Formal total syntheses of classic natural product target molecules via palladium-catalyzed enantioselective alkylation

• Yiyang Liu,
• Marc Liniger,
• Ryan M. McFadden,
• Jenny L. Roizen,
• Jacquie Malette,
• Corey M. Reeves,
• Douglas C. Behenna,
• Masaki Seto,
• Jimin Kim,
• Justin T. Mohr,
• Scott C. Virgil and
• Brian M. Stoltz

Beilstein J. Org. Chem. 2014, 10, 2501–2512, doi:10.3762/bjoc.10.261

• , terminal alcohol silylation, and tertiary alcohol dehydration, affording methylene cyclohexane (−)-20. Treatment of this silyl ether with Jones reagent simultaneously cleaved the silyl group and oxidized the resulting alcohol, furnishing carboxylic acid (−)-12 in 65% yield. With this enantioenriched acid

• Novak routes to quinic acid (21). Conversion of dioxanone 25 to a cyclohexylimine enabled alkylation via a metalloenamine. On acidic work-up, imine hydrolysis furnished an alkylated dioxanone in good yield. The targeted silyl enol ether 26 was prepared by thermodynamic silylation in 66% yield [43

The effect of permodified cyclodextrins encapsulation on the photophysical properties of a polyfluorene with randomly distributed electron-donor and rotaxane electron-acceptor units

• Aurica Farcas,
• Ana-Maria Resmerita,
• Pierre-Henri Aubert,
• Flavian Farcas,
• Iuliana Stoica and
• Anton Airinei

Beilstein J. Org. Chem. 2014, 10, 2145–2156, doi:10.3762/bjoc.10.222

• . The roughness exponent, α, was calculated as the slope of roughness versus scan length in a double logarithmic plot, log(Lsc), before saturation. Synthesis of TMS-β-CD and TMS-γ-CD: TMS-β-CD and TMS-γ-CD were obtained by the silylation of native β-CD and γ-CD with 1-trimethylsilylimidazole [32

Synthesis of phosphoramidites of isoGNA, an isomer of glycerol nucleic acid

• Keunsoo Kim,
• Venkateshwarlu Punna,
• Phaneendrasai Karri and
• Ramanarayanan Krishnamurthy

Beilstein J. Org. Chem. 2014, 10, 2131–2138, doi:10.3762/bjoc.10.220

• . Results and Discussion Initial synthetic routes We started with commercially available (S)-solketal (1), which was protected as the benzyl ether 2. Ketal deprotection followed by the silylation of the primary hydroxy group with tert-butyldiphenylsilyl chloride provided the substrate 4, which is suitable

Synthesis of zearalenone-16-β,D-glucoside and zearalenone-16-sulfate: A tale of protecting resorcylic acid lactones for regiocontrolled conjugation

• Hannes Mikula,
• Julia Weber,
• Dennis Svatunek,
• Philipp Skrinjar,
• Gerhard Adam,
• Rudolf Krska,
• Christian Hametner and
• Johannes Fröhlich

Beilstein J. Org. Chem. 2014, 10, 1129–1134, doi:10.3762/bjoc.10.112

• regiocontrolled glucosylation of resorcylic acid esters and lactones. Regioselective silylation of 9 and ZEN (1) was readily achieved affording compounds 21 and 22 (14-TIPS-ZEN), respectively, in nearly quantitative yields by reaction with TIPS-Cl and imidazole in dry CH2Cl2. Applying this strategy we were

Deoxygenative gem-difluoroolefination of carbonyl compounds with (chlorodifluoromethyl)trimethylsilane and triphenylphosphine

• Fei Wang,
• Lingchun Li,
• Chuanfa Ni and
• Jinbo Hu

Beilstein J. Org. Chem. 2014, 10, 344–351, doi:10.3762/bjoc.10.32

• silylation of ozone-depleting-substances bromotrifluoromethane (CF3Br) [35], bromochlorodifluoromethane (CF2BrCl) [36][37], and dibromodifluoromethane (CF2Br2) [36][37] with chlorotrimethylsilane (TMSCl). In recent years, Prakash and co-workers have discovered two Freon-free methods for the synthesis of

• , 3JP-F = 97 Hz, 3JF-H = 3.3 Hz, 1F; δ −106.6, ddd, 2JF-F = 298 Hz, 3JP-F = 101 Hz, 3JF-H = 24 Hz, 1F) was detected as the major product (for details, see Supporting Information File 1). The formation of 4 is supposed to arise from a ready silylation of the addition intermediate betaine 3 by TMSBr. When

