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

• -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

• reactions to be run in water at room temperature using the cationic palladium catalyst [Pd(MeCN)4](BF4)2 (Figure 4, 5a–c, conditions A). While this reaction proceeded with a number of alkyl anilide derivatives, as well as ureas as directing groups (5c), the substrate scope was otherwise somewhat limited

Recent advances in C(sp³)–H bond functionalization via metal–carbene insertions

• Bo Wang,
• Di Qiu,
• Yan Zhang and
• Jianbo Wang

Beilstein J. Org. Chem. 2016, 12, 796–804, doi:10.3762/bjoc.12.78

• development of various directing groups for controlling the site-selectivity of the reaction. Regardless of the great efforts devoted to the field, the intermolecular C(sp3)–H bond activation of simple alkanes still remains a formidable challenge, obviously attributed to the inertness and ubiquitous nature of

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

• ). Despite the high temperature, the reaction provided α-alkylated piperazines 79–83 in good yield. The reaction is atom-economic and does not require directing groups which sets it apart from previously discussed models. Simple mono-alkylated or -arylated piperazines and terminal olefins were used as

Recent advances in N-heterocyclic carbene (NHC)-catalysed benzoin reactions

• Rajeev S. Menon,
• Akkattu T. Biju and
• Vijay Nair

Beilstein J. Org. Chem. 2016, 12, 444–461, doi:10.3762/bjoc.12.47

• ). The NHC-catalysed chemoselective intermolecular cross-benzoin condensation reaction of aromatic and aliphatic aldehydes was reported by Yang and co-workers. The chemoselectivity was achieved by using a large excess of the aliphatic aldehyde (molar ratio of 1:15) [25]. Thus, directing groups on the

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

• have a dramatic effect on the reactivity. More importantly, we have observed that the use of substrates that facilitate the formation of diaurated species such as gem-diaurated or σ,π-digold–acetylide species, hinder the catalytic activity. Moreover, we have identified that the use of directing groups

• tolerated steric hindrance is very low, in contrast to the results observed for the nucleophile. In addition, in the case of unsymmetrical alkynes, the use of electron-rich alkynes appears to favour a better selectivity than their electron-poor counterparts. Enhancing regioselectivity using directing groups

• facilitate the formation of diaurated species such as gem-diaurated or σ,π-digold–acetylide species, hinder the catalytic activity. We have identified that the use of directing groups in unsymmetrical alkynes can help achieve regioselectivity in the hydrophenoxylation reaction. With these studies, we have

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

• of copper salts and N,N’-dual coordinated directing groups [18][19][20][21][22]. By the employment of a similar approach, our group reported a straightforward route to the isoquinolinone scaffold via copper-mediated C–H(sp2)/C–H(sp3) coupling [23]. In light of previous works, we envisioned the

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

• present review summarizes primary publications on the cross-dehydrogenative C–O coupling, with special emphasis on the studies published after 2000. The focus is on the reactions described by general Scheme 2. Review 1 C-Reagents containing directing groups in cross-dehydrogenative C–O coupling Nitrogen

• -containing moieties (amide, pyridine, oxime, etc.) are most commonly used as directing groups, which are responsible for the regioselectivity of the C–O coupling. Most transformations of this type are catalyzed by Pd(II) compounds. Examples of the use of copper and ruthenium compounds as catalysts were also

• [25][26][27][28][29][30][31][32]. 1.1 Reactions involving C(sp2)–H bonds of aromatic C-reagents In one of the first publications on the preparative introduction of the –OR group into CH-reagents containing directing groups, 8-methylquinoline, 2-arylpyridines, N-phenylpyrazole, azobenzene, and

Sequential decarboxylative azide–alkyne cycloaddition and dehydrogenative coupling reactions: one-pot synthesis of polycyclic fused triazoles

• Kuppusamy Bharathimohan,
• Thanasekaran Ponpandian,
• A. Jafar Ahamed and
• Nattamai Bhuvanesh

