Transition-metal-catalyzed C–H bond activation as a sustainable strategy for the synthesis of fluorinated molecules: an overview

• Louis Monsigny,
• Floriane Doche and
• Tatiana Besset

Beilstein J. Org. Chem. 2023, 19, 448–473, doi:10.3762/bjoc.19.35

• -promoted trifluoromethylthiolation of benzamide derivatives 1 at the ortho-position by C–H bond activation [114]. Indeed, using a bidentate directing group (amide derived from the 8-aminoquinoline), the mono- and difunctionalized compounds were obtained when Cu(OAc)2 (0.5 equiv) and the toxic and volatile

• were obtained in 30% and 20% yields, respectively. Several mechanistic experiments revealed that the C(sp2)–H bond activation step was reversible and represented the rate-determining step (KIE = 2.4). First, the chelation of the palladium(II) catalyst with the bidentate directing group, followed by the

• primary C(sp3) centers by transition-metal-catalyzed C–H activation with the Munavalli or the Billard reagents as the trifluoromethylthiolation source (Scheme 14) [126]. Using a bidentate directing group, this methodology allowed the functionalization of a large range of aliphatic amides with a primary β

Synthetic strategies for the preparation of γ-phostams: 1,2-azaphospholidine 2-oxides and 1,2-azaphospholine 2-oxides

• Jiaxi Xu

Beilstein J. Org. Chem. 2022, 18, 889–915, doi:10.3762/bjoc.18.90

• )aminoalkanoic acids 86 (Scheme 15) [35][36]. This is a convenient way to synthesize γ-phosphonolactams 85. They further extended their method to synthesize cyclic O,O- and O,S-bidentate ligands with a P–N–P backbone. The substitution reaction of 3-bromopropylamine hydrogen bromide (87) and chloroethoxyphosphine

Menadione: a platform and a target to valuable compounds synthesis

• Acácio S. de Souza,
• Ruan Carlos B. Ribeiro,
• Dora C. S. Costa,
• Fernanda P. Pauli,
• David R. Pinho,
• Matheus G. de Moraes,
• Fernando de C. da Silva,
• Luana da S. M. Forezi and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 381–419, doi:10.3762/bjoc.18.43

• % selectivity. According to the authors, the reaction mechanism involves the formation of an active selenium peroxo species. Additionally, they mentioned that the catalyst was easily separated from the reaction mixture by simple filtration [56]. Serindağ and co-workers disclosed the bidentate tertiary

Amamistatins isolated from Nocardia altamirensis

• Till Steinmetz,
• Wolf Hiller and
• Markus Nett

Beilstein J. Org. Chem. 2022, 18, 360–367, doi:10.3762/bjoc.18.40

• metallic ions depends on the presence of suitable ligand groups. Hydroxamates, 2,3-dihydroxybenzoates, and α-hydroxycarboxylates make excellent bidentate ligand groups, as their negatively charged oxygen atoms can maintain strong interactions with ferric iron [3]. But there are also many siderophores

• structural features of these molecules. Amamistatin B (5) exhibits three bidentate ligand groups and can thus form an octahedral complex with ferric iron. The removal of one of these groups (e.g., the hydroxamate function at the ε terminus of the lysine residue) already leads to a considerable loss of iron

• affinity, as observed for compound 2. This trend continues in 1, 3, and 4, each of which features only a single bidentate ligand group. Compound 6 possesses the least iron affinity with a DC50 value of 5008 ± 222 μM. The results show a clear correlation between the number of ligands in a molecule and its

A Se···O bonding catalysis approach to the synthesis of calix[4]pyrroles

• Qingzhe Tong,
• Zhiguo Zhao and
• Yao Wang

Beilstein J. Org. Chem. 2022, 18, 325–330, doi:10.3762/bjoc.18.36

• interactions between catalysts Ch1, Ch2 and acetone were examined by 13C NMR experiments in CD2Cl2. The interaction between bidentate catalyst Ch1 or monodentate catalyst Ch2 and acetone could result in a variation of the 13C signal of the carbonyl group. Analysis of a 1:1 mixture of Ch1 and acetone in CD2Cl2

• monodentate and bidentate catalysts could activate ketones. Accordingly, either a single activation or a double activation mode could be an effective driving force to promote this transformation, albeit with distinct catalytic activity. Conclusion In summary, we developed a Se···O bonding catalysis approach

• to the synthesis of calix[4]pyrroles. In the presence of 5 mol % selenide catalyst, calix[4]pyrrole products were obtained in moderate to good yields at room temperature. The experimental results showed that both bidentate and monodentate catalysts were catalytically active in the condensation

Biological properties and conformational studies of amphiphilic Pd(II) and Ni(II) complexes bearing functionalized aroylaminocarbo-N-thioylpyrrolinate units

