Sequential hydrozirconation/Pd-catalyzed cross coupling of acyl chlorides towards conjugated (2E,4E)-dienones

• Benedikt Kolb,
• Daniela Silva dos Santos,
• Sanja Krause,
• Anna Zens and
• Sabine Laschat

Beilstein J. Org. Chem. 2023, 19, 176–185, doi:10.3762/bjoc.19.17

• analogues, whereas the variation of the acyl chlorides did not affect the reaction significantly. The synthetic application is demonstrated by formation of non-natural and natural dienone-containing terpenes such as β-ionone which was available in 4 steps and 6% overall yield. Keywords: cross coupling

• ethers 12 [19] and metal-catalyzed cross coupling of alkenes 13 and enones 14 [20][21] have been reported. However, these reactions face multiple disadvantages such as limited substrate scope, use of hazardous solvents and harsh reaction conditions such as high temperatures or acidic/basic conditions

• ][33][34][35][36][37][38][39][40] as well as in several total syntheses of natural products [41][42][43][44][45][46]. Especially the combination of hydrozirconation and Pd or Ni-catalyzed cross coupling was elaborated by several groups (Scheme 3) [47][48][49][50][51][52][53][54]. Negishi extended

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

• sustainable synthetic procedures involving cheap, non-toxic and efficient additives is also discussed, as well as the mechanistic features guiding the reactivity of such catalytic systems. Keywords: catalysis; cross-coupling; insect pheromones; iron; Introduction Public health issues related to

• ]) are linear syntheses involving a great number of steps and purifications as well as cryogenic temperatures. Moreover, the introduction of the C=C unsaturation is achieved via a Wittig reaction or a Pd-catalyzed Sonogashira cross-coupling followed by a reduction by a borane reagent, methods which lead

• to overall processes with a low atom economy, generating a significant amount of chemical waste, and which can be expensive when noble metals such as palladium salts are required (Scheme 1). The high efficiency of transition-metal-catalyzed cross-coupling methods in C–C bond formation processes

1,4-Dithianes: attractive C2-building blocks for the synthesis of complex molecular architectures

• Bram Ryckaert,
• Ellen Demeyere,
• Frederick Degroote,
• Hilde Janssens and
• Johan M. Winne

Beilstein J. Org. Chem. 2023, 19, 115–132, doi:10.3762/bjoc.19.12

• °C and 0 °C, temperatures at which these organometallic reagents are also reported to be quite stable. The zincated dithiins can also be prepared by transmetalation of the magnesiated dithiins at −30 °C, and these organozinc reagents can then be used in room temperature Pd-catalyzed cross-coupling

• , including cross-coupling-type chemistries on a conformationally stable cis-vinyl zinc building block. 3 Diels–Alder reactivity of 1,4-dithiin-based dienophiles and dienes Vinyl sulfones and vinyl sulfoxides are classical synthetic equivalents of ethylene in Diels–Alder reactions, and have been widely used

Practical synthesis of isocoumarins via Rh(III)-catalyzed C–H activation/annulation cascade

• Qian-Ci Gao,
• Yi-Fei Li,
• Jun Xuan and
• Xiao-Qiang Hu

Beilstein J. Org. Chem. 2023, 19, 100–106, doi:10.3762/bjoc.19.10

• for the synthesis of isocoumarin scaffolds. Traditional synthetic strategies including 1) intramolecular cyclization of 2-alkenyl benzoic acids or o‑alkynylbenzoates (Scheme 1b, I) [6][7][8][9][10], 2) oxidation of isochromans (Scheme 1b, II) [11][12], or 3) metal-catalyzed cross-coupling/cyclization

• approach towards isocoumarins [17][18]. Pioneering examples relying on the Pd, Ru, and Ir-catalyzed C–H cross coupling of benzoic acids with alkenes and alkynes were realized by the groups of Miura [19], Lee [20], Ackermann [21], Zhang [22], Jiang [23], and Jeganmohan [24] et al. Despite these impressive

