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

• unique reactivity of the benziodoxolone hypervalent iodine reagent. The scope and limitations of the reaction were then studied (Scheme 2). The diversification of the directing group was examined first. The unsubstituted pyridine group led to the formation of product 7a in 86% yield. The electron-rich 5

• not be used as directing group (5e), confirming what has already been reported by others authors [13]. Quinoline 7f was obtained in 79% yield. Concerning the pyridinone core, both an electron-donating methyl group and electron-withdrawing trifluoromethyl and fluoro groups (7g–i) were well tolerated in

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

• benzyl esters from non-functionalized aromatic hydrocarbons, and thus has attracted continuous interest in the community of synthetic chemists. Significant advances for realizing such transformations have been made over the last decade, however, strategies that do not utilize a directing group to

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

• , directing group-assisted arene C–H activation reactions have been extensively studied over the last few decades to offer a broad array of atom and step-economical methods for the synthesis of functionalized aromatic compounds [1][2][3][4][5][6]. Among various C–H transformations, the introduction of alkenyl

• -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

• previously reported cobalt-catalyzed ortho C–H functionalization reactions [22][23][28][29], this regioselectivity may be ascribed to the role of the oxygen or fluorine atom as a secondary directing group to have an electrostatic interaction with the cobalt center during the C–H activation. For compound 3ja

Synthesis and stability of strongly acidic benzamide derivatives

• Frederik Diness,
• Niels J. Bjerrum and
• Mikael Begtrup

Beilstein J. Org. Chem. 2018, 14, 523–530, doi:10.3762/bjoc.14.38

• ][32][33]. Finally, two examples of syntheses via palladium-catalyzed carbonylation of trifluoromethanesulfonamide (1) have been reported [34][35]. The N-triflylbenzamides have only been explored as substrates in a few reactions. A recent report describes using N-triflylbenzamide as a directing group

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

• the ditrifluoromethylation product was formed as well. Recently, Tan and co-workers [55] designed a highly mono-selective ortho-trifluoromethylation of benzamides assisted with an 8-aminoquinoline directing group. This reaction employed simple copper salt CuBr as the promoter and Togni’s reagent II as

Intramolecular glycosylation

• Xiao G. Jia and
• Alexei V. Demchenko

Beilstein J. Org. Chem. 2017, 13, 2028–2048, doi:10.3762/bjoc.13.201

• mediated IAD. DISAL as the leaving group that favors the intramolecular glycosylation pathway. Boronic acid as a directing group in the leaving group-based glycosylation method. Acknowledgements The authors are indebted to the National Institute of General Medical Sciences (GM111835 and GM120673) for

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

• was the only acid able to deliver the desired THIQ 10b. However, in the presence of a deactivating, ortho/para-directing group, such as chlorine (9c) or bromine (9e), HClO4 afforded the desired cyclized product only in the position directed by the substituent. In addition, even HClO4 failed to

Strategies toward protecting group-free glycosylation through selective activation of the anomeric center

• A. Michael Downey and
• Michal Hocek

Beilstein J. Org. Chem. 2017, 13, 1239–1279, doi:10.3762/bjoc.13.123

• -deoxyglucose exclusively the α-anomeric product was observed, but, unfortunately, no explanation for this anomaly has been provided. Although the author did not provide any definitive mechanistic insight, he suggested that the C2–OH may act as a directing group or is involved in neighboring group participation

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

• according to the proposed reaction mechanism. In 2015, Jiao and co-workers employed an oxime methyl ester as directing group and achieved the hydroxylation of arenes [67]. The reaction used Pd(OAc)2 as catalyst, PPh3 or DEAD as ligand and oxone as oxidant, affording the corresponding phenols in gratifying

• hydroxylated oxime could be readily converted to o-acylphenol or o-aminomethylphenol. In 2016, Sunoj and co-workers disclosed the first meta-hydroxylation of arenes using a tethered -CN directing group [68]. The conversion proceeded at 70 °C in hexafluoro-2-propanol (HFIP) in the presence of Pd(OAc)2, PhI(TFA

• afforded phenols in good to excellent yields (Scheme 52). In most cases, para-hydroxylation predominantly occurred, showing good regioselectivity. This protocol is suitable for hydroxylation of simple arenes as no particular directing group was required. In 2015, the Huang group prepared a type of vanadium

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

• removal of a beneficial functional group. The electron-withdrawing properties of the nitrile functional group appear beneficial in a variety of reactions [1][2]. This group coordinates metal complexes and can be used as a directing group for C–H bond activation reactions catalyzed by transition metals [3

Silyl-protective groups influencing the reactivity and selectivity in glycosylations

• Mikael Bols and
• Christian Marcus Pedersen

Beilstein J. Org. Chem. 2017, 13, 93–105, doi:10.3762/bjoc.13.12

• -DTBS group has been shown to be an α-directing group in galactosylation reactions. Kiso and co-workers found that the galactosyl donor 66 (Scheme 13) reacted with several different acceptor alcohols giving exclusively the α-galactoside despite having a potentially β-directing benzoate group in the 2

