Recent developments in the engineered biosynthesis of fungal meroterpenoids

• Zhiyang Quan and
• Takayoshi Awakawa

Beilstein J. Org. Chem. 2024, 20, 578–588, doi:10.3762/bjoc.20.50

• cross-coupling between two aromatic rings [43]. In the future, further developments in bioinformatics, structural biology, and AI techniques will enable the design of biosynthetic enzymes and pathways to produce desired bioactive compounds, although understanding the chemistry catalyzed by individual

Mechanisms for radical reactions initiating from N-hydroxyphthalimide esters

• Carlos R. Azpilcueta-Nicolas and
• Jean-Philip Lumb

Beilstein J. Org. Chem. 2024, 20, 346–378, doi:10.3762/bjoc.20.35

• of parameters with which to control reactivity. In this perspective, we provide an overview of the different mechanisms for radical reactions involving NHPI esters, with an emphasis on recent applications in radical additions, cyclizations and decarboxylative cross-coupling reactions. Within these

• years and in the past, they were perceived as fleeting reaction intermediates. Recent progress in photoredox catalysis [6][7][8], electrochemistry [9][10], and the use of transition-metal (TM) catalysts in radical cross-coupling reactions [11] have dramatically expanded the use of radicals in synthesis

• decarboxylative cross-coupling (DCC) of NHPI esters with organometallic reagents, resembling classic Kumada, Negishi, and Suzuki couplings, has been enabled by nickel (Ni), cobalt (Co), iron (Fe), and copper (Cu) catalysts [84][85][86][87][88][89][90][91] (Scheme 23A). The typical mechanism begins by

Synthesis of π-conjugated polycyclic compounds by late-stage extrusion of chalcogen fragments

• Aissam Okba,
• Pablo Simón Marqués,
• Kyohei Matsuo,
• Naoki Aratani,
• Hiroko Yamada,
• Gwénaël Rapenne and
• Claire Kammerer

Beilstein J. Org. Chem. 2024, 20, 287–305, doi:10.3762/bjoc.20.30

• corresponding boronic acid 9 and a Suzuki–Miyaura cross-coupling between 8 and 9 gave rise to dimer 10, followed by the oxidation of both acenaphthene units into 1,8-naphthalic anhydrides. Installation of the thiepine ring was achieved by a double nucleophilic aromatic substitution induced by sodium sulfide

• corresponding bis(thiophenyl) thioether, which then underwent successive bromination and iodination to give intermediate 18. Next, a two-fold Suzuki–Miyaura cross-coupling occurring chemoselectively on the iodinated positions allowed the symmetric extension of the hydrocarbon scaffold, with the insertion of two

• thiepine via a two-fold Suzuki–Miyaura cross-coupling with 1,2-phenylenediboronic pinacol ester. The resulting S-doped extended tribenzothiepine 21 proved stable under ambient conditions for several months and exhibited good solubility in common organic solvents, which is ascribed to the boat-shape

Nucleophilic functionalization of thianthrenium salts under basic conditions

• Xinting Fan,
• Duo Zhang,
• Xiangchuan Xiu,
• Bin Xu,
• Yu Yuan,
• Feng Chen and
• Pan Gao

Beilstein J. Org. Chem. 2024, 20, 257–263, doi:10.3762/bjoc.20.26

• regioselectivity. Significant advancements in the synthesis of arylthianthrenium salts have prompted a growing interest in their utilization as versatile precursors for the conversion of C–H bonds in arenes into C–C/X bonds through transition-metal-catalyzed cross-coupling processes [12][13][14][15][16][17][18][19

• -metal-catalyzed cross-coupling [32][33] and aminofunctionalization [34] of alkenes were achieved, benefiting from the unique reactivity of organothianthrenium species that are generated through the reaction of alkenes and thianthrene sulfoxide (TT=O) or thianthrene (TT) (Scheme 1b). Alcohols are widely