• recently, the same group developed an efficient Rh(III)-catalyzed C–H cross-coupling of enaminones with diazodicarbonyls for the divergent construction of isocoumarins and naphthalenes [27]. Moreover, Loh et al. disclosed a Rh-catalyzed formal [4 + 2] cycloaddition of enaminones with diazocarbonyls [28

Organophosphorus chemistry: from model to application

• György Keglevich

Beilstein J. Org. Chem. 2023, 19, 89–90, doi:10.3762/bjoc.19.8

• ” topics of the discipline under discussion. Cross-coupling reactions are also of importance in organophosphorus chemistry. Taddei and co-workers applied an alternative method to the classical Hirao reaction [1]. They utilized the Ni-catalyzed double Michaelis–Arbuzov reaction of bis(bromoaryl) species and

Combining the best of both worlds: radical-based divergent total synthesis

• Kyriaki Gennaiou,
• Antonios Kelesidis,
• Maria Kourgiantaki and
• Alexandros L. Zografos

Beilstein J. Org. Chem. 2023, 19, 1–26, doi:10.3762/bjoc.19.1

• chemoselective manner [3]. The development of persistent radicals [4] as synthons in chemical synthesis, coupled with the advancements in generating and manipulating transient radicals [5] as cross-coupling partners in an array of chemical reactions, gives access to a wide variety of “new” retrosynthetic

• reactions of transition metal hydrides (Fe, Co, Mn, etc) with alkenes (e.g., Mukaiyama hydration) [20]. The last decade saw the development of milder methods for generating carbon-centered radicals as the advancement of their reactivity in cross-coupling reactions, the concept of photoredox catalysis [21

• nickel-mediated decarboxylative Giese reactions and decarboxylative radical zinc-mediated cross-coupling reactions of redox-active esters, established from previous works of the group [27][28], for the key C–C bonds of the diverse congeners. To this end, a hypothetical intermediate 3 was envisioned for

Total synthesis of grayanane natural products

• Nicolas Fay,
• Rémi Blieck,
• Cyrille Kouklovsky and
• Aurélien de la Torre

Beilstein J. Org. Chem. 2022, 18, 1707–1719, doi:10.3762/bjoc.18.181

• -membered triflate 71 was synthesized from diketone 26 in 5 steps and 37% overall yield. Both fragments were assembled by a Sonogashira cross-coupling, affording 72 in 72% yield. In a first attempt, TBS protection was considered on the bicylo[3.2.1]octane. However, later in the strategy, the deprotection

Redox-active molecules as organocatalysts for selective oxidative transformations – an unperceived organocatalysis field

• Elena R. Lopat’eva,
• Igor B. Krylov,
• Dmitry A. Lapshin and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2022, 18, 1672–1695, doi:10.3762/bjoc.18.179

• introduction of an electron-withdrawing acetoxy group. The DABCO cation radical is less reactive compared to quinuclidine-derived cation radicals. It was involved in the Ni-catalyzed oxidative C–C cross-coupling involving aldehyde C–H bond cleavage with the formation of acyl radicals according to the proposed

• catalyzed by ABNO-type amine-N-oxyl radicals. Hydrogen atom transfer (HAT) and single-electron transfer (SET) as basic principles of amine cation radical oxidative organocatalysis. Electrochemical quinuclidine-catalyzed oxidation involving unactivated C–H bonds. DABCO-mediated photocatalytic C–C cross

• -coupling involving aldehyde C–H bond cleavage. DABCO-derived cationic catalysts in inactivated C–H bond cleavage for alkyl radical addition to electron-deficient alkenes under photoredox catalysis conditions. Electrochemical diamination and dioxygenation of vinylarenes catalyzed by triarylamines

Synthetic study toward the diterpenoid aberrarone

• Liang Shi,
• Zhiyu Gao,
• Yiqing Li,
• Yuanhao Dai,
• Yu Liu,
• Lili Shi and
• Hong-Dong Hao