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

• process despite the advances that have been made in this field [1]. The directing group strategies are widely used and developed to achieve enantioselective metal-catalyzed C–H bond functionalizations in recent years. Unactivated alkyl C–H bond activation (i.e., without any directing group) is of great

Synthesis of β-arylated alkylamides via Pd-catalyzed one-pot installation of a directing group and C(sp³)–H arylation

• Yunyun Liu,
• Yi Zhang,
• Xiaoji Cao and
• Jie-Ping Wan

Beilstein J. Org. Chem. 2016, 12, 1122–1126, doi:10.3762/bjoc.12.108

• accessed. Keywords: alkylamides; C–H arylation; directing group; in situ installation; one-pot; Introduction The elaboration of inert C–H bonds is regarded as the longstanding aim of modern organic synthesis. Upon the extensive efforts during the past decades, the exploration and application of C–H

• activation/functionalization has won splendid success [1][2][3][4][5][6]. Among the numerous elegant examples of C–H activation reactions, the DG (directing group) assisted C–H activation is obviously the most generally applicable tactic because of the irreplaceable function of the DG in facilitating the

Cationic Pd(II)-catalyzed C–H activation/cross-coupling reactions at room temperature: synthetic and mechanistic studies

• Takashi Nishikata,
• Alexander R. Abela,
• Shenlin Huang and
• Bruce H. Lipshutz

Beilstein J. Org. Chem. 2016, 12, 1040–1064, doi:10.3762/bjoc.12.99

• under milder conditions than those previously reported. The nature of the directing group was found to be critical for achieving room temperature conditions, with the urea moiety the most effective in promoting facile coupling reactions at an ortho C–H position. This methodology has been utilized in a

• -directing groups [71][72][73][74][75][76][77][78][79][80][81][82][83][84][85] have been found to effectively promote selective C–H activation, typically by aiding in the formation of a palladacycle intermediate. Careful tuning of the structure of the directing group, with functionalities including a variety

• products in good yields. In order to successfully carry out these reactions at ambient temperature, several considerations must be addressed, as illustrated in Figure 1. Optimization studies initially focused on the choice of an ortho-directing group together with a cationic palladium(II) catalyst

Opportunities and challenges for direct C–H functionalization of piperazines

• Zhishi Ye,
• Kristen E. Gettys and
• Mingji Dai

Beilstein J. Org. Chem. 2016, 12, 702–715, doi:10.3762/bjoc.12.70

• maintaining excellent yields. Regioselectivity issues have been encountered in the case of C3-substituted piperazine substrates resulting in a mixture of 70 and 71. Notably, when 1-hexene was used, a mixture of 73–75 was produced. When the 2-pyridinyl directing group was switched to simple aryl groups, only

Iridium/N-heterocyclic carbene-catalyzed C–H borylation of arenes by diisopropylaminoborane

• Mamoru Tobisu,
• Takuya Igarashi and
• Naoto Chatani

Beilstein J. Org. Chem. 2016, 12, 654–661, doi:10.3762/bjoc.12.65

• borylation; iridium; N-heterocyclic carbene; Introduction Catalytic C–H borylation of arenes has become an essential tool in organic synthesis [1]. The eminent features of this methodology include 1) no directing group is needed, allowing the direct functionalization of simple arenes; 2) the

• example, in the ortho-selective C–H borylation of arenes containing a directing group [13], and to improve the meta/para-selectivity of monosubstituted benzenes [14][15]. Despite considerable progress in the C–H borylation reaction, the scope of the boryl group that can be introduced is relatively limited

Scope and limitations of the dual-gold-catalysed hydrophenoxylation of alkynes

• Adrián Gómez-Suárez,
• Yoshihiro Oonishi,
• Anthony R. Martin and
• Steven P. Nolan

Beilstein J. Org. Chem. 2016, 12, 172–178, doi:10.3762/bjoc.12.19

• 1o afforded, with complete regioselectivity, the corresponding vinyl ether 3ot [32]. As expected, when homopropargylic ether 1p was used diminished selectivity was observed. Thus supporting our hypothesis that regioselectivity can be obtained by assistance of a directing group, either by polarization

Recent advances in copper-catalyzed C–H bond amidation

• Jie-Ping Wan and
• Yanfeng Jing

Beilstein J. Org. Chem. 2015, 11, 2209–2222, doi:10.3762/bjoc.11.240

• sulfonimidation [55]. In contrast to the direct transformation of the weakly acidic C–H bonds in these electron deficient arenens/heteroarenes, the amidation of normal aryl C–H bonds usually relied on the presence of a directing group (DG). In 2010, Li et al. [56] reported the o-amidation of 2-arylpyridines 34

C–H bond halogenation catalyzed or mediated by copper: an overview

• Wenyan Hao and
• Yunyun Liu

Beilstein J. Org. Chem. 2015, 11, 2132–2144, doi:10.3762/bjoc.11.230

• a few examples giving mixed mono- and dihalogenated products. In all these known arene C–H halogenation protocols with pyridine as directing group (DG), the chemo-selectivity remained as a challenge since either mixed mono- and dihalogenated products or only one of the two potential products could

