Oligomeric epoxide–amine adducts based on 2-amino-N-isopropylacetamide and α-amino-ε-caprolactam: Solubility in presence of cyclodextrin and curing properties

• Julian Fischer and
• Helmut Ritter

Beilstein J. Org. Chem. 2013, 9, 2803–2811, doi:10.3762/bjoc.9.315

• refluxed for 3 h and stirred at room temperature overnight. The phases were separated, the aqueous phase was washed twice with 30 mL of methylene chloride and the organic phases were combined. After drying over magnesium sulfate and filtration thereof methylene chloride was distilled off under reduced

Diastereoselectivity in the Staudinger reaction of pentafluorosulfanylaldimines and ketimines

• Alexander Penger,
• Cortney N. von Hahmann,
• Alexander S. Filatov and
• John T. Welch

Beilstein J. Org. Chem. 2013, 9, 2675–2680, doi:10.3762/bjoc.9.303

• converted to the corresponding imine 5 in dichloromethane using anhydrous magnesium sulfate as a dehydrating agent (Scheme 2). Other desiccants, especially inherently basic materials, such as potassium carbonate lead to little imine formation. While the crude imine solution likely contained unreacted amine

Garner’s aldehyde as a versatile intermediate in the synthesis of enantiopure natural products

• Mikko Passiniemi and
• Ari M.P. Koskinen

Beilstein J. Org. Chem. 2013, 9, 2641–2659, doi:10.3762/bjoc.9.300

• a moderate 5:1 anti/syn-selectivity. By changing the metal to magnesium (vinylMgBr) the selectivity slightly dropped to 3:1 (anti/syn) still favouring adduct 20. Addition of a Lewis acid (TiCl4) did not affect the diastereoselectivity with vinyllithium species. The addition of vinyllithium to (S)-1

Cu-catalyzed trifluoromethylation of aryl iodides with trifluoromethylzinc reagent prepared in situ from trifluoromethyl iodide

• Yuzo Nakamura,
• Motohiro Fujiu,
• Tatsuya Murase,
• Yoshimitsu Itoh,
• Hiroki Serizawa,
• Kohsuke Aikawa and
• Koichi Mikami

Beilstein J. Org. Chem. 2013, 9, 2404–2409, doi:10.3762/bjoc.9.277

• organometallic reagents such as lithium and magnesium, which are widely utilized in non-fluorine organic synthesis, cannot be used. These trifluoromethyl metal reagents are generally too unstable to prepare even at low temperature because of facile α-fluoro elimination generating the singlet difluoromethylene

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

• thiazolidinedione 1.48 in the presence of a catalytic amount of piperidinium acetate reportedly leads to the exclusive formation of the desired Z-isomer product. Interestingly, the newly installed double bond was efficiently reduced using magnesium in methanol thus circumventing catalyst poisoning issues pertaining

• circumventing the problem describes the use of bench stable magnesium nitride, a solid material which upon hydrolysis liberates the required ammonia in situ (Scheme 23) [64]. However, there have been several reports on explosions caused by runaway reactions so extreme care must be administrated when using this

Post-Ugi gold-catalyzed diastereoselective domino cyclization for the synthesis of diversely substituted spiroindolines

• Amit Kumar,
• Dipak D. Vachhani,
• Sachin G. Modha,
• Sunil K. Sharma,
• Virinder S. Parmar and
• Erik V. Van der Eycken

Beilstein J. Org. Chem. 2013, 9, 2097–2102, doi:10.3762/bjoc.9.246

• mL). The organic layer was washed with brine (50 mL), dried over magnesium sulfate, and evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (10% diethyl ether in dichloromethane) to afford compound 6a–q. Gold-catalyzed approaches towards

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

• reduction, acetylation and a magnesium sulfate induced rearrangement of the epoxide to the allylic alcohol. The synthesis of cytochalasin B 52 (15 steps from 73) proceeded in a similar fashion and was highlighted in detail by Hertweck [44]. The authors state that this approach is highly diversifiable and

Organocatalyzed enantioselective desymmetrization of aziridines and epoxides

• Ping-An Wang

Beilstein J. Org. Chem. 2013, 9, 1677–1695, doi:10.3762/bjoc.9.192

• with aq HCl to generate metal-free chiral phosphoric acid OC-21, which was reused as the catalyst, and the corresponding ring-opening products were obtained in moderate yields as racemates. By using a 1:1 mixture of calcium and magnesium phosphate salts of OC-21 as the catalyst, the corresponding ring

• -opening product 28 was produced in 94% yield and 91% ee. Therefore, calcium and magnesium phosphate salts of OC-21 proved to be the true catalysts in these processes. The author suggested that these metal phosphates may be generated through the purification of OC-21 on silica gel column. A dual Lewis-base