Beilstein J. Org. Chem. 2022, 18, 1625–1628, doi:10.3762/bjoc.18.173

• was further confirmed through X-ray crystallographic analysis. With the key intermediate 10 in hand, we were in a position to test the planned two-step transformation including the palladium-catalyzed reductive cross coupling with HCO2H followed by Pd/C-catalyzed hydrogenation. To our surprise, the

• –Martin oxidation. At this stage, the pivotal C–H insertion step was tried under the reported conditions [34], and cyclopentenone 8 was successfully obtained. Further study with cross coupling or halogen–magnesium exchange shows this moiety is inert for functional group transformation. The attempt for

A new route for the synthesis of 1-deazaguanine and 1-deazahypoxanthine

• Raphael Bereiter,
• Marco Oberlechner and
• Ronald Micura

Beilstein J. Org. Chem. 2022, 18, 1617–1624, doi:10.3762/bjoc.18.172

• the cross coupling reaction. We also mention that we did not decide for a direct transformation [27][28] of 6-iodo-1-deazapurine into 6-hydroxy-1-deazapurine for reasons of solubility and desired regioselectivity of the subsequent nitration reaction. 1-Deazahypoxanthine Synthesis of 1

Simple synthesis of multi-halogenated alkenes from 2-bromo-2-chloro-1,1,1-trifluoroethane (halothane)

• Yukiko Karuo,
• Atsushi Tarui,
• Kazuyuki Sato,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2022, 18, 1567–1574, doi:10.3762/bjoc.18.167

• difluoroalkyl ethers (1), along with small amounts of fluoroalkenyl ethers (2), which were obtained from 1 via an E2-elimination mechanism (Scheme 1B) [14][15]. The fluoroalkenyl group in 2 is a potentially useful moiety that could participate in cross-coupling reactions for replacement of the bromine atom with

• HF from 1 provides 2 as an E/Z mixuture (E/Z = 1:1). We speculated that the stability of the E isomer was equal to that of the Z isomer under these conditions. To expand the scope of this reaction, we subjected product 2 to a Sonogashira cross-coupling reaction (Scheme 3). This gave a highly

• functionalized enyne structure that will be useful in various molecular transformations [27][28][29]. On the basis of a previous report, Sonogashira cross-coupling of 2 with trimethylsilylacetylene was performed with a bis(triphenylphosphine)palladium(II) dichloride. The reaction proceeded smoothly to give

An alternative C–P cross-coupling route for the synthesis of novel V-shaped aryldiphosphonic acids

• Stephen J. I. Shearan,
• Enrico Andreoli and
• Marco Taddei

Beilstein J. Org. Chem. 2022, 18, 1518–1523, doi:10.3762/bjoc.18.160

• order of addition of reactants to perform the transition-metal-catalyzed C–P cross-coupling reaction, often referred to as the Tavs reaction, employing NiCl2 as a pre-catalyst in the phosphonylation of aryl bromide substrates using triisopropyl phosphite. This new method was employed in the synthesis of

• three novel aryl diphosphonate esters which were subsequently transformed to phosphonic acids through silylation and hydrolysis. Keywords: arylphosphonic acids; cross-coupling reaction; phosphonate esters; transition-metal catalysis; Introduction Phosphonates and phosphonic acids are a very

• ][25][26]. These catalytic cross-coupling reactions tend to follow similar pathways to the Michaelis–Arbuzov reaction, with the inclusion of a catalytic intermediate step. A number of suitable catalysts have been identified, ranging from nickel(II) bromide and nickel(II) chloride, to palladium(II

Microelectrode arrays, electrosynthesis, and the optimization of signaling on an inert, stable surface

• Kendra Drayton-White,
• Siyue Liu,
• Yu-Chia Chang,
• Sakashi Uppal and
• Kevin D. Moeller

