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

• -materials. Keywords: alkynylation; BODIPY; direct C–H functionalization; gold(I); Introduction Boron-dipyrromethene (BODIPY, 1) and its derivatives are representative families of fluorophores that have been widely used in applications for bioimaging [1][2][3][4][5][6], photodynamic therapy [7][8][9][10

• the synthesis of ethynyl-substituted BODIPY derivatives 3–6 by gold(I)-catalyzed direct C–H functionalization (Figure 1c). By taking advantage of the reactivity of β-(2 and 6)-positions of BODIPY (1), which are susceptible to electrophilic reactions, β,β'-diethynyl-substituted BODIPYs 5 and 6 were

• 5a and 6a agreed with the fact that the photoexcited dynamics of β-substituted BODIPYs intend to the rapid decay with structural relaxation. Conclusion In summary, we have synthesized novel regioselectively alkynylated BODIPY derivatives via a gold(I)-catalyzed direct C–H functionalization with TIPS

Synthesis of triphenylene-fused phosphole oxides via C–H functionalizations

• Md. Shafiqur Rahman and
• Naohiko Yoshikai

Beilstein J. Org. Chem. 2020, 16, 524–529, doi:10.3762/bjoc.16.48

• through two distinct C–H functionalization reactions as key steps. The phosphole ring was constructed by a three-component coupling of 3-(methoxymethoxy)phenylzinc chloride, an alkyne, and dichlorophenylphosphine, involving the regioselective C–H activation of the C2 position of the arylzinc intermediate

• nature as hybrids of triphenylene and benzo[b]phosphole. Keywords: C–H functionalization; fluorescence; phosphole; polycyclic aromatic hydrocarbons; triphenylene; Introduction The phosphorus-containing five-membered ring, phosphole, has attracted significant attention as a structural motif in π

• phosphole oxides through C–H functionalization and cross-coupling reactions. The phosphole ring was constructed in the early stage of the synthesis by a three-component assembly method featuring a 1,4-cobalt migration as the key step. Unlike other C–H activation/alkyne annulation approaches to benzo[b

Six-fold C–H borylation of hexa-peri-hexabenzocoronene

• Mai Nagase,
• Kenta Kato,
• Akiko Yagi,
• Yasutomo Segawa and
• Kenichiro Itami

Beilstein J. Org. Chem. 2020, 16, 391–397, doi:10.3762/bjoc.16.37

• on a NEC LX 110Rh system was used for optimization (B3LYP/6-31G(d)) [28][29]. Structures were optimized without any symmetry assumptions. C–H functionalization of HBCs. (a) Perchlorinated HBC. (b) Borylated HBC substituted by 2,4,6-trimethylphenyl (Mes) groups. (c) Six-fold C–H borylation of HBC

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

• both high molecular weight and regioregularity, and elevated reaction temperatures are typically required [3]. Mild conditions for C–H functionalization is of growing interest within the broader synthetic community as an opportunity to improve functional group tolerance, and environmental impact [4][5

• . There are limited examples across the aryl C–H functionalization literature indicating a transition metal-catalyzed radical process, limited largely to cobalt catalysis [31][32]. While there are several reports of palladium-catalyzed systems for room-temperature direct arylation (i.e., no directing

• Center for Selective C–H Functionalization (CHE-1700982).

Recent developments in photoredox-catalyzed remote ortho and para C–H bond functionalizations

• Rafia Siddiqui and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 248–280, doi:10.3762/bjoc.16.26

• functionalizations. Herein, we will broadly discuss the different catalytic systems that facilitate ortho and para C–H functionalization by utilization of effective and feasible photoredox catalysts (with the aid of transition metals), hydrogen atom transfer, and aerobic oxidation. Over the last two decades, direct

• easily. Recently, aerobic oxidation with visible light and photoredox catalysts has also gained a lot of attention in the modification and generation of new C–H functionalization methodologies [81][82]. The above-mentioned advantages make the photoredox processes a versatile tool in diverse fields, and

• -worker’s results [86], in 2015, Rueping and co-workers reported reoxidation reactions via visible photoredox catalysis [87]. In their study, they used photoredox catalyst 9 along with a Ru catalyst for ortho C–H functionalization of phenol derivatives, viz, ortho-(2-pyridyl)phenols (Pyr, Scheme 2