Synthesis of the B-seco limonoid core scaffold

• Hanna Bruss,
• Hannah Schuster,
• Rémi Martinez,
• Markus Kaiser,
• Andrey P. Antonchick and
• Herbert Waldmann

Beilstein J. Org. Chem. 2014, 10, 194–208, doi:10.3762/bjoc.10.15

• (−)-quinic acid (16) according to the route reported by Arthurs et al. [40] with minor modifications. After Baylis–Hillman reaction and subsequent silylation of the resulting free primary hydroxy group, substrate-controlled α-methylation of the lithium enolate proceeded with full stereocontrol [41][42

• and Baylis–Hillman reaction proceeded uneventfully to afford compound 62. Deprotection of the butane-2,3-diacetal under acidic conditions followed by selective silylation of the primary and the allylic hydroxy groups gave alcohol 63. The second quaternary center of the bicyclic C–D system 66 was

• control [58]. The configuration was determined by the high coupling constant (JH4/H5 = 12.6 Hz) indicating the trans-diaxial orientation of H4 and H5. Silylation of the primary hydroxy group afforded compound 84 that was converted into the epoxide with complete stereocontrol [59]. The epoxide underwent

Recent applications of the divinylcyclopropane–cycloheptadiene rearrangement in organic synthesis

• Sebastian Krüger and
• Tanja Gaich

Beilstein J. Org. Chem. 2014, 10, 163–193, doi:10.3762/bjoc.10.14

• 211 in solvent-dependent ratios. The sole product arising from the desired DVCPR via 208'' is the major product 210. The two remaining products arise from trans-silylation and fragmentation (208' to 209) or via ionic intermediate 208''' and fragmentation to give 211. The different product distribution

Total synthesis of the endogenous inflammation resolving lipid resolvin D2 using a common lynchpin

• John Li,
• May May Leong,
• Alastair Stewart and
• Mark A. Rizzacasa

Beilstein J. Org. Chem. 2013, 9, 2762–2766, doi:10.3762/bjoc.9.310

• the ylide derived from 9 provided the alkene 10 [9] with excellent stereoselectivity. Oxidation of 10 with Dess–Martin periodinane then afforded aldehyde 7. The phosphonium salt 6 [21][22] was produced from propargyl bromide via silylation of the derived sodium salt with TIPSCl followed by reaction

• )-Mosher ester [28][29]. Integration of the 1H MMR spectrum indicated the e.r. was 93.7:6.3 and Mosher analysis (See Supporting Information File 2 for details) confirmed the stereochemistry of the new asymmetric center of the major enantiomer as S in accord with the predicted outcome [25]. Silylation gave

The total synthesis of D-chalcose and its C-3 epimer

• Jun Sun,
• Song Fan,
• Zhan Wang,
• Guoning Zhang,
• Kai Bao and
• Weige Zhang

Beilstein J. Org. Chem. 2013, 9, 2620–2624, doi:10.3762/bjoc.9.296

• . Aldehyde IV would be generated from commercial ethyl (R)-3-hydroxybutyrate (1) via reduction. The synthesis began by protecting the commercial ethyl (R)-3-hydroxybutyrate (1) using a nearly quantitative silylation of the free hydroxy group under classical conditions (TBDPSCl, imidazole, DMF, rt) [17] to

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

• developed, initial masking of the acid (1.104) is achieved by silylation with subsequent borane chelate formation. Addition of the amine nucleophile 1.105 under basic conditions then renders the desired product in high yield. The available patent literature however does not comment on regioselectivity

Flexible synthesis of anthracycline aglycone mimics via domino carbopalladation reactions

• Markus Leibeling and
• Daniel B. Werz

Beilstein J. Org. Chem. 2013, 9, 2194–2201, doi:10.3762/bjoc.9.258

• terminal silyl substituent (or terminal hydrogen) at one side and a silane moiety at the other (Scheme 4). It is possible to access differently substituted dialkynes 16 by the silylation of 16e. This approach was not considered because of the low tolerance of 16e against base and the expensive starting

