Integration of enabling methods for the automated flow preparation of piperazine-2-carboxamide

• Richard J. Ingham,
• Claudio Battilocchio,
• Joel M. Hawkins and
• Steven V. Ley

Beilstein J. Org. Chem. 2014, 10, 641–652, doi:10.3762/bjoc.10.56

• which demonstrated the hydration of broad classes of nitriles by passing aqueous–organic solutions through a packed bed of manganese dioxide [21], we have found that heteroaromatic nitriles possessing a β-heteroatom can also be hydrolysed using hydrous zirconia [22][23] in a similar fashion (Figure 3

• packed beds facilitates recycling of the catalyst, providing a further cost advantage. Interestingly, we have now found that no activation of the zirconia is needed (this is the same as for nitrile hydrations with manganese dioxide, but unlike the use of zirconia as a heterogeneous catalyst for Meerwein

A new manganese-mediated, cobalt-catalyzed three-component synthesis of (diarylmethyl)sulfonamides

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

Beilstein J. Org. Chem. 2014, 10, 425–431, doi:10.3762/bjoc.10.39

• related compounds by a new manganese-mediated, cobalt-catalyzed three-component reaction between sulfonamides, carbonyl compounds and organic bromides is described. This organometallic Mannich-like process allows the formation of the coupling products within minutes at room temperature. A possible

• mechanism, emphasizing the crucial role of manganese is proposed. Keywords: carbonyl compounds; cobalt; manganese; multicomponent reaction; organic bromides; sulfonamides; Introduction (Diarylmethyl)amines constitute an important class of pharmacologically active compounds, displaying e.g. antihistaminic

• and versatility of multicomponent procedures, we describe herein a new manganese-mediated, cobalt-catalyzed three-component reaction, which circumvents the above-mentioned limitations by allowing the synthesis of an extended range of (diarylmethyl)sulfonamides (and related compounds) within minutes at

Synthesis of five- and six-membered cyclic organic peroxides: Key transformations into peroxide ring-retaining products

• Alexander O. Terent'ev,
• Dmitry A. Borisov,
• Vera A. Vil’ and
• Valery M. Dembitsky

Beilstein J. Org. Chem. 2014, 10, 34–114, doi:10.3762/bjoc.10.6

• -dioxanes Modern approaches to the synthesis of 1,2-dioxanes are based on reactions with singlet oxygen, the oxidative coupling of carbonyl compounds and alkenes in the presence of manganese and cerium salts, the co-oxidation of alkenes and thiols with oxygen, the Isayama–Mukaiyama peroxidation, the

• -dioxan-3-ol (202) and 6-(prop-1-en-2-yl)-1,2-dioxane-3-imine (204), containing the hydroxy and imine groups, respectively (Scheme 56) [304]. 3.2. Oxidative coupling of carbonyl compounds and alkenes in the presence of manganese or cerium salts The synthesis of 1,2-dioxanes 207 is based on the addition of

• alkene 205 and oxygen to carbonyl compound 206 via the intermediate formation of carbon-centered peroxide radicals. The reaction occurs in the presence of catalytic amounts of manganese or cerium salts, which are involved in a redox cycle. It is assumed that the oxidation of β-dicarbonyl compounds

Biosynthesis of rare hexoses using microorganisms and related enzymes

• Zijie Li,
• Yahui Gao,
• Hideki Nakanishi,
• Xiaodong Gao and
• Li Cai

Beilstein J. Org. Chem. 2013, 9, 2434–2445, doi:10.3762/bjoc.9.281

• biocatalysts for industrial-scale applications. The active site in D-psicose 3-epimerase (DPEase) in the presence of D-fructose, showing the metal coordinating site and the substrate-binding site. The purple ball indicates the manganese(II) ion coordinating with key amino acid residues (Glu150, Asp183, His209

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

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

• ; Introduction Oxidation of alcohols to carbonyl compounds plays an important role in organic chemistry. The transformation is traditionally achieved by using chromium-based reagents such as the Collins reagent, activated manganese dioxide, or procedures known as the Swern [1], Pfitzner–Moffatt [2] or Parikh

