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

Synthesis of diverse indole libraries on polystyrene resin – Scope and limitations of an organometallic reaction on solid supports

• Kerstin Knepper,
• Sylvia Vanderheiden and
• Stefan Bräse

Beilstein J. Org. Chem. 2012, 8, 1191–1199, doi:10.3762/bjoc.8.132

• after thin-layer chromatography. A slightly higher temperature was optimal for the reaction of (3-methyl-4-nitrophenyl)carboxymethyl-polystyrene (1{i}) with the less active vinyl magnesium bromide 2{a} (Figure 3). In addition to this, we also varied the amount of Grignard reagent for the reaction of 1{h

• , and the filtrate is hydrolyzed with water and subsequently extracted with ethyl acetate three times. After being dried over magnesium sulfate, the solvent is removed under reduced pressure and the residue is purified by column chromatography by using cyclohexane/ethyl acetate, 3:1 as eluent

Screening of ligands for the Ullmann synthesis of electron-rich diaryl ethers

• Nicola Otto and
• Till Opatz

Beilstein J. Org. Chem. 2012, 8, 1105–1111, doi:10.3762/bjoc.8.122

• ). It turned out that caesium carbonate as a base without addition of molecular sieves did not result in any diaryl ether formation, presumably due to the formation of water inactivating the base. With chemical drying agents such as magnesium sulfate, only trace amounts of the product were obtained. In

Toward unidirectional switches: 2-(2-Hydroxyphenyl)pyridine and 2-(2-methoxyphenyl)pyridine derivatives as pH-triggered pivots

• Christina Tepper and
• Gebhard Haberhauer

Beilstein J. Org. Chem. 2012, 8, 977–985, doi:10.3762/bjoc.8.110

• over magnesium sulfate, and the solvent was removed in vacuo. The residue was purified by column chromatography over silica gel (n-hexane/AcOEt 1:1). The product was obtained as a colorless solid (77 mg, 39%). 1H NMR (500 MHz, CDCl3) δ 7.74 (dd, 3JH,H = 7.6 Hz, 4JH,H = 1.9 Hz, 1H, Har), 7.59–7.58 (m

• poured into a dichloromethane/water mixture. The organic layer was separated and dried over magnesium sulfate, and the solvent was removed in vacuo. The product was obtained as a colorless solid (32 mg, 95%). 1H NMR (500 MHz, CDCl3) δ 14.72 (bs, 1H, OH), 7.86 (dd, 3JH,H = 8.0 Hz, 4JH,H = 1.6 Hz, 1H, Har

• afterwards 2-methoxyphenylboronic acid (14 mg, 0.092 mmol) was added and the mixture was heated to 80 °C for 4 h. After cooling to room temperature, water and ethyl acetate were added. The aqueous phase was extracted with ethyl acetate. The organic layers were combined and dried over magnesium sulfate, and

Two-directional synthesis as a tool for diversity-oriented synthesis: Synthesis of alkaloid scaffolds

• Kieron M. G. O’Connell,
• Monica Díaz-Gavilán,
• Warren R. J. D. Galloway and
• David R. Spring

Beilstein J. Org. Chem. 2012, 8, 850–860, doi:10.3762/bjoc.8.95

• intramolecular conjugate addition. Three of these compounds (1–3) were obtained from the corresponding alcohols [19][20] in three steps: Mitsunobu reaction with NH-Boc-tosylate, followed by tosyl deprotection with magnesium, and finally two-directional cross metathesis with ethyl acrylate to install the desired

2-Allylphenyl glycosides as complementary building blocks for oligosaccharide and glycoconjugate synthesis

• Hemali D. Premathilake and
• Alexei V. Demchenko

Beilstein J. Org. Chem. 2012, 8, 597–605, doi:10.3762/bjoc.8.66

• <40 °C. CH2Cl2 and ClCH2CH2Cl were distilled from CaH2, directly prior to application. Anhydrous DMF (EM Science) was used as received. Methanol was dried by heating under reflux with magnesium methoxide, distilled and stored under argon. Pyridine and acetonitrile were dried by heating under reflux

Volatile organic compounds produced by the phytopathogenic bacterium Xanthomonas campestris pv. vesicatoria 85-10

• Teresa Weise,
• Marco Kai,
• Anja Gummesson,
• Armin Troeger,
• Stephan von Reuß,
• Silvia Piepenborn,
• Francine Kosterka,
• Martin Sklorz,
• Ralf Zimmermann,
• Wittko Francke and
• Birgit Piechulla

Beilstein J. Org. Chem. 2012, 8, 579–596, doi:10.3762/bjoc.8.65

• dried over magnesium sulfate. The solvent was removed in vacuo, and the residue was submitted to flash chromatography (silica; cyclohexane/ethyl acetate 40:1) yielding 2.44 g (29.8 mmol, 83%) of 2-benzyloxypent-3-yne (A). A solution of 2.70 g (15.5 mmol) of A in 50 mL dry THF was cooled to −78 °C and