Beilstein J. Org. Chem. 2022, 18, 1488–1498, doi:10.3762/bjoc.18.156

• peptide so that the thiol group in the sidechain could be used to place the molecule the array with the use of an electrochemically initiated Cu(I)-catalyzed cross-coupling reaction (Scheme 1) [9]. To this end, the Cu(I) catalyst needed for the reaction was generated at the electrodes by the reduction of

• for the confinement strategy to keep up. The result is a loss in confinement. It is important to point out that the reaction shown in Scheme 1 is not a typical electrosynthetic reaction. The cross-coupling reaction shown is a Cu(I)-catalyzed transformation that requires no recycling of a reagent

• 12 electrodes each functionalized with pyrene-butanol at various places on the array. For the placement reaction, the Cu(I)-catalyzed cross-coupling reaction used above (Scheme 1) was employed for 4 cycles (90 s on and 180 s off). The chemistry placed enough of the alcohol by the electrodes for the

One-pot synthesis of 2-arylated and 2-alkylated benzoxazoles and benzimidazoles based on triphenylbismuth dichloride-promoted desulfurization of thioamides

• Arisu Koyanagi,
• Yuki Murata,
• Shiori Hayakawa,
• Mio Matsumura and
• Shuji Yasuike

Beilstein J. Org. Chem. 2022, 18, 1479–1487, doi:10.3762/bjoc.18.155

• cyclopropanes with arenes [29]. They have also been used in Pd-catalyzed cross-coupling reactions to react with hypervalent iodonium salts, organostananes, and vinyl epoxides [30][31][32]. Moreover, there are reports of them serving as oxidizing agents for alcohols [33]. Two papers have recently reported

Design, synthesis, and evaluation of chiral thiophosphorus acids as organocatalysts

• Karen R. Winters and
• Jean-Luc Montchamp

Beilstein J. Org. Chem. 2022, 18, 1471–1478, doi:10.3762/bjoc.18.154

• cross-coupling [34] in excellent yield. Esterification of 6 with monomethyl H-phosphonate tert-butylamine salt [35] resulted in the mixed H-phosphonate ester 7 in excellent yield. Cyclization using our homolytic aromatic substitution methodology [36] gave P-heterocycle 8 in modest yield. Other methods

• cross-coupling, and 2) immobilization on a solid support via reduction and reaction of the aniline with an electrophile such as polystyrene isocyanate. DOPO scaffold We previously reported the syntheses of both enantiomers of 8-phenyl DOPO 3 [38]. The syntheses proceed in only three steps (including the

Synthesis and electrochemical properties of 3,4,5-tris(chlorophenyl)-1,2-diphosphaferrocenes

• Almaz A. Zagidullin,
• Farida F. Akhmatkhanova,
• Mikhail N. Khrizanforov,
• Robert R. Fayzullin,
• Tatiana P. Gerasimova,
• Ilya A. Bezkishko and
• Vasili A. Miluykov

Beilstein J. Org. Chem. 2022, 18, 1338–1345, doi:10.3762/bjoc.18.139

• transition metal-catalyzed cross-coupling reactions broadly used for the preparation of different diarylacetylenes and, rarely, bis(chlorophenyl)acetylenes. Next, starting substituted benzaldehydes were treated with an excess of SOCl2 for 24 h at 25 °C. Corresponding substituted benzal chlorides 4 were

Modular synthesis of 2-furyl carbinols from 3-benzyldimethylsilylfurfural platforms relying on oxygen-assisted C–Si bond functionalization

• Sebastien Curpanen,
• Per Reichert,
• Gabriele Lupidi,
• Giovanni Poli,
• Julie Oble and
• Alejandro Perez-Luna

