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

Acid- mediated reactions under microfluidic conditions: A new strategy for practical synthesis of biofunctional natural products

• Katsunori Tanaka and
• Koichi Fukase

Beilstein J. Org. Chem. 2009, 5, No. 40, doi:10.3762/bjoc.5.40

• reactive sialyl donors having C-5 cyclic imides (Table 1), especially N-phthalimide 1a, by virtue of the “fixed-dipole moment effects” (α-only, 92% on 50 mg scale) [41]. The scale-up in a batch process, however, significantly decreased the yield and selectivity. Thus, a 100 mg scale reaction of 1a gave

Mitomycins syntheses: a recent update

• Jean-Christophe Andrez

Beilstein J. Org. Chem. 2009, 5, No. 33, doi:10.3762/bjoc.5.33

• [4.1.0] ring system. It was necessary to methanolyse the lactone 69 prior to removal of the phthalimide with methyl hydrazine, which occurred with concomitant cyclization to form penultimate intermediate 70. The final ring closure was realized by treatment with camphorsulfonic acid to form lactam 71 in

Synthesis and enzymatic evaluation of 2- and 4-aminothiazole- based inhibitors of neuronal nitric oxide synthase

• Graham R. Lawton,
• Haitao Ji,
• Pavel Martásek,
• Linda J. Roman and
• Richard B. Silverman

Beilstein J. Org. Chem. 2009, 5, No. 28, doi:10.3762/bjoc.5.28

• diastereomers was formed, but both were oxidized to α-bromoketone 12. Condensation with thiourea gave the 2-aminothiazole (13). Diprotection of the amine with Boc groups and deprotection of the TBS ether gave trans-alcohol 15. A Mitsunobu reaction was used to install a nitrogen atom in the form of a phthalimide

• does not need to be diprotected to allow the Mitsunobu reaction with phthalimide as the nucleophile to proceed (28a-c). This is presumably because the thiazole nitrogen is less nucleophilic. Cleavage of the phthalimide group gave amines 29a-c. The syntheses of 4a-c were completed by reductive amination

• (2.5 equiv), DMAP, THF, rt, 16 h; viii) TBAF, THF, rt 16 h; ix) PPh3, DIAD, phthalimide, THF, rt, 16 h; x) H2NNH2 (aq), MeOH, rt, 16 h, then 2N HCl, rt, 30 min. Synthesis of compound 3. i) 4-chlorobenzylchloride, EtOH, reflux, 4 h; ii) Boc2O, TEA, MeOH, 3 h; iii) 1 N NaOH, MeOH, rt, 4 h; iv) EDC, HOBt

N-Arylation of amines, amides, imides and sulfonamides with arylboroxines catalyzed by simple copper salt/EtOH system

• Zhang-Guo Zheng,
• Jun Wen,
• Na Wang,
• Bo Wu and
• Xiao-Qi Yu

Beilstein J. Org. Chem. 2008, 4, No. 40, doi:10.3762/bjoc.4.40

• -containing substrates with arylboroxine conducted in protic solvent only with the use of copper salts has not been explored previously. Results and Discussion Firstly, we chose phthalimide and phenylboroxine as model substrates to optimize the catalytic conditions (copper source, temperature, solvent, amount

• system. Being of lower toxicity, easier to process and environmentally benign, EtOH was chosen as reaction medium for this coupling reaction. The ratio of phthalimide to arylboroxine and the amount of Cu(OTf)2 are both important factors for this coupling reaction (Table 4, entries 1–7). We found that

• variety of substrates bearing methyl- and bromophenylboroxines using phthalimide under our generalized conditions (Table 5, entries 2–3). The results demonstrated that there was little difference between the effect of an electron-rich aryl ring and an electron-deficient aryl ring in this cross-coupling

Combining two-directional synthesis and tandem reactions, part 11: second generation syntheses of (±)-hippodamine and (±)-epi-hippodamine

• Annabella F. Newton,
• Martin Rejzek,
• Marie-Lyne Alcaraz and
• Robert A. Stockman

Beilstein J. Org. Chem. 2008, 4, No. 4, doi:10.1186/1860-5397-4-4

• acrylate as the cross-metathesis coupling partner. In fact, due to the non-co-ordinating nature of ethyl acrylate (in comparison to acrylonitrile) and the inert phthalimide group, this reaction proved to be an outstanding success, delivering diester 6 in 88% yield over one step after a five day reaction in

• -metathesis reaction is shown in Scheme 2. Having refined our synthesis of diester 7 by providing a shortened synthesis of its precursor, we decided to see if we could attain a synthesis of this common intermediate for the synthesis of both hippodamine and epi-hippodamine without the use of the phthalimide