Intramolecular carbonickelation of alkenes

• Rudy Lhermet,
• Muriel Durandetti and
• Jacques Maddaluno

Beilstein J. Org. Chem. 2013, 9, 710–716, doi:10.3762/bjoc.9.81

• method are the use of an easily prepared Ni(II)bipy complex in combination with manganese dust as a reducing agent, which is not air sensitive, is compatible with fragile functions, and can be used in a catalytic amount. We showed that this nickel catalysis applies to cross-coupling reactions

• for the carbonickelation of triple bonds [19], we exposed 1a–c to a mixture containing 0.2 equiv of NiBr2bipy and 2 equiv of finely grown manganese in DMF containing trace amounts of trifluoroacetic acid at 50 °C (Table 1). Disappointingly, using 1a the major new product recovered was the dimer 4a

• intramolecular carbonickelation of alkenes To a solution of aryliodide (0.5–1 mmol, 1 equiv) in anhydrous DMF (5 mL) under argon atmosphere at 50 °C is added manganese (2 equiv) followed by NiBr2bipy (0.2 equiv) then rapidly TFA (20 μL). The medium is vigorously stirred at 50 °C, and disappearance of the

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

• mersicarpine (60), is another illustration [31]. The aromatisation process in this example was incomplete under the usual conditions and required further treatment with manganese dioxide. The possibility of associating the radical chemistry of xanthates with various ionic reactions represents another powerful

Spin state switching in iron coordination compounds

• Philipp Gütlich,
• Ana B. Gaspar and
• Yann Garcia

Beilstein J. Org. Chem. 2013, 9, 342–391, doi:10.3762/bjoc.9.39

• further examples of iron(II) SCO compounds have been published [7][8][9][10][11][12][13][16][17][18][19][20][21][22][23][24][25][26][27][28], and other coordination compounds of 3d transition elements such as cobalt(II) [29][30], and to a much lesser extent cobalt(III), chromium(II), manganese(II

• ), manganese(III), and nickel were found to exhibit thermal ST phenomena [31][32][33]. But practically no example of thermal ST with coordination compounds of the 4d and 5d transition metal series has been reported up to now, which is well understood on the basis of ligand field theory [34][35]. The purpose of

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

• ). Methyl-, ethyl-, and phenylmagnesium reagents could be employed for the reaction. Aside from the examples shown in Scheme 5 and Scheme 6, alkynes that possess a directing group usually undergo syn-addition. Oshima reported manganese-catalyzed regio- and stereoselective carbomagnesiation of homopropargyl

• product (58% yield) from 44 kg of 1-phenyl-1-butyne. Oshima reported manganese-catalyzed phenylmagnesiation of a wide range of arylacetylenes (Table 4) [102]. Notably, directing groups, such as ortho-methoxy or ortho-amino groups, facilitated the reaction (Table 4, entries 2 and 3 versus entry 4

• ][139][140][141][142][143]. Manganese-catalyzed regioselective allylmetalation of allenes was reported (Scheme 53) [144]. The regioselectivity of the manganese-catalyzed addition reaction was opposite to that of the rhodium-catalyzed reactions, and vinylmagnesium intermediates were formed. Although

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

• or hydrophilicity. Recently, we reported on the identification of a novel CPP, sC18, which is derived from the C-terminus of the 18 kDa cationic antimicrobial protein. Furthermore, we demonstrated successful application of sC18 for the delivery of functionalized cyclopentadienyl manganese tricarbonyl

• -homing agent, which accumulates in hypoxic tissue [10]. Furthermore, we reported on the delivery of functionalized cyclopentadienyl manganese tricarbonyl (cymantrene) complexes with the help of sC18, which lead to significant induction of cytotoxicity in tumor cells [11][12][13], which was even more

An easily accessible sulfated saccharide mimetic inhibits in vitro human tumor cell adhesion and angiogenesis of vascular endothelial cells

