Recent applications of chiral calixarenes in asymmetric catalysis

• Mustafa Durmaz,
• Erkan Halay and
• Selahattin Bozkurt

Beilstein J. Org. Chem. 2018, 14, 1389–1412, doi:10.3762/bjoc.14.117

• asymmetric alkylation of tert-butyl glycinate benzophenone Schiff base 3 with alkyl halides 4 in a toluene–50% KOH biphasic system (Scheme 1). The corresponding α-alkyl-α-amino acid derivatives 5 were obtained in excellent yields with very low enantioselectivities (up to 9%). This is the first example of

• phosphinoferrocenyl-substituted calixarene ligands 27–29. Asymmetric coupling reaction of aryl boronates and aryl halides in the presence of calixarene mono and di(ferrocenylphosphine) ligands 27 and 28. Asymmetric allylic alkylation in the presence of calix[4]arene ligand (S,S)-29. Asymmetric Tsuji–Trost reaction in

Rapid transformation of sulfinate salts into sulfonates promoted by a hypervalent iodine(III) reagent

• Elsa Deruer,
• Vincent Hamel,
• Samuel Blais and
• Sylvain Canesi

Beilstein J. Org. Chem. 2018, 14, 1203–1207, doi:10.3762/bjoc.14.101

• tolerates spectator functionalities such as primary halides or alkynes (Table 2). We were disappointed to observe no reaction in the presence of tertiary alcohols such as tert-butanol (Table 2, entry n). However, the reaction proceeded efficiently with a hindered secondary neopentylic alcohol 5 despite the

Iodine(III)-mediated halogenations of acyclic monoterpenoids

• Laure Peilleron,
• Tatyana D. Grayfer,
• Joëlle Dubois,
• Robert H. Dodd and
• Kevin Cariou

Beilstein J. Org. Chem. 2018, 14, 1103–1111, doi:10.3762/bjoc.14.96

• trisubstituted double bond occurred with excellent selectivity and moderate to good yields. Keywords: halogenation; hypervalent iodine; monoterpenes; Introduction In nature, mostly in marine environments, halogenated compounds are produced by means of various enzymes that rely on widely available halides as

• , which contains both iodine and chlorine atoms (Figure 1) [5]. This structural richness has fuelled the development of many synthetic strategies that take inspiration from these enzymatic machineries. A key aspect is to be able to mildly oxidize the halides into halenium equivalents in order to promote

The first Pd-catalyzed Buchwald–Hartwig aminations at C-2 or C-4 in the estrone series

• Ildikó Bacsa,
• Dávid Szemerédi,
• János Wölfling,
• Gyula Schneider,
• Lilla Fekete and
• Erzsébet Mernyák

Beilstein J. Org. Chem. 2018, 14, 998–1003, doi:10.3762/bjoc.14.85

• application of a Pd-catalyzed Buchwald–Hartwig amination. In recent years, extensive efforts have been made on the Pd(0)-catalyzed amination of aryl halides or triflates in order to achieve the efficient synthesis of substituted anilines [6][7][8][9]. Buchwald et al. stated that the Pd source is determining

Mechanochemistry of nucleosides, nucleotides and related materials

• Olga Eguaogie,
• Joseph S. Vyle,
• Patrick F. Conlon,
• Manuela A. Gîlea and
• Yipei Liang

Beilstein J. Org. Chem. 2018, 14, 955–970, doi:10.3762/bjoc.14.81

• achieved within 40 minutes at 25 Hz in the presence of ethyl acetate although the integrity of the vessel was compromised and significant levels of metallic copper were removed from the walls during work-up. Expeditious displacement of tosylate or halides from 5′-derivatised nucleosides was achieved using

Bromide-assisted chemoselective Heck reaction of 3-bromoindazoles under high-speed ball-milling conditions: synthesis of axitinib

• Jingbo Yu,
• Zikun Hong,
• Xinjie Yang,
• Yu Jiang,
• Zhijiang Jiang and
• Weike Su

Beilstein J. Org. Chem. 2018, 14, 786–795, doi:10.3762/bjoc.14.66

• reagent in the reaction, the substrate 1a was converted to 4a in 27% yield (conditions a), while the dehalogenation was exacerbated in the presence of Pd(OAc)2/PPh3 (conditions b). This phenomenon was in agreement with previous reports [14][15][16], that Pd-catalyzed homocoupling of aryl halides under

