Copper-catalysed alkylation of heterocyclic acceptors with organometallic reagents

• Yafei Guo and
• Syuzanna R. Harutyunyan

Beilstein J. Org. Chem. 2020, 16, 1006–1021, doi:10.3762/bjoc.16.90

• Yafei Guo Syuzanna R. Harutyunyan Stratingh Institute for Chemistry, University of Groningen, Nijenborgh 4, 9747 AG, Groningen, The Netherlands 10.3762/bjoc.16.90 Abstract Copper-catalysed asymmetric C–C bond-forming reactions using organometallic reagents have developed into a powerful tool for

• organometallic reagents to various acceptors is a useful strategy for C–C bond-forming reactions [1][2][3][4]. These important transformations have been thoroughly developed in the last few decades and were widely used in the synthesis of chiral natural products and bioactive molecules [5][6][7][8]. The majority

• acceptors in highly enantioselective C–C bond-forming reactions with organometallics. The work highlighted in this minireview is divided into two sections, based on the position where the bond is formed. The first part focuses on acceptors in which the reacting unsaturated double bond is embedded into the

Recent applications of porphyrins as photocatalysts in organic synthesis: batch and continuous flow approaches

• Rodrigo Costa e Silva,
• Luely Oliveira da Silva,
• Aloisio de Andrade Bartolomeu,
• Timothy John Brocksom and
• Kleber Thiago de Oliveira

Beilstein J. Org. Chem. 2020, 16, 917–955, doi:10.3762/bjoc.16.83

• metal-organic (MOF) and covalent-organic frameworks (COF), have significantly expanded the use of these compounds in photoredox catalysis due to the singular electronic features of these materials and chemical robustness as catalysts. The appearance of porphyrins as photoredox catalysts for C–C bond

Copper catalysis with redox-active ligands

• Agnideep Das,
• Yufeng Ren,
• Cheriehan Hessin and
• Marine Desage-El Murr

Beilstein J. Org. Chem. 2020, 16, 858–870, doi:10.3762/bjoc.16.77

• phenols, ketones and 1,3-dienes (Scheme 6) [27]. C–C bond formation Complexes of radical and redox-active ligands with transition metals are known to be able to promote radical reactions through single-electron transfer (SET) processes [28]. Expanding on the research area pioneered by Wieghardt and

Photocatalytic deaminative benzylation and alkylation of tetrahydroisoquinolines with N-alkylpyrydinium salts

• David Schönbauer,
• Carlo Sambiagio,
• Timothy Noël and
• Michael Schnürch

Beilstein J. Org. Chem. 2020, 16, 809–817, doi:10.3762/bjoc.16.74

• methods for C–C bond formation at the α position of these amines have been studied under photoredox catalysis (Scheme 1) [23][24][25][26]. Among the functionalized THIQs, 1-benzyl-substituted analogues were shown to be able to modulate Ca/K channels, and the synthesis of these compounds is therefore of

• . Further investigations in this direction are ongoing in our labaratories. Kinetic profile for the benzylation of 1 to 3. Examples of photocatalytic C–C bond formation by nucleophilic trapping of a reactive THIQ intermediate. Benzylation of N-phenyl-THIQ. Benzylation of substituted N-arylTHIQs. Removal of

One-pot synthesis of dicyclopenta-fused peropyrene via a fourfold alkyne annulation

• Ji Ma,
• Yubin Fu,
• Junzhi Liu and
• Xinliang Feng

Beilstein J. Org. Chem. 2020, 16, 791–797, doi:10.3762/bjoc.16.72

• (Figure 2c). In addition, the C–C bond lengths in 1 are shown in Figure 2d. The short lengths of the black bold bonds (1.368–1.392 Å) in 1 suggested their double bond character (C=C is typically 1.337 Å). These results are in good agreement with the resonance structure of 1 that is assigned by Clar’s

Reaction of indoles with aromatic fluoromethyl ketones: an efficient synthesis of trifluoromethyl(indolyl)phenylmethanols using K₂CO₃/n-Bu₄PBr in water