Beilstein J. Org. Chem. 2014, 10, 3031–3037, doi:10.3762/bjoc.10.321

• (90–105 kcal/mol) to form a new, weaker C–M bond (50–80 kcal/mol), followed by generation of a new C–C bond. Generally, transition metal-catalyzed sp2 C–H activation is facilitated by directing groups [10][11][12][13] or heteroatoms in the heterocyclic compounds [14][15][16][17][18]. This methodology

Regio- and stereoselective synthesis of new diaminocyclopentanols

• Evgeni A. Larin,
• Valeri S. Kochubei and
• Yuri M. Atroshchenko

Beilstein J. Org. Chem. 2014, 10, 2513–2520, doi:10.3762/bjoc.10.262

• aminoglycosides [7], and nucleosides containing 9H-purin-6-amine as a nucleobase portion. High levels of stereoselectivity have been observed in substrate-controlled diastereoselective epoxidation of cyclic alkenes with O- and N-allylic directing groups [20][21]. Several 3-substituted diastereomeric epoxides have

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

• immediately. Although a broad range of (hetero)arenes undergo C–H-arylation under copper catalysis, heterocycles possessing acidic N–H bonds react at the nitrogen preferentially [52][53]. Moreover, directing groups such as acetyl (in combination with a hypervalent iodine aryl source) [42], or 2-pyridinyl

Organophosphorus chemistry

• Paul R. Hanson

Beilstein J. Org. Chem. 2014, 10, 2087–2088, doi:10.3762/bjoc.10.217

• their use as recyclable heterogeneous reagents, the Atherton–Todd reaction, cyclic phosphonium ionic liquids with distinct properties, photo-removable phosphate protecting groups, new methods of C–H functionalization using phosphoryl-related directing groups, the exciting chemistry of substituted

Hindered aryl bromides for regioselective palladium-catalysed direct arylation at less favourable C5-carbon of 3-substituted thiophenes

• Rongwei Jin,
• Charles Beromeo Bheeter and
• Henri Doucet

Beilstein J. Org. Chem. 2014, 10, 1239–1245, doi:10.3762/bjoc.10.123

• thiophenes without the use of a blocking group at carbon C2. To our knowledge, ortho-substituents on aryl bromides have not been employed as directing groups for palladium-catalysed direct arylation of 3-substituted thiophenes. The use of congested aryl bromides for such couplings would certainly modify the

Synthesis of ethoxy dibenzooxaphosphorin oxides through palladium-catalyzed C(sp²)–H activation/C–O formation

• Seohyun Shin,
• Dongjin Kang,
• Woo Hyung Jeon and
• Phil Ho Lee

Beilstein J. Org. Chem. 2014, 10, 1220–1227, doi:10.3762/bjoc.10.120

• and the LUMO of the Pd–C bond is unfavorable and the Pd–O bond has a significantly ionic character [18][19][20][21][22][23]. To expand this scope, we are interested in the development of C–H activation/C–O formation by means of new directing groups. Recently, a variety of C–H activations by using new

• phosphoryl-related directing groups have been reported by our [24][25][26][27][28][29][30][31][32] and other groups [33][34][35][36][37][38][39][40][41]. More recently, we developed a method allowing for synthetic access to benzoxaphosphole 1- and 2-oxides starting from phosphonic and phosphinic acids via Pd

Recent advances in transition metal-catalyzed Csp²-monofluoro-, difluoro-, perfluoromethylation and trifluoromethylthiolation

• Grégory Landelle,
• Armen Panossian,
• Sergiy Pazenok,
• Jean-Pierre Vors and
• Frédéric R. Leroux

Beilstein J. Org. Chem. 2013, 9, 2476–2536, doi:10.3762/bjoc.9.287

• trifluoromethoxy group meta to the directing group shuts down the reaction completely. Other directing groups were investigated. When hydrogen was replaced by methyl on nitrogen in the starting acetanilide, no reaction occurred; on the other hand, N-pivaloyl- and N-benzoylanilines were trifluoromethylated, albeit