A Lewis acid-promoted Pinner reaction

• Dominik Pfaff,
• Gregor Nemecek and
• Joachim Podlech

Beilstein J. Org. Chem. 2013, 9, 1572–1577, doi:10.3762/bjoc.9.179

• used. A possible mechanism of this reaction is given in Scheme 7. Double silylation leads to the formation of a good leaving group and the highly electrophilic benzylic carbon is attacked by the nitrile yielding a nitrilium cation. The reaction is finalized by hydrolysis furnishing the carboxamide

• . Apparently the double silylation is not possible with electron-deficient substrates. Conclusion The Lewis acid-promoted Pinner reaction is a mild and chemoselective alternative for the synthesis of carboxylic esters starting with alcohols and nitriles. The esterification of primary aliphatic alcohols is

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

• mesylate derived from known alcohol 9 [24] (Scheme 2). Then, coupling of methyl γ-hydroxybutyrate (10) [25] with lithiated (+)-pseudoephedrine afforded amide 11 in excellent yield. Selective silylation of the primary alcohol of 11 delivered substrate 12. Alkylation of the enolate derived from 12 with 8

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

• full resolution. Assuming that the hydrogen atom at the substituted end of 3 is not replaced by the TMS-group for steric and electronic reasons, four monosilylated products are possible, i.e., silylation at the unsubstituted end of 3 leading to two diastereomers. General structure 21 (Scheme 4

• ) accounts for our experimental observations. Regardless of the exact structures of the silylation products 21, we did not observe any selectivity in this transformation. Quenching of 4 with N,N-dimethylformamide (DMF) and acetone Metalated allenes are known to be converted into allenic aldehydes on DMF

• -yielding synthetic transformations from simple substrates, are useful starting materials for the preparation of a plethora of novel organic compounds. The alkylated conjugated bisallenes 1– 3 as model systems for polar reactions. Alkylation and silylation of 2. Allylation of the monoanion 4. Metalation

Reactions of salicylaldehyde and enolates or their equivalents: versatile synthetic routes to chromane derivatives

• Ishmael B. Masesane and
• Zelalem Yibralign Desta

Beilstein J. Org. Chem. 2012, 8, 2166–2175, doi:10.3762/bjoc.8.244

• [28], as catalytic reagents for silylation of alcohols, phenols, and thiols using hexamethyldisilazane [29], in conversion of urazoles to triazolinediones [30], and in oxidation of 1,3,5-trisubstituted pyrazolines [31]. Molecular sieves have been used as solid-phase catalysts in the preparation of 2

Synthesis and characterization of low-molecular-weight π-conjugated polymers covered by persilylated β-cyclodextrin

• Aurica Farcas,
• Ana-Maria Resmerita,
• Andreea Stefanache,
• Mihaela Balan and
• Valeria Harabagiu

Beilstein J. Org. Chem. 2012, 8, 1505–1514, doi:10.3762/bjoc.8.170

• and methods PS-βCD was obtained by the silylation of native βCD with 1-trimethylsilylimidazole [36]. 9,9-dioctylfluorene-2,7-bis(trimethylene borate) (DOF, 97%), tetrakis(triphenylphosphane)palladium (99%), and 5,5'-dibromo-2,2'-bithiophene (BT) were purchased from Aldrich and used as received; 3

Stereoselective synthesis of trans-fused iridoid lactones and their identification in the parasitoid wasp Alloxysta victrix, Part I: Dihydronepetalactones

• Nicole Zimmermann,
• Robert Hilgraf,
• Lutz Lehmann,
• Daniel Ibarra and
• Wittko Francke

Beilstein J. Org. Chem. 2012, 8, 1246–1255, doi:10.3762/bjoc.8.140

• furnish the primary alcohol 31, which upon oxidation will yield the corresponding aldehyde that can be epimerized to the diastereomers 32/32* as shown above. Subsequent reduction of 32/32*, silylation of the resulting primary alcohols and saponification will produce a mixture of the diastereoisomers 33/33

Synthesis and antifungal properties of papulacandin derivatives

• Marjolein van der Kaaden,
• Eefjan Breukink and
• Roland J. Pieters

Beilstein J. Org. Chem. 2012, 8, 732–737, doi:10.3762/bjoc.8.82

• synthesis started with the saponification of 15, followed by the protection of O-4 and O-6 by using di-tert-butylsilyl bis(trifluoromethanesulfonate). Subsequent protection of O-3 with TES-Cl, gave the fully protected glucal 18. According to Denmark et al. [31], lithiation and silylation of 18 should give