• Thanigaimalai Pillaiyar,
• Masoud Sedaghati and
• Gregor Schnakenburg

Beilstein J. Org. Chem. 2020, 16, 778–790, doi:10.3762/bjoc.16.71

• advantages of this protocol. Keywords: C–C-bond formation; C3-funtionalization of indole; diindolylmethane; Friedel–Crafts reaction; indole; indole-3-carbinol; large-scale synthesis; recyclability; Introduction (1H-Indol-3-yl)methanols have emerged as versatile pre-electrophiles for C–C functionalization

• makes a hydrogen bond interaction with the NH of the 5-methoxyindole (1a) and form the adduct B. This interaction assists 1a reacting with an electrophilic ketone (2a) to form the intermediate D via C–C bond formation (C). Re-aromatization of D generates E, which then protonates to form the desired

Recent advances in Cu-catalyzed C(sp³)–Si and C(sp³)–B bond formation

• Balaram S. Takale,
• Ruchita R. Thakore,
• Elham Etemadi-Davan and
• Bruce H. Lipshutz

Beilstein J. Org. Chem. 2020, 16, 691–737, doi:10.3762/bjoc.16.67

• enantioselectivity was reported by Hartwig et al. in 2016 [99]. The newly formed C–B bond reacted with a range of electrophiles to deliver products containing C–C, C–N, and C–X (X = Br, Cl) bonds (e.g., 349, 350). Efforts to explore the mechanism revealed a decrease in regioselectivity when the C=C bond is further

• through subsequent C–C bond formation (Scheme 72) [135]. The proposed mechanism involves the formation of L–Cu–O–t-Bu 458 which reacts with B2pin2 to generate L-Cu-Bpin 459. The subsequent coordination to the aldehyde results in the intermediate 461. Upon protonation of 461 the desired enantiomerically

• an appropriate electrophile led to C–C bond formation, ultimately delivering chiral tertiary alcohols. Mechanistic studies and DFT calculations showed that an in situ-formed borylcopper(I) species is responsible for the 1,2-addition (Scheme 73) [136]. C,O-Diboration of ketones 464 was explored using

Synthesis of organic liquid crystals containing selectively fluorinated cyclopropanes

• Zeguo Fang,
• Nawaf Al-Maharik,
• Peer Kirsch,
• Matthias Bremer,
• Alexandra M. Z. Slawin and
• David O’Hagan

Beilstein J. Org. Chem. 2020, 16, 674–680, doi:10.3762/bjoc.16.65

• should induce a large value for dielectric anisotropy. Compounds 8 and 9 were found to exhibit the expected negative Δε values, however, the overall polarity is low (8 = −0.5, 9 = −0.2). This is presumably due to the ability of the C–C bond attached to cyclopropane to rotate, and thus the compound will

• conformational analysis of 11a (and 11b) was conducted computationally (ωB97X-D/6-311+G(2d,p)//ωB97X-D/6-31G(d) + ZPE level (see Supporting Information File 1)). There are many potential low energy conformations arising from alkyl side chain C–C bond rotations which would not be anticipated to change the overall

• properties significantly, however, we were interested in assessing the energy required for the bispirocyclohexane ring to adopt an axial rather than the lower energy equatorial arrangement. For 11a, the lowest energy conformer found was a rotamer around the central C–C bond linking the cyclohexane rings, but

Regioselectively α- and β-alkynylated BODIPY dyes via gold(I)-catalyzed direct C–H functionalization and their photophysical properties

• Takahide Shimada,
• Shigeki Mori,
• Masatoshi Ishida and
• Hiroyuki Furuta

Beilstein J. Org. Chem. 2020, 16, 587–595, doi:10.3762/bjoc.16.53

• novel functional fluorescent materials. (a) Chemical structures of BODIPY (1) and dipyrromethane (2). (b) C–C bond forming alkynylations of pyrrole and its derivatives by Sonogashira coupling and electrophilic alkynylation. (c) Peripheral alkynylated BODIPY derivatives (3–6) prepared in this work. TIPS