• -catalyzed perfluoroalkylation of arenes in the absence of directing groups [70]. Perfluoroalkyl iodides were used as the source of the fluorinated alkyl group. Under the optimized reaction conditions, a mixture of the iodide, 5 mol % Pd2dba3, 20 mol % BINAP, cesium carbonate (2 equiv) and the arene (large

Recent advances in transition-metal-catalyzed intermolecular carbomagnesiation and carbozincation

• Kei Murakami and
• Hideki Yorimitsu

Beilstein J. Org. Chem. 2013, 9, 278–302, doi:10.3762/bjoc.9.34

• reacts with allyl bromide to give 1i in 60% yield. Carbomagnesiation and carbozincation of alkynes bearing a directing group Directing groups have been utilized in successful carbometalation with high regio- and stereoselectivity. Classically, hydroxy groups on propargylic alcohols are used in

• product (58% yield) from 44 kg of 1-phenyl-1-butyne. Oshima reported manganese-catalyzed phenylmagnesiation of a wide range of arylacetylenes (Table 4) [102]. Notably, directing groups, such as ortho-methoxy or ortho-amino groups, facilitated the reaction (Table 4, entries 2 and 3 versus entry 4

• -bearing hydroxy group. Arylmagnesiation of (2-pyridyl)silyl-substituted alkynes. Synthesis of tamoxifen from 2g. Controlling regioselectivity of carbocupration by attaching directing groups. Rhodium-catalyzed carbozincation of ynamides. Synthesis of 4-pentenenitriles through carbometalation followed by

Rh(III)-catalyzed directed C–H bond amidation of ferrocenes with isocyanates

• Satoshi Takebayashi,
• Tsubasa Shizuno,
• Takashi Otani and
• Takanori Shibata

Beilstein J. Org. Chem. 2012, 8, 1844–1848, doi:10.3762/bjoc.8.212

• ] catalyzed the C–H bond amidation of ferrocenes possessing directing groups with isocyanates in the presence of 2 equiv/Rh of HBF4·OEt2. A variety of disubstituted ferrocenes were prepared in high yields, or excellent diastereoselectivities. Keywords: amidation; C–H activation; C–H functionalization

Extending the utility of [Pd(NHC)(cinnamyl)Cl] precatalysts: Direct arylation of heterocycles

• Anthony R. Martin,
• Anthony Chartoire,
• Alexandra M. Z. Slawin and
• Steven P. Nolan

Beilstein J. Org. Chem. 2012, 8, 1637–1643, doi:10.3762/bjoc.8.187

• directing groups or particular catalyst selectivity [1][2][3][4][5]. Thus, heteroaromatic scaffolds, which are a common feature in biologically relevant compounds and in materials science [6][7] can be selectively arylated as the heteroatom can act as an intrinsic orientating group [8]. Despite the

Synthesis of chiral sulfoximine-based thioureas and their application in asymmetric organocatalysis

• Marcus Frings,
• Isabelle Thomé and
• Carsten Bolm

Beilstein J. Org. Chem. 2012, 8, 1443–1451, doi:10.3762/bjoc.8.164

• findings include their use as fluoromethylation reagents, as fluorophores or as directing groups [16][17][18][19]. Two quality characteristics make them particularly attractive for asymmetric synthesis: 1) The stereogenic sulfur atom which is stable towards many reaction conditions, and 2) the ease of

Liquid-crystalline nanoparticles: Hybrid design and mesophase structures

• Gareth L. Nealon,
• Romain Greget,
• Cristina Dominguez,
• Zsuzsanna T. Nagy,
• Daniel Guillon,
• Jean-Louis Gallani and
• Bertrand Donnio