Synthesis and optoelectronic properties of benzoquinone-based donor–acceptor compounds

• Daniel R. Sutherland,
• Nidhi Sharma,
• Georgina M. Rosair,
• Ifor D. W. Samuel,
• Ai-Lan Lee and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2019, 15, 2914–2921, doi:10.3762/bjoc.15.285

• St Andrews, St Andrews, KY16 9ST, UK Organic Semiconductor Centre, SUPA School of Physics and Astronomy, University of St Andrews, St Andrews, KY16 9SS, UK 10.3762/bjoc.15.285 Abstract Herein, we report a mild and efficient palladium-catalyzed C–H functionalization method to synthesize a series of

• arylboronic acids are readily accessible, we envisaged that our Pd-catalyzed direct C–H functionalization method would be ideal for attempting a facile and direct route to a series of novel substituted benzoquinone-based charge-transfer derivatives, with the aim of exploring their electroluminescent (EL

• because it should lead to a more red-shifted emission. As described above, with a mild and efficient method to functionalize BQs now in hand, we decided to exploit the C–H functionalization methodology developed within our group [14] to readily synthesize a series of benzoquinone-based charge-transfer

Recent advances in transition-metal-catalyzed incorporation of fluorine-containing groups

• Xiaowei Li,
• Xiaolin Shi,
• Xiangqian Li and
• Dayong Shi

Beilstein J. Org. Chem. 2019, 15, 2213–2270, doi:10.3762/bjoc.15.218

• formed from A with Selectfluor or NFSI instead of an organometallic intermediate as usual. Then, the activated Pd(IV)–F electrophile B would be capable of electrophilic fluorination of weakly nucleophilic arenes. This unusual mechanism of catalysis may provide a new idea to the catalysis of C–H

• functionalization reactions. Aryl C–H fluorination with various directing groups: With Pd(OTf)2(MeCN)4 and N-methyl-2-pyrrolidinone (NMP) used as the catalyst system, in 2011 the Yu group [57] described the ortho-fluorination of benzoic acid substrates with a directing group, an electron-deficient removable acidic

Cyclopropanation–ring expansion of 3-chloroindoles with α-halodiazoacetates: novel synthesis of 4-quinolone-3-carboxylic acid and norfloxacin

• Sara Peeters,
• Linn Neerbye Berntsen,
• Pål Rongved and
• Tore Bonge-Hansen

Beilstein J. Org. Chem. 2019, 15, 2156–2160, doi:10.3762/bjoc.15.212

• : catalysis; cyclopropanation; indole; norfloxacin quinoline; quinolone; Rh(II); ring expansion; Introduction The development and use of metal carbenes occupy a central part in the field of the C–H functionalization [1]. Among the metal carbenes, the transient Rh carbenes, usually made by Rh-catalyzed

Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage

• Gagandeep Kour Reen,
• Ashok Kumar and
• Pratibha Sharma

Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165

• of iodine in the absence of copper did not result in the desired product keeping the reaction conditions intact. However, based on control experiments and the works of Zhang and Ma’s group [103][104], oxidative C–H functionalization was expected to be more likely involved in the cyclization strategy

• of biologically active imidazo[1,2-a] pyridine derivatives [108]. Encouraged by the direct synthetic strategies for imidazo[1,2-a]pyridines (IPs), Donthiri et al. have reported an efficient Cu-catalyzed C–H functionalization of pyridines with vinyl azide derivatives [109]. Their use of vinyl azide

• ) allow it to catalyze a number of organic reactions viz., nucleophilic substitutions, addition reactions, hydrogenations/hydrosilylations, cycloisomerizations, electrophilic aromatic substitutions, cross-coupling reactions, oxidative additions and reductive eliminations [66]. Iron–catalyzed C–H

Mechanochemistry of supramolecules

• Anima Bose and
• Prasenjit Mal

Beilstein J. Org. Chem. 2019, 15, 881–900, doi:10.3762/bjoc.15.86

• (pyridin-4-yl)ethylene and 4,6-dichlororesorcinol. Halogen-bonded co-crystals via a) I···P, b) I···As, and c) I···Sb bonds [112]. Transformation of contact-explosive primary amines and iodine(III) into a successful chemical reaction for amide synthesis. Undirected C–H functionalization by using the acidic

• hydrogen to control basicity of the amines [114]. a) Identified exothermic reactions. b) Successful reaction by quenching the heat intramolecularly. c) The plausible mechanism of acidic C–H functionalization intramolecularly. Acknowledgements A.B. thank CSIR (India) for fellowship.

