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

Hypervalent iodine compounds for anti-Markovnikov-type iodo-oxyimidation of vinylarenes

• Igor B. Krylov,
• Stanislav A. Paveliev,
• Mikhail A. Syroeshkin,
• Alexander A. Korlyukov,
• Pavel V. Dorovatovskii,
• Yan V. Zubavichus,
• Gennady I. Nikishin and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2018, 14, 2146–2155, doi:10.3762/bjoc.14.188

• imide-N-oxyl radicals are used as effective mediators for CH-functionalization with formation of C–C, C–O, C–S, and C–N bonds [11][16][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42]. Phthalimide-N-oxyl (PINO) is one of the most known imide-N-oxyl

• on the literature data describing the formation of the phthalimide-N-oxyl radical (PINO) from NHPI under the action of PhI(OAc)2 [34][55][59][76][77], and based on information about the reaction of the PINO radical with styrenes [45] and interaction of benzyl radicals with iodine [78][79], a

β-Hydroxy sulfides and their syntheses

• Mokgethwa B. Marakalala,
• Edwin M. Mmutlane and
• Henok H. Kinfe

Beilstein J. Org. Chem. 2018, 14, 1668–1692, doi:10.3762/bjoc.14.143

• few years ago, Denmark and co-workers revealed an impressive catalytic asymmetric thiofunctionalization of unactivated alkenes 102 with the commercially available arylsulfenylating agent N-(phenylthio)phthalimide (103) using selenophosphoramide 104 as a catalyst in the presence of methanesulfonic acid

Anomeric modification of carbohydrates using the Mitsunobu reaction

• Julia Hain,
• Patrick Rollin,
• Werner Klaffke and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2018, 14, 1619–1636, doi:10.3762/bjoc.14.138

• with simple alcohols (Scheme 20) [81][82]. In this case, of course, the sugar thioglycoside takes the role of the nucleophile rather than of the alcohol component in the Mitsunobu reaction. Reactions with NH acids to achieve N-glycosides Early on, phthalimide was regarded as a good Mitsunobu reagent

• -dialkoxycarbonylhydrazines [84]. This anomeric N-phthalimidation was later implemented by Nishimura et al. for the iminosugar 114 with phthalimide to give 115 in a high yield, en route to a new family of α-L-fucosidase inhibitors (Scheme 21) [85]. More generally, the preparation of modified glycosylamines under Mitsunobu

• (6.3), N-hydroxyphthalimide was early considered in Mitsunobu reactions, for example by Grochowski and Jurczak to form an anomeric phthalimide–oxy bond as shown in several sugar series [109][110][111]. This gives access to new O-glycosylhydroxylamines, namely for the construction of glycosidic N–O

Imide arylation with aryl(TMP)iodonium tosylates

• Souradeep Basu,
• Alexander H. Sandtorv and
• David R. Stuart

Beilstein J. Org. Chem. 2018, 14, 1034–1038, doi:10.3762/bjoc.14.90

• Souradeep Basu Alexander H. Sandtorv David R. Stuart Department of Chemistry, Portland State University, Portland OR 97201, United States 10.3762/bjoc.14.90 Abstract Herein, we describe the synthesis of N-aryl phthalimides by metal-free coupling of potassium phthalimide with unsymmetrical aryl

• )iodonium salts [12][13][14] and describe here the development of a C–N coupling of a phthalimide anion with non-sterically biased aryl groups. The protocol is compatible with ortho-, meta-, and para-substitution on the aryl group and the phthalimide moiety may also provide access to anilines. Results and

• Discussion We initiated our optimization of the arylation of the potassium phthalimide nucleophile with diaryliodonium electrophiles by surveying several reaction conditions: dummy ligand (Aux), counter anion, solvent and volume, reaction temperature, and stoichiometry (Table 1). Consistent with an

Synthesis of a sucrose-based macrocycle with unsymmetrical monosaccharides "arms"

• Karolina Tiara,
• Mykhaylo A. Potopnyk and
• Sławomir Jarosz

Beilstein J. Org. Chem. 2018, 14, 634–641, doi:10.3762/bjoc.14.50

• alternative way to the desired amine 12a, based on the SN2 reaction of the activated alcohol 13 [34][35] with benzylamine, also failed (Scheme 2). The Mitsunobu approach to convert the hydroxy group into an amine function was also unsuccessful. Although 13 reacted with phthalimide gave the desired product 13a

The photodecarboxylative addition of carboxylates to phthalimides as a key-step in the synthesis of biologically active 3-arylmethylene-2,3-dihydro-1H-isoindolin-1-ones

• Ommid Anamimoghadam,
• Saira Mumtaz,
• Anke Nietsch,
• Gaetano Saya,
• Cherie A. Motti,
• Jun Wang,
• Peter C. Junk,
• Ashfaq Mahmood Qureshi and
• Michael Oelgemöller

Beilstein J. Org. Chem. 2017, 13, 2833–2841, doi:10.3762/bjoc.13.275

• ; arylmethylenedihydroisoindolinones; photochemistry; photodecarboxylation; phthalimide; Introduction Phthalimides and their related 3-alkyl- and 3-arylmethylene-2,3-dihydro-1H-isoindolin-1-ones play an important role in medicinal chemistry due to their biological activities for a wide range of therapeutic applications [1][2][3][4

• [41], followed by amination [42] furnishes the desired target compounds. The amino group is introduced in the final step as it would otherwise interfere with the desired photoreaction. In fact, amines are very potent electron donors and are easily oxidized by the excited phthalimide chromophore [43

• ][44][45][46]. Results and Discussion Initial irradiation experiments were conducted with N-(2-bromoethyl)phthalimide (1a) and potassium phenylacetate (2a) as a model system (Scheme 2 and Table 1). The salt 2a, generated from the corresponding phenylacetic acid and potassium carbonate, was used in

Palladium-catalyzed Heck-type reaction of secondary trifluoromethylated alkyl bromides

• Tao Fan,
• Wei-Dong Meng and
• Xingang Zhang

Beilstein J. Org. Chem. 2017, 13, 2610–2616, doi:10.3762/bjoc.13.258

• , aldehyde, and phthalimide (4e, 4f, 4j and 4k), were all applicable to the reaction, thus offering good opportunities for downstream transformations and highlighting the utility of the current process further. (3-Bromo-4,4,4-trifluorobutyl)benzene and 4-bromo-5,5,5-trifluoropentyl benzoate were also