Molecular recognition of isomeric protonated amino acid esters monitored by ESI-mass spectrometry

• Andrea Liesenfeld and
• Arne Lützen

Beilstein J. Org. Chem. 2014, 10, 825–831, doi:10.3762/bjoc.10.78

• started from 1-bromo-4-methoxybenzene which was transferred into 2-bromo-4’-methoxybiphenyl (3) in 92% yield via lithiation with t-BuLi, transmetallation with zinc(II) bromide, and subsequent Negishi cross-coupling reaction with 1-bromo-2-iodobenzene [14][15]. 3 was then transformed into the corresponding

• , followed by hydrolysis to afford phenol 6 which was finally transferred into the corresponding triflate 7 in 64% yield (Scheme 1). Triflate 7 was then subjected to a Sonogashira cross-coupling reaction and a Suzuki cross-coupling reaction followed by treatment with boron tribromide to obtain the

Phosphinate-containing heterocycles: A mini-review

• Olivier Berger and
• Jean-Luc Montchamp

Beilstein J. Org. Chem. 2014, 10, 732–740, doi:10.3762/bjoc.10.67

• . Tandem Kabacknik–Fields/C–N cross-coupling reaction. Tandem Kabacknik–Fields/C-P cross-coupling reaction. Heterocyclization via amide formation. Cyclization via reductive amination. H-Phosphinate alkylation. Cyclization through intramolecular Michael addition. Double Arbuzov reaction of bis

Self-assembly of metallosupramolecular rhombi from chiral concave 9,9’-spirobifluorene-derived bis(pyridine) ligands

• Rainer Hovorka,
• Sophie Hytteballe,
• Torsten Piehler,
• Georg Meyer-Eppler,
• Filip Topić,
• Kari Rissanen,
• Marianne Engeser and
• Arne Lützen

Beilstein J. Org. Chem. 2014, 10, 432–441, doi:10.3762/bjoc.10.40

• in our previous work (see [35]).) (S)-1, however, was reacted in a nickel-catalysed Kumada cross-coupling reaction to furnish 2,2’-dimethylated spirobifluorene (S)-4 which was then brominated twice to afford tetrafunctionalised spirobifluorene (S)-5. Finally, (S)-5 could be transformed into the

Synthesis of 3,4-dihydro-1,8-naphthyridin-2(1H)-ones via microwave-activated inverse electron-demand Diels–Alder reactions

• Salah Fadel,
• Youssef Hajbi,
• Mostafa Khouili,
• Said Lazar,
• Franck Suzenet and
• Gérald Guillaumet

Beilstein J. Org. Chem. 2014, 10, 282–286, doi:10.3762/bjoc.10.24

• electron-demand Diels–Alder reaction from 1,2,4-triazines bearing an acylamino group with a terminal alkyne side chain. Alkynes were first subjected to the Sonogashira cross-coupling reaction with aryl halides, the product of which then underwent an intramolecular inverse electron-demand Diels–Alder

• envisaged to evaluate the reactivity of internal alkynes towards the inverse electron-demand Diels–Alder reaction. To reach this goal, we decided to functionalize the alkynes 6–9 employing the Sonogashira cross-coupling reaction. Preparation of aryl-N-triazinylpentynamides The terminal alkynes 6–9 were then

• subjected to a Sonogashira cross-coupling reaction. Thus, treating compounds 6–9 in DME with Pd(PPh3)2Cl2 (5 mol %), CuI, Et3N and aryl iodide, gave the cross-coupling products 14–21 in very good yields (Scheme 5). The results are summarized in Table 4. Intramolecular inverse electron-demand Diels–Alder

Consecutive cross-coupling reactions of 2,2-difluoro-1-iodoethenyl tosylate with boronic acids: efficient synthesis of 1,1-diaryl-2,2-difluoroethenes

