Photocatalysis with organic dyes: facile access to reactive intermediates for synthesis

• Stephanie G. E. Amos,
• Marion Garreau,
• Luca Buzzetti and
• Jerome Waser

Beilstein J. Org. Chem. 2020, 16, 1163–1187, doi:10.3762/bjoc.16.103

• the nature of the halide: as a trend, aryl iodides are easier to reduce than aryl bromides and aryl chlorides [67][77]. Under organophotocatalytic conditions, the reduction can be achieved following two main strategies for accessing stronger reduction potentials: (a) tuning the electronics of the

• heteroarylated to give the desired dehalogenated products 13.3 or arylheteroarenes 13.4. Other organic dyes, such as dicyanoanthracene (OD5) and rhodamine 6G (OD14), have been successfully used in similar conPET strategies for the aryl radical-mediated derivatization of aryl bromides [82][83]. A similar double

• corresponding pyridinium and the desired carbamoyl radical. The latter can be intercepted by an organonickel species resulting from the oxidative addition of the nickel catalyst to the aryl bromides 19.2. The arylamides 19.3 are obtained following a reductive elimination, and the resulting Ni(I) species is

Copper-based fluorinated reagents for the synthesis of CF₂R-containing molecules (R ≠ F)

• Louise Ruyet and
• Tatiana Besset

Beilstein J. Org. Chem. 2020, 16, 1051–1065, doi:10.3762/bjoc.16.92

•  14, a). One year later, they demonstrated that these copper-based reagents ((Phen)CuCF2RF, RF = F, CF3 and CF2CF3) were efficient in a two-step sequence reaction (borylation/perfluoroalkylation) allowing the functionalization of either sterically hindered arenes or aryl bromides with the CF2CF3 and

• dealt with the copper-mediated perfluororalkyaltion of (hetero)aryl bromides using the previously developed PhenCuRF [69]. Although the trifluoromethylation reaction was mainly studied, the methodology was efficiently extended to the pentafluoroethylation of various heteroarenes such as pyridine

• (hetero)aryl bromides (11 examples, up to 98% 19F NMR yield) via the in situ generation of the suitable CuCF2CF3 from CuCl, KOt-Bu or NaOt-Bu and ethyl pentafluoropropionate [73]. Note that the methodology was also applied to the functionalization of a vinylboronic acid and a vinyl bromide (Scheme 18

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

• , 29 combinations of bicycloalkylamines or spirocyclic amines with (hetero)aryl bromides were probed using this workflow, and the results are depicted in Scheme 2 and Scheme 3. To provide attractive heterocyclic sp2–sp3 fragments, we mainly focused on coupling 3-bromopyridine to five different classes

• reactions, and ranged from 6% to 50% for copper-catalyzed cross-coupling reactions [13]. Much information could be obtained from this screening. Electron-deficient aryl bromides led to better yields than neutral and electron-rich partners, as observed in previous reports on photochemically- or

Synthesis and properties of tetrathiafulvalenes bearing 6-aryl-1,4-dithiafulvenes

• Aya Yoshimura,
• Hitoshi Kimura,
• Kohei Kagawa,
• Mayuka Yoshioka,
• Toshiki Itou,
• Dhananjayan Vasu,
• Takashi Shirahata,
• Hideki Yorimitsu and
• Yohji Misaki

Beilstein J. Org. Chem. 2020, 16, 974–981, doi:10.3762/bjoc.16.86

• Abstract Novel multistage redox tetrathiafulvalenes (TTFs) bearing 6-aryl-1,4-dithiafulvene moieties were synthesized by palladium-catalyzed direct C–H arylation. In the presence of a catalytic amount of Pd(OAc)2, P(t-Bu3)·HBF4, and an excess of Cs2CO3, the C–H arylation of TTF with several aryl bromides

