Application of heterocyclic aldehydes as components in Ugi–Smiles couplings

• Katelynn M. Mason,
• Michael S. Meyers,
• Abbie M. Fox and
• Sarah B. Luesse

Beilstein J. Org. Chem. 2016, 12, 2032–2037, doi:10.3762/bjoc.12.191

• Katelynn M. Mason Michael S. Meyers Abbie M. Fox Sarah B. Luesse Department of Chemistry, Southern Illinois University Edwardsville, Edwardsville, Illinois 62026, USA 10.3762/bjoc.12.191 Abstract Efficient one-pot Ugi–Smiles couplings are reported for the use of furyl-substituted aldehyde

• and have inspired the development of new multicomponent coupling reactions. Isocyanide-based multicomponent couplings [1], led by the foundational Ugi four-component coupling [2][3], have been used extensively for the synthesis of natural products and the preparation of diverse heterocyclic scaffolds

• couplings in combination with post-condensation processes to efficiently increase structural complexity [8][9][10]. One of the most effective routes to polycyclic core structures uses intramolecular Diels–Alder reactions (IMDA) of tethered, substituted furans to provide stereoselective construction of

Catalytic Chan–Lam coupling using a ‘tube-in-tube’ reactor to deliver molecular oxygen as an oxidant

• Carl J. Mallia,
• Paul M. Burton,
• Alexander M. R. Smith,
• Gary C. Walter and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2016, 12, 1598–1607, doi:10.3762/bjoc.12.156

• -rich (65% yield) and electron-poor (38% yield) 2-substituted phenylboronic acids, most likely due to steric factors (31 and 35, Scheme 2). It is noteworthy that for all of the 3-phenyl-1H-pyrazole couplings, only the 1,3-disubsituted pyrazole products were obtained with no 1,5-disubsituted isomers

Unusual traits of cis and trans-2,3-dibromo-1,1-dimethylindane on the way from 1,1-dimethylindene to 2-bromo-, 3-bromo-, and 2,3-dibromo-1,1-dimethylindene

• Rudolf Knorr,
• David S. Stephenson,
• Ernst Lattke,
• Petra Böhrer and
• Jakob Ruhdorfer

Beilstein J. Org. Chem. 2016, 12, 1178–1184, doi:10.3762/bjoc.12.113

• -bromo-1,1-dimethylindene. Keywords: base-free dehydrobromination; cis/trans stereochemistry; five-membered ring conformation; indenes; NMR couplings; Introduction The basic mechanistic features of competing suprafacial and antarafacial additions of elemental bromine to an olefin are reasonably well

Synthesis of highly functionalized 2,2'-bipyridines by cyclocondensation of β-ketoenamides – scope and limitations

• Paul Hommes and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2016, 12, 1170–1177, doi:10.3762/bjoc.12.112

• couplings. Thus, a library of specifically substituted bipyridine derivatives was generated, showing the versatility of the simple 1,3-diketone-based approach to this important class of ligands. Keywords: 2,2-bipyridines; cross couplings; cyclocondensation; β-ketoenamides; nonaflates; Introduction In 2009

• the corresponding N-oxide 8. Suzuki-couplings of 2,2'-bipyrid-4-yl nonaflates 5a and 5b to compounds 9 and 10. Palladium-catalyzed couplings of chloro-substituted 2,2'-bipyrid-4-yl nonaflate 5g leading to compounds 11, 12 and 13. Attempted TMSOTf/DIPEA-promoted cyclocondensations of β-ketoenamides 3a

Cationic Pd(II)-catalyzed C–H activation/cross-coupling reactions at room temperature: synthetic and mechanistic studies

• Takashi Nishikata,
• Alexander R. Abela,
• Shenlin Huang and
• Bruce H. Lipshutz

Beilstein J. Org. Chem. 2016, 12, 1040–1064, doi:10.3762/bjoc.12.99

• electrophilic palladation step, potentially gaining entry to C–H activation under even milder reaction conditions for selected couplings than have previously been observed (Scheme 1, bottom) [120][121][122]. Metal cations, in general, are well known to increase the reactivity of C–C and C–N double bonds due to

