

• Margareta Sohora,
• Leo Mandić and
• Nikola Basarić

Beilstein J. Org. Chem. 2020, 16, 1296–1304, doi:10.3762/bjoc.16.110

• reactions [8]. Azomethine ylides can be formed by several photochemical or thermal catalytic methods [5][6][7], including photodecarboxylation of phthalimide derivatives of α-amino acids such as N-phthaloylglycine (1) [9][10]. Phthalimide is a versatile chromophore that has been used in the synthesis of

• the macrocyclic host affected the stereochemistry of the reaction. Moreover, we studied photodecarboxylation reactions initiated by the phthalimide chromophore [17][18][19] and applied them in cyclizations with memory of chirality [20] and diastereoselective peptide cyclizations [21

• for solubilization of drugs or drug delivery [48], it would be interesting to investigate its effects to the photodecarboxylation reaction. Therefore, we investigated photochemical reactivity of phthalimide derivatives 1–3 (Figure 1) in solution without β-CD and in the β-CD inclusion complexes

Ferrocenyl-substituted tetrahydrothiophenes via formal [3 + 2]-cycloaddition reactions of ferrocenyl thioketones with donor–acceptor cyclopropanes

• Grzegorz Mlostoń,
• Mateusz Kowalczyk,
• André U. Augustin,
• Peter G. Jones and
• Daniel B. Werz

Beilstein J. Org. Chem. 2020, 16, 1288–1295, doi:10.3762/bjoc.16.109

• thioketones to form nearly equal amounts of both diastereoisomeric tetrahydrothiophenes. A low selectivity was also observed in the reaction of a 2-phthalimide-derived cyclopropane with ferrocenyl phenyl thioketone. Keywords: [3 + 2]-cycloaddition reactions; donor–acceptor cyclopropanes; ferrocenyl

• separation. Moreover, a mixture of nearly equal amounts of isomeric trans-9m and cis-9m was also observed in the reaction of 5a with ferrocenyl fur-2-yl thioketone (8g). The reaction of the phthalimide-derived cyclopropane 5g with thioketone 8a led to a 4:1 mixture of both isomers cis- and trans-9n. Based on

Photocatalysis with organic dyes: facile access to reactive intermediates for synthesis

• Stephanie G. E. Amos,
• Marion Garreau,
• Luca Buzzetti and
• Jerome Waser

Beilstein J. Org. Chem. 2020, 16, 1163–1187, doi:10.3762/bjoc.16.103

• exploited as an organic photocatalyst to trigger the reductive fragmentation of phthalimide-based redox-active esters [47]. Other oxidative fragmentations In addition to the decarboxylation reactions, organic photoredox catalysis can be exploited to access C(sp3) radicals via the oxidative fragmentation of

Fluorinated phenylalanines: synthesis and pharmaceutical applications

• Laila F. Awad and
• Mohammed Salah Ayoup

Beilstein J. Org. Chem. 2020, 16, 1022–1050, doi:10.3762/bjoc.16.91

• ] (Scheme 33). 2.7. Photocatalyzed benzylic fluorination of N-phthalimido phenylalanine The photocatalyzed benzylic fluorination of phthalimide-protected phenylalanine methyl ester 145, using the photosensitizer 1,2,4,5-tetracyanobenzene (TCB), and Selectfluor in acetonitrile was carried out using a pen

Recent advances in photocatalyzed reactions using well-defined copper(I) complexes

• Mingbing Zhong,
• Xavier Pannecoucke,
• Philippe Jubault and
• Thomas Poisson

Beilstein J. Org. Chem. 2020, 16, 451–481, doi:10.3762/bjoc.16.42

• reaction conditions. The authors suggested first the photoexcitation of a [Cu(I)] species. Then, the excited [Cu(I)]* species reduces the NHP ester to form a carboxyl radical and the phthalimide anion, which binds to the [Cu(II)] species. After the elimination of CO2, the recombination of the alkyl radical

• with the [Cu(II)] species bearing the phthalimide forms the product and regenerates the active [Cu(I)] catalyst. Collins and co-workers described the use of [Cu(I)(dq)(binap)]BF4 as an efficient catalyst for the reductive decarboxylative coupling of a NHP ester derived from cyclohexanecarboxylic acid