• Samet Poyraz,
• Samet Belveren,
• Sabriye Aydınoğlu,
• Mahmut Ulger,
• Abel de Cózar,
• Maria de Gracia Retamosa,
• Jose M. Sansano and
• H. Ali Döndaş

Beilstein J. Org. Chem. 2021, 17, 2812–2821, doi:10.3762/bjoc.17.192

• , C. tropicalis, and C. glabrata standard strains. A deep conformational survey was monitored using DFT calculations with the aim to explain the importance of the final conformation in the biological experimental results. Keywords: antituberculosis; bidentate ligands; DFT; nickel; palladium

Copper-catalyzed monoselective C–H amination of ferrocenes with alkylamines

• Zhen-Sheng Jia,
• Qiang Yue,
• Ya Li,
• Xue-Tao Xu,
• Kun Zhang and
• Bing-Feng Shi

Beilstein J. Org. Chem. 2021, 17, 2488–2495, doi:10.3762/bjoc.17.165

• groups. Kumar and co-workers developed a Cu-mediated C–H chalcogenation and sulfonation of ferrocenes [27][28][29]. The use of a bidentate 1,10-phenathroline ligand was critical to achieve mono-selectivity in the chacogenation reactions [28]. Meanwhile, Co(III)-catalyzed ortho-C–H amidation of ferrocene

Halides as versatile anions in asymmetric anion-binding organocatalysis

• Lukas Schifferer,
• Martin Stinglhamer,
• Kirandeep Kaur and
• Olga García Macheño

Beilstein J. Org. Chem. 2021, 17, 2270–2286, doi:10.3762/bjoc.17.145

• C1 position. Analogously to the Pictet–Spengler cyclization, the group initially speculated that the thiourea catalyst 6 interacts with the carbonyl function of the amide intermediate I and, thus, a SN2-type mechanism via hydrogen bonding catalysis was proposed. A similar bidentate carbonyl

• % ee [63]. Evolution of catalyst designs: from bidentate to supramolecular multidentate anion-binding catalysts Despite the evident potential that anion-binding catalysis showed in the pioneering publications – especially in regard to exerting high stereocontrol –, the strategy was still faced with

• example highlighting the importance of sidechain catalyst design was given by Jacobsen et al. in the tail-to-head cyclization of neryl chloride and derivatives 59 (Scheme 13) [17]. Mechanistic studies and DFT calculations revealed that an extended π-system in the sidechain of the bidentate urea catalyst

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

Copper-mediated oxidative C−H/N−H activations with alkynes by removable hydrazides

• Feng Xiong,
• Bo Li,
• Chenrui Yang,
• Liang Zou,
• Wenbo Ma,
• Linghui Gu,
• Ruhuai Mei and
• Lutz Ackermann

Beilstein J. Org. Chem. 2021, 17, 1591–1599, doi:10.3762/bjoc.17.113

• unfortunately proven elusive [35]. 2-(1-Methylhydrazinyl)pyridine (MHP) [36] was identified as a powerful removable bidentate directing group, which found widespread application in various cobalt-catalyzed C−H activations [37][38][39][40]. Thus, our group also accomplished a set of electrochemical cobalt

Free-radical cyclization approach to polyheterocycles containing pyrrole and pyridine rings

• Ivan P. Mosiagin,
• Olesya A. Tomashenko,
• Dar’ya V. Spiridonova,
• Mikhail S. Novikov,
• Sergey P. Tunik and
• Alexander F. Khlebnikov

Beilstein J. Org. Chem. 2021, 17, 1490–1498, doi:10.3762/bjoc.17.105

• ). It is important that the reaction of iodide 1m with 2-pyridyl substituent gave a good yield of the product 3m, which could be used for the preparation of bidentate ligand for metal complexes. Reaction of salts 1 with electron-donating para-substituents (Me, MeO, Me2N) in the pyridine ring (1n–p,s

Highly regio- and stereoselective phosphinylphosphination of terminal alkynes with tetraphenyldiphosphine monoxide under radical conditions

• Dat Phuc Tran,
• Yuki Sato,
• Yuki Yamamoto,
• Shin-ichi Kawaguchi,
• Shintaro Kodama,
• Akihiro Nomoto and
• Akiya Ogawa

Beilstein J. Org. Chem. 2021, 17, 866–872, doi:10.3762/bjoc.17.72

• as 1,2-bis(diphenylphosphino)ethane (Ph2PCH2CH2PPh2, dppe) are employed as bidentate ligands and are effective in controlling important catalytic reactions such as cross-coupling reactions [9][10][11][12][13][14][15][16][17][18]. 1,2-Bis(diphenylphosphino)ethylene (Ph2PCH=CHPPh2, dppen) is among

