Homologated amino acids with three vicinal fluorines positioned along the backbone: development of a stereoselective synthesis

• Raju Cheerlavancha,
• Ahmed Ahmed,
• Yun Cheuk Leung,
• Aggie Lawer,
• Qing-Quan Liu,
• Marina Cagnes,
• Hee-Chan Jang,
• Xiang-Guo Hu and
• Luke Hunter

Beilstein J. Org. Chem. 2017, 13, 2316–2325, doi:10.3762/bjoc.13.228

• the electrophilic fluorination reagent NFSI (compared with nucleophilic fluorination reagents such as DeoxoFluor). Accordingly, two aldehyde substrates (7a and 7b) were prepared [21][22], containing either a phthalimide or a Boc protecting group. Electrophilic fluorination was attempted according to

• 7a (containing the phthalimide protecting group) suggested that the undesired difluorinated compound 12 was formed as the major product. An additional complication was that the phthalimide protecting group of 12 seemed to be at least partially sensitive to sodium borohydride [23]. In contrast, the

Phosphonic acid: preparation and applications

• Charlotte M. Sevrain,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2017, 13, 2186–2213, doi:10.3762/bjoc.13.219

• dealkylation and compatible with the presence of other groups such as allyl, ketone, primary alcohol, phthalimide, ester or thioether as illustrated with the transformation of the phosphonate 79 to the phosphonic acid 80 (Figure 23). The best results were obtained when 0.9 equivalents of BBr3 per phosphonate

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

• reaction time, hazardous organic solvent, and tedious isolation procedure are implemented. Dekamin and co-workers have demonstrated the synthesis of pyrans using potassium phthalimide (POPI) as a catalyst under ball-milling which is found to be advantageous over solution phase synthesis [158]. Malonitrile

Mechanochemical N-alkylation of imides

• Anamarija Briš,
• Mateja Đud and
• Davor Margetić

Beilstein J. Org. Chem. 2017, 13, 1745–1752, doi:10.3762/bjoc.13.169

• organic solvents. Ex situ IR spectroscopy (ATR) of milling of imides 11–17 with K2CO3 was used for monitoring the reaction progress, which showed for instance, that potassium phthalimide [29] was formed after one hour of grinding (Figure 2). This salt was, without isolation, subjected to further milling

• deprotonation of the imides with pKa values at least within the range of 8.3–9.9 units [30] under ball milling conditions. Deprotonation of phthalimide in solution is usually carried out with the use of bases stronger than K2CO3 [31] and this difference in reactivity in comparison to solvent free conditions has

• need for tetrabutylammonium iodide as phase-transfer catalyst to increase the limited solubility of 14. The selectivity was observed for certain substrates. For example, the alkylation of phthalimide 12 with 1,4-bis(bromomethyl)benzene led to the formation of two products, namely 28 and 29. By keeping

Oxidative dehydrogenation of C–C and C–N bonds: A convenient approach to access diverse (dihydro)heteroaromatic compounds

• Santanu Hati,
• Ulrike Holzgrabe and
• Subhabrata Sen

Beilstein J. Org. Chem. 2017, 13, 1670–1692, doi:10.3762/bjoc.13.162

• phthalimide-N-oxyl radical (PINO) via transfer of hydrogen from NHPI to O2. Co2+-assisted this step by associating with oxygen to generate a Co3+–oxygen complex. It then abstracts the hydrogen from NHPI. Next, PINO abstracted a hydrogen from the DHP produced to generate radical X which aromatizes via hydrogen

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

• )imide 7 with triarylphosphonium tetrafluoroborate was melted at 85–140 °C in the presence of NaBr as a catalyst under reduced pressure (0.1–0.2 mmHg) for 0.5–10 h (Table 2). Phthalimide-derived phosphonium salts 5 (A = o-C6H4) were usually obtained in good to excellent yields, whereas the yields of

• reaction product. It seems that the steric congestion caused by two methoxy groups in ortho positions to the attacking carbon caused the displacement of a phthalimide anion by triarylphosphine in the primary reaction product and thus leading to the phosphonium salt 10 as an unexpected side product (Scheme

• isomers was obtained only in the case of 1-imidoalkylphosphonium salts derived from succinimide, with a relatively small imide ring (Table 3, entries 14 and 15). On the other hand, phosphonium salts derived from phthalimide gave in all cases some excess of the para isomers. Bulky phenyl or isobutyl