Selective benzylic C–H monooxygenation mediated by iodine oxides

• Kelsey B. LaMartina,
• Haley K. Kuck,
• Linda S. Oglesbee,
• Asma Al-Odaini and
• Nicholas C. Boaz

Beilstein J. Org. Chem. 2019, 15, 602–609, doi:10.3762/bjoc.15.55

• intractable products, which were in many cases polyfunctionalized. Additionally, substrates containing arene rings were shown to inhibit aliphatic C–H functionalization via electrophilic trapping of reactive halogen species to form aryl chlorides and iodides. Utilizing NHPI as a less reactive hydrogen atom

Annulation of 1H-pyrrole-2,3-diones by thioacetamide: an approach to 5-azaisatins

• Aleksandr I. Kobelev,
• Ekaterina E. Stepanova,
• Maksim V. Dmitriev and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2019, 15, 364–370, doi:10.3762/bjoc.15.32

• developed via an unprecedented annulation of pyrrolo[2,1-c][1,4]benzoxazine-1,2,4-triones by thioacetamide. A new way of C–H functionalization of thioacetamide has been discovered. The reaction proceeds under green catalyst-free conditions. Keywords: annulation; domino reactions; isatin; nitrogen

• serve for a catalyst-free C–H functionalization of thioacetamide and mild introduction of this fragment in other molecules, which is valuable in terms of synthetic organic chemistry. Approaches to the synthesis of the 5-azaisatin core. Our previous work on the interaction of PBTs 2 with thioamides

Metal-free C–H mercaptalization of benzothiazoles and benzoxazoles using 1,3-propanedithiol as thiol source

• Yan Xiao,
• Bing Jing,
• Xiaoxia Liu,
• Hongyu Xue and
• Yajun Liu

Beilstein J. Org. Chem. 2019, 15, 279–284, doi:10.3762/bjoc.15.24

• 10.3762/bjoc.15.24 Abstract A facile and effective C–H functionalization strategy for the synthesis of 2-mercaptobenzothiazoles and 2-mercaptobenzoxazoles is described. 1,3-Propanedithiol was employed to convert benzothiazoles and benzoxazoles to the corresponding heteroarylthiols in the presence of

• potassium hydroxide and DMSO. This novel protocol is featured by direct C–H mercaptalization of heteroarenes and a simple reaction system. Keywords: benzothiazole; benzoxazole; C–H functionalization; mercaptalization; 1,3-propanedithiol; Introduction Both 2-mercaptobenzothiazoles and 2

• [22] and 1,2-ethanedithiol [23]. In the past decades, C–H functionalization has become an effective strategy for constructing different molecules directly from simple arenes and alkanes. C–H functionalization is an important method for C–S coupling reactions [24][25]. For example, transition metal

Transition metal-free oxidative and deoxygenative C–H/C–Li cross-couplings of 2H-imidazole 1-oxides with carboranyl lithium as an efficient synthetic approach to azaheterocyclic carboranes

• Lidia A. Smyshliaeva,
• Mikhail V. Varaksin,
• Pavel A. Slepukhin,
• Oleg N. Chupakhin and
• Valery N. Charushin

Beilstein J. Org. Chem. 2018, 14, 2618–2626, doi:10.3762/bjoc.14.240

• 10.3762/bjoc.14.240 Abstract The direct C–H functionalization methodology has first been applied to perform transition metal-free C–H/C–Li cross-couplings of 2H-imidazole 1-oxides with carboranyllithium. This atom- and step-economical approach, based on one-pot reactions of nucleophilic substitution of

• hydrogen (SNH) in non-aromatic azaheterocycles, affords novel imidazolyl-modified carboranes of two types (N-oxides and their deoxygenative analogues), which are particularly of interest in the design of advanced materials. Keywords: carboranes; C–H functionalization; C–H/C–Li cross-coupling; 2H-imidazole

• . An alternative approach to exploit the C–X/C–M cross-coupling reactions, leading to heterocyclic boron clusters, is based on the C–H/C–M coupling strategy. One of the ways to realize these cross couplings is the transition metal-free methodology for direct C–H functionalization of azaheterocyclic

