Beyond catalyst deactivation: cross-metathesis involving olefins containing N-heteroaromatics

• Kevin Lafaye,
• Cyril Bosset,
• Lionel Nicolas,
• Amandine Guérinot and
• Janine Cossy

Beilstein J. Org. Chem. 2015, 11, 2223–2241, doi:10.3762/bjoc.11.241

• of the reasons of this success is the discovery of well-defined, stable, highly chemoselective and now commercially available catalysts particularly the Grubbs catalysts 1st and 2nd generation (GI and GII) and the Grubbs–Hoveyda II catalyst (G-HII) (Figure 1) [13]. A large array of functional groups

Efficient synthesis of π-conjugated molecules incorporating fluorinated phenylene units through palladium-catalyzed iterative C(sp²)–H bond arylations

• Fatiha Abdelmalek,
• Fazia Derridj,
• Safia Djebbar,
• Jean-François Soulé and
• Henri Doucet

Beilstein J. Org. Chem. 2015, 11, 2012–2020, doi:10.3762/bjoc.11.218

• very chemoselective, as the reactions only involve desulfitative coupling even in the presence of C–halogen bonds [57], which allow further orthogonal transformations. Moreover, a wide scope of benzenesulfonyl chlorides is commercially available at an affordable cost. We report herein, a new synthetic

Recent applications of ring-rearrangement metathesis in organic synthesis

• Sambasivarao Kotha,
• Milind Meshram,
• Priti Khedkar,
• Shaibal Banerjee and
• Deepak Deodhar

Beilstein J. Org. Chem. 2015, 11, 1833–1864, doi:10.3762/bjoc.11.199

• dimerized 16-membered ring product 101 in 57% yield, which was generated by a RRM–dimerization sequence and its monomer 100 in 14% yield along with 99 in 26% yield (Scheme 20). Bicyclo[2.2.1]heptene derivatives Holtsclaw and Koreeda [25] have explored a chemoselective RRM of the enone containing norbornene

The synthesis of active pharmaceutical ingredients (APIs) using continuous flow chemistry

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2015, 11, 1194–1219, doi:10.3762/bjoc.11.134

• pharmaceutical. For this endeavour dihydroartimisinic acid (56), an advanced building block that is available via chemoselective batch reduction of bioengineered artemisinic acid (57), was chosen as the starting point. The key transformations to yield artemisinin thus demanded a reaction cascade including a

Cathodic hydrodimerization of nitroolefins

• Michael Weßling and
• Hans J. Schäfer

Beilstein J. Org. Chem. 2015, 11, 1163–1174, doi:10.3762/bjoc.11.131

• applied. The reaction is chemoselective as only the double bond but not the nitro group undergoes reaction, is regioselective as a ß,ß-coupling with regard to the nitro group and forms preferentially two out of six possible diastereomers as major products. Keywords: cathodic hydrodimerization; C–C bond

• different 1-aryl and mostly 2-methyl substituents. Likewise the cathodic cyclization of a dinitrodiene could be realized. The dimerization is chemoselective: the fairly easy reduction of the nitro group can be suppressed and aryl C–Cl and aryl C–F bonds are not cleaved. Additionally a good regioselectivity

Regioselective synthesis of chiral dimethyl-bis(ethylenedithio)tetrathiafulvalene sulfones

• Flavia Pop and
• Narcis Avarvari

Beilstein J. Org. Chem. 2015, 11, 1105–1111, doi:10.3762/bjoc.11.124

• -dibromoethane to afford the chiral monosulfones (S,S)-1 and (R,R)-1. Thus, the oxidation of one of the outer sulfur atoms takes place in situ as the intermediate DM-EDT-TTF dithiolates are reactive towards oxygen. Interestingly, the reaction is regio- and chemoselective, as only compound 1 was isolated after

Highly selective palladium–benzothiazole carbene-catalyzed allylation of active methylene compounds under neutral conditions

• Antonio Monopoli,
• Pietro Cotugno,
• Carlo G. Zambonin,
• Francesco Ciminale and
• Angelo Nacci

Beilstein J. Org. Chem. 2015, 11, 994–999, doi:10.3762/bjoc.11.111

• -2-ylidene complex I was found to be a chemoselective catalyst for the Tsuji–Trost allylation of active methylene compounds carried out under neutral conditions and using carbonates as allylating agents. The proposed protocol consists in a simplified procedure adopting an in situ prepared catalyst

• chemoselective, but occurs under very mild temperature conditions and the operating procedure is further simplified employing the catalyst prepared in situ. In addition, benzothiazol-2-ylidene ligands proved to be not only more efficient in terms of selectivity than the toxic phosphanes but can compete