• Ju Hee Kim,
• Su Jeong Choi and
• In Howa Jeong

Beilstein J. Org. Chem. 2013, 9, 2470–2475, doi:10.3762/bjoc.9.286

• yields. Unsymmetrical di-coupled products 4 were obtained in high yields from the reactions of 3 with 2 equiv of boronic acids in the presence of catalytic amounts of Pd(OAc)2 and Na2CO3. Keywords: boronic acids; cross-coupling reaction; 1,1-diaryl-2,2-difluoroethene; 1,1-difluoro-1,3-dienes; 2,2

• [9][10][11][12]. Although numerous methods for the preparation of 2,2-disubstituted-1,1-difluoroethenes have been reported in the previous literature [13][14][15][16][17][18][19][20][21][22], a consecutive cross-coupling reaction of a proper precursor such as a 1,1-difluoroethenylidene species

• the consecutive cross-coupling reaction of the 2,2-difluoro-1-bromoethenylzinc reagent with aryl iodides, followed by arylboronic acids [17]. Recently, we also prepared 2,2-difluoro-1-tributylstannylethenyl tosylate and (2,2-difluoroethenylidene)bis(tributylstannane) which were utilized in the

Oxidative 3,3,3-trifluoropropylation of arylaldehydes

• Akari Ikeda,
• Masaaki Omote,
• Shiho Nomura,
• Miyuu Tanaka,
• Atsushi Tarui,
• Kazuyuki Sato and
• Akira Ando

Beilstein J. Org. Chem. 2013, 9, 2417–2421, doi:10.3762/bjoc.9.279

• . Approximately at the same time, our research group demonstrated that (E)-trimethyl(3,3,3-trifluoroprop-1-en-1-yl)silane (1) effectively participated in a Hiyama cross-coupling reaction with aryl iodide to construct β-trifluoromethylstyrenes in good to excellent yield [31][32]. In the course of this study, we

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

• recently reported an approach to forming the first aryl–aryl C–C bond by a directed lithiation of a pyridine 1.91 followed by conversion to its organozinc derivative. This intermediate then undergoes a high-yielding Negishi cross-coupling reaction with an arylbromide (Scheme 17) [52]. After acidic

Raman spectroscopy as a tool for monitoring mesoscale continuous-flow organic synthesis: Equipment interface and assessment in four medicinally-relevant reactions

• Trevor A. Hamlin and
• Nicholas E. Leadbeater

Beilstein J. Org. Chem. 2013, 9, 1843–1852, doi:10.3762/bjoc.9.215

• interfacing a Raman spectrometer with a scientific microwave unit [31]. This has allowed us to monitor reactions from both a qualitative [32][33][34][35] and quantitative [36][37] perspective. A recent report of the use of Raman spectroscopy for monitoring a continuous-flow palladium-catalyzed cross-coupling

• reaction [38] sparked our interest in interfacing our Raman spectrometer with one of our continuous-flow units and employing it for inline reaction monitoring of a number of key medicinally-relevant organic transformations. Our results are presented here. Results and Discussion Interfacing the spectrometer

Camera-enabled techniques for organic synthesis

• Steven V. Ley,
• Richard J. Ingham,
• Matthew O’Brien and
• Duncan L. Browne

Beilstein J. Org. Chem. 2013, 9, 1051–1072, doi:10.3762/bjoc.9.118

• function of the microwave was disabled during a metal-catalysed cross-coupling reaction, aggregated palladium metal deposited on the glass surface of the vial and led to arcing within the microwave cavity; an effect that was quite obvious on the video footage (Figure 8d). The authors point out that such

• footage was used by Jensen and co-workers to investigate metal aggregation in a palladium-catalysed cross-coupling reaction [52], this time within a microreactor where such aggregation can lead to pressure spikes and reactor plugging (Figure 9). Data collected using this monitoring technique allowed them

Titanium-mediated reductive cross-coupling reactions of imines with terminal alkynes: An efficient route for the synthesis of stereodefined allylic amines

• Kebin Mao,
• Guoqin Fan,
• Yuanhong Liu,
• Shi Li,
• Xu You and
• Dan Liu

Beilstein J. Org. Chem. 2013, 9, 621–627, doi:10.3762/bjoc.9.69

• derivative (7) of 5l [43]. Titanium-mediated reductive cross-coupling reaction of imines with ethynylcyclopropane. When ethynylcyclopropane was used as the coupling partner of imines 2 in the titanium-mediated reaction, 1,3-amino group migration occurred unexpectedly during the purification of the products