A convenient route to symmetrically and unsymmetrically substituted 3,5-diaryl-2,4,6-trimethylpyridines via Suzuki–Miyaura cross-coupling reaction

• Dariusz Błachut,
• Joanna Szawkało and
• Zbigniew Czarnocki

Beilstein J. Org. Chem. 2016, 12, 835–845, doi:10.3762/bjoc.12.82

• ), reaction conditions (the nature of the palladium/ligand, temperature, base, solvents) and the steric interactions between both cross-coupling partners. Minard et al. [59] pointed out that if an arylboronic acid involved in sequential couplings bears substituents with electron-withdrawing and electron

• construction of unsymmetrically arylated pyrroles, thiophenes and 2,6- and 3,5-diarylpyridines. In order to test the utility of the above mentioned approach, a series of trial cross couplings were performed on a microscale according to route 3 with a variety of electron-poor and electron-rich boronic acids

• diarylpyridines 46–56, directly from 1 by two sequential cross couplings with the isolation and full characterization of the intermediates 3 and 43–45. Thus, the treatment of 1 with 1.1 equiv of phenyl-, 2-methylphenyl-, 4-methylphenyl and 2-naphthylboronic acid in dioxane in the presence of PdCl2(dppf) × CH2Cl2

Elucidation of a masked repeating structure of the O-specific polysaccharide of the halotolerant soil bacteria Azospirillum halopraeferens Au4

• Elena N. Sigida,
• Yuliya P. Fedonenko,
• Alexander S. Shashkov,
• Nikolay P. Arbatsky,
• Evelina L. Zdorovenko,
• Svetlana A. Konnova,
• Vladimir V. Ignatov and
• Yuriy A. Knirel

Beilstein J. Org. Chem. 2016, 12, 636–642, doi:10.3762/bjoc.12.62

• calibration. Two-dimensional NMR experiments were performed using standard Bruker software. Spin lock time in TOCSY experiments and mixing time in ROESY experiments were set to 60 and 200 ms, respectively. The HMBC spectrum was recorded with a 60-ms delay for evolution of long-range couplings. Samples were

cis–trans-Amide isomerism of the 3,4-dehydroproline residue, the ‘unpuckered’ proline

• Vladimir Kubyshkin and
• Nediljko Budisa

Beilstein J. Org. Chem. 2016, 12, 589–593, doi:10.3762/bjoc.12.57

• . Previously we speculated that the CF3-group in 3 should adopt an equatorial conformation, and thus stabilize the exo-pucker, based upon considerations of the vicinal J-couplings (in Ac-TfmPro-OMe, 7) [35]. Considering that the CF3-substituent should be located within the plane of the 3-pyrroline ring in 4

New synthetic strategies for xanthene-dye-appended cyclodextrins

• Milo Malanga,
• Andras Darcsi,
• Mihaly Balint,
• Gabor Benkovics,
• Tamas Sohajda and
• Szabolcs Beni

Beilstein J. Org. Chem. 2016, 12, 537–548, doi:10.3762/bjoc.12.53

• Information File 1, Figure S19), two different kinds of aromatic coupling can be detected. The different values of the 3JH-H and 4JH-H couplings permit the unambiguous assignment of the coupled protons H5/H7 and H8/H10. In the proton spectrum in Figure 7, the good resolution of the anomeric region can be also

Copper-mediated arylation with arylboronic acids: Facile and modular synthesis of triarylmethanes

• H. Surya Prakash Rao and
• A. Veera Bhadra Rao

Beilstein J. Org. Chem. 2016, 12, 496–504, doi:10.3762/bjoc.12.49

• towards transition metal-catalyzed cross-couplings [43][44][45][46][47][48] or CH arylation followed by an arylative desulfonation [49][50]. The coupling reactions provide an opportunity to install an unactivated aryl group on a carbon bearing two more aryl groups to synthesize the triarylmethane motif