Orthogonal dual-modification of proteins for the engineering of multivalent protein scaffolds

• Michaela Mühlberg,
• Michael G. Hoesl,
• Christian Kuehne,
• Jens Dernedde,
• Nediljko Budisa and
• Christian P. R. Hackenberger

Beilstein J. Org. Chem. 2015, 11, 784–791, doi:10.3762/bjoc.11.88

• use of chemical labeling methods to study structure and function of proteins in vitro and in vivo, chemoselective conjugation techniques are also used to functionalize artificial protein scaffolds, such as viral capsids [5][6][7]. Such templates have self-assembled hierarchical structures that allow

• engineer multivalent glycoprotein conjugates, we have used the incorporation of non-canonical amino acids (NCAA) [13] by supplementation based incorporation (SPI) [14][15][16][17] in auxotroph expression systems followed by the chemoselective Cu-catalyzed azide–alkyne cycloaddition (CuAAC) to attach

• carbohydrate ligands to the protein barstar [18]. In the current study, we aimed to extend this approach to the dual modification of proteins using a combination of two chemoselective, orthogonal conjugation reactions for the introduction of glycan ligands and biotin to a protein. Our main objective in this

DNA display of glycoconjugates to emulate oligomeric interactions of glycans

• Alexandre Novoa and
• Nicolas Winssinger

Beilstein J. Org. Chem. 2015, 11, 707–719, doi:10.3762/bjoc.11.81

• different chemistries used in the glycoconjugations and the different strategies used to display the glycans with DNA templates. Review Glycan–DNA conjugates An initial solution used in the pioneering work of Kobayashi [17] for nucleic acid–glycan conjugation was the chemoselective reaction of p

Chemoselective O-acylation of hydroxyamino acids and amino alcohols under acidic reaction conditions: History, scope and applications

• Tor E. Kristensen

Beilstein J. Org. Chem. 2015, 11, 446–468, doi:10.3762/bjoc.11.51

• renders possible chemoselective O-acylation, furnishing the corresponding side-chain esters directly, on multigram-scale, in a single step, and without chromatographic purification. Assuming a certain degree of stability under acidic reaction conditions, the method is also applicable for a number of

• more elaborate procedures for chemoselective O-acylation reactions, spur its further development, and finally to chronicle the informative, but poorly documented history of its development. Keywords: amino alcohols; chemoselectivity; DOPA; hydroxyamino acids; hydroxyproline; O-acylation

• , thus enabling direct chemoselective conversion of the hydroxyamino acid to the O-acyl derivative. Precipitation of the reaction product as a (preferably) crystalline amine salt would further aid the convenience and attractiveness of this methodology. But, such methodology has in fact existed for a

Direct access to pyrido/pyrrolo[2,1-b]quinazolin-9(1H)-ones through silver-mediated intramolecular alkyne hydroamination reactions

• Hengshuai Wang,
• Shengchao Jiao,
• Kerong Chen,
• Xu Zhang,
• Linxiang Zhao,
• Dan Liu,
• Yu Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2015, 11, 416–424, doi:10.3762/bjoc.11.47

• elaborating the synthesis of fused quinazolinone derivatives. Herein, we present our recent findings of the synthesis of fused pyrrolo[2,1-b]quinazolin-9(1H)-ones by a silver-mediated chemoselective and regioselective intramolecular hydroamination cyclization (Scheme 1). Results and Discussion To establish

A simple and efficient method for the preparation of 5-hydroxy-3-acyltetramic acids

• Johanna Trenner and
• Evgeny V. Prusov

Beilstein J. Org. Chem. 2015, 11, 323–327, doi:10.3762/bjoc.11.37

• chemoselective reduction of the corresponding maleimides [5] and oxidation of pyrrolinones was reported by Clayden [6]. Therefore, we decided to develop a simple method to produce these interesting compounds. At first we prepared three nitrogen-protected 3-acyltetramic acids (7–9) according to the Matsuo [7

Synthesis of antibacterial 1,3-diyne-linked peptoids from an Ugi-4CR/Glaser coupling approach

• Martin C. N. Brauer,
• Ricardo A. W. Neves Filho,
• Bernhard Westermann,
• Ramona Heinke and
• Ludger A. Wessjohann

Beilstein J. Org. Chem. 2015, 11, 25–30, doi:10.3762/bjoc.11.4

• synthesized through an Ugi four-component reaction (U-4CR) followed by a copper-catalysed alkyne homocoupling (Glaser reaction). The short and chemoselective reaction sequence allows generating diverse (pseudo) dimeric peptoids. A combinatorial version allows the one-pot preparation of, e.g., six-compound

