Practical tetrafluoroethylene fragment installation through a coupling reaction of (1,1,2,2-tetrafluorobut-3-en-1-yl)zinc bromide with various electrophiles

• Ken Tamamoto,
• Shigeyuki Yamada and
• Tsutomu Konno

Beilstein J. Org. Chem. 2018, 14, 2375–2383, doi:10.3762/bjoc.14.213

• ), which can efficiently construct a new C–C bond [30][31][32]. Thus, we aimed at the development of an efficient preparation of a thermally stable organozinc reagent, possessing a CF2CF2 fragment as a thermally stable tetrafluoroethylenating agent, and successive C–C bond formation to produce a wide

• tetrafluoroethyllithium [12][25] and -magnesium species [22][23]. The synthetic uses of 2-Zn as a promising tetrafluorinating agent were tested in several reactions. First, we demonstrated a typical C–C bond formation reaction. Treating freshly prepared 2-Zn (ca. 0.70 M in DMF) with 5.0 equiv of iodobenzene (3a) in the

A challenging redox neutral Cp*Co(III)-catalysed alkylation of acetanilides with 3-buten-2-one: synthesis and key insights into the mechanism through DFT calculations

• Andrew Kenny,
• Alba Pisarello,
• Arron Bird,
• Paula G. Chirila,
• Alex Hamilton and
• Christopher J. Whiteoak

Beilstein J. Org. Chem. 2018, 14, 2366–2374, doi:10.3762/bjoc.14.212

• energy difference between the C–H activation and C–C bond formation steps makes identification of the rate limiting step difficult by DFT calculations alone, however, parallel kinetic isotope effect (KIE) experiments do suggest that the C–H activation step is not rate limiting (KIE = 1.3), which is not

Hydroarylations by cobalt-catalyzed C–H activation

• Rajagopal Santhoshkumar and
• Chien-Hong Cheng

Beilstein J. Org. Chem. 2018, 14, 2266–2288, doi:10.3762/bjoc.14.202

• found intermolecular kinetic isotope effect (KIE) of kH/kD = 2.1 and H/D crossover studies strongly suggest that the reaction proceeds through an oxidative addition of a C–H bond to low-valent cobalt followed by alkyne insertion and reductive elimination. Furthermore, the new C–C bond formation occurred

• took place selectively at the more hindered C-2 position of aziridines, which results in high regioselectivity. 5.2 Cobalt(III)-catalyzed hydroarylation of C=X bonds As the Co(III)Cp* catalyst acts an efficient air-stable catalyst for hydroarylation of the C=C bond, it would also provide a user

Tetrathiafulvalene – a redox-switchable building block to control motion in mechanically interlocked molecules

• Hendrik V. Schröder and
• Christoph A. Schalley

Beilstein J. Org. Chem. 2018, 14, 2163–2185, doi:10.3762/bjoc.14.190

• paramagnetic radicals, the resulting dimer has a diamagnetic character due to radical pairing. Although the distance of ≈3.5 Å between the two 1●+ molecules in the dimer is considerably large in comparison to a C–C bond (≈1.5 Å), the interaction can be considered as a type of multi-centered two-electron bond

Hypervalent iodine compounds for anti-Markovnikov-type iodo-oxyimidation of vinylarenes

• Igor B. Krylov,
• Stanislav A. Paveliev,
• Mikhail A. Syroeshkin,
• Alexander A. Korlyukov,
• Pavel V. Dorovatovskii,
• Yan V. Zubavichus,
• Gennady I. Nikishin and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2018, 14, 2146–2155, doi:10.3762/bjoc.14.188

• the examined hypervalent iodine oxidants (PIDA, PIFA, IBX, DMP) PhI(OAc)2 proved to be the most effective; yields of iodo-oxyimides are 34–91%. A plausible reaction pathway includes the addition of an imide-N-oxyl radical to the double C=C bond and trapping of the resultant benzylic radical by iodine

• the reactions of styrenes with imide-N-oxyl radicals, in which the latter add to the terminal position of the double C=C bond with the formation of stabilized benzyl radicals, which undergo the subsequent functionalization. In the presence of oxygen or tert-butyl hydroperoxide, oxidation proceeds to