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

• phthalimide-protected compounds were synthesised as UV active analogues that would facilitate analysis. Aminoalcohols 1 and 2 were Boc- and Pht-protected under standard conditions to provide alcohols 3–6 in good yield. Oxidation of alcohol 3 to aldehyde 7 was achieved in moderate yield using standard Parikh

• to the phthalimide-protected dienes 15,16. When the same reaction was performed with rose bengal on diene 16 a very low yield of endoperoxide 19 was obtained and most starting material was recovered (78%) even after prolonged reaction time (40 h). However, the reaction outcome was greatly improved by

• was encouraging and gave access to a variety of novel protected azasugar precursors. We conclude that the choice of amine and dihydroxy protecting groups can have an impact on the success of the endoperoxide synthesis and its thermal stability, and that employing phthalimide and acetonide groups for N

Pd- and Cu-catalyzed approaches in the syntheses of new cholane aminoanthraquinone pincer-like ligands

• Nikolay V. Lukashev,
• Gennadii A. Grabovyi,
• Dmitry A. Erzunov,
• Alexey V. Kazantsev,
• Gennadij V. Latyshev,
• Alexei D. Averin and
• Irina P. Beletskaya.

Beilstein J. Org. Chem. 2017, 13, 564–570, doi:10.3762/bjoc.13.55

• (6a) is readily aminated by phthalimide using classical Ullmann conditions (15% Cu powder, quinoline, 200 °C in PhNO2) [41]. However, the reaction of 3c with 6a using the same conditions, as well as the addition of stronger bases (DABCO, DIPEA, DBU) afforded extremely low yields (7–12%) of aminated

A versatile route to polythiophenes with functional pendant groups using alkyne chemistry

• Xiao Huang,
• Li Yang,
• Rikard Emanuelsson,
• Jonas Bergquist,
• Maria Strømme,
• Martin Sjödin and
• Adolf Gogoll

Beilstein J. Org. Chem. 2016, 12, 2682–2688, doi:10.3762/bjoc.12.265

• -bromoterephthalate and 2-bromo-4,4’-bipyridine were prepared according to reported procedures [38][39]. The electron acceptor phthalimide (PT) was attached to EDOT via cycloaddition between the alkyne and an alkylazide to produce derivative 13 (Scheme 4). Regioselective formation of 13 involved the Cu(I)-catalyzed

• Huisgen 1,3-dipolar cycloaddition between N-(2-azidoethyl)phthalimide and the alkyne terminal of pyEDOT under ultrasound conditions in 73% yield. Detailed synthetic routes are presented in Supporting Information File 1. Figure 1a shows the cyclic voltammograms (CVs) for electrochemical polymerization of

• phthalimide-EDOT derivative 13 failed to polymerize. A plausible reason could be an interference of the electron rich aromatic moieties with the thiophene radical cations formed during polymerization, in analogy to previous suggestions from Bäuerle et al. for triazolomethyl-substituted EDOT. Post

Conjugate addition–enantioselective protonation reactions

• James P. Phelan and
• Jonathan A. Ellman

Beilstein J. Org. Chem. 2016, 12, 1203–1228, doi:10.3762/bjoc.12.116

• enantioselective synthesis of β-amino esters 62 via the addition of arylboronic acids 47 to α-methylaminoacrylates 61 (Scheme 14) [35]. The authors identified (S)-difluorphos (44, Figure 2) and phthalimide as the optimal ligand and proton source combination, respectively. Additionally, the bulky tert-butyl ester

Mycothiol synthesis by an anomerization reaction through endocyclic cleavage

• Shino Manabe and
• Yukishige Ito

Beilstein J. Org. Chem. 2016, 12, 328–333, doi:10.3762/bjoc.12.35

• phthalimide group in the 2-position, was converted to α-glycoside 4, by introducing an N-acetyl 2,3-trans-carbamate group (Scheme 3) and by conducting an anomerization reaction. The glycosylation reaction of phthalimido-protected glucosamine thioglycoside 5 with inositol 6 [24] afforded β-linked pseudo

Copper-catalyzed intermolecular oxyamination of olefins using carboxylic acids and O-benzoylhydroxylamines