Learning from B₁₂ enzymes: biomimetic and bioinspired catalysts for eco-friendly organic synthesis

• Keishiro Tahara,
• Ling Pan,
• Toshikazu Ono and
• Yoshio Hisaeda

Beilstein J. Org. Chem. 2018, 14, 2553–2567, doi:10.3762/bjoc.14.232

• presence of 1 in methanol/n-Bu4NClO4 to form Co(III)–RF complexes with deiodination. These complexes released RF radicals on the Co(III)-bond cleavage through visible-light irradiation. The resultant radicals reacted with aromatic reagents to form the target products through direct C–H functionalization

Synthesis of aryl sulfides via radical–radical cross coupling of electron-rich arenes using visible light photoredox catalysis

• Amrita Das,
• Mitasree Maity,
• Simon Malcherek,
• Burkhard König and
• Julia Rehbein

Beilstein J. Org. Chem. 2018, 14, 2520–2528, doi:10.3762/bjoc.14.228

• /arylzinc reagents [35][36]. However, most of these methods require harsh reaction conditions, external additives and high temperatures. The reactions need prefunctionalized arenes, while a direct C–S sulfenylation by C–H functionalization would be more desirable and cost effective. So far, only a few

• reports on direct C–H functionalization using transition metals or metal free [37][38][39] conditions and different sources of sulfur, for example arylsulfonyl chlorides, sodium arylsulfinates, sulfinic acids and arylsulfonyl hydrazides have been reported (Scheme 1). However, the protocols require

• charge transfer using Cs2CO3 as base [41]. Two recent reports showed the synthesis of C-3 sulfenylated indoles and 3-sulfenylimidazopyridine via C–H functionalization using Rose Bengal as photocatalyst [42][43]. In general, the arylation reactions use the reductive cycle of the photocatalyst and for this

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

• synthesis owing to the necessity of green chemistry for the modern universe [1][2][3]. In this context, catalytic C–H functionalization has been acknowledged as an atom- and step-economical process [4][5][6]. A wide range of transition metal-catalyzed non-directed or directing group assisted C–H activation

• activation reactions (Scheme 1) [29][30]. Following to these pioneering works, the groups of Kochi [31], Kisch [32], Klein [33][34], and Brookhart [35] have made their crucial contributions in the cobalt-mediated/catalyzed C–H functionalization. In recent years, Yoshikai [36], Kanai/Matsunaga [37], and

• -valent cobalt system for C–H functionalization [16][36]. Thus, the reaction of 2-aryl pyridines 3 with internal alkynes in the presence of 10 mol % CoBr2, 20 mol % PMePh2, and 1 equiv of MeMgCl as a reductant yielded ortho alkenated products 4 with high regio- and stereoselectivities (Scheme 5) [36]. The

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

• of aryl iodide. The latter is then used for a sequential ruthenium-catalyzed ortho-C–H functionalization directed by the pyrazole group (Scheme 37) [76]. Starting from non-symmetrical diaryl-λ3-iodanes, the electron-poorest or more sterically hindered aromatic group is first transferred to the 3,5

Rhodium-catalyzed C–H functionalization of heteroarenes using indoleBX hypervalent iodine reagents

• Erwann Grenet,
• Ashis Das,
• Paola Caramenti and
• Jérôme Waser

Beilstein J. Org. Chem. 2018, 14, 1208–1214, doi:10.3762/bjoc.14.102

• procedures have been described for the modification of pyridinones to introduce other substituents, especially based on highly efficient C–H functionalization methods [10]. Very recently, several research groups have selectively functionalized the C-6 C–H bond by using a 2-pyridyl directing group on the

• -methylindole and 2-iodobenzoic acid [24]. While the reaction conditions previously developed in our group for the C–H functionalization of 2-phenylpyridine [24] failed for the coupling of 5a with 6a (Table 1, entry 1), we were pleased to see that addition of 0.15 equiv Zn(OTf)2 allowed a full conversion to the

• compounds with pyridinone, quinolone and indole cores. C–H functionalization of pyridinones and quinoline N-oxides. Scope and limitations of the Rh-catalyzed C–H activation of [1,2'-bipyridin]-2-one. Scope of the Rh-catalyzed peri C–H activation of quinoline N-oxides. Product modifications. Optimization of

Selective carboxylation of reactive benzylic C–H bonds by a hypervalent iodine(III)/inorganic bromide oxidation system

