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

• routes to afford molecular complexity from simple precursors, while concomitantly limiting the number of steps and waste generation. Following this general key objective, the landscape of organic synthesis has been clearly changed by the development of ecofriendly methodologies such as metal-catalyzed C

• –H activations, visible-light-induced photocatalysis, electrosynthesis, enzyme catalysis, and others. Each of these techniques aims at accessing complex molecules while limiting ecological footprint. Over the last decade, the metal-catalyzed C–H activation established itself as one of the most

• rapidly expanding domain of organic synthesis [1][2][3][4][5][6][7][8][9][10][11][12][13][14]. Indeed, this approach tends in rendering the classical metal-catalyzed cross-coupling more environmentally friendly, as simple, non-prefunctionalized substrates could be used in the presence of a metallic

Tuneable access to indole, indolone, and cinnoline derivatives from a common 1,4-diketone Michael acceptor

• Dalel El-Marrouki,
• Sabrina Touchet,
• Abderrahmen Abdelli,
• Hédi M’Rabet,
• Mohamed Lotfi Efrit and
• Philippe C. Gros

Beilstein J. Org. Chem. 2020, 16, 1722–1731, doi:10.3762/bjoc.16.144

• ][38][39] or triketones [10][13] and enaminones [40][41][42][43] as starting materials. For the synthesis of cinnoline derivatives, aryldiazenes and aryltriazenes are substrates of choice for transition-metal-catalyzed (Rh, Pd, Cu) cross-coupling reactions, followed by intramolecular cyclizations [44

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

• the design of dye-sensitized solar cells (DSSC) [4]. Typical methods for the construction of a phenanthrene core involve transition-metal-catalyzed cycloisomerizations starting from arynes [5][6], o-alkynyl-biaryls [7][8], or substituted N-tosylhydrazones [9]. However, since the introduction in 1964

• , among the others, the anionic ring-closure of 2-cyanobiaryls by using organometallic reagents [19][20], and an impressive number of transition-metal-catalyzed C(sp2)–C(sp2) cross-coupling processes [21][22][23]. In the last decade, however, photochemical reactions, especially those promoted by a

One-pot synthesis of 1,3,5-triazine-2,4-dithione derivatives via three-component reactions

• Gui-Feng Kang and
• Gang Zhang

Beilstein J. Org. Chem. 2020, 16, 1447–1455, doi:10.3762/bjoc.16.120

• with the reaction conditions and yielded the corresponding products (6oa–va, 48–92%), allowing for further functionalization through subsequent transition-metal-catalyzed coupling reactions. Intriguingly, it was found that compounds with bicycloaryl and heteroaryl ring systems were also viable

Oxime radicals: generation, properties and application in organic synthesis

• Igor B. Krylov,
• Stanislav A. Paveliev,
• Alexander S. Budnikov and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2020, 16, 1234–1276, doi:10.3762/bjoc.16.107

• oximes can be achieved through different ways including addition of electrophiles to the C=C double bond of the unsaturated oxime followed by intramolecular nucleophilic attack of the oxime group [97][98][99][100], metal-catalyzed cyclization [98][101][102][103][104][105][106][107][108], cyclization

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

• the corresponding (R)-N-acetyl ester 60 with >99.5% ee [50] (Scheme 13). The synthesis of 3-bromo-4-fluoro-(S)-Phe (65) was carried out by reacting 3-bromo-4-fluorobenzaldehyde (61) and N-acetylglycine (51a) to provide intermediate 63 in high yield and without purification. Then, the transition-metal

• -catalyzed asymmetric hydrogenation of the α-amidocinnamic acid 63 using the less frequently used ferrocene-based ligand Me-BoPhoz led to the N-acetyl-ʟ-phenylalanine derivative 64 with complete conversion and with 94% ee. The desired enantiomer (S)-65 was obtained as a single isomer (>99% ee) after

Accelerating fragment-based library generation by coupling high-performance photoreactors with benchtop analysis