A carbohydrate approach for the formal total synthesis of (−)-aspergillide C

• Pabbaraja Srihari,
• Namballa Hari Krishna,
• Ydhyam Sridhar and
• Ahmed Kamal

Beilstein J. Org. Chem. 2014, 10, 3122–3126, doi:10.3762/bjoc.10.329

• the desired trans-olefin geometry, but required a one-carbon homologation to access the matched seco acid 4. To achieve the one-carbon homologation with appropriate functionality, it was necessary to perform sequential chemoselective transformations. In this regard, we proceeded by selectively

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

• was crossed with methyl vinyl ketone in 62% yield [34]. Reduction of enone 34 was achieved in the presence of Pd/C with H2 in EtOAc to furnish diketone 35 [34]. Chemoselective Wittig mono-olefination of 35 provided ω-enone (−)-32, spectroscopically identical to the material in Danishefsky’s racemic

A modular phosphate tether-mediated divergent strategy to complex polyols

• Paul R. Hanson,
• Susanthi Jayasinghe,
• Soma Maitra,
• Cornelius N. Ndi and
• Rambabu Chegondi

Beilstein J. Org. Chem. 2014, 10, 2332–2337, doi:10.3762/bjoc.10.242

• starting from trienes 5 and 6 in a two-pot operation (Scheme 2). The first operation entailed a one-pot, sequential RCM/CM/chemoselective hydrogenation protocol [32], yielding two bicyclo[n.3.1]phosphate intermediates 8 and 9, and a second pot LiAlH4 reduction to provide the Z-configured tetraol subunits

• for the successful CM reactions in order to avoid the formation of isomerized ketone byproducts. Subsequent chemoselective diimide reduction with o-nitrobenzenesulfonylhydrazine (o-NBSH) [38][39][40] in CH2Cl2 at room temperature afforded bicyclo[5.3.1]phosphate 8 in 33% overall yield, representing а

• triene 6, a one-pot RCM/CM/chemoselective H2 was performed to obtain the bicyclo[4.3.1]phosphate 9 in 40% yield over 3 reaction steps in a one-pot operation (72% avg/rxn). In this example, the RCM reaction was performed in dicholoroethane (DCE) at 70 °C for 2 h, since lower reactivity was observed in

Reversibly locked thionucleobase pairs in DNA to study base flipping enzymes

• Christine Beuck and
• Elmar Weinhold

Beilstein J. Org. Chem. 2014, 10, 2293–2306, doi:10.3762/bjoc.10.239

• of base flipping to the overall binding affinity of the DNA adenine-N6 MTase from Thermus aquaticus (M.TaqI) as an example. Results Selective cross-linking of thionucleobase pairs in DNA by bis-alkylation with 1,2-diiodoethane Thionucleobases are excellent soft nucleophiles, and chemoselective

De novo macrolide–glycolipid macrolactone hybrids: Synthesis, structure and antibiotic activity of carbohydrate-fused macrocycles

• Richard T. Desmond,
• Anniefer N. Magpusao,
• Chris Lorenc,
• Jeremy B. Alverson,
• Nigel Priestley and
• Mark W. Peczuh

Beilstein J. Org. Chem. 2014, 10, 2215–2221, doi:10.3762/bjoc.10.229

• remainder of the synthesis separately. Transacetalization of the C4,C6-O-benzylidene protecting group in methanol provided diols 9a and 9b, respectively in nearly quantitative yields. Chemoselective, DCC-mediated acylation of the primary alcohol group of 9a and 9b at 0 °C with pentenoic acid gave 10a (58

• group. This was possible by virtue of the original C4,C6 diol 9a; chemoselective acylation of the primary alcohol (C6’) unit left the C4’ alcohol available for additional reactions. Analogs were prepared under precedented conditions to give 11–16 in good yields. Analog 17, which contains a saturated

Palladium-catalysed cyclisation of alkenols: Synthesis of oxaheterocycles as core intermediates of natural compounds

• Miroslav Palík,
• Jozef Kožíšek,
• Peter Koóš and
• Tibor Gracza

Beilstein J. Org. Chem. 2014, 10, 2077–2086, doi:10.3762/bjoc.10.216

• DIBAL-H [32] providing the known allylic alcohol in very good yield. Following protection of the primary alcohol yielded fully protected alkene-tetraol and subsequent chemoselective removal of the acetonide protecting group in one pot led to substrates 24–26. The synthesis of substrate 28 bearing a

