Photoredox catalysis harvesting multiple photon or electrochemical energies

• Mattia Lepori,
• Simon Schmid and
• Joshua P. Barham

Beilstein J. Org. Chem. 2023, 19, 1055–1145, doi:10.3762/bjoc.19.81

• reductants as a theme of ongoing debate [39]. Nonetheless, this protocol enabled the reduction of various electron-poor aryl iodides and aryl bromides and, for the first time, the reduction of aryl chlorides (albeit electron-poor ones) via visible light PRC in good to excellent yields (35–98%) (Figure 4A

• infra, Figure 69), the Wickens group developed a conPET protocol using 2,4,5,6-tetrakis(diphenylamino)isophthalonitrile (4-DPAIPN) for the reduction of electron-rich aryl chlorides [55]. With 4-DPAIPN as an electron-primed photocatalyst, substrates with reduction potentials as deep as Epred = −3.4 V vs

• hydroarylation of tert-butyl vinylcarbamate and unactivated alkenes like 1-octene and 3-buten-1-ol although the vinyl carbamate substrate (Epred = −2.2 V vs SCE) is significantly easier to reduce than most aryl chlorides. This selectivity, especially considering the need for an excess of the vinyl carbamate

Total synthesis of insect sex pheromones: recent improvements based on iron-mediated cross-coupling chemistry

• Eric Gayon,
• Guillaume Lefèvre,
• Olivier Guerret,
• Adrien Tintar and
• Pablo Chourreu

Beilstein J. Org. Chem. 2023, 19, 158–166, doi:10.3762/bjoc.19.15

• combination with a variety of alkenyl chlorides and (hetero)aryl chlorides [18]. Importance of the leaving groups: use of enol phosphates In order to overcome the delicate choice of either NMP or one of its surrogates as a suitable co-solvent, it has also been demonstrated that amide-free catalytic procedures

Palladium-catalyzed solid-state borylation of aryl halides using mechanochemistry

• Koji Kubota,
• Emiru Baba,
• Tamae Seo,
• Tatsuo Ishiyama and
• Hajime Ito

Beilstein J. Org. Chem. 2022, 18, 855–862, doi:10.3762/bjoc.18.86

• halides in a test tube [15]. They found that a Pd(dba)2/DPEphos catalytic system was effective for aryl bromides, and aryl chlorides reacted more efficiently when XPhos was used as the ligand [15]. Although their achievements are remarkable, this protocol is only applicable to liquid substrates, which can

Recent developments and trends in the iron- and cobalt-catalyzed Sonogashira reactions

• Surendran Amrutha,
• Sankaran Radhika and
• Gopinathan Anilkumar

Beilstein J. Org. Chem. 2022, 18, 262–285, doi:10.3762/bjoc.18.31

• higher reactivity and less active aryl chlorides were successfully coupled to give the desired products in acceptable yields. The reaction carried out by both catalysts gave excellent yields of up to 98% for Co-NHC@MWCNTs and a still good yield of up to 91% for reactions catalyzed by Co-NPs. It was

Iron-catalyzed domino coupling reactions of π-systems

• Austin Pounder and
• William Tam

Beilstein J. Org. Chem. 2021, 17, 2848–2893, doi:10.3762/bjoc.17.196

• classically sensitive functionalities like esters and aryl chlorides. Exposure of the iron catalyst to one equivalent of aryl Grignard reagent 2b in the absence of the halide substrate afforded the bimetallic Fe(II) complex FeBr2[Mg(acac)2](THF)2. Using FeBr2[Mg(acac)2](THF)2 in place of Fe(acac)3 in the

Photoredox catalysis in nickel-catalyzed C–H functionalization

• Lusina Mantry,
• Rajaram Maayuri,
• Vikash Kumar and
• Parthasarathy Gandeepan

Beilstein J. Org. Chem. 2021, 17, 2209–2259, doi:10.3762/bjoc.17.143

• arylation of cyclic and acyclic ethers 9 with aryl chlorides 8 under photoredox nickel catalysis (Scheme 5) [56]. Here, aryl chlorides 8 serve as cross-coupling partners and the chlorine radical source, which rapidly abstracts an α-oxy C(sp3)−H of the ethers to form the key α-oxyalkyl radical intermediate

