Gold(I)-catalysed synthesis of a furan analogue of thiamine pyrophosphate

• Amjid Iqbal,
• El-Habib Sahraoui and
• Finian J. Leeper

Beilstein J. Org. Chem. 2014, 10, 2580–2585, doi:10.3762/bjoc.10.270

• was the protection of 3-butynol (6) and 1,3-dihydroxyacetone (8) as their TBDMS ethers, 7 and 9. The alkyne 7 was then coupled with ketone 9 using n-BuLi. TBAF-mediated deprotection gave unsaturated alcohol 11, the substrate for dehydrative cyclization with AuCl. The order of addition, reaction time

Selenium halide-induced bridge formation in [2.2]paracyclophanes

• Laura G. Sarbu,
• Henning Hopf,
• Peter G. Jones and
• Lucian M. Birsa

Beilstein J. Org. Chem. 2014, 10, 2550–2555, doi:10.3762/bjoc.10.266

• introduction of new bridges to [2.2]paracyclophanes, we decided to investigate a double addition reaction of 1 equiv of selenium dichloride to both triple bonds of 4,13-bis(ethynyl)[2.2]paracyclophane 1; a bis(vinyl)selenide bridge should result from this interaction. Thus, by reacting 1 with one equivalent of

• importance for the reaction mechanism of selenium dihalide addition to pseudo-geminal bis(acetylene) 1. The unexpected formation of [2.3.2](1,2,4)cyclophane derivatives 2, 3 and 5, 6, then induced us to investigate the addition reaction of phenylselenyl chloride to 4,13-bis(ethynyl)[2.2]paracyclophane

End group functionalization of poly(ethylene glycol) with phenolphthalein: towards star-shaped polymers based on supramolecular interactions

• Carolin Fleischmann,
• Hendrik Wöhlk and
• Helmut Ritter

Beilstein J. Org. Chem. 2014, 10, 2263–2269, doi:10.3762/bjoc.10.235

• (PP-NH2) was obtained through a Michael addition reaction of PP-AAm and cysteamine hydrochloride. The hydrochloride was chosen in order to disable the competing nucleophilic addition of the amine and therefore, to prevent the formation of side products. The purified PP-NH2 was then converted into the

Reaction of selected carbohydrate aldehydes with benzylmagnesium halides: benzyl versus o-tolyl rearrangement

• Maroš Bella,
• Bohumil Steiner,
• Vratislav Langer and
• Miroslav Koóš

Beilstein J. Org. Chem. 2014, 10, 1942–1950, doi:10.3762/bjoc.10.202

• -anomeric free aldehyde function (C-5 position of the furanose) of an O-alkyl (methyl and isopropylidene)-protected carbohydrate. First, the addition reaction of aldehyde 3 with 1 under the standard Grignard reaction conditions (method A, see Experimental part) was examined. Based on the NMR spectral data

Concise total synthesis of two marine natural nucleosides: trachycladines A and B

• Haixin Ding,
• Wei Li,
• Zhizhong Ruan,
• Ruchun Yang,
• Zhijie Mao,
• Qiang Xiao and
• Jun Wu

Beilstein J. Org. Chem. 2014, 10, 1681–1685, doi:10.3762/bjoc.10.176

• cleavage of the 2-O-benzyl group at perbenzylated 1-O-methylribofuranose analogues. Dess–Martin oxidation of compound 9 provided ketone 10 in 92% yield. Next, the addition reaction with CH3MgBr in dry ether gave 11 exclusively with the requisite β-methyl configuration at C-2. NOE experiments showed correct

Improving the reactivity of phenylacetylene macrocycles toward topochemical polymerization by side chains modification

• Simon Rondeau-Gagné,
• Jules Roméo Néabo,
• Maxime Daigle,
• Katy Cantin and
• Jean-François Morin

