In silico rationalisation of selectivity and reactivity in Pd-catalysed C–H activation reactions

• Liwei Cao,
• Mikhail Kabeshov,
• Steven V. Ley and
• Alexei A. Lapkin

Beilstein J. Org. Chem. 2020, 16, 1465–1475, doi:10.3762/bjoc.16.122

• was proposed for classifying whether the carbon atoms are active or inactive toward electrophilic aromatic substitution [17]. Also, a quantum mechanical approach was introduced to compute ortho-directing groups (DGs) in palladium-catalysed aromatic C–H activation reactions [18]. However, there is a

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

• address a single C–H bond selectively without compromising the others. To circumvent this problem, directing groups can be installed, which guide a metal catalyst to a specific C–H bond [4][5]. In case the directing group is not needed in the final product, this strategy accounts for additional reaction

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

• prepared regioselectively, through the C–H alkynylation of 1 without any directing groups. In addition, the corresponding dipyrromethane 2, which is a precursor of BODIPY, was first transformed into the alkynylated form under catalytic conditions, and subsequent oxidation followed by boron complexation to

Copper-catalyzed remote C–H arylation of polycyclic aromatic hydrocarbons (PAHs)

• Anping Luo,
• Min Zhang,
• Zhangyi Fu,
• Jingbo Lan,
• Di Wu and
• Jingsong You

Beilstein J. Org. Chem. 2020, 16, 530–536, doi:10.3762/bjoc.16.49

• products in moderate to good yields (Scheme 3, 4m–o). This catalytic system was also compatible with substrates bearing other directing groups except tert-butylaminocarbonyl (Scheme 3, 4p–s). When employing methylaminocarbonyl and cyclohexylaminocarbonyl as directing groups, the 7-arylation products of

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

• coordination chemistry, and also valuable protecting or directing groups in catalysis [1][2][3]. 2-Oxazolines are a readily stable class of heterocycles resistant to a range of nucleophiles, bases, or radicals [4][5], which can be easily generated from amino alcohols and carboxylic acids, and from alkenes or

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

• functionalization has been done either using transition metal catalysis or organocatalysis, through the installation of directing groups next to the targeted C–H bond, or by employing radical tactics based on single-electron transfer (SET) [15][16][17][18][19][20][21][22][23][24][25][26][27]. Although

• products, organic materials, etc., in such a way [116][117]. They used a Pd catalyst and a photoredox catalyst 12a at room temperature to generate reactive intermediates (Scheme 10) [115]. This novel method was applicable to various directing groups and had a high functional group tolerance, whereas the

• regioselectivity, the requirement of directing groups and preactivation of the compounds were the major drawbacks [141][142][143]. On the other hand, when the reaction was carried out with photoredox catalyst 6 and 11, respectively, no product was obtained, showcasing the necessity of a highly oxidizing photoredox

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

• regioselectivity, can be overcome when a suitable directing group assists the reaction [46][47]. Traditional directing groups for C–H activation include amide, hydroxamide, carboxylate, pyridyl, quinolyl, carbonyl, ether, hydroxy, oxazolinyl and cyano [47]. For example, Ackermann et al. reported a Ru(II)-catalyzed

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

• 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

• crucial promoter and the benzothiazoles as the directing groups (Scheme 20). This strategy plays an important role in the pharmaceutical and agrochemical industries. Meanwhile, Xu’s group [59] used O-methyl oxime as the directing group for the Pd-catalyzed ortho-fluorination of aromatic and olefinic C(sp2

• –H fluorination of benzaldehydes. Notably, these transformations were achieved with orthanilic acids as new transient directing groups (TDGs) in DCE in the presence of air (Scheme 23). This approach employed 1-fluoro-2,4,6-trimethylpyridinium salts as a bystanding F+ oxidant or an electrophilic

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

Cobalt-catalyzed peri-selective alkoxylation of 1-naphthylamine derivatives

• Jiao-Na Han,
• Cong Du,
• Xinju Zhu,
• Zheng-Long Wang,
• Yue Zhu,
• Zhao-Yang Chu,
• Jun-Long Niu and
• Mao-Ping Song