• Quentin Lefebvre,
• Christophe Salomé and
• Thomas C. Fessard

Beilstein J. Org. Chem. 2020, 16, 982–988, doi:10.3762/bjoc.16.87

• collections. These are of high value to medicinal chemists to provide defined exit vectors and facilitate rational lead evolution [2][3][4][5][6][7]. Thus, we were interested in developing reliable synthetic methods and technologies to apply metal-catalyzed cross-coupling reactions to such scaffolds, which

Preparation of 2-phospholene oxides by the isomerization of 3-phospholene oxides

• Péter Bagi,
• Réka Herbay,
• Nikolett Péczka,
• Zoltán Mucsi,
• István Timári and
• György Keglevich

Beilstein J. Org. Chem. 2020, 16, 818–832, doi:10.3762/bjoc.16.75

• ][4]. A heterocyclic ring containing a P atom appears in many popular P(III)-ligands, such as BPE, DuPhos, TangPhos, DuanPhos, ZhangPhos [5][6][7][8][9][10][11], among which a number of species may be considered as privileged ligands for transition metal-catalyzed enantioselective transformations [12

Combining enyne metathesis with long-established organic transformations: a powerful strategy for the sustainable synthesis of bioactive molecules

• Valerian Dragutan,
• Ileana Dragutan,
• Albert Demonceau and
• Lionel Delaude

Beilstein J. Org. Chem. 2020, 16, 738–755, doi:10.3762/bjoc.16.68

• -metal-catalyzed transformations were needed to achieve the total synthesis of des-epoxy-amphidinolide N, including a palladium asymmetric allylic alkylation (Pd-AAA), a Mukaiyama aldol reaction (with Sn), and a Krische allylation (with Ir) [72]. As special feature of this procedure, an Evans aldol

• in the pyrrolidine ring catalyzed by RhCl3·H2O, followed by debenzylation, amidation, and aminal generation using the Stille protocol [77]. (–)‐Clavukerin A and related sesquiterpenes Applying original organocatalytic/metal-catalyzed tactics, Metz et al. [78] reported a tandem dienyne RCM for the

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

• reactions are discussed. Keywords: C–B bonds; copper catalysis; C–Si bonds; enantioselective reactions; sp3 carbon functionalization; Introduction Transition-metal-catalyzed silylation and borylation are useful transformations [1], widely studied because organosilicon [2][3] and organoboron compounds [4

Direct borylation of terrylene and quaterrylene

• Haruka Kano,
• Keiji Uehara,
• Kyohei Matsuo,
• Hironobu Hayashi,
• Hiroko Yamada and
• Naoki Aratani

Beilstein J. Org. Chem. 2020, 16, 621–627, doi:10.3762/bjoc.16.58

• , 2) the product obtained is soluble in common organic solvents so that the separation and characterization would be readily performed, and 3) the resultant pure soluble terrylene derivative as a versatile unit can be functionalized by using conventional metal-catalyzed coupling reactions. Results and

Efficient synthesis of 3,6,13,16-tetrasubstituted-tetrabenzo[a,d,j,m]coronenes by selective C–H/C–O arylations of anthraquinone derivatives

• Seiya Terai,
• Yuki Sato,
• Takuya Kochi and
• Fumitoshi Kakiuchi

Beilstein J. Org. Chem. 2020, 16, 544–550, doi:10.3762/bjoc.16.51

• groups to form biaryl frameworks. Traditionally, transition-metal-catalyzed cross-coupling reactions of aryl halides or pseudohalides with arylmetal reagents have been employed for the connection of two aryl units [5][6][7][8][9]. However, in search of more efficient synthetic routes, C–H arylation

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

• molecules, thus having drawn much attention. Transition metal-catalyzed C–X/C–M cross-coupling reactions such as Suzuki and Stille couplings are the main approaches to achieve the arylation of PAHs [7][8][9][10][11]. However, the selective arylation of the C7-position of 1-naphthoic acid derivatives remains