Beilstein J. Org. Chem. 2022, 18, 1256–1263, doi:10.3762/bjoc.18.131

• -catalyzed cross-coupling reactions, such as arylation reactions catalyzed by Pd2(dba)3/CuI, as well as allylation and methylation reactions catalyzed by CuI⋅PPh3. C3-Benzyldimethylsilyl-appended furfurals are thus introduced as versatile platforms, providing a modular access to 3-substituted 2-furyl

• on the SiMe(OSiMe3)2 unit, which were readily converted through Pd- or Cu-catalyzed electrophilic substitution reactions into an array of furfurals decorated at C3 with carbon- or heteroatom-containing substituents (Scheme 1). Conversely, all of our subsequent efforts to achieve cross-coupling

• cross-coupling chemistry [30][31], could be accessed from 2-[(3-benzyldimethylsilyl)furyl] carbinols. C3–Si bond functionalization through siloxane formation In an attempt to isolate cyclic siloxane 16, we then considered a protocol reported by Anderson and co-workers to prepare cyclic siloxanes by

Heterogeneous metallaphotoredox catalysis in a continuous-flow packed-bed reactor

• Wei-Hsin Hsu,
• Susanne Reischauer,
• Peter H. Seeberger,
• Bartholomäus Pieber and
• Dario Cambié

Beilstein J. Org. Chem. 2022, 18, 1123–1130, doi:10.3762/bjoc.18.115

• (catalyst) separation in one step. The use of a packed bed simplifies the translation of optimized batch reaction conditions to continuous flow, as the only components present in the reaction mixture are the substrate and a base. The metallaphotoredox cross-coupling of sulfinates with aryl halides was used

• systematically study the cross-coupling using the packed-bed reactor, we decided to equip the continuous-flow setup with a dedicated tool for in-line analysis. Such techniques enable rapid investigations of process-related parameters [34]. In particular, the presence of a trifluoromethyl group in the substrate

A Streptomyces P450 enzyme dimerizes isoflavones from plants

• Run-Zhou Liu,
• Shanchong Chen and
• Lihan Zhang

Beilstein J. Org. Chem. 2022, 18, 1107–1115, doi:10.3762/bjoc.18.113

• dimers or cross-coupling products, starting from simple monomers [17][18][19]. Nevertheless, our knowledge of enzyme-mediated dimerization is still limited in contrast to the numerous reported dimeric natural products. Phenol coupling in plant polyphenol biosynthesis is one of the earliest documented

Electrochemical formal homocoupling of sec-alcohols

• Kosuke Yamamoto,
• Kazuhisa Arita,
• Masashi Shiota,
• Masami Kuriyama and
• Osamu Onomura

Beilstein J. Org. Chem. 2022, 18, 1062–1069, doi:10.3762/bjoc.18.108

• -coupling reaction of two different benzyl alcohols (Scheme 3). Pleasingly, the reaction using a 1:1 mixture of 1a and 1f under the standard reaction conditions provided the cross-coupling product 2af (dr = 94:6) together with the homocoupling products 2a and 2f. To demonstrate the scalability of the

• /mol, 0 °C, under air. a100 mA cc. b6 F/mol, imidazole (0.075 equiv). c6 F/mol. d8 F/mol, imidazole (0.1 equiv) e8 F/mol, MeCN/MeOH (4:1, 5 mL) without H2O. Investigation of cross-coupling reaction. Large-scale experiment. Control experiments. aDetermined by 1H NMR using 1,3,5-trimethoxybenzene as an

• diastereoselectivity [47]. Benzhydrol derivatives (1n–p) were found to be good substrates for the present reaction, affording the corresponding benzopinacols (2n–p) in good yields after the passage of 8 F/mol in a mixed solvent of MeCN/MeOH. Next, we examined the possibility to extend the present process to the cross

Automated grindstone chemistry: a simple and facile way for PEG-assisted stoichiometry-controlled halogenation of phenols and anilines using N-halosuccinimides