Controlled synthesis of poly(3-hexylthiophene) in continuous flow

• Helga Seyler,
• Jegadesan Subbiah,
• David J. Jones,
• Andrew B. Holmes and
• Wallace W. H. Wong

Beilstein J. Org. Chem. 2013, 9, 1492–1500, doi:10.3762/bjoc.9.170

• thiophene Grignard monomer 2 is prepared from the magnesium exchange reaction of an alkyl Grignard reagent and 2,5-dibromo-3-hexylthiophene (1, Scheme 1a). It should be noted here that a mixture of Grignard monomers 2a and 2b is produced in this step, typically in a ratio of 75:25. Only 2a participates in

Hypervalent iodine/TEMPO-mediated oxidation in flow systems: a fast and efficient protocol for alcohol oxidation

• Nida Ambreen,
• Ravi Kumar and
• Thomas Wirth

Beilstein J. Org. Chem. 2013, 9, 1437–1442, doi:10.3762/bjoc.9.162

• time of 4.5 min. The reaction mixture exiting the flow reactor was quenched with water and, after completion of the reaction, extracted with CH2Cl2. The combined organic layers were dried over magnesium sulfate and the solvents were removed in vacuo. Direct analysis with GC allowed the determination of

• had been achieved, 200 mL of the reaction solution was collected in a flask containing water (20 mL) as a quenching agent. After completion of the reaction, the organic phase was removed and the aqueous phase was extracted with CH2Cl2 (3 × 20 mL). The combined organic layers were dried over magnesium

• . After the completion of the reaction the solvent was evaporated, and the reaction mixture was extracted with CH2Cl2 and water. The organic layers were dried over magnesium sulfate and the solvents were removed in vacuo. The 1H NMR analysis showed a clean spectrum of the condensation product. Flow setup

Total synthesis of ochnaflavone

• Monica M. Ndoile and
• Fanie R. van Heerden

Beilstein J. Org. Chem. 2013, 9, 1346–1351, doi:10.3762/bjoc.9.152

• was added, and the mixture was extracted with 3 × 20 mL CHCl3. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was removed in vacuo. The residue obtained was purified by silica-gel column chromatography (EtOAc/hexanes, 3:7) as eluent to yield 748 mg (89%) of 4 as a light

• added, followed by extraction with 3 × 20 mL CHCl3. The obtained organic layer was dried over anhydrous magnesium sulfate, and the solvent was removed in vacuo. The residue was purified by silica gel column chromatography (EtOAc/hexanes, 1:9) to afford 5 (291 mg, 50%) as a white solid. 1H NMR (400 MHz

• anhydrous magnesium sulfate. CH2Cl2 was removed in vacuo and the resulting residue was purified by silica-gel column chromatography with EtOAc/hexanes (1:1) to afford 100 mg (25%) of the ether-linked biflavanone 8 as a light-yellow solid. 1H NMR (400 MHz, CDCl3) δH 7.40 (d, J = 8.5 Hz, 2H), 7.26 (dd, J

Exploration of an epoxidation–ring-opening strategy for the synthesis of lyconadin A and discovery of an unexpected Payne rearrangement

• Brad M. Loertscher,
• Yu Zhang and
• Steven L. Castle

Beilstein J. Org. Chem. 2013, 9, 1179–1184, doi:10.3762/bjoc.9.132

• in Scheme 6. Coordination of a Lewis acid (likely a copper or magnesium species) to the trityl ether moiety of 25 could promote migration of the trityl group [31][32] to the epoxide, generating intermediate A. Payne rearrangement of A would then furnish epoxide B. Finally, attack of the vinylcopper

Synthesis of the tetracyclic core of Illicium sesquiterpenes using an organocatalyzed asymmetric Robinson annulation

• Lynnie Trzoss,
• Jing Xu,
• Michelle H. Lacoske and
• Emmanuel A. Theodorakis

Beilstein J. Org. Chem. 2013, 9, 1135–1140, doi:10.3762/bjoc.9.126

• enone 10 (>10 grams) for further functionalization. Conversion of 10 to 9 was accomplished based on our previously reported strategy (Scheme 3) [25]. Treatment of 10 with magnesium methyl carbonate (MMC) [79][80][81] yielded the C-5 carboxylic acid that, without further purification, was esterified

Synthesis of guanidinium–sulfonimide ion pairs: towards novel ionic liquid crystals

• Martin Butschies,
• Manuel M. Neidhardt,
• Markus Mansueto,
• Sabine Laschat and
• Stefan Tussetschläger