• a challenging task due to the inaccessibility of the corresponding 7-halonaphthalene substrates [12]. Recently, transition metal-catalyzed C–H bond functionalization has emerged as a powerful tool to construct various biaryl skeletons [13][14][15][16][17]. The direct C7−H arylation of 1-naphthoic

• acid derivatives is undoubtedly a more effective route for the synthesis of 7-arylnaphthalene derivatives. Although the transition metal-catalyzed C2−H and C8−H arylations of 1-naphthoic acid derivatives have been widely reported, the studies on their C7−H arylation remain rare [18][19][20][21][22][23

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

• . 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

• group, transition-metal catalyzed), a radical mechanism has not been previously discussed. Some of these reports indicate a marked difference in selectivity between elevated and ambient temperatures, which we found may be due to a change in mechanism (Supporting Information File 1, Table S1, Figure S1

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

• methodology was also faster than the metal-catalyzed phosphorylation route reported by the same authors. The use of multiply halogenated compounds opens up opportunities to synthesize multidentate ligands. Zhang et al. [64] reported on a sequential synthetic route of multichelate pyridylphosphines 15, 16 and

• chlorodiphenylphosphine, afforded 1-methyl-4,5-bis(diphenylphosphino)imidazole (85). Finally, N-methylation gave the imidazolium salt derivative 86 in good yield (65%). Preparation of N-heterocyclic phosphines via metal-catalyzed P–C/N bond formation There is limited availability of certain N-containing precursors and

• the quinazoline ring (Scheme 17) and the phosphine was introduced via metal-catalyzed phosphorylation. The ligands were synthesized in eight steps with relatively good yield. The reaction between substituted nitrile derivatives 87 and anthranilic acid (88) catalyzed by sodium methoxide formed

Combination of multicomponent KA² and Pauson–Khand reactions: short synthesis of spirocyclic pyrrolocyclopentenones

• Riccardo Innocenti,
• Elena Lenci,
• Gloria Menchi and
• Andrea Trabocchi

Beilstein J. Org. Chem. 2020, 16, 200–211, doi:10.3762/bjoc.16.23

• Information File 1), as it can promote metal-catalyzed reactions [53]. The scope of the combined approach employing KA2 and Pauson–Khand reactions was studied by varying the alkyne and ketone components, along with the acylating moiety being installed before the Pauson–Khand reaction (Scheme 2 and Table 1

Microwave-assisted synthesis of 2-substituted 4,5,6,7-tetrahydro-1,3-thiazepines from 4-aminobutanol

• María C. Mollo,
• Natalia B. Kilimciler,
• Juan A. Bisceglia and
• Liliana R. Orelli

Beilstein J. Org. Chem. 2020, 16, 32–38, doi:10.3762/bjoc.16.5

• as building blocks in drug discovery, and as ligands in metal-catalyzed reactions [11][12][13][14][15][16]. Their six-membered homologues (5,6-dihydro-4H-1,3-thiazines) are also compounds of broad interest [17], due to their bioactivities [18][19] and as valuable synthetic intermediates [20][21][22

Palladium-catalyzed Sonogashira coupling reactions in γ-valerolactone-based ionic liquids

• László Orha,
• József M. Tukacs,
• László Kollár and
• László T. Mika

Beilstein J. Org. Chem. 2019, 15, 2907–2913, doi:10.3762/bjoc.15.284

• chemistry; ionic liquids; Introduction In the past few decades, the transition-metal-catalyzed coupling reaction has represented one of the most powerful and atom economical strategies for the efficient assembly of new carbon–carbon bonds. It has therefore become the most attractive approach to the

• reaction environment could have a significant effect on the efficiency of a transition-metal-catalyzed reaction. Because [TBP][4EtOV] was isolated from an aqueous solution, the investigation of possible influence of the residual water content on the reaction was highly desired. We found that no decrease in

Iodine-mediated hydration of alkynes on keto-functionalized scaffolds: mechanistic insight and the regiospecific hydration of internal alkynes

• Zachary Lee,
• Brandon R. Jones,
• Nyochembeng Nkengbeza,
• Michael Phillips,
• Kayla Valentine,
• Alexis Stewart,
• Brandon Sellers,
• Nicholas Shuber and
• Karelle S. Aiken