• Grazia Marano,
• Claas Gronewold,
• Martin Frank,
• Anette Merling,
• Christian Kliem,
• Sandra Sauer,
• Manfred Wiessler,
• Eva Frei and
• Reinhard Schwartz-Albiez

Beilstein J. Org. Chem. 2012, 8, 787–803, doi:10.3762/bjoc.8.89

• , revealed specific docking of GSF to the same binding site as the natural peptidic ligands of this integrin. The sulfate in the molecule coordinated with one manganese ion in the binding site. These studies show that this chemically easily accessible molecule GSF, synthesized in three steps from 3,4-bis

Aryl nitrile oxide cycloaddition reactions in the presence of pinacol boronic acid ester

• Sarah L. Harding,
• Sebastian M. Marcuccio and
• G. Paul Savage

Beilstein J. Org. Chem. 2012, 8, 606–612, doi:10.3762/bjoc.8.67

• halogenation–dehydrohalogenation process is most common, several methods involving direct oxidative dehydrogenation of aldoximes have been reported, including the use of lead tetraacetate [22][23], mercury(II) acetate [24], hypervalent iodine [25][26], and manganese(IV) oxide [27]. We were interested in

Sexithiophenes as efficient luminescence quenchers of quantum dots

• Christopher R. Mason,
• Yang Li,
• Paul O’Brien,
• Neil J. Findlay and
• Peter J. Skabara

Beilstein J. Org. Chem. 2011, 7, 1722–1731, doi:10.3762/bjoc.7.202

• ), manganese dioxide (10× excess w/w, ~101 g) was added portionwise and the mixture was stirred for approximately 2 min. The mixture was filtered through a silica plug (eluted with dichloromethane) and the solvent removed under reduced pressure to afford B as a yellow solid (9.50 g, 90% from 1,3-dithiole-2

Manganese dioxide mediated one-pot synthesis of methyl 9H-pyrido[3,4-b]indole-1-carboxylate: Concise synthesis of alangiobussinine

• Jessica Baiget,
• Sabin Llona-Minguez,
• Stuart Lang,
• Simon P. MacKay,
• Colin J. Suckling and
• Oliver B. Sutcliffe

Beilstein J. Org. Chem. 2011, 7, 1407–1411, doi:10.3762/bjoc.7.164

• analogues containing the carboline heterocyclic moiety. A manganese dioxide mediated one-pot method starting with an activated alcohol and consisting of alcohol oxidation, Pictet–Spengler cyclisation, and oxidative aromatisation, offers a convenient process that allows access to β-carbolines. This one-pot

• costs and in addition has the advantage that there is less waste associated with reactions of this nature and therefore less environmental impact. Taylor et al. [16][17][18][19] have shown manganese dioxide to be a robust reagent for carrying out oxidations on a wide range of activated alcohols. They

• glycolate (1) to manganese dioxide would result in the formation of aldehyde 2. This can then undergo a condensation process with tryptamine (3) allowing the generation of imine 4. This intermediate is set up appropriately to undergo a Pictet–Spengler cyclization reaction resulting in the formation of

Multicomponent reaction access to complex quinolines via oxidation of the Povarov adducts

• Esther Vicente-García,
• Rosario Ramón,
• Sara Preciado and
• Rodolfo Lavilla

Beilstein J. Org. Chem. 2011, 7, 980–987, doi:10.3762/bjoc.7.110

• tetrahydroquinolines obtained through the Povarov multicomponent reaction have been oxidized to the corresponding quinoline, giving access to a single product through a two-step sequence. Several oxidizing agents were studied and manganese dioxide proved to be the reagent of choice, affording higher yields, cleaner

• reactions and practical protocols. Keywords: manganese dioxide; multicomponent reactions; oxidation; Povarov; quinolines; tetrahydroquinolines; Introduction Heterocycles are ubiquitous scaffolds in pharmaceuticals, natural products and biologically active compounds. Quinoline systems in particular

• aromatic species. The literature contains scattered reports of the use of oxidants for this transformation: 2,3-Dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), ceric ammonium nitrate (CAN), nitrobenzene, elemental sulfur, palladium and manganese dioxide among others, all of them far from being ideally suited