• generation of alkyl radicals [39]. After that, a series of methods for the modification of alkylthianthrenium salts have been developed, including the transition-metal-catalyzed cross-coupling with terminal alkynes [40], sulfonylation with DABCO·(SO2)2 [41][42][43], or alkylation of active alkenes [44][45

Optimizations of lipid II synthesis: an essential glycolipid precursor in bacterial cell wall synthesis and a validated antibiotic target

• Milandip Karak,
• Cian R. Cloonan,
• Brad R. Baker,
• Rachel V. K. Cochrane and
• Stephen A. Cochrane

Beilstein J. Org. Chem. 2024, 20, 220–227, doi:10.3762/bjoc.20.22

• mixture underwent a cross-coupling reaction with prenyl monophosphates [46] in DMF/THF over a four-day period, yielding fully protected versions of lipid II and its analogues. Subsequent global deprotection reactions, using aqueous NaOH, led to the formation of lipid II (11), with an overall yield of 16

Metal-catalyzed coupling/carbonylative cyclizations for accessing dibenzodiazepinones: an expedient route to clozapine and other drugs

• Amina Moutayakine and
• Anthony J. Burke

Beilstein J. Org. Chem. 2024, 20, 193–204, doi:10.3762/bjoc.20.19

• via a cross-coupling reaction with NH3 [13]. The reaction was undertaken in the presence of a catalytic amount of a palladium catalyst and afforded a library of dibenzodiazepinones in good to excellent yields (Scheme 1a). In 2013, Zhang et al. developed a synthetic route leading to structurally

Visible-light-induced radical cascade cyclization: a catalyst-free synthetic approach to trifluoromethylated heterocycles

• Chuan Yang,
• Wei Shi,
• Jian Tian,
• Lin Guo,
• Yating Zhao and
• Wujiong Xia

Beilstein J. Org. Chem. 2024, 20, 118–124, doi:10.3762/bjoc.20.12

• their biological activity and potential applications, continuous efforts have been dedicated to the synthesis of DHPI derivatives. Various synthetic strategies have been explored (Scheme 1), including transition-metal-catalyzed cross-coupling reactions [8][9][10], annulation reaction of carbenoids [11

Using the phospha-Michael reaction for making phosphonium phenolate zwitterions

• Matthias R. Steiner,
• Max Schmallegger,
• Larissa Donner,
• Johann A. Hlina,
• Christoph Marschner,
• Judith Baumgartner and
• Christian Slugovc

Beilstein J. Org. Chem. 2024, 20, 41–51, doi:10.3762/bjoc.20.6

• trifluoromethyl groups [20] and the cross-coupling of aryl halides [21]. Like phosphonium salts in general are used as catalysts [22][23], phosphonium salts based on ortho-hydroxy-substituted phosphines received particular attention because of their zwitterionic nature and have been used as catalysts in the

Facile access to pyridinium-based bent aromatic amphiphiles: nonionic surface modification of nanocarbons in water

• Lorenzo Catti,
• Shinji Aoyama and
• Michito Yoshizawa

Beilstein J. Org. Chem. 2024, 20, 32–40, doi:10.3762/bjoc.20.5

• -dibromopyridine. Negishi cross-coupling with 9-anthrylzinc chloride in the presence of PdCl2(PhCN)2/P(t-Bu)3 as catalyst afforded the common precursor 3,5-dianthrylpyridine (prePA), a simple yet novel bent building block, in 81% yield. For the synthesis of the methyl derivative, prePA was N-alkylated with excess

Biphenylene-containing polycyclic conjugated compounds

• Cagatay Dengiz

Beilstein J. Org. Chem. 2023, 19, 1895–1911, doi:10.3762/bjoc.19.141

• through Sonogashira cross-coupling reactions with alkynes featuring different protecting groups such as TIPS, TES, and TIBS. Scheme 7 illustrates the derivatization process using one of the chosen examples, specifically the TIPS group. Accordingly, the cross-coupling products 33a–c were obtained in yields