• of aryl chlorides 8 through selective 2-functionalization of 1,3-dioxolane (13) followed by a mild acidic workup (Scheme 9) [61]. Here, the photocatalyst Ir[dF(CF3)ppy]2(dtbbpy)PF6 and nickel catalyst NiCl2·DME with dtbbpy as ligand, along with K3PO4 as base under irradiation with blue LEDs enabled

• the regioselective 2-functionalization of 1,3-dioxolane (13) with aryl chlorides 8. It was found that the electron-deficient aryl chlorides resulted in better yields within shorter reaction times over the electron-rich substrates. A possible catalytic cycle was shown to account for the reaction mode

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

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

Disposable cartridge concept for the on-demand synthesis of turbo Grignards, Knochel–Hauser amides, and magnesium alkoxides

• Mateo Berton,
• Kevin Sheehan,
• Andrea Adamo and
• D. Tyler McQuade

Beilstein J. Org. Chem. 2020, 16, 1343–1356, doi:10.3762/bjoc.16.115

• well-packed column: 98%. System scope: Next, we probed the limit of this transformation for primary (bromoethane, bromooctane, chlorobutane, and iodomethane) and secondary (2-bromopropane, 2-chloropropane, and 2-chlorobutane) alkyl halides as well as benzyl (chloromethylbenzene) and aryl chlorides

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

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

• conditions, a rare cross-coupling takes place (Scheme 62) [115]. The cooperative effect of a catalytic system consisting of Cu/Ni (e.g., Ni(acac)2, CuCl, and PCy3) was also reported by Nakao et al. leading to regio- and stereoselective arylboration of 1-arylalkenes with aryl chlorides or tosylates. The

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

• , but in low yields due to a partial conversion of these aryl bromides. It should be mentioned that the use of aryl chlorides instead of aryl bromides did not allow to improve the regioselectivities or the reaction yields. With 4-chlorobenzonitrile, product 2 was obtained in 80% regioselectivity and in

• 38% yield; whereas the use of 2-chlorobenzonitrile afforded 12 in 62% regioselectivity and in 34% yield. In both cases, partial conversions of the aryl chlorides were observed. Pyridines and quinoline heterocycles are very important structures in pharmaceutical chemistry as more than 100 currently

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

Selective benzylic C–H monooxygenation mediated by iodine oxides

• Kelsey B. LaMartina,
• Haley K. Kuck,
• Linda S. Oglesbee,
• Asma Al-Odaini and
• Nicholas C. Boaz

Beilstein J. Org. Chem. 2019, 15, 602–609, doi:10.3762/bjoc.15.55

• intractable products, which were in many cases polyfunctionalized. Additionally, substrates containing arene rings were shown to inhibit aliphatic C–H functionalization via electrophilic trapping of reactive halogen species to form aryl chlorides and iodides. Utilizing NHPI as a less reactive hydrogen atom

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

Applications of organocatalysed visible-light photoredox reactions for medicinal chemistry

• Michael K. Bogdos,
• Emmanuel Pinard and
• John A. Murphy

Beilstein J. Org. Chem. 2018, 14, 2035–2064, doi:10.3762/bjoc.14.179

• the presence of triethylamine (Scheme 5) [46]. The biggest breakthrough in this case is the excitation of PDI by two photons, creating a radical anion in an excited state, giving the catalyst a much higher reducing power, allowing the reduction of aryl chlorides (see product 5b). This is the first

• report of the reduction of aryl chlorides without the use of a strong base, UV radiation or highly reactive neutral organic reducing agents. The PDI catalytic cycle is different to the general catalytic cycle presented in the introduction and is presented in Figure 7. The group also showed that it is

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

• ; but required stoichiometric amounts of tetra-n-butylammonium bromide (TBAB) to effect the reaction of inactivated aryl bromides [35]. A further limitation of these catalysts is their incapability to catalyse the coupling reaction when either activated or inactivated aryl chlorides are employed as

• . The slightly lower yield of the reaction in the preparation of 23i could be ascribed to steric encumbrance exerted by the NO2-substituent located at the ortho-position of the aryl bromide. Encouraged by these results, the reactivities of aryl chlorides were investigated under the optimised conditions

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

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation. Part 1: Use of CF₃SO₂Na

• Hélène Guyon,
• Hélène Chachignon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2764–2799, doi:10.3762/bjoc.13.272