Efficient Cu-catalyzed base-free C–S coupling under conventional and microwave heating. A simple access to S-heterocycles and sulfides

• Silvia M. Soria-Castro and
• Alicia B. Peñéñory

Beilstein J. Org. Chem. 2013, 9, 467–475, doi:10.3762/bjoc.9.50

• and 2i (Table 3, entries 3 and 9). The reaction between 4-iodoaniline and 1 under CuI/1,10-phenanthroline catalysis afforded quantitatively the corresponding 4-iodoacetanilide as the only product. The acetylation of the amino group competes effectively with the cross-coupling reaction. A similar

• concomitant decrease of the reaction times to only 2 h is noteworthy. Afterwards we applied this procedure to the synthesis of heterocycles by the cross-coupling reaction of suitable o-substituted aryl iodides with KSCOMe. The reduced form of the Beaucage reagent 6, a sulfurizing reagent used for the

Dipyrazolo[1,5-a:4',3'-c]pyridines – a new heterocyclic system accessed via multicomponent reaction

• Wolfgang Holzer,
• Gytė Vilkauskaitė,
• Eglė Arbačiauskienė and
• Algirdas Šačkus

Beilstein J. Org. Chem. 2012, 8, 2223–2229, doi:10.3762/bjoc.8.251

• formylation (with concomitant transformation of the oxygen into a chlorine substituent), followed by Sonogashira cross-coupling reaction of the obtained 5-chloropyrazole-4-carbaldehydes with appropriate alkynes, has been described by us in a former publication [21]. Compounds 1 containing an alkyne function

Highly stereocontrolled synthesis of trans-enediynes via carbocupration of fluoroalkylated diynes

• Tsutomu Konno,
• Misato Kishi and
• Takashi Ishihara

Beilstein J. Org. Chem. 2012, 8, 2207–2213, doi:10.3762/bjoc.8.249

• in situ generated vinylcuprates could react very smoothly with an excess amount of iodine, the vinyl iodides being obtained in high yields. Thus-obtained iodides underwent a very smooth Sonogashira cross-coupling reaction to afford various trans-enediynes in high yields. Keywords: carbocupration

• stereoselective manner. Finally, we attempted the Sonogashira cross-coupling reaction of the obtained iodide 13a (Scheme 4). Thus, treatment of 13a with 1.2 equiv of terminal alkynes and 40 equiv of Et3N in the presence of 10 mol % each of Pd(PPh3)4 and CuI in THF at 70 °C for 2–5 h gave the corresponding

• . Finally, the thus-obtained iodide underwent a smooth Sonogashira cross-coupling reaction to afford the various desired trans-enediyne derivatives in high yields. trans-Enediyne. Regio- and stereoisomers. Synthetic strategy for the preparation of trifluoromethylated diynes. Preparation of various enynes. A

A bisazobenzene crosslinker that isomerizes with visible light

• Subhas Samanta,
• Harris I. Qureshi and
• G. Andrew Woolley

Beilstein J. Org. Chem. 2012, 8, 2184–2190, doi:10.3762/bjoc.8.246

• synthesized by a cross-coupling reaction of bromobenzene with 1-phenylpiperazine in the presence of t-BuOK. As with previous crosslinkers, attachment to a target peptide or protein would involve replacement of the two terminal acetamido units with chloro- or iodoacetamide units to enable reaction with Cys

Palladium-catalyzed C–N and C–O bond formation of N-substituted 4-bromo-7-azaindoles with amides, amines, amino acid esters and phenols

• Rajendra Surasani,
• Dipak Kalita,
• A. V. Dhanunjaya Rao and
• K. B. Chandrasekhar