Beilstein J. Org. Chem. 2018, 14, 2090–2097, doi:10.3762/bjoc.14.183

• ][35][36][37][38][39][40][41][42] have successfully reported alkoxylation reactions with the auxiliary of directing groups. However, the transition-metal-catalyzed C–H alkoxylation is still largely limited to palladium- [28][33][34][35][36][37][38][39][40] or copper- [26][27][29][41][42] catalyzed

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

• donors [83]. Since the reactions often were unselective in the absence of C2 acetate-directing groups, Bennett et al. investigated the compatibility of the above-mentioned reaction in nitrile solvents documented to have a β-directing effect, with the aim of developing a glycosylation that can be

• selectively achieved in the absence of directing groups. After preliminary screens, they found that the reaction in the presence of phenyl(trifluoroethyl)iodonium triflimide 160 and the non-nucleophilic base 2,4,6-tri-tert-butylpyrimidine (TTBP) at 0 °C with the solvent combination of 2:1 CH2Cl2/pivalonitrile

Thiocarbonyl-enabled ferrocene C–H nitrogenation by cobalt(III) catalysis: thermal and mechanochemical

• Santhivardhana Reddy Yetra,
• Zhigao Shen,
• Hui Wang and
• Lutz Ackermann

Beilstein J. Org. Chem. 2018, 14, 1546–1553, doi:10.3762/bjoc.14.131

• motifs of powerful transition metal catalyst ligands and organocatalysts (Figure 1) [94][95][96][97]. During the preparation of this article, the use of strongly-coordinating, difficult to remove directing groups has been reported [70][71]. In sharp contrast, notable features of our approach include (i

Atom-economical group-transfer reactions with hypervalent iodine compounds

• Andreas Boelke,
• Peter Finkbeiner and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2018, 14, 1263–1280, doi:10.3762/bjoc.14.108

• dithiocarbamates 7 and 7’ from one equivalent of diaryliodonium salt 1. Synthesis of substituted isoindolin-1-ones 9 from 2-formylbenzonitrile 8 and the postulated reaction mechanism. Domino C-/N-arylation of indoles 10. Domino modification of N-heterocycles 12 via in situ-generated directing groups. Synthesis of

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

• -methoxypyridine and the electron-poor 5-trifluoromethylpyridine directing groups gave products 7b and 7c in 82% and 72% yield, respectively. When a nitro group was present on the pyridine (5d), the product was not observed, probably due to a weaker coordination of the nitrogen on the pyridine. Pyrimidine could

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

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

• construction of C–X bonds. With the development of transition-metal-catalyzed cross-coupling reactions, a series of halogenations at the ortho-position of the directing groups have been disclosed [5][6][7][8][9][10][11][12][13][14][15][16][17][18]. Nevertheless, from the viewpoint of green chemistry, the

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

• , the unsatisfactory separation of 1-methylisoquinoline intermediate 4 from its unmethylated precursor 3 rendered this protocol unattractive. This is a problem that is common to numerous methylation protocols, including methylation of metalated arenes [16], methylation of arenes bearing directing groups

Syntheses, structures, and stabilities of aliphatic and aromatic fluorous iodine(I) and iodine(III) compounds: the role of iodine Lewis basicity

• Tathagata Mukherjee,
• Soumik Biswas,
• Andreas Ehnbom,
• Subrata K. Ghosh,
• Ibrahim El-Zoghbi,
• Nattamai Bhuvanesh,
• Hassan S. Bazzi and
• John A. Gladysz

Beilstein J. Org. Chem. 2017, 13, 2486–2501, doi:10.3762/bjoc.13.246

• with the iodination of 1,3-(Rf6)2C6H4, in which the substituents function as meta directing groups. As shown in Scheme 6, reactions of C6F6 or perfluoroheptane solutions of 1,2,4-(Rf8CH2CH2)2C6H3I and NaOCl/HCl gave the corresponding iodine(III) dichloride 1,2,4-(Rf8CH2CH2)2C6H3ICl2 [50] as a white

A novel approach to oxoisoaporphine alkaloids via regioselective metalation of alkoxy isoquinolines

• Benedikt C. Melzer and
• Franz Bracher

Beilstein J. Org. Chem. 2017, 13, 1564–1571, doi:10.3762/bjoc.13.156

• [33] that cooperative effects of directing groups lead to directed ortho-metalation (DoM) at their common ortho-position (C-6 in this case, located ortho to both the amide and the methoxy group). Nevertheless, under reversible metalation conditions, typically existing when amide bases like LDA are