Nanoreactors for green catalysis

• M. Teresa De Martino,
• Loai K. E. A. Abdelmohsen,
• Floris P. J. T. Rutjes and
• Jan C. M. van Hest

Beilstein J. Org. Chem. 2018, 14, 716–733, doi:10.3762/bjoc.14.61

• unstable [Pd(allyl)Cl]2 intermediate from air. Micelles were also used to perform cross-coupling between benzyl and aryl halides in water [65]. This reaction is known to result in very limited yields due to the undesired homo-coupling reaction between electron-rich and electron-poor benzyl bromides [69

• et al. described a nanogel composed of poly(N-isopropylacrylamide) brushes grafted on Pd-NPs (Pd@PNIPAM) to carry out coupling reactions in water under mild conditions [120]. They showed highly efficient coupling of several hydrophobic aryl halides with phenylboronic acid, which in all cases resulted

Cobalt-catalyzed directed C–H alkenylation of pivalophenone N–H imine with alkenyl phosphates

• Wengang Xu and
• Naohiko Yoshikai

Beilstein J. Org. Chem. 2018, 14, 709–715, doi:10.3762/bjoc.14.60

• demonstrated that the combination of a cobalt–N-heterocyclic carbene (NHC) catalyst and a Grignard reagent allows for the arene C–H functionalization with organic halides and pseudohalides under the assistance of nitrogen directing groups [17][22][23][24][25][26][27]. In this connection, Ackermann developed a

• alkenes and alkylation/arylation using organic halides [29][30]. These previous studies have prompted us to expand the scope of cobalt catalysis for the C–H alkenylation and thus to develop an ortho C–H alkenylation reaction of pivalophenone N–H imine with alkenyl phosphates using a new cobalt–NHC

Liquid-assisted grinding and ion pairing regulates percentage conversion and diastereoselectivity of the Wittig reaction under mechanochemical conditions

• Kendra Leahy Denlinger,
• Lianna Ortiz-Trankina,
• Preston Carr,
• Kingsley Benson,
• Daniel C. Waddell and
• James Mack

Beilstein J. Org. Chem. 2018, 14, 688–696, doi:10.3762/bjoc.14.57

• halides (Table 4). Pairing of a hard acid (Li+ or Na+) with a moderately soft base (Br−) leads to no or poor conversion to stilbene products. Conversely, the best conversion resulted when combining Cs+ (soft acid) with Br− (borderline soft base). The benzyl benzoate side-product observed in trials 1, 2

• polystyrene, 2% cross-linked with divinylbenzene (PS-C6H4-PPh2) was obtained from Biotage® and used without further purification. Benzaldehyde was obtained from Sigma Aldrich and used without further purification. Alkyl halides and carbonate bases were obtained from Fisher Scientific and used without further

AuBr₃-catalyzed azidation of per-O-acetylated and per-O-benzoylated sugars

• Jayashree Rajput,
• Srinivas Hotha and
• Madhuri Vangala

Beilstein J. Org. Chem. 2018, 14, 682–687, doi:10.3762/bjoc.14.56

• -alkynic glycosyl donors, glycosyl halides [18], armed O-methyl glycosides [19], armed and disarmed thioglycosides [20] as well as trichloroacetimidate [21][22] donors were successfully applied to O- and C-glycosylations. Of the gold-catalyzed N-glycosylation reactions, Yu et al. demonstrated the effective

• ], glycoconjugates [30][31][32], N-glycosyl heterocycles [33][34], N-glycosyl triazole [35][36], etc. Glycosyl azides can be accessed from the corresponding glycosyl halides [37][38][39][40] by nucleophilic displacement with NaN3 or using trimethylsilyl azide in the presence of a phase transfer catalyst [41][42][43

Heterogeneous Pd catalysts as emulsifiers in Pickering emulsions for integrated multistep synthesis in flow chemistry

• Katharina Hiebler,
• Georg J. Lichtenegger,
• Manuel C. Maier,
• Eun Sung Park,
• Renie Gonzales-Groom,
• Bernard P. Binks and
• Heidrun Gruber-Woelfler