Beilstein J. Org. Chem. 2012, 8, 2004–2018, doi:10.3762/bjoc.8.227

• .8.227 Abstract Simple and efficient procedures for palladium-catalyzed cross-coupling reactions of N-substituted 4-bromo-7-azaindole (1H-pyrrole[2,3-b]pyridine), with amides, amines, amino acid esters and phenols through C–N and C–O bond formation have been developed. The C–N cross-coupling reaction of

• amides, amines and amino acid esters takes place rapidly by using the combination of Xantphos, Cs2CO3, dioxane and palladium catalyst precursors Pd(OAc)2/Pd2(dba)3. The combination of Pd(OAc)2, Xantphos, K2CO3 and dioxane was found to be crucial for the C–O cross-coupling reaction. This is the first

• obtained (Table 1, entries 6 and 7). When tertiary ligand PCy3 (L4) was used as a ligand for the cross-coupling reaction no product formation was observed (Table, entry 5). Cross-coupling reaction of N-benzyl-4-bromo-7-azaindole (1e) and benzamide (2a) with other bases, e.g., K2CO3 and K3PO4, by using Pd

The chemistry of bisallenes

• Henning Hopf and
• Georgios Markopoulos

Beilstein J. Org. Chem. 2012, 8, 1936–1998, doi:10.3762/bjoc.8.225

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

• )-alt-5,5'-bithiophene/PS-βCD] (PDOF-BTc), was synthesized by Suzuki cross-coupling reaction between 5,5'-dibromo-2,2'-bithiophene (BT), as an inclusion complex in PS-βCD cavities, and the bulky molecule 9,9-dioctylfluorene-2,7-bis(trimethylene borate) (DOF), (Scheme 1). Of particular interest is the

• ability of cross-coupling reaction of BT and DOF to proceed close to the cavity surface of PS-βCD, which will provide a deeper insight into the use of these new host molecules (more soluble in nonpolar organic solvents) for the construction of mechanically interlocked molecules with conjugated polymers

• . Results and Discussion The paper describes the preparation of poly[2,7-(9,9-dioctylfluorene)-alt-5,5'-bithiophene/PS-βCD] (PDOF-BTc) main-chain polyrotaxane and its noncomplexed PDOF-BT counterpart copolymer by Suzuki cross-coupling reaction. The preparation of copolymer polyrotaxane (PDOF-BTc) involves a

On the bromination of the dihydroazulene/vinylheptafulvene photo-/thermoswitch

• Virginia Mazzanti,
• Martina Cacciarini,
• Søren L. Broman,
• Christian R. Parker,
• Magnus Schau-Magnussen,
• Andrew D. Bond and
• Mogens B. Nielsen

Beilstein J. Org. Chem. 2012, 8, 958–966, doi:10.3762/bjoc.8.108

• structure analysis (Figure 3d). Moreover, a Suzuki cross-coupling reaction with boronic acid 16 gave the product 17, albeit in rather low yield (Scheme 7). The substitution was confirmed by NOESY 1D experiments (see Supporting Information File 1). Finally, we observed that upon storage at room temperature

Diarylethene-modified nucleotides for switching optical properties in DNA

• Sebastian Barrois and
• Hans-Achim Wagenknecht

Beilstein J. Org. Chem. 2012, 8, 905–914, doi:10.3762/bjoc.8.103

• , forms the central cyclopentane ring of diarylethene 10. Subsequently, the ethynyl linker is attached to 10 by treatment with TMS-protected acetylene in a Pd-catalyzed cross-coupling reaction. Careful evaluation of this synthetic step revealed that the best yield (43%) of the mono-ethinylated product 11

meta-Oligoazobiphenyls – synthesis via site-selective Mills reaction and photochemical properties

• Raphael Reuter and
• Hermann A. Wegner

Beilstein J. Org. Chem. 2012, 8, 877–883, doi:10.3762/bjoc.8.99

• revealed that the overall degree of switching was independent of the connected azo-units. However, one of the azobonds in the bis-azobiphenyl is isomerized preferentially despite the high structural similarity. Keywords: azobenzene; cross-coupling reaction; foldamer; molecular switches; photochromism