Copper-catalyzed enantioselective conjugate reduction of α,β-unsaturated esters with chiral phenol–carbene ligands

• Shohei Mimura,
• Sho Mizushima,
• Yohei Shimizu and
• Masaya Sawamura

Beilstein J. Org. Chem. 2020, 16, 537–543, doi:10.3762/bjoc.16.50

• , while an achiral NHC/copper catalyst has successfully been utilized in this reaction [13]. Meanwhile, we devoted our effort to develop novel enantioselective C–C bond formation reactions utilizing chiral phenol–NHC/copper catalyst systems [14][15][16][17][18], in which the phenol group of the NHC ligand

Controlling alkyne reactivity by means of a copper-catalyzed radical reaction system for the synthesis of functionalized quaternary carbons

• Goki Hirata,
• Yu Yamane,
• Naoya Tsubaki,
• Reina Hara and
• Takashi Nishikata

Beilstein J. Org. Chem. 2020, 16, 502–508, doi:10.3762/bjoc.16.45

• Pd-catalyzed cascade reaction (C–C bond formation/C–H cyclization process) of N-arylpropynamide 4 for the preparation of indolinone derivatives 5 was previously reported by Li’s group [34][35]. In another report on C–H cyclization by Lei’s group, Ni-catalyzed aromatic C–H alkylation occurs via a

KOt-Bu-promoted selective ring-opening N-alkylation of 2-oxazolines to access 2-aminoethyl acetates and N-substituted thiazolidinones

• Qiao Lin,
• Shiling Zhang and
• Bin Li

Beilstein J. Org. Chem. 2020, 16, 492–501, doi:10.3762/bjoc.16.44

• to synthesize thiazolidinone derivatives through a Barton–McCombie pathway in 2015 [17] (Scheme 1b). Recently, potassium tert-butoxide has been shown to be an efficient promoter for C–C-bond formation reactions [18][19][20][21][22]. However, only few reports described C–N-bond cross-coupling

Visible-light-induced addition of carboxymethanide to styrene from monochloroacetic acid

• Kaj M. van Vliet,
• Nicole S. van Leeuwen,
• Albert M. Brouwer and
• Bas de Bruin

Beilstein J. Org. Chem. 2020, 16, 398–408, doi:10.3762/bjoc.16.38

• of photoredox catalytic C–C bond formation, its application in the field of atom transfer radical addition (ATRA) reactions is very important. Remarkably, this type of C–C bond formation became only popular in 2011, while the first example was already published by Barton in 1994 [28]. Recently

• contains a carboxyl group that could perhaps be oxidatively decarboxylated to generate a chloromethyl radical. In this study, we investigated the possibility of redox neutral, visible light photoredox catalyzed C–C bond formation with monochloroacetic acid. Results and Discussion First, we used cyclic

• monochloroacetic acid. Based on these data, we concluded that the visible-light-promoted reductive photoredox C–C bond coupling reaction with monochloroacetic acid should be possible. As such, we chose fac-[Ir(ppy)3] and [Cu(dap)2]Cl for the photoredox reaction between monochloroacetic acid and styrene in

Room-temperature Pd/Ag direct arylation enabled by a radical pathway

• Amy L. Mayhugh and
• Christine K. Luscombe

Beilstein J. Org. Chem. 2020, 16, 384–390, doi:10.3762/bjoc.16.36

• growth are the expensive, toxic, and energy-intensive methods in which these materials are typically prepared [1]. Direct arylation is one solution to these problems, which allows improved atom and step economy in polymer synthesis. Traditional coupling methods form a new C–C bond using a reactive C–M

Synthesis of 3-alkenylindoles through regioselective C–H alkenylation of indoles by a ruthenium nanocatalyst