• aqueous solution of ammonium chloride was added. After separation, the aqueous layer was extracted with three portions of diethyl ether at 50 mL each. The combined organic solutions were washed with brine and dried over magnesium sulfate. The solvent was removed in vacuo, and the residue was submitted to

A ferrocene redox-active triazolium macrocycle that binds and senses chloride

• Nicholas G. White and
• Paul D. Beer

Beilstein J. Org. Chem. 2012, 8, 246–252, doi:10.3762/bjoc.8.25

• organic fractions were dried (magnesium sulfate), taken to dryness under reduced pressure and then purified by column chromatography (silica, gradient: 3% methanol in dichloromethane) to give 3 as an orange powder. Yield: 0.065 g (54%). 1H NMR (CDCl3) δ 7.44 (s, 2H, trz-H), 5.06 (s, 4H, Fc-CH2-trz), 4.15

Efficient oxidation of oleanolic acid derivatives using magnesium bis(monoperoxyphthalate) hexahydrate (MMPP): A convenient 2-step procedure towards 12-oxo-28-carboxylic acid derivatives

• Jorge A. R. Salvador,
• Vânia M. Moreira,
• Rui M. A. Pinto,
• Ana S. Leal and
• José A. Paixão

Beilstein J. Org. Chem. 2012, 8, 164–169, doi:10.3762/bjoc.8.17

• /bjoc.8.17 Abstract A new, straightforward and high yielding procedure to convert oleanolic acid derivatives into the corresponding δ-hydroxy-γ-lactones, by using the convenient oxidizing agent magnesium bis(monoperoxyphthalate) hexahydrate (MMPP) in refluxing acetonitrile, is reported. In addition, a

• ][24], but weak selectivity and low isolated yields were observed. Alternatively, oxidation reagents such as H2O2 in acetic acid [25][26], the inorganic salt mixture KMnO4/CuSO4 [27], ozone [15][28][29] and m-chloroperoxybenzoic acid (mCPBA) [30][31] have also been reported. Magnesium bis

• dissolved in acetonitrile under reflux, and MMPP (2.0–3.0 equiv) was added to the solution under strong magnetic stirring. After completion of the reaction, the magnesium salts were easily filtered off after evaporation of the acetonitrile and suspension of the resulting white solid in ethyl acetate. We

Fluorescent hexaaryl- and hexa-heteroaryl[3]radialenes: Synthesis, structures, and properties

• Antonio Avellaneda,
• Courtney A. Hollis,
• Xin He and
• Christopher J. Sumby

Beilstein J. Org. Chem. 2012, 8, 71–80, doi:10.3762/bjoc.8.7

• water (40 mL) and extracted with dichloromethane (50 mL) followed by further dichloromethane (5 × 25 mL). The organic extracts were combined, dried over anhydrous magnesium sulfate, and the solvent was evaporated to yield a red–brown oil. Purification via alumina chromatography eluting with 9:1 CH2Cl2

• % w/v, 5 mL). The mixture was extracted with dichloromethane (6 × 10 mL). The organic fractions were combined and washed with 1 M hydrochloric acid solution (20 mL), 1 M sodium thiosulfate solution (20 mL), dried over anhydrous magnesium sulfate and the solvent was evaporated under vacuum to yield a

• mixture was diluted with ethyl acetate (40 mL) and the resultant solution was washed with concentrated ammonia solution (30 mL), water (20 mL) and brine (20 mL). Then, it was dried over anhydrous magnesium sulfate and the solvent evaporated under vacuum to yield 6 as an off-white solid (0.33 g, 90%). Mp

Binding of group 15 and group 16 oxides by a concave host containing an isophthalamide unit

• Jens Eckelmann,
• Vittorio Saggiomo,
• Svenja Fischmann and
• Ulrich Lüning

Beilstein J. Org. Chem. 2012, 8, 11–17, doi:10.3762/bjoc.8.2

• of triethylamine was evaporated under reduced pressure. The residue was dissolved in chloroform (25 mL) and water (25 mL). The water phase was extracted once with chloroform (25 mL), the combined organic layer was dried with magnesium sulfate and evaporated under reduced pressure to yield a yellow

• residue was dissolved in chloroform (25 mL) and water (25 mL). The aqueous phase was extracted with chloroform (25 mL). The organic layers were collected, dried with magnesium sulfate and the solvent was evaporated under reduced pressure. The product was isolated by column chromatography (silica

Functionalization of heterocyclic compounds using polyfunctional magnesium and zinc reagents

• Paul Knochel,
• Matthias A. Schade,
• Sebastian Bernhardt,
• Georg Manolikakes,
• Albrecht Metzger,
• Fabian M. Piller,
• Christoph J. Rohbogner and
• Marc Mosrin

Beilstein J. Org. Chem. 2011, 7, 1261–1277, doi:10.3762/bjoc.7.147

• the most important procedures for the preparation of functionalized organzinc and organomagnesium reagents. In addition, new methods for the preparation of polyfunctional aryl- and heteroaryl zinc- and magnesium compounds, as well as new Pd-catalyzed cross-coupling reactions, are reported herein