Beilstein J. Org. Chem. 2014, 10, 1613–1619, doi:10.3762/bjoc.10.167

• , on the critical parameters needed for polymerization through 1,4-addition reaction [38]. In fact, the acetanilide configuration provides macrocycles which can barely self-assemble in organic solvents while the benzamide configuration yields macrocycles with much greater gelation properties that allow

4-Hydroxy-6-alkyl-2-pyrones as nucleophilic coupling partners in Mitsunobu reactions and oxa-Michael additions

• Michael J. Burns,
• Thomas O. Ronson,
• Richard J. K. Taylor and
• Ian J. S. Fairlamb

Beilstein J. Org. Chem. 2014, 10, 1159–1165, doi:10.3762/bjoc.10.116

• desired product. The phacelocarpus 2-pyrones 1 and 2. Generalised O-functionalisation of 6-alkyl-4-hydroxy-2-pyrones 3. Synthesis of alkylated 2-pyrones 3b–e. Michael addition of 3a to allene 8 and internal alkyne 10. Synthesis of 2-pyronyl ethers 4a–l. Michael addition reaction optimisation. Synthesis of

Preparation of phosphines through C–P bond formation

• Iris Wauters,
• Wouter Debrouwer and
• Christian V. Stevens

Beilstein J. Org. Chem. 2014, 10, 1064–1096, doi:10.3762/bjoc.10.106

• . The methodologies for catalytic asymmetric hydrophosphination of olefins are limited. Chiral metal complexes have been used to promote and control the asymmetric P–H addition reaction. Recent reviews covering the asymmetric hydrophosphination reaction catalyzed by metal catalysts have been published

• unactivated alkynes were investigated as substrates. Phosphines as well as silylphosphines [65][66][226][227] or phosphine–borane complexes can be used as phosphinating agents. The addition reaction has been initiated in several ways including base [228][229][230][231][232][233], radical (thermal radical [234

Primary-tertiary diamine-catalyzed Michael addition of ketones to isatylidenemalononitrile derivatives

• Akshay Kumar and
• Swapandeep Singh Chimni

Beilstein J. Org. Chem. 2014, 10, 929–935, doi:10.3762/bjoc.10.91

• ][45]. We describe herein that a similar catalyst system could also efficiently catalyze the asymmetric Michael addition reaction between ketones 2 and isatylidenemalononitrile derivatives 3 to procure highly functionalized 3,3'-disubstituted oxindoles 4 which could easily be transformed into

Visible-light-induced, Ir-catalyzed reactions of N-methyl-N-((trimethylsilyl)methyl)aniline with cyclic α,β-unsaturated carbonyl compounds

• Dominik Lenhart and
• Thorsten Bach

Beilstein J. Org. Chem. 2014, 10, 890–896, doi:10.3762/bjoc.10.86

• enones were made by Hoffmann et al., who established the use of aromatic ketones as suitable PET catalysts for these reactions [31][32][33][34][35][36][37]. In Scheme 1, the addition reaction of N,N-dimethylaniline (1) to (5R)-menthyloxyfuran-2(5H)-one (2) is shown, which proceeds to the intriguing

• (Boc) and 4-toluenesulfonyl (Ts) derivatives 18a and 18b were prepared [52]. In CH2Cl2 as the solvent, the attempted addition reaction of N-methyl-N-((trimethylsilyl)methyl)aniline (5) turned out to be sluggish. With substrate 18a, product 19a was isolated in 23% yield after an irradiation time of 24

• higher type selectivity. The domino process was suppressed and the plain addition product 22 was obtained in 75% yield (Scheme 7). The latter result suggested that the previously discussed (Scheme 3) addition reaction to 5,6-dihydro-2H-pyran-2-one (12) might also lead to a single product if performed

Addition of H-phosphonates to quinine-derived carbonyl compounds. An unexpected C9 phosphonate–phosphate rearrangement and tandem intramolecular piperidine elimination