The facile construction of the phthalazin-1(2H)-one scaffold via copper-mediated C–H(sp²)/C–H(sp) coupling under mild conditions

• Wei Zhu,
• Bao Wang,
• Shengbin Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2015, 11, 1624–1631, doi:10.3762/bjoc.11.177

• conditions. Through the removal of the directing group, the resulting moiety could easily be transformed into the phthalazin-1(2H)-one scaffold, which is known to be a privileged moiety and a bioactive nucleus in pharmaceuticals. Keywords: C–H activation; copper; phthalazin-1(2H)-one; Introduction The

• temperature (120 °C) with excessive copper salts (3 equivalents). In addition, failure to remove the directing group partly prevented the practicality and application of the transformation [22]. Herein, we reveal a copper-mediated direct C–H(sp2)-C–H(sp) bond construction and simultaneous annulations under

• milder conditions with less equivalents of copper salts and oxygen atmosphere at a lower temperature (80 °C). Even more important, the resulting products could be smoothly transformed into preconceived 4-benzylphthalazin-1(2H)-one derivatives with the removal of the directing group by treatment with

Diastereoselective and enantioselective conjugate addition reactions utilizing α,β-unsaturated amides and lactams

• Katherine M. Byrd

Beilstein J. Org. Chem. 2015, 11, 530–562, doi:10.3762/bjoc.11.60

• -acylpyrroles [265] (Scheme 39). In their work, diethylzinc and 147 acts as a bifunctional catalyst system where the α,β-unsaturated system is activated through Lewis acid coordination and the catalyst acts as a directing group for the phosphite. Overall the reaction proceeds in both high yield and

Cross-dehydrogenative coupling for the intermolecular C–O bond formation

• Igor B. Krylov,
• Vera A. Vil’ and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2015, 11, 92–146, doi:10.3762/bjoc.11.13

• reported. It is commonly assumed that the reaction proceeds via the C–metal bond formation accompanied by the C–H bond cleavage assisted by the directing group of the substrate, which forms a complex with the metal ion. The mechanism of this type of reactions was considered in detail in the publications

• = F (Scheme 3). The pyridine moiety served as the directing group in many works to accomplish the ortho-acyloxylation of arenes 4 giving products 5 (Table 1). The reactions were catalyzed by copper, palladium, or rhodium salts. Carboxylic acids or their salts, as well as aldehydes, methylarenes

• arenes (Scheme 4). The pyridine, pyrimidine, or pyrazole moiety serves as the directing group in the oxidative ortho-alkoxylation of arenes 16 with the Cu(OAc)2/AgOTf/O2 system giving coupling products 17 (Scheme 5) [47]. It is supposed that copper is inserted into the C–H bond of arene, the resulting Cu

Inherently chiral calix[4]arenes via oxazoline directed ortholithiation: synthesis and probe of chiral space

• Simon A. Herbert,
• Laura J. van Laeren,
• Dominic C. Castell and
• Gareth E. Arnott

Beilstein J. Org. Chem. 2014, 10, 2751–2755, doi:10.3762/bjoc.10.291

• determined either by NMR spectroscopy or HPLC traces. The assignment of the configuration of the major/minor diastereomers when using the tert-butyloxazoline directing group was confirmed by hydrolysis of the oxazoline and comparison with an identical sample of known configuration (see Supporting Information

Exploration of C–H and N–H-bond functionalization towards 1-(1,2-diarylindol-3-yl)tetrahydroisoquinolines

• Michael Ghobrial,
• Marko D. Mihovilovic and
• Michael Schnürch

Beilstein J. Org. Chem. 2014, 10, 2186–2199, doi:10.3762/bjoc.10.226

• attached to the nitrogen of the indole, are required to facilitate copper-catalyzed C2-arylations [54]. We intended to avoid a directing group on the indole since this would require two additional reaction steps to install and cleave such a group. Due to these limitations, palladium was considered as

P(O)R₂-directed Pd-catalyzed C–H functionalization of biaryl derivatives to synthesize chiral phosphorous ligands

• Rong-Bin Hu,
• Hong-Li Wang,
• Hong-Yu Zhang,
• Heng Zhang,
• Yan-Na Ma and
• Shang-dong Yang

Beilstein J. Org. Chem. 2014, 10, 2071–2076, doi:10.3762/bjoc.10.215

• ]. Despite the progress in this area, only limited development has been accomplished through metal-catalyzed C–H activation to build C–P bonds [17][18]. As an alternative, we disclosed a novel protocol of palladium-catalyzed C–H functionalization by using the P(O)R2 moiety as a new directing group to

• system of P(O)R2-directed Pd-catalyzed C–H activation. These compounds could be transformed to trivalent phosphorus compounds by silane to obtain the corresponding phosphorous ligands. Conclusion In summary, a series of substrates with axially chiral biaryl compounds containing a P(O)Ar2 directing group

• chiral [1,1'-binaphthalen]-2-yldiphenylphosphine oxide as a substrate [35]. In the process of alkenylation and acetoxylation, the corresponding products 2a and 2b were obtained in moderate yields and high enantioselectivities. Next, we examined the substituent effect with P(O)(p-Tol)2 as a directing