Beilstein J. Org. Chem. 2018, 14, 648–658, doi:10.3762/bjoc.14.52

• , Pd-catalysed C–C cross-coupling reactions have become indispensable in many modern synthetic protocols both in the laboratory and on an industrial scale. A highly important representative of this class of transformation is the Suzuki–Miyaura reaction [5][6], involving the coupling of aryl halides

Palladium-catalyzed ortho-halogenations of acetanilides with N-halosuccinimides via direct sp² C–H bond activation in ball mills

• Zi Liu,
• Hui Xu and
• Guan-Wu Wang

Beilstein J. Org. Chem. 2018, 14, 430–435, doi:10.3762/bjoc.14.31

• corresponding N-halosuccinimides. Keywords: acetanilide; ball milling; C–H activation; halogenation; mechanochemistry; N-halosuccinimide; palladium catalysis; Introduction Aryl halides have been widely utilized in organic syntheses, which give access to a range of complex natural products [1][2]. However

Recent developments in the asymmetric Reformatsky-type reaction

• Hélène Pellissier

Beilstein J. Org. Chem. 2018, 14, 325–344, doi:10.3762/bjoc.14.21

• ,R)-32a–p in moderate to good yields (56–85%) and moderate to excellent diastereoselectivities (72–90% de). As illustrated in Scheme 12, the asymmetric process tolerated a broad range of functional groups. For example, the reactions of chiral ketimines 25i–o bearing methyl, methoxy, halides, and

• ) and zinc in 2-Me-THF at 0 °C in the presence of CuCl. As shown in Scheme 13, a range of products 33a–m were obtained in both moderate to high yields (65–91%) and diastereoselectivities (70–96% de). Indeed, various substituents on each carbon (C4–C7) of the indolinone ring, such as halides, alkyl

Progress in copper-catalyzed trifluoromethylation

• Guan-bao Li,
• Chao Zhang,
• Chun Song and
• Yu-dao Ma

Beilstein J. Org. Chem. 2018, 14, 155–181, doi:10.3762/bjoc.14.11

• trifluoromethylation reagents. Review Copper-catalyzed trifluoromethylation of aryl and alkyl halides The first example of copper-promoted perfluoroalkylation of aromatic halides was presented in a US patent 1968 [9]. Since then, the copper-catalyzed trifluoromethylation of aromatic compounds has entered a stage of

• halides with traditional trifluoromethylation reagents and a trifluoromethyl-substituted sulfonium ylide as a new reagent The CuI-mediated cross-coupling protocol using TESCF3 was firstly reported by Urata and Fuchikami [11]. The proposed mechanism of this reaction was demonstrated in Scheme 1. But it was

• . Trifluoromethylation of aryl halides using trifluoroacetates as the trifluoromethyl source Reactions employing expensive electrophilic CF3 species such as Umemoto’s reagent or Togni’s reagent, were unpractical and limited on a large-scale synthesis. After comparison of the prices of different CF3 reagents, attention

Photocatalytic formation of carbon–sulfur bonds

• Alexander Wimmer and
• Burkhard König

Beilstein J. Org. Chem. 2018, 14, 54–83, doi:10.3762/bjoc.14.4

• disulfide, thioamide derivatives and sulfides Disulfides and thiosulfates Sulfoxides Sulfinic acids, sulfinate salts and sulfinamides Sulfonyl halides, sulfonyl hydrazines, thionyl chloride and sulfur dioxide C–S bond formations initiated by irradiation with light of wavelengths shorter than 380 nm or by

• of 4 equivalents of the thiol is needed for the reaction. The authors addressed this limitation in a later report (vide infra). Functional groups like alcohols, Boc-protected amines, carbonyls, esters and halides are tolerated. One year later, Yoon and co-workers described a redox mediator concept

• form an aryl radical. This reactive intermediate reacts with the anion of the respective thiol to form the corresponding diaryl sulfide adducts. The reaction conditions tolerate functional groups like alcohols, esters, halides, the trifluoromethyl group and heterocyclic substrates like thiazoles or

Reactivity of bromoselenophenes in palladium-catalyzed direct arylations

• Aymen Skhiri,
• Ridha Ben Salem,
• Jean-François Soulé and
• Henri Doucet

Beilstein J. Org. Chem. 2017, 13, 2862–2868, doi:10.3762/bjoc.13.278

• recent years, the Pd-catalyzed arylation, via a C–H bond activation, of a broad range of heteroaromatics using aryl halides as reaction partners was demonstrated to be particularly effective for the preparation of bi(hetero)aryls [22][23][24][25][26][27][28][29][30][31]. Among the reported results, a few