• Łukasz Górecki,
• Artur Mucha and
• Paweł Kafarski

Beilstein J. Org. Chem. 2014, 10, 883–889, doi:10.3762/bjoc.10.85

• % yield. The obtained aldehydes 4, 6, and 8 were reacted with 1.1 equiv of diethyl phosphite. The presence of the tertiary amino group of quinuclidine was expected to be a sufficient catalytic base for the addition reaction, and furthermore to induce a diastereoselectivity. However, the expected

Group-assisted purification (GAP) chemistry for the synthesis of Velcade via asymmetric borylation of N-phosphinylimines

• Jian-bo Xie,
• Jian Luo,
• Timothy R. Winn,
• David B. Cordes and
• Guigen Li

Beilstein J. Org. Chem. 2014, 10, 746–751, doi:10.3762/bjoc.10.69

• the treatment of multiple myeloma and mantle cell lymphoma [21]. This product is usually synthesized in three representative processes: (1) to use (1S,2S,3R,5S)-(+)-2,3-pinanediol as the chiral auxiliary for the addition reaction followed by chlorination and amination [14][15]; (2) to perform copper

Silver and gold-catalyzed multicomponent reactions

• Giorgio Abbiati and
• Elisabetta Rossi

Beilstein J. Org. Chem. 2014, 10, 481–513, doi:10.3762/bjoc.10.46

• alkyne π-complex I with the acidification of the acetylenic hydrogen atom. Deprotonation by the imine produces the electrophilic iminium ion with simultaneous production of the Au(I)-acetylide II. An addition reaction produces propargylamine III and regenerates the gold cation. Amine III is trapped with

New hydrogen-bonding organocatalysts: Chiral cyclophosphazanes and phosphorus amides as catalysts for asymmetric Michael additions

• Helge Klare,
• Jörg M. Neudörfl and
• Bernd Goldfuss

Beilstein J. Org. Chem. 2014, 10, 224–236, doi:10.3762/bjoc.10.18

• on the selectivity and also on the efficacy with electron-withdrawing groups. While the flexible open-chain triamide catalysts (6, 7a) proved to be strong promoters of the addition reaction with excellent yields, we assumed that the rigid cyclodiphosphazanes 14a/15/16 would be more selective catalyst

• lower accuracy of the employed SVP-basis set in describing H-bonded systems. Conclusion A series of new phosphorus (tri)amides, which includes the first chiral PV-cyclodiphosphazane, is synthesized and is successfully employed as HB organocatalysts in the Michael addition reaction of 2

One-pot cross-enyne metathesis (CEYM)–Diels–Alder reaction of gem-difluoropropargylic alkynes

• Santos Fustero,
• Paula Bello,
• Javier Miró,
• María Sánchez-Roselló,
• Günter Haufe and
• Carlos del Pozo

Beilstein J. Org. Chem. 2013, 9, 2688–2695, doi:10.3762/bjoc.9.305

• moiety via vinylalkylidene intermediates [4][5][6]. This is an atom economical process since it is an addition reaction and non-olefin byproducts are formed. Furthermore, a sequential use of EYM and Diels–Alder reactions generates highly functionalized carbo- and heterocyclic frameworks [7][8][9][10][11

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

• for the introduction of chirality to substrates. This review presents a general overview of the synthesis and use of Garner’s aldehyde in natural product synthesis. Particular attention will be paid on the preservation of chiral information in the addition reaction of nucleophiles to the aldehyde

• formed the nucleophile reductively from pentadecyne with iBu2AlH in THF [44]. This vinylalane provided the syn-adduct 16 in modest stereoselectivity (1:2 anti/syn). For the addition reaction to be feasible for asymmetric synthesis, the configurational integrity during this step is important. Garner and

• many others have demonstrated that there is practically no epimerization of the α-carbon center of 1 during the addition reaction [38]. While working on the synthesis of thymine polyoxin C, Garner coupled the lithium salt of ethyl propiolate with (R)-1 (Scheme 9) in HMPT/THF at −78 °C. The reaction was