• pharmaceutical research. In this review article, we describe the approaches to this problem that use functionalized magnesium and zinc heterocyclic intermediates. Some typical experimental procedures are indicated in each case for the most important methods. New Pd-catalyzed cross-coupling procedures are also

• require the use of transition metal catalysts. The preparation of aryl and heteroaryl zinc derivatives is conveniently achieved by three general procedures: the direct insertion of zinc dust to aryl or heteroaryl iodides or bromides; the direct insertion of magnesium in the presence of Zn(II) salts to

Combined directed ortho-zincation and palladium-catalyzed strategies: Synthesis of 4,n-dimethoxy-substituted benzo[b]furans

• Verónica Guilarte,
• M. Pilar Castroviejo,
• Estela Álvarez and
• Roberto Sanz

Beilstein J. Org. Chem. 2011, 7, 1255–1260, doi:10.3762/bjoc.7.146

• ), the introduction in the last years of new organometallic “ate” complexes [8][9], which combine an alkali metal with either magnesium, zinc, aluminium, or copper, has allowed more selective metallation reactions. The milder reaction conditions required make these deprotonation reactions tolerant to the

Meta-metallation of N,N-dimethylaniline: Contrasting direct sodium-mediated zincation with indirect sodiation-dialkylzinc co-complexation

• David R. Armstrong,
• Liam Balloch,
• Eva Hevia,
• Alan R. Kennedy,
• Robert E. Mulvey,
• Charles T. O'Hara and
• Stuart D. Robertson

Beilstein J. Org. Chem. 2011, 7, 1234–1248, doi:10.3762/bjoc.7.144

• different components. The work of Knochel uncovered a special reactivity and selectivity that can be realised with a mixed lithium halide–magnesium amide complex sometimes labelled a “turbo-Grignard” reagent [8]. It has been proposed that LiCl breaks up the magnesium amide aggregates allowing more soluble

A practical route to tertiary diarylmethylamides or -carbamates from imines, organozinc reagents and acyl chlorides or chloroformates

• Erwan Le Gall,
• Antoine Pignon and
• Thierry Martens

Beilstein J. Org. Chem. 2011, 7, 997–1002, doi:10.3762/bjoc.7.112

• imine/carbonyl-containing compound mixture and the resulting mixture was stirred at rt for 30 min. The solution was poured into a sat. NH4Cl solution (100 mL), extracted with diethyl ether (2 × 75 mL) and the combined organic fractions were dried with magnesium sulfate, filtrated and then concentrated

Synthesis of novel 5-alkyl/aryl/heteroaryl substituted diethyl 3,4-dihydro-2H-pyrrole-4,4-dicarboxylates by aziridine ring expansion of 2-[(aziridin-1-yl)-1-alkyl/aryl/heteroaryl-methylene]malonic acid diethyl esters

• Satish S. More,
• T. Krishna Mohan,
• Y. Sateesh Kumar,
• U. K. Syam Kumar and
• Navin B. Patel

Beilstein J. Org. Chem. 2011, 7, 831–838, doi:10.3762/bjoc.7.95

• -chloromethylene)malonates 19. The chloro alkenyl malonates 19 were synthesized in two steps from diethyl malonate and acid chlorides. The acylation of diethyl malonate was carried out with various acyl chlorides in the presence of anhydrous magnesium chloride and triethylamine, as per the reaction conditions

An overview of the key routes to the best selling 5-membered ring heterocyclic pharmaceuticals

• Marcus Baumann,
• Ian R. Baxendale,
• Steven V. Ley and
• Nikzad Nikbin

Beilstein J. Org. Chem. 2011, 7, 442–495, doi:10.3762/bjoc.7.57

• chloride 89 are added concurrently from two different sides of the reactor to stop these reagents reacting with each other. This method of adding the reagents circumvents the necessity to isolate the magnesium salt of the indole and increases the yield from 50 to 82%. The carbonyl group of the proline side

Oxidative allylic rearrangement of cycloalkenols: Formal total synthesis of enantiomerically pure trisporic acid B

• Silke Dubberke,
• Muhammad Abbas and
• Bernhard Westermann

Beilstein J. Org. Chem. 2011, 7, 421–425, doi:10.3762/bjoc.7.54

• cyclohexenone (+)-7, which is the key building block in our synthesis, was the incorporation of a C2 unit into β-ketoester (−)-1c (Scheme 3). This was achieved by adding ethynyl magnesium bromide in THF at room temperature. The cyclohexenol (+)-6 can be isolated in 79% yield with a diastereomeric ratio of 96:4

• -dimethylcyclohex-3-ene-1-carboxylate (6). To a solution of (−)-1c (0.50 g, 2.75 mmol) in THF (5 mL), was added dropwise over a period of 30 min ethynyl magnesium bromide (0.5 M in THF; 9.05 mL, 4.53 mmol) at 20 °C. Stirring at this temperature was continued for 1 h, and then the reaction mixture was quenched by