• Toshifumi Dohi,
• Shohei Ueda,
• Kosuke Iwasaki,
• Yusuke Tsunoda,
• Koji Morimoto and
• Yasuyuki Kita

Beilstein J. Org. Chem. 2018, 14, 1087–1094, doi:10.3762/bjoc.14.94

• ), phenyliodine(III) bis(trifluoroacetate) (PIFA), and iodosobenzene, has since become a popular choice for benzylic oxidations, which further expanded the scope and availability of methods for direct C–H functionalization and several coupling reactions [42][43][44][45][46][47][48][49][50]. As such, we reported

• /ethyl acetate) to give the benzylic C–H carboxylation product in the indicated yield; the physical and spectral data of the carboxylation products (3h, 4h, 5h, 6h) matched those previously reported (see Supporting Information File 1). Hypervalent iodine(III)-induced benzylic C–H functionalization for

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

• ) from ketones [13][14][15][16][17]. Over the last several years, we and others have developed a series of directed arene C–H functionalization reactions with organic electrophiles under low-valent cobalt catalysis [18][19][20][21]. In particular, our group and the Ackermann group have independently

• 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

• -directed arene C–H alkenylation reaction with alkenyl phosphates using a different cobalt–NHC catalyst (Scheme 1b) [28]. Meanwhile, we have also demonstrated that pivaloyl N–H imine serves as a powerful directing group for cobalt-catalyzed arene C–H functionalization reactions such as the hydroarylation of

Functionalization of N-arylglycine esters: electrocatalytic access to C–C bonds mediated by n-Bu₄NI

• Mi-Hai Luo,
• Yang-Ye Jiang,
• Kun Xu,
• Yong-Guo Liu,
• Bao-Guo Sun and
• Cheng-Chu Zeng

Beilstein J. Org. Chem. 2018, 14, 499–505, doi:10.3762/bjoc.14.35

• electrochemical C–H bond functionalization, leading to the formation of new C–C, C–N, C–O and C–S bonds [28][29][30][31]. Herein, we report the electrochemical α-C–H functionalization of N-arylglycine esters with C–H nucleophiles using n-Bu4NI as redox catalyst (Scheme 1). The chemistry was performed in an

Aminomethylation/hydrogenolysis as an alternative to direct methylation of metalated isoquinolines – a novel total synthesis of the alkaloid 7-hydroxy-6-methoxy-1-methylisoquinoline

• Benedikt C. Melzer,
• Jan G. Felber and
• Franz Bracher

Beilstein J. Org. Chem. 2018, 14, 130–134, doi:10.3762/bjoc.14.8

• methods have been published over the decades for the construction of highly substituted isoquinolines [4]. Alternatively, subsequent functionalization of isoquinolines is feasible, e.g., via Pd-catalyzed C–H functionalization [5] or regioselective direct ring metalation (at C1) [6][7][8]. General aspects

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

• ]. Advantageously this methodology was applicable for both solid and liquid olefins. Mechanochemical C–H functionalization Transition-metal-catalyzed activation and functionalization of inert C–H bonds of organic molecules provides a broad avenue in the synthesis of wide range of compounds. In 2015, Bolm and co

• Rh, Cu(OAc)2 as a redox modulator and dioxygen as a terminal oxidant (Scheme 50). This efficient technique was turned out to be a greener alternative to the common and mechanistically similar solution based method. They have also extended mechanochemical C–H functionalization methodology by varying

• developed a mechanochemical synthesis of an indole moiety via a Rh-catalyzed C–H functionalization strategy under planetary ball mill [187]. Using acetanilide and diphenylacetylene as the alkyne component in presence of 5 mol % Rh catalyst and 2.5 mol % Cu(OAc)2 and 1 atm O2 as terminal oxidant they could

Transition-metal-catalyzed synthesis of phenols and aryl thiols

• Yajun Liu,
• Shasha Liu and
• Yan Xiao

Beilstein J. Org. Chem. 2017, 13, 589–611, doi:10.3762/bjoc.13.58

• the chlorination and other C–H functionalization of (2-pyridyl)arenes. Together with this work, some other work on C–H acyloxylation provided an indirect pathway for the synthesis of phenols from arenes [54]. In 2014, Shi and co-workers designed a removable bidentate functional group, which could