Enabling technologies and green processes in cyclodextrin chemistry

• Giancarlo Cravotto,
• Marina Caporaso,
• Laszlo Jicsinszky and
• Katia Martina

Beilstein J. Org. Chem. 2016, 12, 278–294, doi:10.3762/bjoc.12.30

• CD derivatives. Several examples of sonochemical selective modification of native α-, β- and γ-CDs have been reported including heterogeneous phase Pd- and Cu-catalysed hydrogenations and couplings. Microwave irradiation has emerged as the technique of choice for the production of highly substituted

• interaction and may promote the formation of metal nanoparticle clustering. Cu(I)-based system have been used in alkyne/azide [3 + 2] cycloadditions, while Pd(II)-based catalysts have been used in C–C couplings reactions (Scheme 7) [34]. An example of water-soluble β- and γ-CD/chitosan derivatives have been

Determination of formation constants and structural characterization of cyclodextrin inclusion complexes with two phenolic isomers: carvacrol and thymol

• Miriana Kfoury,
• David Landy,
• Steven Ruellan,
• Lizette Auezova,
• Hélène Greige-Gerges and
• Sophie Fourmentin

Beilstein J. Org. Chem. 2016, 12, 29–42, doi:10.3762/bjoc.12.5

• NOE cross correlation peaks between the protons of guest and CD indicates space couplings and confirms that protons are close in space (<4Å). We performed 2D ROESY experiments for inclusion complexes of both β-CD/1 and β-CD/2 prepared at equimolar ratios. Partial contour plots of the ROESY spectra of

Recent advances in copper-catalyzed asymmetric coupling reactions

• Fengtao Zhou and
• Qian Cai

Beilstein J. Org. Chem. 2015, 11, 2600–2615, doi:10.3762/bjoc.11.280

• -halophenoxyl)-1,3-diols by the same group [54]. However, the palladium catalytic systems suffered from limited substrate scope and poor efficiency and enantioselectivity for the formation of quaternary stereocenters. Recently, Cai et al. carried out such couplings using a CuI/cyclized diamine catalytic system

• ). Copper-catalyzed couplings of allylic halides with nucleophiles Transition metal-catalyzed allylic substitutions are the most important process for carbon–carbon and carbon–heteroatom bond formation in organic synthesis [56][57][58]. Allylic substitution of the substrate with nucleophiles can afford two

Versatile synthesis and biological evaluation of novel 3’-fluorinated purine nucleosides

• Hang Ren,
• Haoyun An,
• Paul J. Hatala,
• William C. Stevens Jr,
• Jingchao Tao and
• Baicheng He

Beilstein J. Org. Chem. 2015, 11, 2509–2520, doi:10.3762/bjoc.11.272

• -ribofuranosyl purine derivatives began with a palladium-catalyzed cross coupling [45][46] to install the aromatic moieties to the 6-position of the purine ring. In order to accomplish efficient cross-couplings of a wide range of aromatic rings, we utilized three different protocols that were employed for Stille

• deprotected with a saturated solution of ammonia in methanol to give the desired analogue 5 with furan-2-yl substituent at position 6 of the purine base. Considering the possible toxicity of organostannyl reagents, we then utilized various organoboronic acids for Suzuki cross couplings [49][50][51] to

Recent highlights in biosynthesis research using stable isotopes

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2015, 11, 2493–2508, doi:10.3762/bjoc.11.271

• -10 excluded a simple mechanistic assembly of the tricyclic system. Instead, advanced NMR experiments focusing on 2JC,C-couplings revealed that C-8 and C-10 originate from the same glucose molecule. To account for this surprising observation, a new mechanistic proposal was suggested involving a carbon

Comparison of the catalytic activity for the Suzuki–Miyaura reaction of (η⁵-Cp)Pd(IPr)Cl with (η³-cinnamyl)Pd(IPr)(Cl) and (η³-1-t-Bu-indenyl)Pd(IPr)(Cl)