• mechanism for the reaction of iodo-oxyimidation of styrenes under the action of the NHPI/I2/PhI(OAc)2 system was proposed (Scheme 3). On the first step, NHPI (2a) is oxidized by PhI(OAc)2 to form PINO radical. The addition of PINO to the double C=C bond of styrene (1a) leads to the formation of intermediate

Applications of organocatalysed visible-light photoredox reactions for medicinal chemistry

• Michael K. Bogdos,
• Emmanuel Pinard and
• John A. Murphy

Beilstein J. Org. Chem. 2018, 14, 2035–2064, doi:10.3762/bjoc.14.179

• related transition metal-catalysed C–C bond forming reactions are in the top 5 most used reactions in medicinal chemistry [45]. Therefore, the development of metal-free variants of these types of reactions is a very attractive goal. An interesting approach was taken by König et al., who report the

• are better suited to be included in the late stage functionalisation (LSF) section. 2.4 Reactions manipulating hydrocarbon backbones The reactions of hydrocarbons are central to building the scaffolds of molecules. This is also true in medicinal chemistry. There are countless C–C bond-forming

Cobalt-catalyzed nucleophilic addition of the allylic C(sp³)–H bond of simple alkenes to ketones

• Tsuyoshi Mita,
• Masashi Uchiyama,
• Kenichi Michigami and
• Yoshihiro Sato

Beilstein J. Org. Chem. 2018, 14, 2012–2017, doi:10.3762/bjoc.14.176

• -olefins (CxH2x) are abundantly present in nature or are readily accessible, they should be appropriate starting materials for C–C bond forming reactions to create organic frameworks of value-added compounds such as natural products, drugs, and fine chemicals. There have been tremendous synthetic methods

• involving catalytic C–C bond construction with the double bond of terminal alkenes (e.g., Heck reaction, hydrometalation followed by functionalization, carbometalation, and olefin metathesis) [10][11][12][13]. However, direct C–C bond formation of the allylic C(sp3)–H bond adjacent to double bonds has

• -catalyzed C–C bond formation using a stoichiometric amount of an oxidant [16][17][18][19][20][21][22], the π-allylpalladium intermediate [23][24][25] is an electrophilic species that exclusively reacts with nucleophiles. Therefore, it would be a formidable challenge for the generation of a nucleophilic π

Synthesis and characterization of π–extended “earring” subporphyrins

• Haiyan Guan,
• Mingbo Zhou,
• Bangshao Yin,
• Ling Xu and
• Jianxin Song

Beilstein J. Org. Chem. 2018, 14, 1956–1960, doi:10.3762/bjoc.14.170

• bonds in the subporphyrin moiety are of similar lengths (1.383(6)–1.447(5) Å). In contrast, the C–C bond lengths in the tripyrrin moiety alternate (1.341(5)–1.472(5) Å). These data clearly indicate that the subporphyrin moiety remains its aromaticity while the tripyrrin moiety participates in an

• the metal does not change the antiaromatic pathways in 3. Fortunately we obtained single crystals of 3Pd from its CH2Cl2/CDCl3/MeOH solution via vapor diffusion. All of the bond lengths were carefully measured based on the diffraction results (Figure 4). We found that despite all peripheral C–C bond

Asymmetric Michael addition reactions catalyzed by calix[4]thiourea cyclohexanediamine derivatives

• Zheng-Yi Li,
• Hong-Xiao Tong,
• Yuan Chen,
• Hong-Kui Su,
• Tangxin Xiao,
• Xiao-Qiang Sun and
• Leyong Wang

Beilstein J. Org. Chem. 2018, 14, 1901–1907, doi:10.3762/bjoc.14.164

• acetylacetone on the nitrostyrene creates a new C–C bond forming binary complex C from which the enantioselective product is released. Conclusion In summary, we have synthesized a series of upper rim-functionalized calix[4]arene-based chiral cyclohexanediamine thiourea catalysts 1–3 and tested as

Synthesis of 9-arylalkynyl- and 9-aryl-substituted benzo[b]quinolizinium derivatives by Palladium-mediated cross-coupling reactions