• Abhijit Paul,
• Debnath Chatterjee,
• Srirupa Banerjee and
• Somnath Yadav

Beilstein J. Org. Chem. 2020, 16, 140–148, doi:10.3762/bjoc.16.16

• recovered catalyst to TEM and TEM–SAED analysis (Figures S12 and S13, Supporting Information File 1) and found that it remained consistent with “fresh” RuNC. Homogeneous vs heterogeneous mechanism of catalysis The actual nature of the catalytic species in metal nanoparticle-catalysed C–C bond formation

[1,3]/[1,4]-Sulfur atom migration in β-hydroxyalkylphosphine sulfides

• Katarzyna Włodarczyk,
• Piotr Borowski and
• Marek Stankevič

Beilstein J. Org. Chem. 2020, 16, 88–105, doi:10.3762/bjoc.16.11

• retained its nucleophilic character. This allowed the coordination of an AlCl3 molecule to the C=C bond, which then became susceptible to an intramolecular nucleophilic attack by a sulfur atom. For α,β-alkenylphosphine sulfide 35, the conjugation of the double bond with thiophosphoryl fragment made the

• with the double bond, yielding IV in a slightly exothermic process. The formed intermediate possessing an activated C=C bond underwent intramolecular carbon–sulfur bond formation through the transition state V. In this case, the reaction proceeded solely at the γ-carbon atom, and all attempts directed

Extension of the 5-alkynyluridine side chain via C–C-bond formation in modified organometallic nucleosides using the Nicholas reaction

• Renata Kaczmarek,
• Dariusz Korczyński,
• James R. Green and
• Roman Dembinski

Beilstein J. Org. Chem. 2020, 16, 1–8, doi:10.3762/bjoc.16.1

• confirmed that the Nicholas reaction can be carried out in a nucleoside presence, leading to a divergent synthesis of novel metallo-nucleosides enriched with alkene, arene, arylketo, and heterocyclic functions, in the deoxy and ribo series. Keywords: alkynes; 5-alkynyluridines; C–C-bond formation; dicobalt

Why do thioureas and squaramides slow down the Ireland–Claisen rearrangement?

• Dominika Krištofíková,
• Juraj Filo,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2019, 15, 2948–2957, doi:10.3762/bjoc.15.290

• h. ωB97X-D/6-31G* calculated uncatalyzed Ireland–Claisen rearrangement of 1c. Charges on allylic oxygen (blue); C–O bond-breaking and C–C bond-forming distances in TS (black). ωB97X-D/6-31G* calculated Schreiner thiourea (12)-catalyzed Ireland–Claisen rearrangement of 1c. Charges on allylic oxygen

• (blue); C–O bond-breaking and C–C bond-forming distances in TS (black); hydrogen-bond distances (black). ωB97X-D/6-31G* calculated Ph-thiourea (top) and squaramide-catalyzed (bottom) Ireland–Claisen rearrangement of 1c. Charges on allylic oxygen (blue); C–O bond-breaking and C–C bond-forming distances

A green, economical synthesis of β-ketonitriles and trifunctionalized building blocks from esters and lactones

• Daniel P. Pienaar,
• Kamogelo R. Butsi,
• Amanda L. Rousseau and
• Dean Brady

Beilstein J. Org. Chem. 2019, 15, 2930–2935, doi:10.3762/bjoc.15.287

• excess of reagents, hazardous, flammable, or toxic reagents and high temperatures are required, which, in turn, may be detrimental to more highly functionalized starting materials. Nevertheless, this reaction under milder conditions is a valuable C–C bond-forming reaction for the preparation of β

Palladium-catalyzed Sonogashira coupling reactions in γ-valerolactone-based ionic liquids

• László Orha,
• József M. Tukacs,
• László Kollár and
• László T. Mika

Beilstein J. Org. Chem. 2019, 15, 2907–2913, doi:10.3762/bjoc.15.284

• wide applicability from syntheses of common building blocks to agrochemicals, just to name a few advantages [4][5][6]. From the series of palladium-assisted C–C bond formation, the Sonogashira coupling reaction has been identified as a viable synthetic method for the preparation of various alkenyl- and

