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

The chemistry of isoindole natural products

• Klaus Speck and
• Thomas Magauer

Beilstein J. Org. Chem. 2013, 9, 2048–2078, doi:10.3762/bjoc.9.243

• (2,3-dihydro-1H-isoindole, 2). Formal oxidation to the 10π-system leads to isoindole (1), which is usually only stable when the labile ortho-quinoid structure is embedded in a π-system [1]. Incorporation of additional oxygen gives the isoindolinone (1,3-dihydro-2H-isoindole-1-one, 3) and phthalimide

• synthesis of isoindoline-type structures and the synthesis, chemical and spectroscopic properties of this substance class were reviewed elsewhere [6][7][8]. In the late 1950s, thalidomide (8), a phthalimide-based drug used by pregnant women against morning sickness, became the most infamous drug in history

• and caused thousands of fatal casualties as well as numerous severe birth defects. Modification of the phthalimide core led to the approval of lenalidomide (9) [9] in 2004 and pomalidomide (10) in 2013 by the Food and Drug Administration (FDA) as drugs against multiple myeloma. The phosphodiesterase 4

An approach towards azafuranomycin analogs by gold-catalyzed cycloisomerization of allenes: synthesis of (αS,2R)-(2,5-dihydro-1H-pyrrol-2-yl)glycine

• Jörg Erdsack and
• Norbert Krause

Beilstein J. Org. Chem. 2013, 9, 1936–1942, doi:10.3762/bjoc.9.229

• -catalyzed cycloisomerization proceeded uneventfully (Scheme 3). Desilylation of allenes 6a and 6b with tetrabutylammonium fluoride trihydrate afforded the α-hydroxyallenes 7a/b in high yield, and these were converted into the aminoallenes 8a/b under standard Mitsunobu conditions (DEAD, PPh3, phthalimide

Organocatalytic asymmetric selenofunctionalization of tryptamine for the synthesis of hexahydropyrrolo[2,3-b]indole derivatives

• Qiang Wei,
• Ya-Yi Wang,
• Yu-Liu Du and
• Liu-Zhu Gong

Beilstein J. Org. Chem. 2013, 9, 1559–1564, doi:10.3762/bjoc.9.177

• -substituted tryptamine and subsequently the proton of the phosphoric acid protonates the phthalimide anion to release phthalimide. Finally, the amide on the side chain of the tryptamine derivatives attacks the resultant iminium cation leading to the formation of the product in an enantioselective manner

α-Bromodiazoacetamides – a new class of diazo compounds for catalyst-free, ambient temperature intramolecular C–H insertion reactions

• Åsmund Kaupang and
• Tore Bonge-Hansen

Beilstein J. Org. Chem. 2013, 9, 1407–1413, doi:10.3762/bjoc.9.157

• gel with CH2Cl2 (precooled to −15 °C), in order to remove the base and phthalimide. Allowing the solution to warm to ambient temperature effected the thermolysis of the α-bromodiazoacetamides (Scheme 2). Although we have not determined the exact temperature at which the thermolysis takes place, the α

Metal-free aerobic oxidations mediated by N-hydroxyphthalimide. A concise review

• Lucio Melone and
• Carlo Punta

Beilstein J. Org. Chem. 2013, 9, 1296–1310, doi:10.3762/bjoc.9.146

• oxidation of organic substrates [7][8][9][10][11]. NHPI acts as a precursor of the phthalimide N-oxyl (PINO) radical, which is the effective catalyst promoting hydrogen-abstraction processes (Scheme 1). The reactivity of NHPI and PINO is related to the bond dissociation energy (BDE) of the O–H group, which

Copper-catalyzed aerobic aliphatic C–H oxygenation with hydroperoxides

• Pei Chui Too,
• Ya Lin Tnay and
• Shunsuke Chiba

Beilstein J. Org. Chem. 2013, 9, 1217–1225, doi:10.3762/bjoc.9.138

• weak bond-dissociation enthalpies (i.e., tertiary alkyl C–H bonds, benzylic C–H bonds, etc.), by phthalimide N-oxyl radicals generated oxidatively from N-hydroxyphthalimide (NHPI), has been reported [20][21][22]. The resulting C-radicals could be trapped with molecular oxygen to form hydroperoxides. It

Intramolecular carbolithiation of N-allyl-ynamides: an efficient entry to 1,4-dihydropyridines and pyridines – application to a formal synthesis of sarizotan

