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

• Federation 10.3762/bjoc.11.231 Abstract α,α-Difluoro-substituted organozinc reagents generated from conventional organozinc compounds and difluorocarbene couple with 1-bromoalkynes affording gem-difluorinated alkynes. The cross-coupling proceeds in the presence of catalytic amounts of copper iodide in

• ][11]. Alternatively, functional group manipulations starting from available CF2-containing building blocks can be considered, but multistep sequences render this approach laborious [12][13][14]. Difluoro-substituted cyclopropanes and cyclopropenes constitute a specific class of compounds accessible by

• tripled simply by adding 2 equiv of DMF additive (Table 1, entries 1 and 2). However, in these experiments, the reaction mixtures contained about 40% of (2,2-difluoro-2-iodoethyl)benzene (PhCH2CF2I) arising from zinc/iodine exchange between 2a and the iodoalkyne. Chloroalkyne 3a-Cl was markedly less

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

• )stannane and 1,4-difluoro-2,5-diiodobenzene (Figure 1a) [3]. However, this methodology required the pre-synthesis of the stannane derivative, which is not eco-friendly. More recently, the direct C–H bond arylation has appeared as one of the most sustainable protocols for the synthesis of poly(hetero)arenes

Selected synthetic strategies to cyclophanes

• Sambasivarao Kotha,
• Mukesh E. Shirbhate and
• Gopalkrushna T. Waghule

Beilstein J. Org. Chem. 2015, 11, 1274–1331, doi:10.3762/bjoc.11.142

Properties of PTFE tape as a semipermeable membrane in fluorous reactions

• Brendon A. Parsons,
• Olivia Lin Smith,
• Myeong Chae and
• Veljko Dragojlovic

Beilstein J. Org. Chem. 2015, 11, 980–993, doi:10.3762/bjoc.11.110

• Teflon AF (poly(2,2-bis(trifluoromethyl)-4,5-difluoro-1,3-dioxide-co-tetrafluoroethylene), a co-polymer with 13% PTFE content [25][26]. A Teflon AF 2400 tubing was also used in a reaction to deliver a gaseous reactant by Ley [27]. Weber carried out a quantitative study on Teflon AF films that were

Highly selective electrochemical fluorination of dithioacetal derivatives bearing electron-withdrawing substituents at the position α to the sulfur atom using poly(HF) salts

• Bin Yin,
• Shinsuke Inagi and
• Toshio Fuchigami

Beilstein J. Org. Chem. 2015, 11, 85–91, doi:10.3762/bjoc.11.12

• cases, fluorodesulfurization product 3b [22] was detected in considerable yield. When CH2Cl2 and MeNO2 were used, a small amount of ethyl α,α-difluoro-α-(phenylthio)acetate (4b) [22] was also detected (Table 2, entries 3 and 4). As a blank test, the electrolytic solution of 1b was mechanically stirred

• )acetonitrile (1h) [36] bearing a strongly electron-withdrawing cyano group underwent α-fluorination exclusively to produce α-fluorinated product 2h in excellent yields regardless of the poly(HF) salts (Table 3, entries 7–12). In case of 1h, no difluoro product was formed at all, which is probably due to a much

Efficient deprotection of F-BODIPY derivatives: removal of BF₂ using Brønsted acids

• Mingfeng Yu,
• Joseph K.-H. Wong,
• Cyril Tang,
• Peter Turner,
• Matthew H. Todd and
• Peter J. Rutledge

Beilstein J. Org. Chem. 2015, 11, 37–41, doi:10.3762/bjoc.11.6

• ; Findings Compounds incorporating the 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (F-BODIPY) motif 1 have found widespread use in fluorescent molecular probes [1][2], photovoltaic devices [3][4] and photodynamic therapy agents [5][6][7][8]. Accordingly, there is considerable interest in extending and

Organic chemistry on surfaces: Direct cyclopropanation by dihalocarbene addition to vinyl terminated self-assembled monolayers (SAMs)