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

• other hand, the C–H hydroxylation, either with heteroatom-containing directing groups or without directing groups, has provided various methods for the synthesis of phenols. Compared with traditional methods, the transition-metal-catalyzed phenol synthesis has several advantages: broad substrate scope

• improved by introduction of various directing groups. 1.2.1 Copper mediated C–H hydroxylation of arenes: A breakthrough was made by Yu and co-workers in 2006. They reported a protocol for the hydroxylation of (2-pyridyl)arenes [53]. Under an atmosphere of oxygen, the reaction proceeded in the presence of a

• Palladium-catalyzed C–H hydroxylation of arenes: Palladium catalysts were proved to be effective in catalyzing C–H hydroxylation of arenes and a variety of directing groups have been extensively studied and demonstrated to work as designed, thus providing plenty of strategies toward the preparation of

The reductive decyanation reaction: an overview and recent developments

• Jean-Marc R. Mattalia

Beilstein J. Org. Chem. 2017, 13, 267–284, doi:10.3762/bjoc.13.30

• , monodecyanation is the major pathway (47b) and decyanations are efficient with sterically demanding ortho-substituents (54, 57) or with ortho-directing groups (45, 48, 50). Aliphatic nitriles underwent decyanation without β-hydride elimination (42a, 52b, 53). Enthaler et al. reported the application of nickel

Direct arylation catalysis with chloro[8-(dimesitylboryl)quinoline-κN]copper(I)

• Sem Raj Tamang and
• James D. Hoefelmeyer

Beilstein J. Org. Chem. 2016, 12, 2757–2762, doi:10.3762/bjoc.12.272

• directing groups can improve the selectivity, but could contribute additional reaction steps and expense. Therefore, C–X/C–H (X = halogen) direct arylations are an important avenue of investigation that may represent a balance between cost, activity, and selectivity [8][9][10][11][12][13]. The C–X/C–H

Copper-catalyzed asymmetric sp³ C–H arylation of tetrahydroisoquinoline mediated by a visible light photoredox catalyst

• Pierre Querard,
• Inna Perepichka,
• Eli Zysman-Colman and
• Chao-Jun Li

Beilstein J. Org. Chem. 2016, 12, 2636–2643, doi:10.3762/bjoc.12.260

• interest in terms of atom economy, nevertheless enantioselectivity is difficult to control due to often-required harsh reaction conditions. Therefore, the development of simple and facile processes to functionalize sp3 C–H bonds under mild conditions in the absence of directing groups is of great interest

TMSBr-mediated solvent- and work-up-free synthesis of α-2-deoxyglycosides from glycals

• Mei-Yuan Hsu,
• Yi-Pei Liu,
• Sarah Lam,
• Su-Ching Lin and
• Cheng-Chung Wang

Beilstein J. Org. Chem. 2016, 12, 1758–1764, doi:10.3762/bjoc.12.164

• at C2, including halogen atoms [11][12][13][14][15][16][17][18], thio [19][20][21], and seleno groups [22][23][24][25], 1,2-migratory glycosylations that involve sulfur [26][27][28][29][30][31][32][33], oxygen [34], or nitrogen [35][36][37] atoms as directing groups and long-range directing

• functionalities at C6 [10][38][39][40][41][42] have also been developed to improve the stereoselectivity. However, additional required steps involving the introduction and removal of directing groups are reducing the efficiency. Thioglycosides are some of the most commonly used donors for glycosylation reactions

Palladium-catalyzed picolinamide-directed iodination of remote ortho-C−H bonds of arenes: Synthesis of tetrahydroquinolines

• William A. Nack,
• Xinmou Wang,
• Bo Wang,
• Gang He and
• Gong Chen

Beilstein J. Org. Chem. 2016, 12, 1243–1249, doi:10.3762/bjoc.12.119

• and Discussion Methods for metal-catalyzed halogenation of ortho C−H bonds at the more remote ε position are scarce, in contrast to the large number of ortho C−H halogenation reactions of arenes effected by more proximal directing groups [23][24][25][26][27][28][29][30][31][32][33]. Fundamentally, it