• the reaction mechanism and suggested the following one: First, the excited in situ-formed copper complex reduced the NHP ester, as demonstrated by the Stern–Volmer quenching experiment. The formed radical anion collapsed into the corresponding alkyl radical and the phthalimide anion. Then, the

A toolbox of molecular photoswitches to modulate the CXCR3 chemokine receptor with light

• Xavier Gómez-Santacana,
• Sabrina M. de Munnik,
• Tamara A. M. Mocking,
• Niels J. Hauwert,
• Shanliang Sun,
• Prashanna Vijayachandran,
• Iwan J. P. de Esch,
• Henry F. Vischer,
• Maikel Wijtmans and
• Rob Leurs

Beilstein J. Org. Chem. 2019, 15, 2509–2523, doi:10.3762/bjoc.15.244

• advanced intermediate 28b (Scheme 3), which was subjected to an aromatic nucleophilic substitution with potassium phthalimide prepared in situ from 29 and K2CO3. Presumably due to the alkaline medium, the phthalimide ring was partially opened as detected by HPLC–MS. Upon attempted re-closing under reflux

Recent advances in transition-metal-catalyzed incorporation of fluorine-containing groups

• Xiaowei Li,
• Xiaolin Shi,
• Xiangqian Li and
• Dayong Shi

Beilstein J. Org. Chem. 2019, 15, 2213–2270, doi:10.3762/bjoc.15.218

Synthesis and anion binding properties of phthalimide-containing corona[6]arenes

• Meng-Di Gu,
• Yao Lu and
• Mei-Xiang Wang

Beilstein J. Org. Chem. 2019, 15, 1976–1983, doi:10.3762/bjoc.15.193

• adopt the conformation in which three phthalimide units are cis,trans-orientated. Acting as electron-deficient macrocyclic hosts, the synthesized O6-corona[3]arene[3]tetrazines self-regulated conformational structures to complex anions in the gas phase and in the solid state owing to the anion–π

• study 3,6-dihydroxyphthalimide derivatives as aromatic diols to construct functionalized O6-corona[3]arene[3]tetrazins. Being different from terephthalate in terms of substitution pattern, we envisioned that the phthalimide unit would flip freely owing to the less steric hindrance. In addition, N

• functionalized coronarene macrocycles. Moreover, the electronic feature of the phthalimide would render the resulting O6-corona[3]arene[3]tetrazines the electron-deficient hosts to form anion-π complexes [32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47]. We report herein the synthesis, structure

Multicomponent reactions (MCRs): a useful access to the synthesis of benzo-fused γ-lactams

• Edorta Martínez de Marigorta,
• Jesús M. de Los Santos,
• Ana M. Ochoa de Retana,
• Javier Vicario and
• Francisco Palacios

Beilstein J. Org. Chem. 2019, 15, 1065–1085, doi:10.3762/bjoc.15.104

• = Bn), along with 34% yield of benzyl phthalimide, probably formed by air oxidation of 53a [95]. 2-Formylbenzoic acid (33) has also been used in another type of three-component cyclization, along with amines 2 and isatoic anhydrides 56, leading to isoindoloquinazolinone derivatives 57, a kind of

• formed by a concerted pathway. Then the fluoride induced ring opening and subsequent cyclization of intermediate 84 would generate phthalimide 79. Although most multicomponent reactions leading to isoindolinones make use of benzoic acid derivatives as one of the starting components, in a few

Strong hyperconjugative interactions limit solvent and substituent influence on conformational equilibrium: the case of cis-2-halocyclohexylamines

• Camila B. Francisco,
• Cleverton S. Fernandes,
• Ulisses Z. de Melo,
• Roberto Rittner,
• Gisele F. Gauze and
• Ernani A. Basso

Beilstein J. Org. Chem. 2019, 15, 818–829, doi:10.3762/bjoc.15.79

• mmol) and phthalimide (6.60 mmol) were dissolved in THF (40 mL). To this mixture was slowly added a solution of diisopropyl azodicarboxylate (DIAD, 40% in THF) and the mixture was stirred at room temperature for 18 h. The solvent was removed under reduced pressure and the reaction mixture was re