Application of cyclic phosphonamide reagents in the total synthesis of natural products and biologically active molecules

• Thilo Focken and
• Stephen Hanessian

Beilstein J. Org. Chem. 2014, 10, 1848–1877, doi:10.3762/bjoc.10.195

• tetrahydropyran 92 as key intermediate of the synthesis. Oxidation of 92 and heating to 220 ºC resulted in a concurrent selenoxide elimination and Claisen rearrangement to give 93 via intermediate 81. Face-selective Simmons–Smith cyclopropanation, reduction of both carbonyl groups, and chemoselective oxidation of

Triazol-substituted titanocenes by strain-driven 1,3-dipolar cycloadditions

• Andreas Gansäuer,
• Andreas Okkel,
• Lukas Schwach,
• Laura Wagner,
• Anja Selig and
• Aram Prokop

Beilstein J. Org. Chem. 2014, 10, 1630–1637, doi:10.3762/bjoc.10.169

• structural feature [31]. The gelation ability of the neutral ester-substituted titanocenes critically depends on the steric demand of the substituents on the cyclopentadienyl ligands. The carboxylates are valuable complexes for mediating highly chemoselective Barbier type allylations [32][33]. These findings

Orthogonal dual thiol–chloroacetyl and thiol–ene couplings for the sequential one-pot assembly of heteroglycoclusters

• Michele Fiore,
• Gour Chand Daskhan,
• Baptiste Thomas and
• Olivier Renaudet

Beilstein J. Org. Chem. 2014, 10, 1557–1563, doi:10.3762/bjoc.10.160

• binary combinations of α-D-Man or β-D-GlcNAc, thus providing rapid access to attractive heteroglycosylated platforms for diverse biological applications. Keywords: chemoselective ligation; heteroglycocluster; multivalency; multivalent glycosystems; one-pot synthesis; Introduction Multivalent

• alkyne–azide cycloaddition (CuAAC) [18] or SN2 reaction [19]. In addition, orthogonal chemoselective ligations were proved more attractive strategies to prepare hGCs in high yields, in part because they require less synthetic and purification steps. For example, oxime and CuAAC ligations have been used

• yield after HPLC purification and gave the expected multicharged ions by electrospray mass spectrometry (Table 1). Conclusion In summary, we have developed the first synthesis of hGCs using a one-pot orthogonal chemoselective route by using dual thiol–chloroacetyl and thiol–ene couplings. The

Selective allylic hydroxylation of acyclic terpenoids by CYP154E1 from Thermobifida fusca YX

• Anna M. Bogazkaya,
• Clemens J. von Bühler,
• Sebastian Kriening,
• Alexandrine Busch,
• Alexander Seifert,
• Jürgen Pleiss,
• Sabine Laschat and
• Vlada B. Urlacher

Beilstein J. Org. Chem. 2014, 10, 1347–1353, doi:10.3762/bjoc.10.137

• mutants were more regio- and chemoselective (except for V286A with geranylacetone (9)). Highest selectivities were observed with the following variants: V286F led mainly to 7-hydroxygeranylacetone (11, 60% of the total product) and V286A produced predominantly 12-hydroxynerylacetone (16, 75% of total

• type activity [20]. Conclusion Finally, in this study we investigated the application of CYP154E1 as regio- and chemoselective biocatalyst for the synthesis of allylic alcohols of acyclic terpenoids. Highest regioselectivity towards geraniol (1) and nerol (2) was observed with the wild type enzyme

Automated solid-phase peptide synthesis to obtain therapeutic peptides

• Veronika Mäde,
• Sylvia Els-Heindl and
• Annette G. Beck-Sickinger

Beilstein J. Org. Chem. 2014, 10, 1197–1212, doi:10.3762/bjoc.10.118

• obtain the desired polypeptide. The condensation can occur via chemoselective ligation techniques such as native chemical ligation (NCL), expressed protein ligation (EPL), Staudinger ligation or click reaction [8][79]. Recently, peptide drugs as the pharmaceuticals Enfuvirtide, Eptifibitide and

Atherton–Todd reaction: mechanism, scope and applications

• Stéphanie S. Le Corre,
• Mathieu Berchel,
• Hélène Couthon-Gourvès,
• Jean-Pierre Haelters and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2014, 10, 1166–1196, doi:10.3762/bjoc.10.117

• phosphite [40]. The presence of DMAP and limited excess of CCl4 (5 equiv) produced the expected aryl phosphate in excellent yield even at a low temperature (−10 °C). Interestingly, this study illustrates that the AT reaction is chemoselective since only the phenol reacts even in the presence of primary or