• examples of Pd-catalyzed direct arylations via the C–H bond activation of selenophenes using aryl halides as coupling partners have been reported [32][33][34][35]. Conversely, C–H bond activation methodology was employed in only in one case for the preparation of a heteroarylated selenophene from a

• , respectively. The use of 2-pentyl- and 2-chlorothiophenes also gave the desired products 10 and 11 in high yields. In general, the Pd-catalyzed direct arylation of 3-substituted thiophenes with aryl halides afforded quite regioselectively the C2-arylated thiophenes [30]. A similar regioselectivity was oberved

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation. Part 1: Use of CF₃SO₂Na

• Hélène Guyon,
• Hélène Chachignon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2764–2799, doi:10.3762/bjoc.13.272

• , scalable, achieved at room temperature, working with a variety of electron-deficient and -rich heteroaromatic systems tolerating various functional groups such as unprotected alcohols, amines, ketones, esters, halides and nitriles. Importantly, the trifluoromethylation proceeded at the innate reactive

Vinylphosphonium and 2-aminovinylphosphonium salts – preparation and applications in organic synthesis

• Anna Kuźnik,
• Roman Mazurkiewicz and
• Beata Fryczkowska

Beilstein J. Org. Chem. 2017, 13, 2710–2738, doi:10.3762/bjoc.13.269

• anticancer drugs, antioxidants, or functional probes into the mitochondria [5][6][7][8]. Review 1. Synthesis of vinylphosphonium salts 1.1. Alkylation of phosphines with alkyl halides One of the most common methods for the preparation of vinylphosphonium salts 1 is the quaternization of vinylphosphines with

• alkyl halides. Shutt and Trippett were able to alkylate vinylphosphines with methyl iodide or benzyl iodide, although attempts to use other alkyl halides, including benzyl bromide, ethyl bromoacetate and ethyl iodoacetate, in the presence of aprotic solvents provided only β-phosphonioylides 2 or

• ][13]. Vinyl halides are relatively less reactive alkylating agents. However, the use of readily available vinyl triflates 5 for the alkylation of triphenylphosphine in THF solution in the presence of a catalytic amount of (Ph3P)4Pd (1–3 mol %) gave the expected vinylphosphonium salts in a yield of 62

Palladium-catalyzed Heck-type reaction of secondary trifluoromethylated alkyl bromides

• Tao Fan,
• Wei-Dong Meng and
• Xingang Zhang

Beilstein J. Org. Chem. 2017, 13, 2610–2616, doi:10.3762/bjoc.13.258

• , developing efficient methods for the synthesis of such valuable structures has received less attention [10][11][12][13][14][15]. Commonly, fluoroalkylated alkenes can be prepared through fluoroalkyl radical addition of alkynes via an atom transfer pathway [16][17] or cross-coupling of alkenyl halides with

• of secondary fluoroalkylated alkyl bromides with alkenes remains a challenge and has not been reported so far [28][29][30][31][32] due to the sluggish oxidative addition [33] of alkyl halides to palladium and facile β-hydride elimination [34][35] of alkylpalladium species. Additionally, the resulting

• successfully employed to couple with a conjugated alkene and afforded the corresponding products 4d and 4h in good yields. The current cross coupling was also applicable to the secondary difluoroalkylated alkyl halides as demonstrated by the representative reaction of secondary ethyl 2,2-difluoro-2-iodoacetate

One-pot three-component route for the synthesis of S-trifluoromethyl dithiocarbamates using Togni’s reagent

• Azim Ziyaei Halimehjani,
• Martin Dračínský and
• Petr Beier

Beilstein J. Org. Chem. 2017, 13, 2502–2508, doi:10.3762/bjoc.13.247

• dithiocarbamates via a one-pot reaction of an amine, CS2 and an electrophile is of great interest due to its simplicity and environmental friendly procedure. Diverse electrophiles including alkyl halides [18], epoxides [19], alkenes [20][21][22], aldehydes [23], and alcohols [24] were applied for the synthesis of

Comparative profiling of well-defined copper reagents and precursors for the trifluoromethylation of aryl iodides