• bidentate diphosphine ligands having a rigid structure and has increased attention as a useful and effective ligand in coordinating with various metals [19][20]. (Z)-Ph2PCH=CHPPh2 is very important as a bidentate ligand for many mononuclear complexes [21][22][23]. On the other hand, (E)-Ph2PCH=CHPPh2 acts

Valorisation of plastic waste via metal-catalysed depolymerisation

• Francesca Liguori,
• Carmen Moreno-Marrodán and
• Pierluigi Barbaro

Beilstein J. Org. Chem. 2021, 17, 589–621, doi:10.3762/bjoc.17.53

• the glycolytic depolymerisation of PET [128][205]. The highest BHET yield (74.7%) was achieved using zinc chloride (0.5% w/w), an EG/PET ratio of 14:1 and reflux conditions (Table 2, entry 8). The use of preformed soluble Co(II) complexes bearing bidentate phosphorus ligands (e.g., 1,2-bis

When metal-catalyzed C–H functionalization meets visible-light photocatalysis

• Lucas Guillemard and
• Joanna Wencel-Delord

Beilstein J. Org. Chem. 2020, 16, 1754–1804, doi:10.3762/bjoc.16.147

• bicoordinating DGs to facilitate C(sp3)–H metalation, Polyzos’s group reported the direct arylation of aliphatic bonds with aryldiazonium salts via a palladium/photoredox dual catalysis (Figure 26) [88]. The method utilized an 8-aminoquinoline-derived bidentate auxiliary, and, in contrast with a vast majority of

• photoinduced by visible light was promoted by copper and used the bidentate 8-aminoquinoline moiety as the DG (Figure 33) [98]. Remarkably, eosin Y, a cheap organic photocatalyst, enhanced the generation of perfluoroalkyl radicals from the corresponding alkyl iodides but a stoichiometric amount of a simple

• a mild and efficient protocol for the remote C4–H sulfonylation of 1-naphthylamine derivatives with sodium sulfinates in the presence of K2S2O8 as the oxidant (Figure 35) [99]. This strategy was based on the use of a bidentate picolinamide DG promoting the direct C–H functionalization of the

Heterogeneous photocatalysis in flow chemical reactors

• Christopher G. Thomson,
• Ai-Lan Lee and
• Filipe Vilela

Beilstein J. Org. Chem. 2020, 16, 1495–1549, doi:10.3762/bjoc.16.125

• recommend exploring the article for further details [95]. Molecules with functional groups such as carboxylic acid present complex surface topologies from bridging and bidentate binding modes [91]. Yoshida and co-workers studied the adsorption of benzene derivatives on TiO2 surfaces by solid-state NMR and

Photocatalyzed syntheses of phenanthrenes and their aza-analogues. A review

• Alessandra Del Tito,
• Havall Othman Abdulla,
• Davide Ravelli,
• Stefano Protti and
• Maurizio Fagnoni

Beilstein J. Org. Chem. 2020, 16, 1476–1488, doi:10.3762/bjoc.16.123

• proximity to each other, prone to be engaged in a bidentate-type metal-coordination complex [75]. 2.2 Synthesis of phenanthridines via photocatalyzed C–N bond formation As mentioned in the introduction, the examples gathered here involve the intermediacy of N-centered radicals. As a representative case, the

Fluorinated phenylalanines: synthesis and pharmaceutical applications

• Laila F. Awad and
• Mohammed Salah Ayoup

Beilstein J. Org. Chem. 2020, 16, 1022–1050, doi:10.3762/bjoc.16.91

• diastereoisomeric purity (dr > 99:1) (Scheme 38). 2.9. Direct fluorination of β-methylene C(sp3)−H The direct fluorination of β-methylene C(sp3)−H bonds of Phe derivatives 157a–v having installed the bidentate auxiliary, 2-(pyridine-2-yl)isopropylamine (PIP-amine) 158, was attempted using Selectfluor in the

Cation-induced ring-opening and oxidation reaction of photoreluctant spirooxazine–quinolizinium conjugates

• Phil M. Pithan,
• Sören Steup and
• Heiko Ihmels

Beilstein J. Org. Chem. 2020, 16, 904–916, doi:10.3762/bjoc.16.82

• discussed in the literature whether metal cations are coordinated in a monodentate fashion to the phenolate oxygen atom or rather in a bidentate fashion both to the phenolate oxygen and the imine nitrogen atoms of the open merocyanine form [25][28]. Furthermore, density functional theory (DFT) calculations

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

• conversion of 2-substituted 1,3-dienes 376 into borocyano products using commercially available phosphine ligands (Scheme 60). Simply switching from a mono to a bidentate ligand resulted in 1,4 to 4,1-borocupration. The formation of allyl–Cu intermediates in the catalytic cycle readily trap available

Design and synthesis of diazine-based panobinostat analogues for HDAC8 inhibition