• Wafa Gati,
• Mohamed M. Rammah,
• Mohamed B. Rammah and
• Gwilherm Evano

Beilstein J. Org. Chem. 2012, 8, 2214–2222, doi:10.3762/bjoc.8.250

• phthalimide in DMF at 90 °C, affording the corresponding N-allylphthalimide. Deprotection of the phthalimide by hydrazinolysis followed by protection of the resulting primary amine as a tert-butyl-carbamate gave the Boc-protected amine 13 required for the synthesis of the substrate of the anionic cyclization

Approaches to α-amino acids via rearrangement to electron-deficient nitrogen: Beckmann and Hofmann rearrangements of appropriate carboxyl-protected substrates

• Sosale Chandrasekhar and
• V. Mohana Rao

Beilstein J. Org. Chem. 2012, 8, 1393–1399, doi:10.3762/bjoc.8.161

• alcohols to carboxylic acids, or the Gabriel phthalimide synthesis cannot be performed in a routine way in the presence of the second functionality. Classical approaches essentially circumvented these limitations and ingenious improvements have evolved over the years [1]. Classical approaches continue to

Organocatalytic asymmetric allylic amination of Morita–Baylis–Hillman carbonates of isatins

• Hang Zhang,
• Shan-Jun Zhang,
• Qing-Qing Zhou,
• Lin Dong and
• Ying-Chun Chen

Beilstein J. Org. Chem. 2012, 8, 1241–1245, doi:10.3762/bjoc.8.139

• catalysis of DABCO. No desired reaction occurred for phthalimide [25] or N-allyl p-toluenesulfonamide [27], which has been successfully applied in the asymmetric amination of MBH carbonates derived from aryl aldehydes. Pleasingly, the reaction took place smoothly to afford product 4a when hydroxylamine 3a

Synthesis of a library of tricyclic azepinoisoindolinones

• Bettina Miller,
• Shuli Mao,
• Kara M. George Rosenker,
• Joshua G. Pierce and
• Peter Wipf

Beilstein J. Org. Chem. 2012, 8, 1091–1097, doi:10.3762/bjoc.8.120

• ring [19]. We have now developed this concept further toward a library synthesis of functionalized azepino-isoindolinone derivatives. Results and Discussion N-Alkylation of phthalimide with 4-penten-1-ol under Mitsunobu conditions, followed by NaBH4 reduction and pivaloate protection of the

Fifty years of oxacalix[3]arenes: A review

• Kevin Cottet,
• Paula M. Marcos and
• Peter J. Cragg

Beilstein J. Org. Chem. 2012, 8, 201–226, doi:10.3762/bjoc.8.22

• ]arene chemistry as debromination of 31 allowed the introduction of new groups in the vacant para-position via the mono-unsubstituted derivative 32 as shown in Scheme 17. The route introduced nitro (33), azide (34), imidazole (35), phthalimide (36), cyano (37) and methoxyether (38) groups, linked to one

A concise synthesis of 3-(1-alkenyl)isoindolin-1-ones and 5-(1-alkenyl)pyrrol-2-ones by the intermolecular coupling reactions of N-acyliminium ions with unactivated olefins

• Nianhong Lu,
• Lihong Wang,
• Zhanshan Li and
• Wei Zhang

Beilstein J. Org. Chem. 2012, 8, 192–200, doi:10.3762/bjoc.8.21

• reduction of the parent phthalimide [35] and maleimide [36] derivatives. In order to explore the effects of the experimental conditions on the coupling reactions, the reaction of 1a with styrene (2a) was selected as a representative and carried out at room temperature under different conditions (Table 1

Microphotochemistry: 4,4'-Dimethoxybenzophenone mediated photodecarboxylation reactions involving phthalimides

• Oksana Shvydkiv,
• Kieran Nolan and
• Michael Oelgemöller

Beilstein J. Org. Chem. 2011, 7, 1055–1063, doi:10.3762/bjoc.7.121

• superior results thus proving the superiority of microphotochemistry over conventional technologies. Keywords: microflow; microreactor; photochemistry; photodecarboxylation; phthalimide; Introduction Organic photochemistry is a highly successful synthesis method that allows the construction of complex

• complete conversions represent the minimum energy efficiencies due to possible contributions from “over-irradiation”. Once all phthalimide is consumed, photoreduction of DMBP becomes the dominant reaction due to its continuing excitation [41]. The degree of these decomposition processes can thus be used as