• air-stable and readily available PdCl2(PPh3)2 was selected as a catalyst precursor to facilitate C–C bond couplings involving various iodoaromatic compounds (1a–l) and phenylacetylene (2a) in [TBP][4EtOV] in the absence of any additional ligands and auxiliary base at 55 °C for 3 h. In general, the

Bacterial terpene biosynthesis: challenges and opportunities for pathway engineering

• Eric J. N. Helfrich,
• Geng-Min Lin,
• Christopher A. Voigt and
• Jon Clardy

Beilstein J. Org. Chem. 2019, 15, 2889–2906, doi:10.3762/bjoc.15.283

• the leaving pyrophosphate group and the nucleophilic alkenes in proximity to initiate the C–C-bond forming, carbocation-mediated cascade reactions [10]. The hydrophobic binding pocket stabilizes the reaction intermediates and tames the propagation of carbocations through cation–π and other

Arylisoquinoline-derived organoboron dyes with a triaryl skeleton show dual fluorescence

• Vânia F. Pais,
• Tristan Neumann,
• Ignacio Vayá,
• M. Consuelo Jiménez,
• Abel Ros and
• Uwe Pischel

Beilstein J. Org. Chem. 2019, 15, 2612–2622, doi:10.3762/bjoc.15.254

• the syn and anti atropisomers because of the slow rotation around the chiral axis at this temperature. Free rotation around the C–C bond was observed at 80 °C and hence, variable-temperature 1H NMR studies showed coalescence of the signals to give an average spectrum (see Supporting Information File 1

• hinders the free rotation around axis A (Scheme 3) of the compounds 16–19; therefore, complex mixtures of the syn/anti atropoisomers (0.45:0.55; syn:anti) were observed in NMR spectroscopy. To facilitate the C–C bond rotation around axis B (Scheme 3) and simplify the NMR spectra, the measurements were

Indium-mediated C-allylation of melibiose

• Christian Denner,
• Manuel Gintner,
• Hanspeter Kählig and
• Walther Schmid

Beilstein J. Org. Chem. 2019, 15, 2458–2464, doi:10.3762/bjoc.15.238

• the elongated unit at the reducing end of the disaccharide. Keywords: carbohydrates; C–C bond formation; indium-mediated allylation; melibiose; ozonolysis; Introduction The tin and indium-mediated allylation (IMA) proved to be useful synthetic tools for the chain elongation of unprotected

Combining the Ugi-azide multicomponent reaction and rhodium(III)-catalyzed annulation for the synthesis of tetrazole-isoquinolone/pyridone hybrids

• Gerardo M. Ojeda,
• Prabhat Ranjan,
• Pavel Fedoseev,
• Lisandra Amable,
• Upendra K. Sharma,
• Daniel G. Rivera and
• Erik V. Van der Eycken

Beilstein J. Org. Chem. 2019, 15, 2447–2457, doi:10.3762/bjoc.15.237

• processes has remained underexploited [27]. Thus, we envisioned that the combination of an Ugi-azide-4CR with modern metal-catalyzed C–C bond-forming methods would enable access to structurally novel compounds featuring hybrid heterocycle platforms. We focused on metal-catalyzed annulation approaches that

Current understanding and biotechnological application of the bacterial diterpene synthase CotB2

• Ronja Driller,
• Daniel Garbe,
• Norbert Mehlmer,
• Monika Fuchs,
• Keren Raz,
• Dan Thomas Major,
• Thomas Brück and
• Bernhard Loll

Beilstein J. Org. Chem. 2019, 15, 2355–2368, doi:10.3762/bjoc.15.228

• deuterium labeling [33][34][35], to form the carbocation located at position C8 of dolabellatrienyl (B). By ring closure and formation of a novel C–C bond the tricyclic 5–8–5 ring system (C) is established. F107, F149, and the pyrophosphate moiety stabilize the carbocation at position C3 (Scheme 2 and