• step from pristine TTF and 5, respectively, through palladium-catalyzed C–H arylation (Table 1). When the aryl bromides 6a,b were allowed to react with TTF under the conditions A, the products 1a,b were produced in 46 and 48% yields, respectively (Table 1, entries 1 and 2). Attempted isolations of

Aldehydes as powerful initiators for photochemical transformations

• Maria A. Theodoropoulou,
• Nikolaos F. Nikitas and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2020, 16, 833–857, doi:10.3762/bjoc.16.76

• salts were also tested, but they did not prove to be more efficient than the one already used. The optimized reaction conditions are presented in Scheme 31. A wide variety of aryl bromides, containing either electron-donating or electron-withdrawing substituents, was found to be compatible with this

• the aldehyde 161 could afford the acyl radical 168 through a HAT process, which then could add to diethyl maleate (154) and afford the desired product 162 through a propagation mechanism. In 2019, König and co-workers presented a catalytic arylation of aromatic aldehydes 170 by aryl bromides 171 using

• solvent, the base, and the irradiation wavelength. Next, they investigated the reaction potential, with most aryl bromides and benzaldehydes tested being compatible to this transformation, affording the products in moderate to excellent yield. The proposed photocatalytic cycle starts with the excitation

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

Recent advances in photocatalyzed reactions using well-defined copper(I) complexes

• Mingbing Zhong,
• Xavier Pannecoucke,
• Philippe Jubault and
• Thomas Poisson

Beilstein J. Org. Chem. 2020, 16, 451–481, doi:10.3762/bjoc.16.42

• yield, with an excellent functional group tolerance. Moreover, a complex steroid derivative was efficiently reduced under the standard conditions. Activated aryl bromides were also readily reduced under similar conditions, even if they were tedious electron-rich aryl bromide substrates, giving low yield

• electron-withdrawing groups in good to excellent yields. Activated aryl bromides and heteroaryl bromides were also successfully converted to the corresponding arylboronic esters in good to excellent yields. The methodology was also extended to a set of vinyl iodides, providing the vinylboronic esters in

Allylic cross-coupling using aromatic aldehydes as α-alkoxyalkyl anions

• Akihiro Yuasa,
• Kazunori Nagao and
• Hirohisa Ohmiya

Beilstein J. Org. Chem. 2020, 16, 185–189, doi:10.3762/bjoc.16.21

• rearrangement and then successfully trapped with aryl bromides under palladium catalysis (Scheme 1). This system was extended to an asymmetric version using the chiral α-silyloxybenzylcopper(I) species having a chiral NHC ligand. In the asymmetric system, one example of allylic carbonate was used as the carbon

Starazo triple switches – synthesis of unsymmetrical 1,3,5-tris(arylazo)benzenes

• Andreas H. Heindl and
• Hermann A. Wegner

Beilstein J. Org. Chem. 2020, 16, 22–31, doi:10.3762/bjoc.16.4

• restored. Conclusion In summary, 1,3,5-tris(arylazo)benzenes 3a/3b were successfully synthesized using Pd-catalyzed coupling reactions of arylhydrazides and aryl bromides followed by CuI-mediated oxidation as key steps. Although the low yield of the first coupling step, due to the preference for double

Acid-catalyzed rearrangements in arenes: interconversions in the quaterphenyl series

• Sarah L. Skraba-Joiner,
• Carter J. Holt and
• Richard P. Johnson

Beilstein J. Org. Chem. 2019, 15, 2655–2663, doi:10.3762/bjoc.15.258

• , samples of m,p’- (13), o,p’- (15), o,m’- (16), and o,o’-quaterphenyl (17) were synthesized as shown in Scheme 3. Suzuki–Miyaura coupling was used to synthesize 13, 15, and 16 from the corresponding aryl bromides and boronic acids [35]. o,o’-Quaterphenyl (17) was synthesized by homo-coupling of 2

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

• , promoting the C–F over C–O bond formation via an inner-sphere pathway. Fluorination of arenes, aryl bromides, -alcohols, -triflates, and -boronic acid derivatives: In 2013, Larhed and co-workers [51] established a one-pot, two-step fluorination of aryl alcohols via aryl nonafluorobutylsulfonates. This