• Malgorzata Adamkiewicz,
• David O’Hagan and
• Georg Hähner

Beilstein J. Org. Chem. 2014, 10, 2897–2902, doi:10.3762/bjoc.10.307

• with dihalocarbenes to generate SAMs, terminated with dihalo- (fluoro, chloro, bromo) cyclopropane motifs with about 30% surface coverage. Keywords: difluoro-; dichloro-; dibromomethylenecyclopropanes; dihalocarbenes; self-assembled monolayers; surface coating; Introduction Self-assembled monolayers

• dibromo- (:CBr2), dichloro- (:CCl2) and difluoro- (:CF2) carbenes [21][22][23]. The resultant SAMs were analysed by X-ray photoelectron spectroscopy (XPS), contact angle goniometry, ellipsometry, and atomic force microscopy. Results and Discussion After exposure to carbenes the vinyl-terminated SAMs were

(2R,1'S,2'R)- and (2S,1'S,2'R)-3-[2-Mono(di,tri)fluoromethylcyclopropyl]alanines and their incorporation into hormaomycin analogues

• Armin de Meijere,
• Sergei I. Kozhushkov,
• Dmitrii S. Yufit,
• Christian Grosse,
• Marcel Kaiser and
• Vitaly A. Raev

Beilstein J. Org. Chem. 2014, 10, 2844–2857, doi:10.3762/bjoc.10.302

• %, respectively). In the case of monofluoro derivative 14c the main product (38%) was trans-(2-methylcyclopropyl)methanol. In the case of the difluoro compound 14b, a mixture of the mono- (25c) and difluoromethylcyclopropylmethanol 25b along with the non-fluorinated alcohol was obtained in a ratio of

Synthesis and properties of novel star-shaped oligofluorene conjugated systems with BODIPY cores

• Clara Orofino-Pena,
• Diego Cortizo-Lacalle,
• Joseph Cameron,
• Muhammad T. Sajjad,
• Pavlos P. Manousiadis,
• Neil J. Findlay,
• Alexander L. Kanibolotsky,
• Dimali Amarasinghe,
• Peter J. Skabara,
• Tell Tuttle,
• Graham A. Turnbull and
• Ifor D. W. Samuel

Beilstein J. Org. Chem. 2014, 10, 2704–2714, doi:10.3762/bjoc.10.285

• these two families were studied in order to determine their suitability as emissive materials in photonic applications. Keywords: absorption spectroscopy; BODIPY; cyclic voltammetry; photoluminescence; star-shaped oligofluorene; Introduction The boron-dipyrromethene (BODIPY) or 4,4-difluoro-4-bora-3a

Solution processable diketopyrrolopyrrole (DPP) cored small molecules with BODIPY end groups as novel donors for organic solar cells

• Diego Cortizo-Lacalle,
• Calvyn T. Howells,
• Upendra K. Pandey,
• Joseph Cameron,
• Neil J. Findlay,
• Anto Regis Inigo,
• Tell Tuttle,
• Peter J. Skabara and
• Ifor D. W. Samuel

Beilstein J. Org. Chem. 2014, 10, 2683–2695, doi:10.3762/bjoc.10.283

• Physics & Astronomy, University of St. Andrews, St. Andrews, KY16 9SS, UK Interdisciplinary Centre for Energy Research, Indian Institute of Science, Bangalore 560012, India 10.3762/bjoc.10.283 Abstract Two novel triads based on a diketopyrrolopyrrole (DPP) central core and two 4,4-difluoro-4-bora-3a,4a

• % when combined with poly(3-hexylthiophene) [30][31]. 4,4-Difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY, 2), and its derivatives have been widely used in the last two decades due to their outstanding chemical and optoelectronic properties [32][33][34]. BODIPY derivatives are promising compounds to be