Beilstein J. Org. Chem. 2013, 9, 1093–1101, doi:10.3762/bjoc.9.121

• ]. Although Heintz was the pioneer, who observed in 1854 melting and clearing transitions upon heating of magnesium myristate [9][10], he did not recognize this as liquid-crystalline behavior. The first regular pyridinium ILCs were reported in 1938 by Knight and Shaw [11][12], followed by seminal findings by

• room temperature. After being stirred for 3 days, the mixture was brought to pH 1 by the addition of concd hydrochloric acid. The solvents were removed in vacuo and the residue was taken up in dichloromethane (50 mL). The resulting solution was dried with magnesium sulfate and filtered, and the

Methylidynetrisphosphonates: Promising C₁ building block for the design of phosphate mimetics

• Vadim D. Romanenko and
• Valery P. Kukhar

Beilstein J. Org. Chem. 2013, 9, 991–1001, doi:10.3762/bjoc.9.114

• than methylenebisphosphonic acid and its alkali-metal salts and also sequester more calcium and magnesium ions, for example, than does H2C(PO3H2)2 [50][51]. The complexation behavior of the polydentate ligand Me2NC(PO3Et2)3 toward Co2+ ion has shown that the trisphosphonate molecule is coordinated in

Preparation and ring-opening reactions of N-diphenylphosphinyl vinyl aziridines

• Ashley N. Jarvis,
• Andrew B. McLaren,
• Helen M. I. Osborn and
• Joseph Sweeney

Beilstein J. Org. Chem. 2013, 9, 852–859, doi:10.3762/bjoc.9.98

• with sodiomalonate and sodium bisphenylsulfonylmethide, again with complete regiocontrol via an SN2′-like reaction to give ring-opened products in acceptable yield (Table 2, entries 7, 8, 11, 12). When aziridines 1 and 2 were reacted with methyl magnesium iodide in Et2O solution, the previously good

• regiocontrol we had observed in the ring opening was not maintained: unlike the reaction of allyl magnesium chloride (Table 2, entry 5) a mixture of products arising from nucleophilic attack at both C-2 and C-4 was isolated, with a preference for a SN2′-like reaction again observed (Scheme 4). The reactions of

• /light petroleum (1:4); gradient elution to ethyl acetate). Ring-opening reaction with methyl magnesium Grignard: To magnesium (5 equiv) in diethyl ether (5 mL), under nitrogen, at 0 °C, was added MeI (5.4 equiv) in diethyl ether (1 mL) and the resulting mixture was stirred for 30 min, creating a grey

Some aspects of radical chemistry in the assembly of complex molecular architectures

• Béatrice Quiclet-Sire and
• Samir Z. Zard

Beilstein J. Org. Chem. 2013, 9, 557–576, doi:10.3762/bjoc.9.61

• possesses an interesting combination of functional groups. Upon treatment with magnesium turnings in methanol, this compound is converted into cyclopentanol 135 by capture of the intermediate ketyl radical by the dichlorovinyl group [55]. Alternatively, protection of the ketone and application of the Corey

Recent advances in transition-metal-catalyzed intermolecular carbomagnesiation and carbozincation

• Kei Murakami and
• Hideki Yorimitsu

Beilstein J. Org. Chem. 2013, 9, 278–302, doi:10.3762/bjoc.9.34

• , organomagnesium and organozinc reagents have been widely employed for organic synthesis due to their versatile reactivity and availability. The most popular method for preparing organomagnesium and organozinc reagents still has to be the classical Grignard method [1], starting from magnesium or zinc metal and

• catalytic amount of copper iodide afforded organozinc intermediate 3e and finally 3f after protonolysis. In 2012, Fox reported the stereoselective copper-catalyzed arylzincation of cyclopropenes with a wider variety of arylzinc reagents [92]. The organozinc reagents were prepared by iodine/magnesium

• titanium-catalyzed allylmagnesiation of isoprene was reported in the 1970s, the scope of the reagents was limited to the allylic magnesium reagents [145][146]. Recently, Terao and Kambe reported copper-catalyzed regioselective carbomagnesiation of dienes and enynes using sec- or tert-alkylmagnesium

Polar reactions of acyclic conjugated bisallenes

• Reiner Stamm and
• Henning Hopf

Beilstein J. Org. Chem. 2013, 9, 36–48, doi:10.3762/bjoc.9.5

• . The oxidation of the tetramethylbisallene 2 was carried out with magnesium monoperoxy phthalate (MMPP) since we had also observed the formation of addition products of 2 (m-chlorobenzoates) when we used MCPBA for epoxidation. Indeed, ketone 36 could be obtained in 80% yield with MMPP (GC analysis

• protocol. The oxidation of these highly unsaturated compounds with magnesium monoperoxyphthalate (MMPP) results predominantly in the formation of cyclopentenone derivatives in a Nazarov-type cyclization. The addition of hydrohalides leads to halo-1,3,5-trienes whereas bromine and iodine addition furnish