• excellent yields with easy to separate byproducts. A year later, the same catalyst was employed for the nucleophilic fluorination of aryl bromides and iodides with AgF and KF [54]. Meanwhile, with a slight modification of the phosphine ligand, Buchwald developed a similar Pd(0) precatalyst [L2Pd]2(cod

Azologization and repurposing of a hetero-stilbene-based kinase inhibitor: towards the design of photoswitchable sirtuin inhibitors

• Christoph W. Grathwol,
• Nathalie Wössner,
• Sören Swyter,
• Adam C. Smith,
• Enrico Tapavicza,
• Robert K. Hofstetter,
• Anja Bodtke,
• Manfred Jung and
• Andreas Link

Beilstein J. Org. Chem. 2019, 15, 2170–2183, doi:10.3762/bjoc.15.214

• available naphthalene-2-ylboronic acid or (3,4-dihydronaphthalen-2-yl)boronic acid (Scheme 1). The latter was synthesized according to a literature procedure [36]. Formation of compounds 2b–h was accomplished through Heck coupling of aryl bromides with the appropriate styrenes (Scheme 2) [37]. Compounds 2b

Regioselective Pd-catalyzed direct C1- and C2-arylations of lilolidine for the access to 5,6-dihydropyrrolo[3,2,1-ij]quinoline derivatives

• Hai-Yun Huang,
• Haoran Li,
• Thierry Roisnel,
• Jean-François Soulé and
• Henri Doucet

Beilstein J. Org. Chem. 2019, 15, 2069–2075, doi:10.3762/bjoc.15.204

• acetate bases in DMA was found to promote the regioselective arylation at α-position of the nitrogen atom of lilolidine with a wide variety of aryl bromides. From these α-arylated lilolidines, a second arylation at the β-position gives the access to α,β-diarylated lilolidines containing two different aryl

• ) might be due to an easier coordination of acetates to palladium which favors the concerted metallation deprotonation (CMD) mechanism [40]. The regioselectivities observed using acetate bases are consistent with a CMD mechanism. Then, a set of aryl bromides was reacted with lilolidine using 2 mol % of

• PdCl(C3H5)(dppb) catalyst, NaOAc or KOAc as bases in DMA at 150 °C (Scheme 2). We initially studied the reactivity of electron-deficient aryl bromides. Acetyl, propionyl, benzoyl and ester as para-substituents on the aryl bromides were tolerated affording the target products 2–6 in 64–77% yields. The

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

Borylation and rearrangement of alkynyloxiranes: a stereospecific route to substituted α-enynes

• Ruben Pomar Fuentespina,
• José Angel Garcia de la Cruz,
• Gabriel Durin,
• Victor Mamane,
• Jean-Marc Weibel and
• Patrick Pale

Beilstein J. Org. Chem. 2019, 15, 1416–1424, doi:10.3762/bjoc.15.141

• ]. Alternatively, Unemaya et al. and more recently Buchwald et al. described a Negishi cross coupling of aryl bromides or chlorides to α-CF3-oxiranyl zincates generated by lithiation of trifluoromethyloxirane and transmetalation with zinc chloride [10][11]. In this context and based on the pioneering work of

Pd-Catalyzed microwave-assisted synthesis of phosphonated 13α-estrones as potential OATP2B1, 17β-HSD1 and/or STS inhibitors

• Rebeka Jójárt,
• Szabolcs Pécsy,
• György Keglevich,
• Mihály Szécsi,
• Réka Rigó,
• Csilla Özvegy-Laczka,
• Gábor Kecskeméti and
• Erzsébet Mernyák