• Brett N. Hemric and
• Qiu Wang

Beilstein J. Org. Chem. 2016, 12, 22–28, doi:10.3762/bjoc.12.4

• Liu reported a palladium-catalyzed introduction of phthalimide (HNPhth) and acetate functionalities to terminal allylic and homoallylic ethers in the presence of an iodine oxidant (Scheme 1B) [13]. The Yoon lab also developed copper- and iron-catalyzed olefin difunctionalization reactions with

Copper-catalyzed aminooxygenation of styrenes with N-fluorobenzenesulfonimide and N-hydroxyphthalimide derivatives

• Yan Li,
• Xue Zhou,
• Guangfan Zheng and
• Qian Zhang

Beilstein J. Org. Chem. 2015, 11, 2721–2726, doi:10.3762/bjoc.11.293

• aminooxygenation reaction of alkenes with phthalimide and (diacetoxyiodo)benzene through cis-aminopalladation and SN2 C–O bond formation [34]. In 2013, Zhu and co-workers described an n-Bu4NI-catalyzed aminooxygenation of inactive alkenes with benzotriazole and water which underwent a nitrogen-centred radical

Copper-catalyzed stereoselective conjugate addition of alkylboranes to alkynoates

• Takamichi Wakamatsu,
• Kazunori Nagao,
• Hirohisa Ohmiya and
• Masaya Sawamura

Beilstein J. Org. Chem. 2015, 11, 2444–2450, doi:10.3762/bjoc.11.265

• accessible through the hydroboration–conjugate addition one-pot protocol with excellent syn stereoselectivities (Table 2). This protocol tolerated functional groups such as methoxy, ester, phthalimide, fluoro, cyano and aldehyde moieties in the alkylboranes and alkynoates (Table 2, entries 1–3, 6–9 and 11

Recent advances in copper-catalyzed C–H bond amidation

• Jie-Ping Wan and
• Yanfeng Jing

Beilstein J. Org. Chem. 2015, 11, 2209–2222, doi:10.3762/bjoc.11.240

• products 49 or 50 by incorporating phthalimide/saccharin 46. Under the standard conditions, however, the reaction of benzamide with 2-phenylpyridine provided product 51 with low yield (Scheme 14). As a special aromatic system, quinoline N-oxides were well investigated in their reactivity for metal

Preparative semiconductor photoredox catalysis: An emerging theme in organic synthesis

• David W. Manley and
• John C. Walton

Beilstein J. Org. Chem. 2015, 11, 1570–1582, doi:10.3762/bjoc.11.173

• )phthalimide was employed by the Overman group in their synthesis of (−)-aplyviolene [11]. Heterogeneous PRCs form a second class consisting of semiconductor materials. These are generally metal oxides or sulfides in the form of fine particles that consequently have the additional advantage of easily being

The enantioselective synthesis of (S)-(+)-mianserin and (S)-(+)-epinastine

• Piotr Roszkowski,
• Jan. K. Maurin and
• Zbigniew Czarnocki

Beilstein J. Org. Chem. 2015, 11, 1509–1513, doi:10.3762/bjoc.11.164

• phthalimide proposed by Moffett [15] may be used for this step with comparable results. The imine 6 was then transformed to the enantiomerically enriched amine 7 with the aid of asymmetric transfer hydrogenation (ATH) process [8][10][11]. As in our synthesis of aptazepine [8], we initially used the chiral

Radical-mediated dehydrative preparation of cyclic imides using (NH₄)₂S₂O₈–DMSO: application to the synthesis of vernakalant

• Dnyaneshwar N. Garad,
• Subhash D. Tanpure and
• Santosh B. Mhaske

Beilstein J. Org. Chem. 2015, 11, 1008–1016, doi:10.3762/bjoc.11.113

• phthalimide was obtained in very good yield (Table 3, entry 6). Furthermore, the scope of the protocol to obtain imides from aliphatic amines and saturated anhydride was explored (Table 4). Primary aliphatic amines with short and long alkyl chains were treated with succinic anhydride and they were found to

Cross-dehydrogenative coupling for the intermolecular C–O bond formation

• Igor B. Krylov,
• Vera A. Vil’ and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2015, 11, 92–146, doi:10.3762/bjoc.11.13