Selective benzylic C–H monooxygenation mediated by iodine oxides

• Kelsey B. LaMartina,
• Haley K. Kuck,
• Linda S. Oglesbee,
• Asma Al-Odaini and
• Nicholas C. Boaz

Beilstein J. Org. Chem. 2019, 15, 602–609, doi:10.3762/bjoc.15.55

• the use of a catalytic system using HNO3, dioxygen, iodine and NHPI in the acetoxylation of C–H bonds [47]. Given this similarity, we believe that the two systems are operating by similar mechanisms. In the Minisci system, a phthalimide N-oxyl (PINO) radical, which is formed by the oxidation of NHPI

Synthesis and SAR of the antistaphylococcal natural product nematophin from Xenorhabdus nematophila

• Frank Wesche,
• Hélène Adihou,
• Thomas A. Wichelhaus and
• Helge B. Bode

Beilstein J. Org. Chem. 2019, 15, 535–541, doi:10.3762/bjoc.15.47

• aluminium chloride (AlCl3) in DCM to give compounds 14 and 21. Subsequent reduction was achieved with triethylsilane (Et3SiH) in TFA to give 15 and 22. For the synthesis of the primary amine, halides 15 and 22 were converted in a Gabriel synthesis with potassium phthalimide in DMF to the appropriate

• in DMF (c 0.1 M), 25 W, 75 °C, 20 min. Synthesis of azatryptamines (4-azatryptamine (4ATRA) and 1-methyl-4-azatryptamine (1M4ATRA)). i) 5.0 equiv AlCl3, 5.0 equiv chloroacetyl chloride in DCM, overnight, rt 67%; ii) 7.0 equiv Et3SiH in TFA, overnight, rt, 93%; iii) 1.1 equiv potassium phthalimide, in

• %; ii) 7.0 equiv Et3SiH in TFA, overnight, rt, 93%; iii) 1.1 equiv potassium phthalimide, in DMF, 100 °C, 56%; iv) 1.2 equiv NaH, 1.0 equiv MeI in DMF, overnight, rt, 57%; v) 5.0 equiv N2H4·H2O in EtOH, 2 h, 90 °C, 25 W, 92% to quant. Summary of synthesized nematophin derivatives (1–12) and their

Enhanced single-isomer separation and pseudoenantiomer resolution of new primary rim heterobifunctionalized α-cyclodextrin derivatives

• Iveta Tichá,
• Gábor Benkovics,
• Milo Malanga and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2018, 14, 2829–2837, doi:10.3762/bjoc.14.261

• sulfonylation agent, dibenzofuran-2,8-disulfonyl chloride, but observed only a negligible selectivity towards the AC regioisomer. Notwithstanding, these researchers were more successful in achieving selectivity for the AB regioisomer by introducing auxiliary groups (phthalimide) [19]. Armspach et al

Synthesis of pyrrolidine-based hamamelitannin analogues as quorum sensing inhibitors in Staphylococcus aureus

• Jakob Bouton,
• Kristof Van Hecke,
• Reuven Rasooly and
• Serge Van Calenbergh

Beilstein J. Org. Chem. 2018, 14, 2822–2828, doi:10.3762/bjoc.14.260

• previous attempts to synthesize 9 failed due to side reactions caused by the strongly electron-withdrawing properties of the nosyl group. The successful synthesis starts with a Pd-catalyzed dynamic kinetic asymmetric transformation of racemic butadiene monoepoxide to 12, employing phthalimide as

• -chlorobenzamide 13. Removal of the Boc-group with TFA resulted in 14. Next, the phthalimide was removed via refluxing with ethylenediamine and the resulting amine protected as para-nitrobenzenesulfonamide to obtain the desired fragment 9. The synthesis of 10 starts from commercially available 2-methylene-1,3

• -propanediol (16), which was selectively monoprotected in high yield as TBS ether (Scheme 3) [25]. The remaining alcohol was then substituted for a phthalimide via Mitsunobu reaction. Phthalimide deprotection, acylation with benzoic acid, and removal of the silyl protecting group furnished 10. Fragments 9 and