• Siva Sankar Murthy Bandaru,
• Darinka Dzubiel,
• Heiko Ihmels,
• Mohebodin Karbasiyoun,
• Mohamed M. A. Mahmoud and
• Carola Schulzke

Beilstein J. Org. Chem. 2018, 14, 1871–1884, doi:10.3762/bjoc.14.161

• along the a axis. In 2a both interactions are with the same neighbor leading to distinct dimeric associates. In the individual molecules, the C–C bond lengths of the alkyne unit are 1.24 Å (C14–C15) for the triple bond and 1.41 Å (C13–C14 and C15–C16) for the single bonds in compound 2a, while in

Host–guest complexes of conformationally flexible C-hexyl-2-bromoresorcinarene and aromatic N-oxides: solid-state, solution and computational studies

• Rakesh Puttreddy,
• Ngong Kodiah Beyeh,
• S. Maryamdokht Taimoory,
• Daniel Meister,
• John F. Trant and
• Kari Rissanen

Beilstein J. Org. Chem. 2018, 14, 1723–1733, doi:10.3762/bjoc.14.146

• relatively high when compared to BrC2 (range, 0.08–1.06 Å) and BrC3 (range, 0.32–1.81 Å) values. In solid-state crystals, the lower-rim hexyl chains which prefer different orientations due to C–C bond flexibility cause BrC6 to crystallise as non-centrosymmetric hosts in all H–G complexes. In our previous

• exo complex [39]. In 12@BrC6 (Figure 2i), the C–C bond rotation in guest 12 allows one aromatic ring to reside inside the cavity at h = 2.83 Å. The H–G molecules are positioned primarily by the π···π contacts rather than C–H···π interactions, with a short C···C contact being ca. 3.20 Å. Furthermore

• , since 11 is able to undergo C–C bond rotation, BrC6 tends to maintain a nearly ideal crown geometry suggesting excellent conformational complementarity between 11 and BrC6. Comparison of ditopic H–G complexes In 3@BrC6, the asymmetric unit contains one host and four guest 3 molecules. Of the four guests

β-Hydroxy sulfides and their syntheses

• Mokgethwa B. Marakalala,
• Edwin M. Mmutlane and
• Henok H. Kinfe

Beilstein J. Org. Chem. 2018, 14, 1668–1692, doi:10.3762/bjoc.14.143

• mechanism adumbrated in Scheme 29 [66]. The thiyl radical resulting from the initial reaction of TBHP and thiophenol selectively adds to the terminal end of the C=C bond of 80 to form intermediate radical 82. Oxidation with O2 leads to the formation of peroxy radical 83, which abstracts a hydrogen radical

Glycosylation reactions mediated by hypervalent iodine: application to the synthesis of nucleosides and carbohydrates

• Yuichi Yoshimura,
• Hideaki Wakamatsu,
• Yoshihiro Natori,
• Yukako Saito and
• Noriaki Minakawa

Beilstein J. Org. Chem. 2018, 14, 1595–1618, doi:10.3762/bjoc.14.137

• alternative method for constructing glycosidic bonds of nucleoside derivatives by using a glycal as sugar donor. Its usefulness was proved by applying the reaction to synthesize new nucleoside derivatives as mentioned above. Synthesis of acyclic nucleosides It is known that the oxidative C–C bond cleavage of

Cobalt-catalyzed C–H cyanations: Insights into the reaction mechanism and the role of London dispersion

• Eric Detmar,
• Valentin Müller,
• Daniel Zell,
• Lutz Ackermann and
• Martin Breugst

Beilstein J. Org. Chem. 2018, 14, 1537–1545, doi:10.3762/bjoc.14.130

• -electron intermediate 8a yielding 9a. Next, the insertion of the cyanating agent 2a into the cobalt–carbon bond takes place through TS3a. Within the four-membered transition state (Figure 2), the C–C bond to be formed is still rather long (C–C distance 1.92 Å), while the C–N distance is already

Hypervalent organoiodine compounds: from reagents to valuable building blocks in synthesis