Regioselective 1,4-trifluoromethylation of α,β-unsaturated ketones via a S-(trifluoromethyl)diphenylsulfonium salts/copper system

• Satoshi Okusu,
• Yutaka Sugita,
• Etsuko Tokunaga and
• Norio Shibata

Beilstein J. Org. Chem. 2013, 9, 2189–2193, doi:10.3762/bjoc.9.257

• Michael addition reaction, even in a racemic, non-stereoselective fashion [1][2][3][4][5]. The nucleophilic trifluoromethylation to conjugated alkenes essentially occurs solely via a 1,2-addition [1][2][3][4][5][6][7][8][9][10][11], not a 1,4-addition (Scheme 1), with the exception of non-general examples

Acid, silver, and solvent-free gold-catalyzed hydrophenoxylation of internal alkynes

• Marcia E. Richard,
• Daniel V. Fraccica,
• Kevin J. Garcia,
• Erica J. Miller,
• Rosa M. Ciccarelli,
• Erin C. Holahan,
• Victoria L. Resh,
• Aakash Shah,
• Peter M. Findeis and
• Robert A. Stockland Jr.

Beilstein J. Org. Chem. 2013, 9, 2002–2008, doi:10.3762/bjoc.9.235

• the addition reaction [11]. Additionally, these cationic gold species can be generated through the reaction of chlorogold compounds with silver salts [1][2][3][4]. Recently, there has been growing interest in developing approaches that generate a catalytically active species under acid-free and silver

• could promote this reaction, JohnPhosAuCl and other gold compounds were investigated under the same reaction conditions (Table 1, entries 2–7). In all cases, the chlorogold compounds were unable to catalyze the addition reaction and analysis of the crude reaction mixtures revealed only starting

• 18). The effectiveness of different gold catalysts on the addition reaction was also studied (Table 1). While 1 was effective at promoting the addition reaction, an arylgold compound bearing a bulkier Buchwald ligand (2) afforded lower yields of the vinyl ether. Adding an additional equivalent of t

Flow Giese reaction using cyanoborohydride as a radical mediator

• Takahide Fukuyama,
• Takuji Kawamoto,
• Mikako Kobayashi and
• Ilhyong Ryu

Beilstein J. Org. Chem. 2013, 9, 1791–1796, doi:10.3762/bjoc.9.208

• reductive radical addition reaction, better known as the Giese reaction, was historically carried out most by using tributyltin hydride as the radical mediator [8][9]. Recently borane derivatives such as borohydride reagents [10][11][12][13] or NHC-boranes [14][15][16][17][18] can be used in simple radical

Computational study of the rate constants and free energies of intramolecular radical addition to substituted anilines

• Andreas Gansäuer,
• Meriam Seddiqzai,
• Tobias Dahmen,
• Rebecca Sure and
• Stefan Grimme

Beilstein J. Org. Chem. 2013, 9, 1620–1629, doi:10.3762/bjoc.9.185

• was therefore employed in further calculations. Corrections for intramolecular London dispersion and solvation effects in the quantum chemical treatment are essential to obtain consistent and accurate theoretical data. For the investigated radical addition reaction it turned out that the polarity of

• similar for 1–3 (121–123°). This angle is substantially larger than for the 5-exo cyclization (108.2°). This is shown for the addition of 1 in Figure 1. Substitution at the radical center We investigated the influence of radical substitution on the rate and the free energy of the addition reaction next

• addition reaction of 9 that has the most electrophilic radical center due to ester substitution. The more nucleophilic radicals 8 and 10 react slower than 1. The –OMe group in 10 is a better electron donor than the –Me group in 8, which should make it more nucleophilic and lead to a slower radical addition

Bioinspired total synthesis of katsumadain A by organocatalytic enantioselective 1,4-conjugate addition