Beilstein J. Org. Chem. 2012, 8, 349–370, doi:10.3762/bjoc.8.39

• surface chemistry and morphology characteristics of the NP under investigation, ensuring a suitable anchoring group and structure-directing groups are present in the molecular structure. In the case of Au NPs, which are by far the most extensively investigated, there are two main methods used for the

Combined directed ortho-zincation and palladium-catalyzed strategies: Synthesis of 4,n-dimethoxy-substituted benzo[b]furans

• Verónica Guilarte,
• M. Pilar Castroviejo,
• Estela Álvarez and
• Roberto Sanz

Beilstein J. Org. Chem. 2011, 7, 1255–1260, doi:10.3762/bjoc.7.146

• compounds and different directing groups have been used to facilitate the deprotonation reaction [1][2][3][4][5]. Various strong bases such as alkyl lithiums and their derivatives (for instance, TMEDA-activated complexes [6] and heavier alkali metal tert-butoxide-complexed alkyl lithium reagents, known as

Meta-metallation of N,N-dimethylaniline: Contrasting direct sodium-mediated zincation with indirect sodiation-dialkylzinc co-complexation

• David R. Armstrong,
• Liam Balloch,
• Eva Hevia,
• Alan R. Kennedy,
• Robert E. Mulvey,
• Charles T. O'Hara and
• Stuart D. Robertson

Beilstein J. Org. Chem. 2011, 7, 1234–1248, doi:10.3762/bjoc.7.144

• and Discussion The original direct meta-zincation reaction. In comparison to tertiary amides and O-carbamates, anilines are relatively modest metallation directing groups [19][29]. Activation of N,N-dimethylaniline transpires primarily from the acidifying effect of the N atom; the coordination effect

• Structural Database [36] found that the bisaryl model has precedent in alkali-metal zincate chemistry, for example, the previously prepared biscarboxamide ((TMEDA)Li{2-(1-C(O)N(i-Pr)2)C6H4}2Zn(t-Bu)) [37], however the donor ability of the different directing groups limits comparison with 4. A salient feature

• least in part by considering the electronic nature of the different directing groups. With respect to NMe2, CF3 exerts an increased inductive effect thus weakening the Zn–Cortho bond to a greater extent, potentially leading to an easier cleavage and thus isomerisation. However, stimulated by this result

The allylic chalcogen effect in olefin metathesis

• Yuya A. Lin and
• Benjamin G. Davis

Beilstein J. Org. Chem. 2010, 6, 1219–1228, doi:10.3762/bjoc.6.140

• have also exploited both allylic and homoallylic hydroxy as directing groups in olefin metathesis for selective formation of key fragments in two recent examples of natural product syntheses. In the synthesis of aspergillide A, a key fragment 19 was synthesized by the CM reaction between diene 16 and

A review of new developments in the Friedel–Crafts alkylation – From green chemistry to asymmetric catalysis

• Magnus Rueping and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2010, 6, No. 6, doi:10.3762/bjoc.6.6

• employed as directing groups. This approach was used by Bach and co-workers employing the α-tert-butyl-substituted benzyl alcohol 107 (Scheme 40A). Various electron-rich arenes and heteroarenes were applied giving rise to chiral arenes 108 with remarkable syn-diastereoselectivities of up to 94 : 6 d.r

The oxanorbornene approach to 3-hydroxy, 3,4-dihydroxy and 3,4,5-trihydroxy derivatives of 2-aminocyclohexanecarboxylic acid

• Ishmael B. Masesane,
• Andrei S. Batsanov,
• Judith A. K. Howard,
• Raju Mondal and
• Patrick G. Steel

Beilstein J. Org. Chem. 2006, 2, No. 9, doi:10.1186/1860-5397-2-9

• selectivity leading to exclusive formation of 12. In a similar fashion, and in agreement with the idea of two directing groups working in concert, epoxidation of the exo derived diene 5 afforded exclusive formation of epoxide 13. Speculating that disruption of any directing effects through the use of more