Beilstein J. Org. Chem. 2018, 14, 2838–2845, doi:10.3762/bjoc.14.262

• . Investigation of inhibitory activities of the newly-synthesized compounds 8–13 against the OATP2B1 transporter protein and 17β-HSD1 or STS cytosolic enzymes was also aimed. Results and Discussion The Hirao reaction is a powerful tool for the synthesis of arylphosphonates from aryl bromides or iodides using

• [29]; namely, 1 equiv in the case of Pd(PPh3)4 and 1.3 equiv when using Pd(OAc)2. It was earlier established that in the microwave-assisted Pd(II)-catalyzed C–P coupling of aryl bromides and dialkyl phosphites, an excess of the applied dialkyl phosphite may serve as phosphorus ligand and reducing

• -phosphonated 13α-estrone derivatives 8–13. The elaborated methodology proved to be suitable for the facile transformation of steroidal aryl bromides 1–6 containing OH, OMe or OBn functions in ortho positions. 2-Regioisomers of 3-OH derivatives 9a,b appeared to be dual OATP2B1 and 17β-HSD1 inhibitors. The most

Cobalt- and rhodium-catalyzed carboxylation using carbon dioxide as the C1 source

• Tetsuaki Fujihara and
• Yasushi Tsuji

Beilstein J. Org. Chem. 2018, 14, 2435–2460, doi:10.3762/bjoc.14.221

• carboxylation of aryl halides and pseudohalides using CO2 is an important reaction to yield benzoic acid derivatives. In 2009, Martin reported the Pd-catalyzed carboxylation of aryl bromides using ZnEt2 as the reductant [31]. In 2012, we first reported the Ni-catalyzed carboxylation of aryl chlorides and vinyl

D-Fructose-based spiro-fused PHOX ligands: synthesis and application in enantioselective allylic alkylation

• Michael R. Imrich,
• Jochen Kraft,
• Cäcilia Maichle-Mössmer and
• Thomas Ziegler

Beilstein J. Org. Chem. 2018, 14, 2082–2089, doi:10.3762/bjoc.14.182

• ligands are prepared in two steps from readily available 1,2-O-isopropylidene protected β-D-fructopyranoses by the BF3·OEt2-promoted Ritter reaction with 2-bromobenzonitrile to construct the oxazoline moiety followed by Ullmann coupling of the resulting aryl bromides with diphenylphosphine. Both steps

• ligands in fair to good yields. For ether-protected substances yields ranged from 67% to 89% (Table 2, entries 1–5). Coupling of aryl bromides with ester-protected substances gave also acceptable yields in a range from 35% to 69% (Table 2, entries 6–10), they were considerably lower. It is known that

Water-soluble SNS cationic palladium(II) complexes and their Suzuki–Miyaura cross-coupling reactions in aqueous medium

• Alphonse Fiebor,
• Richard Tia,
• Banothile C. E. Makhubela and
• Henok H. Kinfe

Beilstein J. Org. Chem. 2018, 14, 1859–1870, doi:10.3762/bjoc.14.160

• . By using only 0.5 mol % loading of the complexes, the coupling of inactivated aryl bromides and activated aryl chlorides with various boronic acids in water was achieved in excellent yields and the catalysts were found to be reusable for three cycles without a significant loss of activity. The

• the literature are the water-soluble pincer complexes 14, 15 and 16 (Figure 2a). While pincer complex 14 provided moderate (38–68%) GC yields over 6 h at 75 °C using 2 mol % catalyst loading with inactivated aryl bromides, pincer complex 15 was found to be incompatible with both activated and

• inactivated aryl bromides according to the study conducted by Bai and Hor [34]. Similarly, Kumar et al. studied the catalytic activity of pincer complex 16 and reported that the catalyst was compatible with activated aryl bromides to provide reasonable yields over 12 h at 100 °C using 2 mol % catalyst loading

Three-component coupling of aryl iodides, allenes, and aldehydes catalyzed by a Co/Cr-hybrid catalyst

• Kimihiro Komeyama,
• Shunsuke Sakiyama,
• Kento Iwashita,
• Itaru Osaka and
• Ken Takaki