Cyanoethylation of the glucans dextran and pullulan: Substitution pattern and formation of nanostructures and entrapment of magnetic nanoparticles

• Kathrin Fiege,
• Heinrich Lünsdorf,
• Sevil Atarijabarzadeh and
• Petra Mischnick

Beilstein J. Org. Chem. 2012, 8, 551–566, doi:10.3762/bjoc.8.63

• of iron oxide nanoparticles, various portions were mixed with the cyanoethylpolysaccharides before dialysis. Polysaccharide structures of pullulan and dextran cyanoethylation with acrylonitrile and NaOH as catalyst; sample preparation for GLC/GLC–MS analysis: depolymerization and silylation. ATR–IR

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

• quantitatively. 3.1.4 Silyl derivatives: In 1996, Hampton investigated the selectivity of silylation on oxacalix[3]arenes to determine the influence of the group in the para-position, the nature of the silylating agent and the reaction conditions [41]. Unsurprisingly, the formation of the partial-cone was

Efficient syntheses of 25,26-dihydrodictyostatin and 25,26-dihydro-6-epi-dictyostatin, two potent new microtubule-stabilizing agents

• María Jiménez,
• Wei Zhu,
• Andreas Vogt,
• Billy W. Day and
• Dennis P. Curran

Beilstein J. Org. Chem. 2011, 7, 1372–1378, doi:10.3762/bjoc.7.161

• starting from commercially available pseudoephedrine amide 10. The syntheses of the bottom fragments 6a and 6b were achieved by applying the previously reported cross-metathesis reactions of readily available 20a,b with (2Z,4E)-methyl hexa-2,4-dienoate followed by silylation to provide 21a,b [39]. These

Amine-linked diglycosides: Synthesis facilitated by the enhanced reactivity of allylic electrophiles, and glycosidase inhibition assays

• Ian Cumpstey,
• Jens Frigell,
• Elias Pershagen,
• Tashfeen Akhtar,
• Elena Moreno-Clavijo,
• Inmaculada Robina,
• Dominic S. Alonzi and
• Terry D. Butters

Beilstein J. Org. Chem. 2011, 7, 1115–1123, doi:10.3762/bjoc.7.128

• unsaturated glycoside 4 to be achieved; phosphomolybdic acid [32] gave the product (α:β, 8:1) in 63% yield. Deacetylation of 4 and regioselective silylation of the primary alcohol gave the threo allylic alcohol 2. The sulfonamide nucleophiles 6, 7 and 9 were prepared from the corresponding amines 5 [33] and 8

Synthesis, reactivity and biological activity of 5-alkoxymethyluracil analogues

• Lucie Brulikova and
• Jan Hlavac

Beilstein J. Org. Chem. 2011, 7, 678–698, doi:10.3762/bjoc.7.80

• protected by the silylation with hexamethyldisilazane. Subsequently, this modified uracil was reacted with protected 2-deoxyribose in the presence of SnCl4. Finally, protected α- and β-anomers 111 and 109 were treated with methanolic sodium methoxide to afford the nucleosides 112 and 110. Synthesis of

Synthesis of glycoconjugate fragments of mycobacterial phosphatidylinositol mannosides and lipomannan

• Benjamin Cao,
• Jonathan M. White and
• Spencer J. Williams

Beilstein J. Org. Chem. 2011, 7, 369–377, doi:10.3762/bjoc.7.47

• Glycosidation of 8-azidooctan-1-ol (Supporting Information File 2) using glycosyl bromide 11 [36] in the presence of AgOTf, and debenzoylation of the crude product gave 12 in 81% yield over 2 steps (Scheme 2). Regioselective silylation of the primary alcohol of 12 with TPSCl followed by benzoylation of the

Chiral recognition of macromolecules with cyclodextrins: pH- and thermosensitive copolymers from N-isopropylacrylamide and N-acryloyl-D/L-phenylalanine and their inclusion complexes with cyclodextrins

• Sabrina Gingter,
• Ella Bezdushna and
• Helmut Ritter

Beilstein J. Org. Chem. 2011, 7, 204–209, doi:10.3762/bjoc.7.27

• conditions (Scheme 1). The molar weight distribution of polymers 3D and 3L were determined by gel permeation chromatography (GPC) after silylation of the free carboxylic groups with trimethylchlorosilane. The resulting copolymer 3D, 3L (1:20) is soluble in water below the critical solution temperature (LCST