• ], and 7 [47] were prepared according to the literature. 10,10'-(5',5'''-(2,5-Bis(2-octyldodecyl)-3,6-dioxo-2,3,5,6-tetrahydropyrrolo[3,4-c]pyrrole-1,4-diyl)bis([2,2'-bithiophene]-5',5-diyl))bis(2,8-diethyl-5,5-difluoro-1,3,7,9-tetramethyl-5H-dipyrrolo[1,2-c:2',1'-f][1,3,2]diazaborinin-4-ium-5-uide) (9

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

• inhibitors with nanomolar potency against PTP1B [110][111]. Taylor and co-workers were interested to study α-monofluoroalkylphosphonic acids as PTP1B inhibitors in comparison to their difluoro analogues and compounds 16a,b and 132,133 were chosen as model PTP1B inhibitors [68]. The enantiopure α

• 3500 µM for S-16a and S-16b, respectively), but 10-fold less potent than the difluoro analogues 132 and 133 (IC50 71 µM and 33 µM, respectively). The inhibition studies indicated that the pro-S fluorine in difluoro inhibitors 132 and 133 is essential for good inhibition, although the pro-R fluorine

Synthesis of ethoxy dibenzooxaphosphorin oxides through palladium-catalyzed C(sp²)–H activation/C–O formation

• Seohyun Shin,
• Dongjin Kang,
• Woo Hyung Jeon and
• Phil Ho Lee

Beilstein J. Org. Chem. 2014, 10, 1220–1227, doi:10.3762/bjoc.10.120

• , difluoro, or ethoxycarbonyl group failed. Next, the Pd-catalyzed oxidative cyclization of 2-(aryl)arylphosphonic acid monoethyl esters 3 were examined to demonstrate the efficiency of the present method (Scheme 5). 4-Methylphenylphosphonic acid monoethyl esters 3a and 3b with a 3-methyl- and 3,4

Simple two-step synthesis of 2,4-disubstituted pyrroles and 3,5-disubstituted pyrrole-2-carbonitriles from enones

• Murat Kucukdisli,
• Dorota Ferenc,
• Marcel Heinz,
• Christine Wiebe and
• Till Opatz

Beilstein J. Org. Chem. 2014, 10, 466–470, doi:10.3762/bjoc.10.44

• class comprises important starting materials for the preparation of the BODIPY dyes (4,4-difluoro-4-bora-3a,4a-diaza-s-indacenes) [37][38] as well as their aza-analogues [39], the 4,4-difluoro-4-bora-3a,4a,8-triaza-s-indacenes. Various methods to prepare 2,4-disubstituted pyrroles have been described in

Aminofluorination of 2-alkynylanilines: a Au-catalyzed entry to fluorinated indoles

• Antonio Arcadi,
• Emanuela Pietropaolo,
• Antonello Alvino and
• Véronique Michelet

Beilstein J. Org. Chem. 2014, 10, 449–458, doi:10.3762/bjoc.10.42

• access to 3,3-difluoro-2-aryl-3H-indoles and 3-fluoro-2-arylindoles are described. An unprecedented aminoauration/oxidation/fluorination cascade reaction of 2-alkynylanilines bearing a linear alkyl group on the terminal triple bond is reported. Keywords: 2-alkynylanilines; fluorination; gold catalysis

• of 3,3-difluoro-2-oxindoles to give the corresponding 3,3-difluoroindoines when electron-withdrawing groups were present as substituents in the benzene nucleus. The 3,3-difluoro-2-oxindoles were prepared by the reaction of appropriately substituted isatin derivatives with DAST [18]. Anodic

• fluorination of various N-acetyl-3-substituted indoles was successfully carried out to provide trans-2,3-difluoro-2,3-dihydroindoles which upon treatment with a base gave monofluoroindole derivatives or monofluoro-3H-indoles depending on the substituents at the 3-position [19]. More recently, the indole ring