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

Syntheses of ¹⁵N-labeled pre-queuosine nucleobase derivatives

• Jasmin Levic and
• Ronald Micura

Beilstein J. Org. Chem. 2014, 10, 1914–1918, doi:10.3762/bjoc.10.199

• pathway of the hypermodified tRNA nucleoside queuosine (Que). The core structure of preQ1 is represented by 7-(aminomethyl)-7-deazaguanine (preQ1 base). Here, we report the synthesis of three preQ1 base derivatives with complementary 15N-labeling patterns, utilizing [15N]-KCN, [15N]-phthalimide, and [15N3

• convenient. First, we prepared the 15N-labeled aldehyde 18 as the key intermediate (Scheme 4). This was achieved by reaction of 3-chloropropanol (15) with [15N]-phthalimide 16 to give [15N]-3-phthalimidopropan-1-ol (17). All further steps were in direct analogy as described for targets 1 and 2, namely

• pyrrolo[2,3-d]pyrimidine ring system is based on the cyclocondensation reaction between α-bromoaldehydes and 2,6-diaminopyrimidin-4-ones and utilizes [15N]-KCN, [15N]-phthalimide, and [15N3]-guanidine for 15N sources to achieve three complementary labeling patterns that cover all five nitrogen atoms of

Aza-Diels–Alder reaction between N-aryl-1-oxo-1H-isoindolium ions and tert-enamides: Steric effects on reaction outcome

• Amitabh Jha,
• Ting-Yi Chou,
• Zainab ALJaroudi,
• Bobby D. Ellis and
• T. Stanley Cameron

Beilstein J. Org. Chem. 2014, 10, 848–857, doi:10.3762/bjoc.10.81

• the N-aryl group undergo intramolecular electrophilic addition to the alkene yielding isoindolo[2,1-a]quinolines under acidic conditions [18]. Isoindolo[2,1-a]quinolone cores have also been prepared via an aldol-type intramolecular cyclization reaction of N-(2-acetylaryl)phthalimide under anhydrous

Direct and indirect single electron transfer (SET)-photochemical approaches for the preparation of novel phthalimide and naphthalimide-based lariat-type crown ethers

• Dae Won Cho,
• Patrick S. Mariano and
• Ung Chan Yoon

Beilstein J. Org. Chem. 2014, 10, 514–527, doi:10.3762/bjoc.10.47

• , Pusan National University, Busan 609-735, Korea 10.3762/bjoc.10.47 Abstract In this review, we describe direct and indirect photochemical approaches that have been developed for the preparation of phthalimide- and naphthalimide-based, lariat-type crown ethers. The direct route utilizes a strategy in

• processes (e.g., Norrish type II reaction) [38][45][46] that produce cyclic amides 5 via 4 (Scheme 2), photoirradiation of phthalimides containing thioether and/or amine chains 2 promotes more rapidly the intramolecular SET from the heteroatom donors (S and N) to the phthalimide excited states. The SET

• , direct and indirect photochemical approaches that we have devised for the preparation of imide- (e.g., phthalimide and naphthalimide) derived lariat-type crown ethers are described. The direct route utilizes a strategy in which nitrogen-linked side chains containing polyethoxy-tethered phthalimides and

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265

Synthesis of enantiomerically pure N-(2,3-dihydroxypropyl)arylamides via oxidative esterification

• Akula Raghunadh,
• Satish S More,
• T. Krishna Chaitanya,
• Yadla Sateesh Kumar,
• Suresh Babu Meruva,
• L. Vaikunta Rao and
• U. K. Syam Kumar

Beilstein J. Org. Chem. 2013, 9, 2129–2136, doi:10.3762/bjoc.9.250

• . Results and Discussion Our strategy for an efficient construction of (R) and (S)-N-(2,3-dihydroxypropyl)benzamide (6a) is outlined in Scheme 1. We envisioned that the opening of the phthalimide ring in (S)-3-(1,3-dioxoisoindolin-2-yl)-2-hydroxypropyl benzoate (5a) would afford the desired benzamide 6a

• . The phthalimido-protected chiral hydroxypropyl benzoate 5a could be synthesized by the reaction of nitrogen heterocyclic carbene, benzaldehyde and phthalimido-epoxide 4a. Phthalimido-epoxide 4a was synthesized by treating (S)-glycidol (3) with phthalimide (2) under Mitsunobu reaction conditions

• the reaction conditions are given in Table 2. All the starting epoxides required for this transformation were prepared by using the reported procedures. After the synthesis of optically pure 3-(1,3-dioxoisoindolin-2-yl)-2-hydroxypropylarylate derivatives (5a–h), the removal of the phthalimide group