• Sivaraman Balasubramaniam,
• Sajith Vijayan,
• Liam V. Goldman,
• Xavier A. May,
• Kyra Dodson,
• Sweta Adhikari,
• Fatima Rivas,
• Davita L. Watkins and
• Shana V. Stoddard

Beilstein J. Org. Chem. 2020, 16, 628–637, doi:10.3762/bjoc.16.59

• [3]. Among these drugs, panobinostat (Farydak, Novartis) an FDA approved drug, has been recognized as a pan-deacetylase inhibitor [9][10]. As a hydroxamic acid pan-HDACi, it is zinc-dependent, capable of binding in a bidentate fashion to the zinc-containing catalytic domain of the HDACs, and

• possesses a −log(Kd) value of 8.36 suggesting that it too would be on a par with panobinostat (8.47). Our previous study showed that the hydroxamate tail of TOI1, TOI2, and TOI4 formed a bidentate interaction with the Zn2+ ion at the base of the HDAC8 receptor, which is consistent with the crystal structure

• (Figure 2). This shift allows for the indole ring of TOI4 to fit in a small hydrophobic pocket at the surface, which is created by the phenyl ring of Phe-207. Like the previously studied compounds (TOI1, TOI2, and TOI4), TOI3-rev is also shown to bind to the HDAC8 receptor by forming a bidentate

Architecture and synthesis of P,N-heterocyclic phosphine ligands

• Wisdom A. Munzeiwa,
• Bernard Omondi and
• Vincent O. Nyamori

Beilstein J. Org. Chem. 2020, 16, 362–383, doi:10.3762/bjoc.16.35

• family of privileged chiral ligands in asymmetric catalysis [12]. In these compounds, the C2 axis of symmetry helps in increasing the selectivity of the formation of certain enantiomers by inhibiting other possible reaction pathways [93]. In particular, biarylphosphines and bidentate 2,2'-bis

Copper-promoted/copper-catalyzed trifluoromethylselenolation reactions

• Clément Ghiazza and
• Anis Tlili

Beilstein J. Org. Chem. 2020, 16, 305–316, doi:10.3762/bjoc.16.30

• ]. Noteworthy, depending on the nature of the bidentate ligand used, the corresponding copper complex could be isolated as monomer or dimer, and both were air-stable. Among the new complexes, the reactivity of [(bpy)CuSeCF3]2 in trifluoromethylselenolations was thoroughly investigated using a large panel of

Synthesis and herbicidal activities of aryloxyacetic acid derivatives as HPPD inhibitors

• Man-Man Wang,
• Hao Huang,
• Lei Shu,
• Jian-Min Liu,
• Jian-Qiu Zhang,
• Yi-Le Yan and
• Da-Yong Zhang

Beilstein J. Org. Chem. 2020, 16, 233–247, doi:10.3762/bjoc.16.25

• -dicarbonyl bidentate chelation with the active center metal, and 2) through favorable sandwich π–π stacking interactions between aromatic rings and the Phe360, Phe403 residues of the active site. Thus, 1,3-dicarbonyl and aromatic moieties are indispensable pharmacophores for potent HPPD-inhibiting compounds

• inhibitors. Initially, molecular docking studies were performed on two representative compounds, namely I39 and I40 [25], in order to explore their binding modes. The result revealed the presence of two main interactions, the sandwich π−π interaction and the bidentate interaction, which are similar to those

Palladium-catalyzed synthesis and nucleotide pyrophosphatase inhibition of benzo[4,5]furo[3,2-b]indoles

• Hoang Huy Do,
• Saif Ullah,
• Alexander Villinger,
• Joanna Lecka,
• Jean Sévigny,
• Peter Ehlers,
• Jamshed Iqbal and
• Peter Langer

Beilstein J. Org. Chem. 2019, 15, 2830–2839, doi:10.3762/bjoc.15.276

• ). Monodentate ligands, like XPhos, SPhos, DavePhos, RuPhos, or P(t-Bu)3·HBF4, were not effective in the reaction and gave product 5b in low yields. Bidentate phosphine ligands, such as BINAP, XantPhos, dppe, or dppf (Table 1), worked very well and allowed to improve the yield of 5b up to 75% (Table 1, entry 4

A chiral self-sorting photoresponsive coordination cage based on overcrowded alkenes

• Constantin Stuckhardt,
• Diederik Roke,
• Wojciech Danowski,
• Edwin Otten,
• Sander J. Wezenberg and
• Ben L. Feringa

Beilstein J. Org. Chem. 2019, 15, 2767–2773, doi:10.3762/bjoc.15.268

• interesting strategy to form responsive coordination complexes, as they feature a large geometric change upon switching [47]. Herein, we report a photoresponsive coordination cage with ligands based on a first generation molecular motor (Figure 1). Cages with a Pd2L4 composition are formed from bidentate