• Yongguang Wang,
• Ruiyang Bao,
• Shengdian Huang and
• Yefeng Tang

Beilstein J. Org. Chem. 2013, 9, 1601–1606, doi:10.3762/bjoc.9.182

• strategy was designed as a fallback, in which katsumadain A could be accessed from the lactol 5a and phosphonate 6 via a tandem Horner–Wadsworth–Emmons (HWE)/oxa-Michael addition reaction [16]. In turn, 5a could be derived from 3 and cinnamaldehyde (7) by an organocatalytic enantioselective 1,4-conjugate

• the electrophile 4. However, all of these reactions failed to provide satisfactory results and only lead to the recovery or the substantial decomposition of the starting material. We then turned our attention to the organocatalytic conjugated addition reaction. Among the various documented conditions

Homolytic substitution at phosphorus for C–P bond formation in organic synthesis

• Hideki Yorimitsu

Beilstein J. Org. Chem. 2013, 9, 1269–1277, doi:10.3762/bjoc.9.143

• Me3M–PPh2 (M = Sn, Si) and V-40 (Table 9) [26]. Secondary and tertiary alkyl iodides participate in the addition reaction while primary alkyl iodide results in direct phosphination prior to the expected addition. Not only acrylate ester but also acrylamide, vinyl sulfone, and acrylonitrile are good

Catalytic asymmetric tandem Friedel–Crafts alkylation/Michael addition reaction for the synthesis of highly functionalized chromans

• Jiahuan Peng and
• Da-Ming Du

Beilstein J. Org. Chem. 2013, 9, 1210–1216, doi:10.3762/bjoc.9.137

• Jiahuan Peng Da-Ming Du School of Chemical Engineering and Environment, Beijing Institute of Technology, Beijing 100081, China 10.3762/bjoc.9.137 Abstract The enantioselective tandem Friedel–Crafts alkylation/Michael addition reaction of indoles with nitroolefin enoates catalyzed by a

• reaction has appeared [50]. Herein, we wish to detail our independent research on the asymmetric tandem Friedel–Crafts alkylation/Michael addition reaction of indoles with nitroolefin enoates catalyzed by bis(oxazoline)-Zn(OTf)2 complexes, resulting in functionalized chiral chromans (dihydrobenzopyrans) in

• enantioselectivities were observed in these cases. 3k was obtained in moderate stereoselectivity (Table 5, entry 11). Conclusion In conclusion, we have developed a convenient catalytic asymmetric tandem Friedel–Crafts alkylation/Michael addition reaction of nitroolefin enoates 1 with indoles 2 catalyzed by a

Synthesis of functionalized spiro[indoline-3,4’-pyridines] and spiro[indoline-3,4’-pyridinones] via one-pot four-component reactions

• Li-Juan Zhang,
• Qun Wu,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2013, 9, 846–851, doi:10.3762/bjoc.9.97

• functionalized spiro[indole-3,4’-pyridines] via the four-component reaction prompted us to study the reaction scope further [25]. Another widely used electron-deficient alkyne reagent, methyl propiolate, was utilized to replace dimethyl acetylenedicarboxylate as one component. The addition reaction of aniline to

• methyl propiolate to give the active adducts, 3-arylaminoacrylates, usually needs more than twelve hours. Thus, we decided firstly to let arylamine and methyl propiolate react in ethanol at room temperature for 24 hours. TLC analysis indicated that the addition reaction had finished, and TLC analysis

A computational study of base-catalyzed reactions of cyclic 1,2-diones: cyclobutane-1,2-dione

• Nargis Sultana and
• Walter M. F. Fabian

Beilstein J. Org. Chem. 2013, 9, 594–601, doi:10.3762/bjoc.9.64

• of an extended conformation Int2’ was attempted. However, such a structure collapsed upon geometry optimization in a concerted proton transfer–nucleophilic addition reaction to intermediate Int2a. By a simple acid–base equilibrium (alcoholate–carboxylic acid → alcohol–carboxylate), this intermediate