• Patrick R. Melvin,
• Nilay Hazari,
• Hannah M. C. Lant,
• Ian L. Peczak and
• Hemali P. Shah

Beilstein J. Org. Chem. 2015, 11, 2476–2486, doi:10.3762/bjoc.11.269

• preliminary reports indicate that (η5-Cp)Pd(NHC)(Cl) precatalysts are highly active. For example, full conversion at room temperature was achieved using simple aryl chlorides as the substrate in Suzuki–Miyaura couplings at relatively low catalyst loadings (1 mol %) [18]. However, despite this impressive

Copper-catalyzed arylation of alkyl halides with arylaluminum reagents

• Bijay Shrestha and
• Ramesh Giri

Beilstein J. Org. Chem. 2015, 11, 2400–2407, doi:10.3762/bjoc.11.261

• , intramolecular coordination to Al also enables the couplings of alkylalanes with organo halides [21]. Knochel [15] and Hoveyda [22] have also shown that organoaluminum reagents are capable of transmetalating to Cu-salts. Inspired by these literature reports and our recent investigations, we envisioned that

• bromides in good to excellent yields. Results and Discussion Recently, we [23][24][25][26][27] and others [10][28][29][30][31][32][33][34][35][36][37][38][39] reported efficient cross-couplings of oganometallic reagents of Si, B, In, Zr, Zn, Mg and Sn with organo halides [40][41]. Under our reaction

• bromides (Table 2, entries 12 and 14) [43]. Based on literature reports and our recent mechanistic work on Cu-catalyzed cross-couplings [23][24][25], we propose a catalytic cycle for the current reaction (Scheme 2). It is evident from the optimization of reaction conditions that both NN-1 and LiCl improve

Copper catalysis in organic synthesis

• Sherry R. Chemler

Beilstein J. Org. Chem. 2015, 11, 2252–2253, doi:10.3762/bjoc.11.244

• Ullmann and Goldberg couplings, asymmetric acetylide additions to carbonyl groups, radical alkylations and asymmetric conjugate additions as well as original contributions in the area of copper-catalyzed C–C cross-coupling, conjugate additions, allylic alkylations, alkene difunctionalizations, heterocycle

Recent advances in copper-catalyzed C–H bond amidation

• Jie-Ping Wan and
• Yanfeng Jing

Beilstein J. Org. Chem. 2015, 11, 2209–2222, doi:10.3762/bjoc.11.240

• alkene C–H bonds, and the alkynylation reactions by making use of direct transformations on the alkyne C–H bonds such as Sonograshira, Glaser couplings were extensively studied and utilized [69][70][71][72]. Under the inspiration of these well-known reaction models, the amidation reaction based on the

Two strategies for the synthesis of the biologically important ATP analogue ApppI, at a multi-milligram scale

• Janne Weisell,
• Jouko Vepsäläinen and
• Petri A. Turhanen

Beilstein J. Org. Chem. 2015, 11, 2189–2193, doi:10.3762/bjoc.11.237

• standard in the 31P measurements. The nJHP couplings were calculated from proton spectra and all J values are given in Hz. The nJCP couplings were calculated from carbon spectra with the coupling constants given in parenthesis as Hertz. Ion-pair chromatography was performed with a VP10 HPLC system using a

Coupling of α,α-difluoro-substituted organozinc reagents with 1-bromoalkynes

• Artem A. Zemtsov,
• Alexander D. Volodin,
• Vitalij V. Levin,
• Marina I. Struchkova and
• Alexander D. Dilman

Beilstein J. Org. Chem. 2015, 11, 2145–2149, doi:10.3762/bjoc.11.231

• reaction provides straightforward access to α,α-difluorinated alkynes [13][14][28][29][30][31]. Our method is based on facile zinc/copper exchange allowing for versatile couplings described for non-fluorinated organozinc compounds [32][33][34][35][36][37]. Results and Discussion Organozinc compound 2a