• Dharmendra Das,
• Akhil A. Bhosle,
• Amrita Chatterjee and
• Mainak Banerjee

Beilstein J. Org. Chem. 2022, 18, 999–1008, doi:10.3762/bjoc.18.100

• halides are valuable compounds with potent bioactivities [1][2][3][4][5] (Figure 1) and are utilized as crucial precursors for various metal-catalyzed cross-coupling reactions [6][7][8][9]. They are frequently used as synthetic intermediates in several value-added syntheses of natural products

• of monoiodo derivatives was successfully prepared in high to excellent yields from phenols and anilines by adding 1.1 equiv of NIS with PEG-400 as the LAG agent (product 2aa–ag, Scheme 3). Notably, both Br- and I-substituents are mainly used as the substrates for cross-coupling reactions indicating

Introducing a new 7-ring fused diindenone-dithieno[3,2-b:2',3'-d]thiophene unit as a promising component for organic semiconductor materials

• Valentin H. K. Fell,
• Joseph Cameron,
• Alexander L. Kanibolotsky,
• Eman J. Hussien and
• Peter J. Skabara

Beilstein J. Org. Chem. 2022, 18, 944–955, doi:10.3762/bjoc.18.94

• [34], dibromodithienothiophene 24 is lithiated with n-butyllithium at −90 °C, and the resulting species is reacted in situ with triisopropyl borate. After aqueous workup, dithieno[3,2-b:2’,3’-d]thiophene-2,6-diylboronic acid (25) is obtained, enabling subsequent Suzuki–Miyaura cross-coupling [36

• ]. This palladium-catalysed cross coupling is preferred over a Stille cross-coupling due to the high toxicity of organotin reagents [37]. Moreover, purification of compound 25 is facile since it can be used for further reactions after re-precipitation in petroleum ether. In a manner similar to [35], it is

• possible to convert 25 into the corresponding pinacol ester, 2,6-bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)dithieno[3,2-b:2’,3’-d]thiophene (26) by stirring 25 with pinacol in refluxing toluene, but this has no beneficial impact on the subsequent cross-coupling. Compound 26 has been published

On Reuben G. Jones synthesis of 2-hydroxypyrazines

• Pierre Legrand and
• Yves L. Janin

Beilstein J. Org. Chem. 2022, 18, 935–943, doi:10.3762/bjoc.18.93

• , respectively. Shifts (δ) are given in ppm with respect to the TMS signal and cross-coupling constants (J) are given in hertz. Column chromatography was performed either on Merck silica gel 60 (0.035–0.070 mm) or neutral alumina containing 1.5% of added water using a solvent pump and an automated collecting

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

• -oxides 42 and 44 in moderate 54–63% yields via the intramolecular copper-catalyzed cross-coupling of ethyl/benzyl 2-bromobenzylphosphonamidates 41 or P-(2-bromobenzyl)-P-(methyl)phosphinamide (43) as a key step. They were prepared from 2-bromobenzyl bromide (38) via three and four steps, respectively

Synthesis of novel alkynyl imidazopyridinyl selenides: copper-catalyzed tandem selenation of selenium with 2-arylimidazo[1,2-a]pyridines and terminal alkynes

• Mio Matsumura,
• Kaho Tsukada,
• Kiwa Sugimoto,
• Yuki Murata and
• Shuji Yasuike

Beilstein J. Org. Chem. 2022, 18, 863–871, doi:10.3762/bjoc.18.87

• selenides [25]. In this reaction, unlike the former, bis(imidazo[1,2-a]pyridin-3-yl) diselenides are generated through C–H selenation at the 3-position of 2-arylimidazopyridines with Se powder, followed by the cross-coupling reaction between diselenides and triarylbismuthines. These one-pot reactions are

• imidazopyridinyl selenides A Cu-catalyzed cross-coupling reaction using benzene ring substituted diaryl diselenides with terminal alkynes in the presence of bases is effective for synthesizing aryl alkynyl selenides [27][28][29][30][31]. We previously reported a simple method for the synthesis of bis(2-arylimidazo