Beilstein J. Org. Chem. 2019, 15, 2747–2752, doi:10.3762/bjoc.15.265

• hydration reaction of alkynes serves as a green alternative to metal-catalyzed procedures. Previous work has shown that this method works well with terminal alkynes on keto-functionalized scaffolds, including 1,3-dicarbonyls and their heteroatom analogues. It was hypothesized that the reaction proceeds

Emission solvatochromic, solid-state and aggregation-induced emissive α-pyrones and emission-tuneable 1H-pyridines by Michael addition–cyclocondensation sequences

• Natascha Breuer,
• Irina Gruber,
• Christoph Janiak and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2019, 15, 2684–2703, doi:10.3762/bjoc.15.262

• fluorophores [19], in particular on aggregation-induced emissive polar dyes [20]. Conceptually, many of these consecutive multicomponent syntheses rely on transition-metal-catalyzed heterocyclic syntheses [21]. By virtue of catalytic generation of alkynones [22] we have recently disclosed consecutive

Chiral terpene auxiliaries V: Synthesis of new chiral γ-hydroxyphosphine oxides derived from α-pinene

• Anna Kmieciak and
• Marek P. Krzemiński

Beilstein J. Org. Chem. 2019, 15, 2493–2499, doi:10.3762/bjoc.15.242

• with chlorophosphines, the reaction of metal phosphides with haloalkanes, and transition-metal-catalyzed cross-coupling reactions to form C–P bonds are the most widely used methods for the synthesis of phosphines [13][14]. Since phosphines are easily oxidized to phosphine oxides, the addition of

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

• comprises an initial Ugi-azide-4CR followed by a cyclization step, involving some of the reactive functionalities previously installed in the multicomponent process [20][21][22][23][24][25][26]. However, the interplay between the multicomponent synthesis of tetrazoles and metal-catalyzed cyclization

• processes has remained underexploited [27]. Thus, we envisioned that the combination of an Ugi-azide-4CR with modern metal-catalyzed C–C bond-forming methods would enable access to structurally novel compounds featuring hybrid heterocycle platforms. We focused on metal-catalyzed annulation approaches that

• could form isoquinolones and pyridones linked to a tetrazole ring, since such class of hybrid compounds is not described in the literature. Several protocols based on C–H activation or metal-catalyzed cyclizations are known to generate the isoquinolone and pyridone moieties and further assist their post

Synthesis of acremines A, B and F and studies on the bisacremines

• Nils Winter and
• Dirk Trauner

Beilstein J. Org. Chem. 2019, 15, 2271–2276, doi:10.3762/bjoc.15.219

• ]. Nevertheless, to the best of our knowledge, no asymmetric entry to this class of natural products has been described. Our retrosynthetic analysis of 5 is depicted in Scheme 1. The prenyl side chain would be introduced by transition metal-catalyzed cross coupling of vinyl iodide 9. Compound 9 in turn could be

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

• , agricultural, and materials industries. The incorporation of fluorine-containing groups into organic molecules can improve their chemical and physical properties, which attracts continuous interest in organic synthesis. Among various reported methods, transition-metal-catalyzed fluorination/fluoroalkylation

• has emerged as a powerful method for the construction of these compounds. This review attempts to describe the major advances in the transition-metal-catalyzed incorporation of fluorine, trifluoromethyl, difluoromethyl, trifluoromethylthio, and trifluoromethoxy groups reported between 2011 and 2019

• brief summary of the recent achievements in the ever-growing field of green fluoroalkylation. However, until now, no comprehensive survey of the literature has been reported on this topic. In this review, we highlight the recent progress of transition-metal-catalyzed fluorination and

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

• decomposition of diazo compounds, are particularly versatile intermediates in organic synthesis, as they partake in cyclopropanation and C–H insertion reactions with high levels of selectivity [2]. This transition-metal-catalyzed carbene transfer has emerged as a mild and attractive route to indole