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

• spiroketal unit, which is introduced in a palladium-catalyzed cross-coupling reaction of a glycal silanolate and an aryl iodide followed by an oxidative spiroketalization. Four different variants were made, differing in the nature of the acyl side chain with respect to the length, and in the number and

• gave a mixture of products. Finally, compound 21 was oxidized to give silanol building block 22. With building blocks 13 and 22 in hand, the palladium-catalyzed cross-coupling reaction was performed by using Pd2(dba)3 to give 23 (Scheme 3). Then the pivaloyl ester was selectively cleaved by using DIBAL

Sonogashira–Hagihara reactions of halogenated glycals

• Dennis C. Koester and
• Daniel B. Werz

Beilstein J. Org. Chem. 2012, 8, 675–682, doi:10.3762/bjoc.8.75

• glycals using several aromatic and aliphatic alkynes. This Pd-catalyzed cross-coupling reaction presents a facile access to alkynyl C-glycosides and sets the stage for a reductive/oxidative refunctionalization of the enyne moiety to regenerate either C-glycosidic structures or pyran derivatives with a

• cross-coupling reaction with iodoarenes. However, it is not only metalated sugar derivatives that have prevailed in the synthesis of C-glycosides, but also some electrophilic coupling reagents, such as glycalyl phosphates, and bromo- and iodoglycals. Glycal phosphates of type 5 were employed as

• electrophiles in a Stille cross-coupling reaction [18]. These building blocks exhibit a high stability and efficiency in their formation and are therefore particularly interesting. In a careful optimization study, Tan and co-workers found that several alkenes hydroborated in situ with 9-BBN can be utilized in a

Syntheses and applications of furanyl-functionalised 2,2’:6’,2’’-terpyridines

• Jérôme Husson and
• Michael Knorr

Beilstein J. Org. Chem. 2012, 8, 379–389, doi:10.3762/bjoc.8.41

• dihydropyridine 32. The latter undergoes aromatization upon reaction with benzoquinone to afford 33 (Scheme 6). Synthesis by cross-coupling reaction Cross-coupling reactions are widely used in organic chemistry [32] to create new C–C bonds. The importance of this technique was recently highlighted by the award of

• . Synthesis of tpy by Stille cross-coupling reaction. Oxidation of the furan ring of furanyl-substituted terpyridines. Direct oxidation of a furan ring attached on Ru(II) tpy complexes. Synthetic pathway to europium(III) and samarium(III) chelates 56 and 57. Synthetic pathway to prepare thiocyanato

Synthesis of multivalent host and guest molecules for the construction of multithreaded diamide pseudorotaxanes

• Nora L. Löw,
• Egor V. Dzyuba,
• Boris Brusilowskij,
• Lena Kaufmann,
• Elisa Franzmann,
• Wolfgang Maison,
• Emily Brandt,
• Daniel Aicher,
• Arno Wiehe and
• Christoph A. Schalley

Beilstein J. Org. Chem. 2012, 8, 234–245, doi:10.3762/bjoc.8.24

• attempts to use the same conditions for the fourfold coupling of 1 to 15 to synthesize tetravalent wheel 16 were unsuccessful, and we finally used another procedure for the cross-coupling reaction [107]. Because the Cu(I) catalyst may interfere with the Zn core of porphyrin 15 or lead to Glaser coupled

Recent advances in direct C–H arylation: Methodology, selectivity and mechanism in oxazole series

• Cécile Verrier,
• Pierrik Lassalas,
• Laure Théveau,
• Guy Quéguiner,
• François Trécourt,
• Francis Marsais and
• Christophe Hoarau

Beilstein J. Org. Chem. 2011, 7, 1584–1601, doi:10.3762/bjoc.7.187

• -metallated oxazole with its ring-open tautomer [67]. Using Pd(0)/Cu(I) catalysis, the C2-cuprated oxazole may act as a transmetallating agent through a standard cross-coupling reaction (Scheme 18, route B) [67]. Under Pd(0)- and Cu(I)-free catalysis, Zhuralev identified a cross-coupling-type mechanism for