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

• ), phenylboronic acid (2.0 equiv), K2CO3 (3.0 equiv) and Pd(PPh3)4 (5 mol %) resulted in coupled products with 96% yield (Scheme 7). The NaCl was used as an additive to make the reaction mixture sufficiently powdery for uniform mixing. The use of aryl chlorides is generally restricted in Suzuki reactions because

• of their low reactivity. Recently, Li and Su with co-workers have developed a liquid-assisted grinding (LAG) method for the Suzuki–Miyaura coupling between aryl chlorides and boronic acids to synthesize the biaryls in nearly quantitative yield. Under optimized conditions 2 mol % Pd(OAc)2 and 4 mol

• 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

An effective Pd nanocatalyst in aqueous media: stilbene synthesis by Mizoroki–Heck coupling reaction under microwave irradiation

• Carolina S. García,
• Paula M. Uberman and
• Sandra E. Martín

Beilstein J. Org. Chem. 2017, 13, 1717–1727, doi:10.3762/bjoc.13.166

• -position. The coupling of styrene with a substrate bearing an acidic proton, 4-iodophenol (1h), was found to proceed efficiently, obtaining a high TOF of 19920 h−1 (entry 8, Table 2). Unfortunately, it was not possible to successfully accomplish the Mizoroki–Heck coupling with aryl chlorides under many

Automating multistep flow synthesis: approach and challenges in integrating chemistry, machines and logic

• Chinmay A. Shukla and
• Amol A. Kulkarni

Beilstein J. Org. Chem. 2017, 13, 960–987, doi:10.3762/bjoc.13.97

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

• synthesized a series of novel imidazole-based phosphine ligands, and their effciency was carefully screened [23]. Among these ligands, the one with two isopropyl groups located at the phenyl ring (L3) was effective in converting aryl chlorides and bromides to the corresponding phenols in moderate to excellent

• aryl iodides and aryl bromides were carried out at 100 °C and 110 °C, respectively. The conversion of aryl chlorides bearing electron-withdrawing groups was achieved at 130 °C. Amino acids and its analogues are another type of N,O-bidentate ligand for copper catalyzed hydroxylation of aryl halides. In

• , copper catalysts are more favorable for aryl bromides and aryl iodides as aryl chlorides require palladium catalysts. Except for special cases, a ligand is indispensable for the conversion. In the view of solvent, DMSO/H2O as mixed solvent or water as sole solvent are popular choices for the

Highly bulky and stable geometry-constrained iminopyridines: Synthesis, structure and application in Pd-catalyzed Suzuki coupling of aryl chlorides

• Yi Lai,
• Zhijian Zong,
• Yujie Tang,
• Weimin Mo,
• Nan Sun,
• Baoxiang Hu,
• Zhenlu Shen,
• Liqun Jin,
• Wen-hua Sun and
• Xinquan Hu

Beilstein J. Org. Chem. 2017, 13, 213–221, doi:10.3762/bjoc.13.24

• activities in the coupling reaction of aryl chlorides. Keywords: aryl chloride; geometry-constrained; iminopyridyl; palladium; Suzuki; Introduction Palladium-promoted C–C coupling reactions are recognized as one of the most powerful tools in organic syntheses, pharmaceutical processes and biological

• , it is still not favored for the cheaper and more widely available aryl chloride substrates. For C–Cl bond activation, the major efforts have focused on using extraordinarily electron-rich ligands to promote the oxidative addition. We assumed that the coupling of aryl chlorides could also be furnished

• under high temperature, if the palladium catalyst is stable enough. The formation of palladium black was observed in reactions of aryl chlorides using the reported palladium catalyst system, which inspired us to improve the thermal stability of the palladium complex. The steric environment adjacent to

Practical synthetic strategies towards lipophilic 6-iodotetrahydroquinolines and -dihydroquinolines

• David R. Chisholm,
• Garr-Layy Zhou,
• Ehmke Pohl,
• Roy Valentine and
• Andrew Whiting

Beilstein J. Org. Chem. 2016, 12, 1851–1862, doi:10.3762/bjoc.12.174

• bromides or aryl chlorides, but initial investigation with 6-bromo-THQs indicated that these were remarkably unreactive in cross-coupling reactions [14], and a reliable and scalable synthesis of the likely more reactive iodides was, therefore, sought. We first considered the retrosynthetic analysis shown