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

• examples include using bis(trifluoromethyl)mercury (Hg(CF3)2) under the promotion of NaI (Scheme 1, reaction 3) [24] and using methyl 2,2-difluoro-2-(fluorosulfonyl)acetate (MDFA) under the promotion of KI (Scheme 1, reaction 4) [25]. Our group has focused on the development and application of new

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

• has been the subject of intense research, and efficient methodologies to access these derivatives have been devised [19][20]. However, the analogues bearing the gem-difluoro moiety next to unsaturated bonds have not received comparable attention, probably due to the limited availability of the

• starting materials. In this context, the recent introduction of difluoropropargyl bromide as fluorinated building block gave access to a wide variety of gem-difluoro-containing alkyne derivatives [21][22]. Recently, we have employed these fluorinated triple bond scaffolds in several types of cyclization

• -difluoro moiety in an efficient manner. However, at this point it is important to mention that when the 1,7-octadiene protocol was applied using maleic anhydride or 4-phenyl-3H-1,2,4-triazole-3,5(4H)-dione as dienophiles (Table 1, method B, entries 1, 6 and 9), a complex mixture was obtained. This is

Recent advances in transition metal-catalyzed Csp²-monofluoro-, difluoro-, perfluoromethylation and trifluoromethylthiolation

• Grégory Landelle,
• Armen Panossian,
• Sergiy Pazenok,
• Jean-Pierre Vors and
• Frédéric R. Leroux

Beilstein J. Org. Chem. 2013, 9, 2476–2536, doi:10.3762/bjoc.9.287

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

• Ju Hee Kim Su Jeong Choi In Howa Jeong Department of Chemistry & Medical Chemistry, Yonsei University, 1 Yonseidae-gil, Wonju, Gangwondo 220-710, Republic of Korea 10.3762/bjoc.9.286 Abstract The cross-coupling reactions of 2,2-difluoro-1-iodoethenyl tosylate (2) with 2 equiv of boronic acids in

• 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

• -difluoro-1-iodoethenyl tosylate; organo-fluorine; Introduction The synthesis of 2,2-disubstituted-1,1-difluoroethenes have received much attention to synthetic organofluorine chemists in recent years because of their unique chemical reactivities toward nucleophiles to produce monofluorinated organic

Synthesis of enones, pyrazolines and pyrrolines with gem-difluoroalkyl side chains

• Assaad Nasr El Dine,
• Ali Khalaf,
• Danielle Grée,
• Olivier Tasseau,
• Fares Fares,
• Nada Jaber,
• Philippe Lesot,
• Ali Hachem and
• René Grée

Beilstein J. Org. Chem. 2013, 9, 1943–1948, doi:10.3762/bjoc.9.230

• bearing a CF3 group on the triple bond could be isomerised to the corresponding enones. In that case, Et3N proved to be sufficient as a catalyst to perform this transformation [28]. The required starting propargylic alcohols were obtained by a reaction of the lithium salt of easily available gem-difluoro

• propargylic derivative 1 [18] with aromatic aldehydes, affording compounds 2a–2e in 71–82% yields (Scheme 2 and Table 1). With these gem-difluoro intermediates, Et3N was not an efficient catalyst since only a low conversion was observed and the reaction was not clean. On the contrary, the DBU-mediated

• used for the preparation of chemical libraries. Strategy towards the target molecules. Synthesis of enones with a gem-difluoroalkyl side chain. Synthesis of pyrazolines with a gem-difluoro side chain. One-pot synthesis of pyrazolines with a gem-difluoro side chain. Synthesis of pyrrolines with a gem

Cyclization of substitued 2-(2-fluorophenylazo)azines to azino[1,2-c]benzo[d][1,2,4]triazinium derivatives