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

• the carbometallation of various carbon–carbon multiple bonds. Lithium, copper, zinc, magnesium, zirconium, titanium, palladium and other metals are suitable for this transformation and considerable progress has recently been made in this area. Among these systems, the carbometallation of alkynes

Stereoselective synthesis of tetrasubstituted alkenes via a sequential carbocupration and a new sulfur–lithium exchange

• Andreas Unsinn,
• Cora Dunst and
• Paul Knochel

Beilstein J. Org. Chem. 2012, 8, 2202–2206, doi:10.3762/bjoc.8.248

• 9 in 77% yield. Direct Pd-catalyzed Negishi cross-coupling [24][25][26][27][28] of 9 with an arylzinc derivative failed. However, the bromide 9 could be readily converted to the corresponding iodide 10 by a bromine–magnesium exchange using iPrMgCl·LiCl [29][30][31][32][33][34][35] followed by

Total synthesis and biological evaluation of fluorinated cryptophycins

• Christine Weiß,
• Tobias Bogner,
• Benedikt Sammet and
• Norbert Sewald

Beilstein J. Org. Chem. 2012, 8, 2060–2066, doi:10.3762/bjoc.8.231

• homoallyl alcohol 16. The magnesium bromide diethyl etherate mediated allylation proceeded under substrate control and with complete diastereoselectivity [23][32]. Cross-metathesis of homoallyl alcohol 16 with the unit B derived acrylamide 17 provided the α,β-unsaturated δ-hydroxy carboxamide 18 (Scheme 2

The chemistry of bisallenes

• Henning Hopf and
• Georgios Markopoulos

Beilstein J. Org. Chem. 2012, 8, 1936–1998, doi:10.3762/bjoc.8.225

• magnesium bromide (20), takes place first. The subsequent addition of CuCl very likely generates a copper organic intermediate, which is then coupled with a second equivalent of 19 to yield 2 and its isomer 21 (1,2-hexadien-5-yne, propargylallene). Formally, the dimerization of 19 to 2 involves two SN2

• shall return in Section 1.4.1. The fully trimethylsilylated bisallene 88 is produced when hexabromide 87 is treated with excess trimethylsilyl chloride and Rieke magnesium at 0 °C (Scheme 20) [69][70]. The yield is low, however, and several other isomers of 88 are present in the reaction mixture. A far

• hexachloro derivative 94 was treated by Gilman and co-workers with excess dimethylsilyl chloride and magnesium in THF, the hexasilylated derivative 95 was produced and again a ring-opening reaction to a conjugated bisallene had taken place (Scheme 23) [70]. In closing this section on silicon-substituted

Dimerization of a cell-penetrating peptide leads to enhanced cellular uptake and drug delivery

• Jan Hoyer,
• Ulrich Schatzschneider,
• Michaela Schulz-Siegmund and
• Ines Neundorf

Beilstein J. Org. Chem. 2012, 8, 1788–1797, doi:10.3762/bjoc.8.204

• medium (DMEM), Ham’s F12 (without L-glutamine), OptiMEM, Dulbecco’s phosphate buffered saline (PBS) without calcium and magnesium, fetal bovine serum (FBS), L-glutamine and trypsin/EDTA (all purchased from PAA, Linz, Austria, or Gibco Life Technologies, Karlsruhe, Germany). Cell culture flasks (75 cm2

Synthesis and evaluation of new guanidine-thiourea organocatalyst for the nitro-Michael reaction: Theoretical studies on mechanism and enantioselectivity

• Tatyana E. Shubina,
• Matthias Freund,
• Sebastian Schenker,
• Timothy Clark and
• Svetlana B. Tsogoeva

Beilstein J. Org. Chem. 2012, 8, 1485–1498, doi:10.3762/bjoc.8.168

• magnesium sulfate. Product 10 was isolated by preparative thin-layer chromatography over silica gel. 1H NMR (300 MHz, DMSO-d6) δ 1.58–1.83 (m, 2H), 2.55–2.82 (m, 2H), 4.05–4.17 (m, 1H), 4.39 (dd, J = 9.3 Hz, J = 12.2 Hz, 1H), 4.71 (dd, J = 3.0 Hz, J = 12.2 Hz, 1H), 5.48 (d, J = 6.4 Hz, 1H), 7.10–7.36 (m, 5H

• with aqueous 20% potassium hydrogen sulfate solution (3 mL) and brine (3 mL). After drying over magnesium sulfate, the organic phase was evaporated and purified by column chromatography over silica gel (petrol ether/ethyl acetate 2:1) to yield 13 (19.00 mg, 76.23 μmol, 54%). 1H NMR (300 MHz, CDCl3) δ