• Gwendal Grelier,
• Benjamin Darses and
• Philippe Dauban

Beilstein J. Org. Chem. 2018, 14, 1508–1528, doi:10.3762/bjoc.14.128

• the limiting components, with nearly quantitative yields and complete diastereoselectivity [102][103][104][105]. Such a highly efficient atom-transfer process has provided the opportunity to design a tandem of C–N and C–C bond-forming reactions that relies on an initial step of catalytic nitrene

Steric “attraction”: not by dispersion alone

• Ganna Gryn’ova and
• Clémence Corminboeuf

Beilstein J. Org. Chem. 2018, 14, 1482–1490, doi:10.3762/bjoc.14.125

• not even a limit and stable diamondoid dimer with a central C–C bond as long as 1.71 Å has been achieved [7][8]. Bulky alkyl groups assist not only in achieving the longest C–C bonds, but also the shortest intermolecular H···H contacts [9], which are otherwise tackled by squeezing them inside the

Spectroelectrochemical studies on the effect of cations in the alkaline glycerol oxidation reaction over carbon nanotube-supported Pd nanoparticles

• Dennis Hiltrop,
• Steffen Cychy,
• Karina Elumeeva,
• Wolfgang Schuhmann and
• Martin Muhler

Beilstein J. Org. Chem. 2018, 14, 1428–1435, doi:10.3762/bjoc.14.120

• varying the potential between 0.77 and 1.17 V vs RHE: at low potentials oxidized C3 species such as mesoxalate and tartronate were formed predominantly, and with increasing potentials C2 and C1 species originating from C–C bond cleavage were identified. The tendency to produce carbonate was found to be

• spectroscopy to determine the nature of the formed products and identified carbonate and oxalate as the main products in addition to traces of glycolate and CO. By comparing the ratio of the integrated band intensities for oxalate and carbonate they concluded that C–C bond scission is influenced by the cation

• oxalate (1310 cm−1) [15][16]. Glycerate and glycolate are presumably also present. Both contain one fully oxidized terminal C atom and by cleaving the C–C bond in glycerate, glycolate can be obtained. Thus, the easiest differentiation would be by a ν(C–O) band at around 1125 cm−1 [15]. This band is not

[3 + 2]-Cycloaddition reaction of sydnones with alkynes

• Veronika Hladíková,
• Jiří Váňa and
• Jiří Hanusek

Beilstein J. Org. Chem. 2018, 14, 1317–1348, doi:10.3762/bjoc.14.113

• found Taran’s suggestion as the most plausible because of the lowest activation free energy (ΔG‡ = 25.4 kcal·mol−1) and due to the observed 1,4-regiocontrol. Intrinsic reaction coordinate (IRC) calculations also showed concerted but asynchronous formation of the pyrazole ring, through initial C–C bond

An unusual thionyl chloride-promoted C−C bond formation to obtain 4,4'-bipyrazolones

• Gernot A. Eller,
• Gytė Vilkauskaitė,
• Algirdas Šačkus,
• Vytas Martynaitis,
• Ashenafi Damtew Mamuye,
• Vittorio Pace and
• Wolfgang Holzer

Beilstein J. Org. Chem. 2018, 14, 1287–1292, doi:10.3762/bjoc.14.110

A survey of chiral hypervalent iodine reagents in asymmetric synthesis

• Soumen Ghosh,
• Suman Pradhan and
• Indranil Chatterjee

Beilstein J. Org. Chem. 2018, 14, 1244–1262, doi:10.3762/bjoc.14.107

• application due to their reduced toxicity, ready availability and lower costs as replacement for transition metals leading to several “metal-free” like chemical transformations. The ongoing demand of modern synthetic chemistry for the development of catalytic enantioselective C–C bond formation reactions

• the enolate intermediate 111 followed by the generation of a C–C bond via conjugate addition delivered intermediate carbene 113. A 1,2-hydrogen shift led to the formation of products 108 with enantioselectivities up to 79% (Scheme 24). Later, Maruoka et al. improved the enantioselectivity up to 95% ee

One hundred years of benzotropone chemistry

• Arif Dastan,
• Haydar Kilic and
• Nurullah Saracoglu

Beilstein J. Org. Chem. 2018, 14, 1120–1180, doi:10.3762/bjoc.14.98

• benzotropylium ion 45. Secondly, 11 is obtained in 18% yield after benzylic bromination of 42 with NBS, followed by in situ elimination reaction of the labile bromide 43 mediated by t-BuOK (Scheme 9). Palladium-catalyzed C–C bond-formation reactions such as Heck and Sonogashira couplings are employed in a wide