• (ET) from the carboxylate function to the triplet excited phthalimide furnishes an unstable carboxy radical, which undergoes rapid decarboxylation to the corresponding carbon radical. Protonation and C–C bond formation yields compounds 4 and 9, and the latter undergoes further dehydration to 10

Photoinduced electron-transfer chemistry of the bielectrophoric N-phthaloyl derivatives of the amino acids tyrosine, histidine and tryptophan

• Axel G. Griesbeck,
• Jörg Neudörfl and
• Alan de Kiff

Beilstein J. Org. Chem. 2011, 7, 518–524, doi:10.3762/bjoc.7.60

• Axel G. Griesbeck Jorg Neudorfl Alan de Kiff University of Cologne, Department of Chemistry, Organic Chemistry, Greinstr. 4, D-50939 Köln, Germany; Fax: +49(221)470 5057 10.3762/bjoc.7.60 Abstract The photochemistry of phthalimide derivatives of the electron-rich amino acids tyrosine, histidine

• cysteine and S-methyl cysteine derivatives [8]. Other proteinogenic amino acids that, in principle, should also be able to show bielectrophoric behavior with aromatic side chains similar to phenylalanine are tyrosine, histidine and tryptophan. The photochemistry of the phthalimide derivatives of these

• three amino acids are described in this publication. Results Synthesis of phthalimide substrates The C-unprotected N-phthaloyl amino acids 8–10 were available from tyrosine, histidine, and tryptophan (Figure 1). The phthalimide derivatives were prepared either by thermal reaction of phthalic anhydride

Photoinduced homolytic C–H activation in N-(4-homoadamantyl)phthalimide

• Nikola Cindro,
• Margareta Horvat,
• Kata Mlinarić-Majerski,
• Axel G. Griesbeck and
• Nikola Basarić

Beilstein J. Org. Chem. 2011, 7, 270–277, doi:10.3762/bjoc.7.36

• 10.3762/bjoc.7.36 Abstract N-(4-homoadamantyl)phthalimide (5) on excitation and population of the triplet excited state underwent intramolecular H-abstractions and gave products 6 and 7. The major product, exo-alcohol 6 was a result of the regioselective δ H-abstraction and the stereoselective cyclization

• type II reaction [18][19][20]. The photochemistry of phthalimide derivatives is often similar to that of simple ketones [21][22][23][24][25][26][27][28][29][30][31][32][33]. For example, phthalimide derivatives in the electronically excited state abstract H-atoms from alcohols to give reduction

• products [34]. Furthermore, suitably substituted phthalimides deactivate from the excited state by intramolecular H-abstractions to yield cyclization products, often benzazepinone derivatives [35][36][37]. Therefore, photoinduced homolytic C–H activation by phthalimide derivatives can, in principle, be

Molecular recognition of organic ammonium ions in solution using synthetic receptors

• Andreas Späth and
• Burkhard König

Beilstein J. Org. Chem. 2010, 6, No. 32, doi:10.3762/bjoc.6.32

Bis(oxazolines) based on glycopyranosides – steric, configurational and conformational influences on stereoselectivity

• Tobias Minuth and
• Mike M. K. Boysen

Beilstein J. Org. Chem. 2010, 6, No. 23, doi:10.3762/bjoc.6.23

• presence of 15-crown-5 [27][28] to afford 10 in similar yields as the oxidation-reduction sequence (Scheme 2). After deprotection of the phthalimide (phthN) [29], the free amine 11 was transformed into the 4,6-O-benzylidene protected ligand by our standard protocol for the preparation of carbohydrate bis

Recognition properties of receptors consisting of imidazole and indole recognition units towards carbohydrates

• Monika Mazik and
• André Hartmann

Beilstein J. Org. Chem. 2010, 6, No. 9, doi:10.3762/bjoc.6.9

• equiv of 2-amino-4,6-dimethylpyridine, CH3CN/THF, K2CO3, r. t., 3 d (20%); d) potassium phthalimide, dimethyl sulfoxide, 95 °C, 8 h, (57%); e) hydrazine hydrate, ethanol/toluene, reflux, 19.5 h, KOH (43%) [27]; f) 4 equiv of 4(5)-imidazole-carbaldehyde (18), CH3OH, 3 d; g) 4 equiv of 3-indole