Beilstein J. Org. Chem. 2018, 14, 1413–1420, doi:10.3762/bjoc.14.118

• resulting in slightly lower yields (4g, 4g’, 4g” and 4h). Next, the generality of the reaction was investigated using aryl iodides (Scheme 7) and allenes (Scheme 8). Although aryl bromides and chlorides did not participate in the coupling, a diverse set of functional groups such as methoxy (4j), halogens

Bromide-assisted chemoselective Heck reaction of 3-bromoindazoles under high-speed ball-milling conditions: synthesis of axitinib

• Jingbo Yu,
• Zikun Hong,
• Xinjie Yang,
• Yu Jiang,
• Zhijiang Jiang and
• Weike Su

Beilstein J. Org. Chem. 2018, 14, 786–795, doi:10.3762/bjoc.14.66

• letermovir [8]. Hitherto, highly effective systems had been developed for the aryliodines that participated in Heck reactions with turn-over numbers of >1000 [9][10]. However, the couplings of bromo and chloro derivatives with unactivated alkenes still remain challenging. Though aryl bromides are always

• dehalogenation of aryl bromides, wherever possible. Herein, 3-bromoindazoles were chosen as model substrates not only for their low activity and easy dehalogenation properties, but also for their potential applications in the synthesis of natural products and pharmaceuticals, such as gamendazole [31][32], YC-1

Nanoreactors for green catalysis

• M. Teresa De Martino,
• Loai K. E. A. Abdelmohsen,
• Floris P. J. T. Rutjes and
• Jan C. M. van Hest

Beilstein J. Org. Chem. 2018, 14, 716–733, doi:10.3762/bjoc.14.61

• quantitative yields were observed when aryl chloride coupling was performed with arylboronic acids. This is indeed remarkable as aryl chlorides are generally not as reactive as aryl bromides or aryl iodides. Lipshutz and Ghorai developed a micellar system called PQS to perform aldol reactions in water [25]. As

Photocatalytic formation of carbon–sulfur bonds

• Alexander Wimmer and
• Burkhard König

Beilstein J. Org. Chem. 2018, 14, 54–83, doi:10.3762/bjoc.14.4

• organic transformations, but also limits the scope of this method. Using 3,7-bis(biphenyl-4-yl)-10-(1-naphthyl)phenoxazine as organic photocatalyst instead of [Ir(dF(CF3)ppy)2(dtbbpy)]PF6, Miyake found out that also aryl bromides could be cross-coupled with a series of different thiols. These were not

Reactivity of bromoselenophenes in palladium-catalyzed direct arylations

• Aymen Skhiri,
• Ridha Ben Salem,
• Jean-François Soulé and
• Henri Doucet

Beilstein J. Org. Chem. 2017, 13, 2862–2868, doi:10.3762/bjoc.13.278

• allowed the coupling of several heteroaromatics such as thiazole, pyrrole, furan or imidazole derivatives with aryl bromides [36]. 2-Bromoselenophene, which was easily prepared by reaction of selenophene with N-bromosuccinimide [37], and 2-ethyl-4-methylthiazole were employed as model substrates for our

• C5-position of 2-arylselenophenes containing nitrile, acetyl or chloro substituents on the aryl moiety, which could be easily obtained in good yields from selenophene and aryl bromides via a Pd-catalyzed direct arylation using a reported procedure [33], afforded the 2-aryl-5-bromoselenophenes 15–17

Mechanochemical synthesis of small organic molecules

• Tapas Kumar Achar,
• Anima Bose and
• Prasenjit Mal

Beilstein J. Org. Chem. 2017, 13, 1907–1931, doi:10.3762/bjoc.13.186

• of styrenes with aryl bromides or aryl chlorides (Scheme 9) [59]. Sonogashira reaction Stolle and co-workers have reported a Sonogashira coupling reaction under ball milling conditions in which the reactions were done in absence of any copper catalyst or any additional ligands [60]. In presence of