Hypervalent iodine-guided electrophilic substitution: para-selective substitution across aryl iodonium compounds with benzyl groups

• Cyrus Mowdawalla,
• Faiz Ahmed,
• Tian Li,
• Kiet Pham,
• Loma Dave,
• Grace Kim and
• I. F. Dempsey Hyatt

Beilstein J. Org. Chem. 2018, 14, 1039–1045, doi:10.3762/bjoc.14.91

• congruence with the reductive iodonio-Claisen rearrangement (RICR) to show that there may be an underlying mechanism which expands the reasoning behind the previously known C–C bond-forming reaction. By rationalizing the hypervalent iodine’s metal-like properties it was concluded that a transmetallation

• that many of these useful reagents became a staple in synthetic chemistry laboratories [1][2]. Although hypervalent iodine reagents are commonly used in oxidation reactions, they have also found their own niche in useful C–C bond-formation and C–H activation reactions [3][4][5]. One such C–C bond

• same reaction conditions as the RICR. The resulting diphenylmethane structure obtained after the C–C bond formation could have relevant medicinal applications since it is the core of many marketed pharmaceutical drugs with antihistaminic and anxiolytic properties [23][24][25][26]. Results and

Anodic oxidation of bisamides from diaminoalkanes by constant current electrolysis

• Tatiana Golub and
• James Y. Becker

Beilstein J. Org. Chem. 2018, 14, 861–868, doi:10.3762/bjoc.14.72

• anodic oxidation of II-3. Anodic splitting of C–C bond in bisamides in the presence of LiClO4 electrolyte. Anodic splitting of C–C bond in bisamides in the presence of Et4NBF4 electrolyte. A suggested mechanism for anodic methoxylation of amides. Mechanisms of formation of fragmentation products

Recent advances in synthetic approaches for medicinal chemistry of C-nucleosides

• Kartik Temburnikar and
• Katherine L. Seley-Radtke

Beilstein J. Org. Chem. 2018, 14, 772–785, doi:10.3762/bjoc.14.65

• . Replacing the hemiaminal (O–C–N) connectivity of the canonical nucleosides with an O–C–C bond (Figure 3) results in a class of compounds called “C-nucleosides” [45][46][47][48][49][50][51]. Further modification to a C–C–C connectivity results in “carbocyclic C-nucleosides” (Figure 3) [52][53]. C-nucleosides

• feature (hetero)aryl aromatic groups such as 9-deazapurines, pyrimidines, pyridines and phenyl groups connected by a C–C bond to a sugar (or sugar mimic) as shown in Figure 4 [30][45][46][47][50][54][55][56][57]. The change in the nature of the glycosidic bond is accompanied by i) increased hydrolytic

• of a pre-synthesized (hetero)aryl with a ribosyl moiety (Figure 5A) [48][49][62]. The C–C bond formation usually involves a functional group at C1' of the ribosyl moiety that is amenable to additional functionalization (Figure 5B). Like other nucleoside coupling approaches (other than the well-known

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

• alkenylation reaction of pivalophenone N–H imine with an alkenyl phosphate. The reaction tolerates various substituted pivalophenone N–H imines as well as cyclic and acyclic alkenyl phosphates. Keywords: alkenylation; C–C bond formation; C–H activation; cobalt; imine; Introduction Transition-metal-catalyzed

• obtained in an E-rich form from an E/Z mixture (1:1) of the starting alkenyl phosphate, demonstrating the E/Z isomerization during the C–C-bond formation. The E/Z isomerization was also observed for the conversion of cyclododecenyl phosphate (E/Z = 9:1) to the product 3af (E/Z = 3:1). Expectedly, 4

• radical to give a diorganocobalt intermediate C. The C–C-bond rotation of the radical anion 2•− or the transiently formed alkenyl radical might be responsible for the stereochemical mutation of the C=C bond observed in some cases. The reductive elimination of C and subsequent transmetalation with the