• Peter T. Kaplan,
• Jessica A. Lloyd,
• Mason T. Chin and
• David A. Vicic

Beilstein J. Org. Chem. 2017, 13, 2297–2303, doi:10.3762/bjoc.13.225

• bear the trifluoromethyl group have great importance in the life sciences and materials fields as well as discovery chemistry in general [1][2][3]. Consequently, transition-metal-catalyzed methods for preparing aromatic trifluoromethyl compounds from readily available aryl halides are an area that has

• seen rapid growth in the past ten years. Copper is one of the most successfully used metals for mediating the trifluoromethylation of aryl halides, and the active form of the reagents is typically a copper(I) complex bearing a trifluoromethyl ligand, i.e., [LnCu–CF3]. Sporadic examples of

• facilitate meaningful comparative studies, such as structural and electrochemical ones [2]. N-Heterocyclic carbene (NHC) complexes of copper such as A1 (Scheme 1) were the first well-defined and structurally characterized copper–CF3 complexes that display activity for the trifluoromethylation of aryl halides

Main group mechanochemistry

• Agota A. Gečiauskaitė and
• Felipe García

Beilstein J. Org. Chem. 2017, 13, 2068–2077, doi:10.3762/bjoc.13.204

• halides (AsI3 and SbCl3) have shown that selection of solution or mechanochemical conditions influence product stereoisomer distributions. In this case, the mechanochemical route increases the C1:C3 stereoisomer ratio in complexes 17 and 18 for As and Sb, respectively (see Scheme 7) [100]. The ability to

• cyclodiphosphazanes. Mechanochemical reactions of potassium 1,3-bis(trimethylsillylallyl) with group 13 (top) and 15 (bottom) halides. Synthesis of adamantoid phosphazane framework from its double-decker isomer for R = iPr and t-Bu (left and right, respectively). Acknowledgements Our work on this field is supported

Solid-state mechanochemical ω-functionalization of poly(ethylene glycol)

• Michael Y. Malca,
• Pierre-Olivier Ferko,
• Tomislav Friščić and
• Audrey Moores

Beilstein J. Org. Chem. 2017, 13, 1963–1968, doi:10.3762/bjoc.13.191

• bromoacyl halides, which introduces unnecessary ester groups instead of direct bromine substitution onto the polymer chain [34][36][37]. Next, we explored the thiolation by milling the mPEG–OTs with NaHS·xH2O for 90 min (Table 2, entries 3 and 4) as reagent, which afforded 1H NMR conversions of 55% and 78

Mechanochemical synthesis of small organic molecules

• Tapas Kumar Achar,
• Anima Bose and
• Prasenjit Mal

Beilstein J. Org. Chem. 2017, 13, 1907–1931, doi:10.3762/bjoc.13.186

• -free Wittig reaction of organic halides with aldehydes or ketones (Scheme 6) [55]. Suzuki Coupling In 2000, Peters and co-workers first reported the palladium-catalyzed Suzuki coupling reaction under ball-milling conditions [56]. In a planetary mill for 30–60 min, the mixture of aryl halide (1.0 equiv

• palladium salts (Pd(OAc)2 or Pd(PPh3)4) and DABCO (1,4-diazabicyclo[2.2.2]octane) various acetylenes and aryl halides were coupled to obtain the Sonogashira coupling products in excellent yields (near quantitative, Scheme 10a). The reactions were reported for aliphatic alkynes as well. In Scheme 10b, an

• significant in organic synthesis because aryl halides are important synthons for the synthesis of many natural and non-natural products [93][94]. In 2005, Rahman and co-workers reported a pioneering solid state benzylic bromination of diquinoline derivatives via N-bromosuccinimide (NBS) [95]. In 2012, Wang

Accessing simply-substituted 4-hydroxytetrahydroisoquinolines via Pomeranz–Fritsch–Bobbitt reaction with non-activated and moderately-activated systems

• Marco Mottinelli,
• Mathew P. Leese and
• Barry V. L. Potter

Beilstein J. Org. Chem. 2017, 13, 1871–1878, doi:10.3762/bjoc.13.182

• aforementioned aims, we envisaged that the synthesis set out in Scheme 2 could deliver access to substrates for the PFB reaction such as 9. After an initial, unfruitful, attempt to obtain the aminoacetals 9 from sequential condensation of aniline and alkyl and aryl halides, a double reductive alkylation that