Copper-mediated synthesis of N-alkenyl-α,β-unsaturated nitrones and their conversion to tri- and tetrasubstituted pyridines

• Dimitra Kontokosta,
• Daniel S. Mueller,
• Dong-Liang Mo,
• Wiktoria H. Pace,
• Rachel A. Simpson and
• Laura L. Anderson

Beilstein J. Org. Chem. 2015, 11, 2097–2104, doi:10.3762/bjoc.11.226

• ][38], fragment couplings [39][40][41][42], and transition metal-catalyzed C–H bond functionalization of α,β-unsaturated imines and oximes [43][44][45][46][47][48][49][50]. We were inspired by the copper-catalyzed coupling of protected α,β-unsaturated oximes and alkenylboronic acids developed by

Preparation of conjugated dienoates with Bestmann ylide: Towards the synthesis of zampanolide and dactylolide using a facile linchpin approach

• Jingjing Wang,
• Samuel Z. Y. Ting and
• Joanne E. Harvey

Beilstein J. Org. Chem. 2015, 11, 1815–1822, doi:10.3762/bjoc.11.197

• , if the α-phosphoranylidene ester or amide is formed in the presence of an aldehyde, ketone or ester, an additional in situ Wittig reaction can occur [12][13][14][15][16][17][18]. In this way, amides, esters and thioesters can be obtained through three-component couplings [14][16]. Intramolecular

• couplings with a Bestmann ylide linchpin have enabled direct lactone and lactam synthesis [12][13][14][15], including the preparation of macrolactones [16][17][18]. An extension of this methodology to γ-hydroxyenone substrates allows the preparation of α-alkylidene-γ-butyrolactones through tandem acylation

Preparative semiconductor photoredox catalysis: An emerging theme in organic synthesis

• David W. Manley and
• John C. Walton

Beilstein J. Org. Chem. 2015, 11, 1570–1582, doi:10.3762/bjoc.11.173

• methods could be enlisted in constructive molecular assembly applications. Our study of SCPC processes revealed that a wide range of carboxylic acids could be deployed in preparatively useful ways. Radical additions to alkenes, cyclizations and tandem addition–cyclizations, as well as homo-couplings, were

• natural products and pharmaceuticals. Transition metals are very successful in catalyzing homo-couplings, particularly for sp2 hybridized C-centers. Radical-based dimerizations are also known to be effective and offer the opportunity to extend the scope to sp3 centers. TiO2 photoredox reactions with

• tubes. TiO2 promoted reactions of aryloxyacetic acids with maleic anhydride and maleimides [53][54]. Photoredox addition–cyclization reactions of aryloxyacetic and related acids promoted by maleimide [63]. SCPC promoted homo-couplings and macrocyclizations with carboxylic acids [64]. TiO2 promoted

Preparation of a disulfide-linked precipitative soluble support for solution-phase synthesis of trimeric oligodeoxyribonucleotide 3´-(2-chlorophenylphosphate) building blocks

• Amit M. Jabgunde,
• Alejandro Gimenez Molina,
• Pasi Virta and
• Harri Lönnberg

Beilstein J. Org. Chem. 2015, 11, 1553–1560, doi:10.3762/bjoc.11.171

• ) (4–6; Scheme 2). The stock solution of the latter reagent (0.2 mol L−1) was prepared as described in our previous report [8]. A trimeric oligodeoxyribonucleotide containing three different 2’-deoxyribonucleosides was assembled on support 3 as depicted in Scheme 3. The couplings were carried out

• , 59.9, 53.7, 44.8, 42.5, 32.8 ppm; ESIMS m/z: [M + H]+ calcd for C53H65N12O8S8, 1253.28; found, 1253.27; m/z: [M + Na]+ calcd for C53H64N12NaO8S8, 1275.26; found, 1275.26. Bis(benzotriazol-1-yl) 2-chlorophenyl phosphate: The couplings were carried out essentially as described previously [8]. A solution