• Aleksandra Jankowiak,
• Emilia Obijalska and
• Piotr Kaszynski

Beilstein J. Org. Chem. 2013, 9, 1873–1880, doi:10.3762/bjoc.9.219

• ); anal. calcd for C19H16FN3O3S: C, 59.21; H, 4.18; N, 10.90; found: C, 58.92; H, 4.09; N, 10.95. 7,9-Difluoro-3-methylpyrido[2,1-c][1,2,4]benzotriazin-11-ium chloride (1d): Method B, yield 40–80% (based on NMR): 1H NMR (300 MHz, CD3CN) δ 2.98 (s, 3H), 7.99 (t, J = 8.1 Hz, 1H), 8.49 (d, J = 5.5 Hz, 1H

Efficient regio- and stereoselective access to novel fluorinated β-aminocyclohexanecarboxylates

• Loránd Kiss,
• Melinda Nonn,
• Reijo Sillanpää,
• Santos Fustero and
• Ferenc Fülöp

Beilstein J. Org. Chem. 2013, 9, 1164–1169, doi:10.3762/bjoc.9.130

• position 4 was efficiently synthesized. Oxidation of the hydroxy group of amino ester 5 with pyridinium chlorochromate (PCC) in CH2Cl2 yielded the corresponding oxo-group-containing amino ester 8, which was then converted with Deoxo-Fluor in CH2Cl2 at 0 °C to the corresponding geminal difluoro amino ester

High-spin intermediates of the photolysis of 2,4,6-triazido-3-chloro-5-fluoropyridine

• Sergei V. Chapyshev,
• Denis V. Korchagin,
• Patrik Neuhaus and
• Wolfram Sander

Beilstein J. Org. Chem. 2013, 9, 733–742, doi:10.3762/bjoc.9.83

• previous studies of dinitrenes 5a–c [29][30][31], the quintet molecule with DQ = 0.215 cm−1 and EQ = 0.0545 cm−1 can safely be assigned to dinitrene 15 with Θ = 115.7°. Thus, for instance, quintet dinitrene 5a showed DQ = 0.202 cm−1 and EQ = 0.0554 cm−1 [30], and its difluoro-derivative 5b displayed DQ

Exploring chemical diversity via a modular reaction pairing strategy

• Joanna K. Loh,
• Sun Young Yoon,
• Thiwanka B. Samarakoon,
• Alan Rolfe,
• Patrick Porubsky,
• Benjamin Neuenswander,
• Gerald H. Lushington and
• Paul R. Hanson

Beilstein J. Org. Chem. 2012, 8, 1293–1302, doi:10.3762/bjoc.8.147

• ], utilizing 3-hydroxypyrrolidine in combination with 2,4-difluoro- and 2,6-difluorobenzenesulfonyl chloride. The nonbridged scaffolds were also prepared as reported previously by a sulfonylation intermolecular Mitsunobu alkylation/intramolecular SNAr protocol [32]. 2,4-Difluoro- and 2,6

Synthetic glycopeptides and glycoproteins with applications in biological research

• Ulrika Westerlind

Beilstein J. Org. Chem. 2012, 8, 804–818, doi:10.3762/bjoc.8.90

• T-antigen, or a difluoro-T-antigen on different positions in the tandem repeat (6–10), showed that high antibody titers were induced in almost all of the immunized mice. Evaluation of the generated antibodies provided evidence that specific immune responses were elicited towards the MUC1 antigens

Enantioselective supramolecular devices in the gas phase. Resorcin[4]arene as a model system

• Caterina Fraschetti,
• Matthias C. Letzel,
• Antonello Filippi,
• Maurizio Speranza and
• Jochen Mattay

Beilstein J. Org. Chem. 2012, 8, 539–550, doi:10.3762/bjoc.8.62

• ’-deoxycytidine dC, cytidine, Cy, cytarabine CT, an epimer of cytidine, and gemcitabine GC, which is the gem-difluoro derivative of 2’-deoxycytidine (Figure 8). Two reaction products were observed in the reaction with the enantiomers (2)-aminobutane: the addition [M·H·G·B]+ and the ligand-exchange [M·H·B