• the synthesis of compound 81 through the utilization of the Negishi cross-coupling reaction and then the removal of TMS groups from this intermediate was achieved using TBAF, resulting in the formation of diyne 82 in 65% yield. The progression towards the synthesis of biphenylene-containing substrate

• selectively synthesize compound 87 through a hybrid approach involving the integration of both solution and surface chemistry techniques [53]. The key compound 96 to be used in the synthesis of POA 87 was synthesized in two steps. In the first step, 94 was obtained using a double Sonogashira cross-coupling

Recent advancements in iodide/phosphine-mediated photoredox radical reactions

• Tinglan Liu,
• Yu Zhou,
• Junhong Tang and
• Chengming Wang

Beilstein J. Org. Chem. 2023, 19, 1785–1803, doi:10.3762/bjoc.19.131

• the photoredox cross-coupling reactions discussed above. A recent elegant study conducted by Chen and colleagues introduced a straightforward method that directly employed sodium iodide for photoinduced deaminative alkenylation processes [11]. This method enabled the synthesis of β,γ-unsaturated

• radicals for alkenylation, was primarily facilitated by the electrostatic interaction between NaI and Katritzky salts 7. This innovative approach not only expanded the scope of photoredox cross-coupling reactions but also offered valuable insights into the role of NaI in facilitating these transformations

• -anion catalysis under visible light irradiation, as depicted in Scheme 9. Subsequent investigations revealed that redox-active esters 3 and Katritzky salts 15 derived from amino acids could be effectively employed in decarboxylative/deaminative cross-coupling reactions [15]. These reactions enabled the

A deep-red fluorophore based on naphthothiadiazole as emitter with hybridized local and charge transfer and ambipolar transporting properties for electroluminescent devices

• Suangsiri Arunlimsawat,
• Patteera Funchien,
• Pongsakorn Chasing,
• Atthapon Saenubol,
• Taweesak Sudyoadsuk and
• Vinich Promarak

Beilstein J. Org. Chem. 2023, 19, 1664–1676, doi:10.3762/bjoc.19.122

• )diboron catalyzed by Pd(dpf)Cl2/KOAc. Finally, TPECNz was obtained as red solid in a reasonable yield by a Suzuki-type cross-coupling reaction between 3 and 4,9-dibromonaphtho[2,3-c][1,2,5]thiadiazole. The chemical structure and purity of compound 3 were verified by 1H NMR, 13C NMR, and high-resolution

Radical chemistry in polymer science: an overview and recent advances

• Zixiao Wang,
• Feichen Cui,
• Yang Sui and
• Jiajun Yan

Beilstein J. Org. Chem. 2023, 19, 1580–1603, doi:10.3762/bjoc.19.116

• ]. The semiquinone radicals formed during the oxidation of catechol can undergo a cross-coupling reaction to form polymers (Scheme 1). One example is the radical polymerization of urushiol. The earliest recorded application of natural radical polymerization can be traced back to the manufacture of

• to produce conductive polymers (Scheme 9B) [76]. Nowadays, most conductive polymers are prepared via metal-catalyzed cross-coupling reactions [77]. However, radical polymerization is also an effective way to synthesize conductive polymers at a relatively low cost. Niemi et al. [78] used FeCl3 as

Synthesis and biological evaluation of Argemone mexicana-inspired antimicrobials

• Jessica Villegas,
• Bryce C. Ball,
• Katelyn M. Shouse,
• Caleb W. VanArragon,
• Ashley N. Wasserman,
• Hannah E. Bhakta,
• Allen G. Oliver,
• Danielle A. Orozco-Nunnelly and
• Jeffrey M. Pruet

Beilstein J. Org. Chem. 2023, 19, 1511–1524, doi:10.3762/bjoc.19.108

• berberine variants none are as easily modulated to rapidly install substituent diversity [31][43][44][45][46][47][48]. The method deemed most amenable to varying substituents involves substituted 2-bromo-1-aminonaphthalenes which are used in subsequent palladium cross-coupling reactions [45]. As such, our

N-Sulfenylsuccinimide/phthalimide: an alternative sulfenylating reagent in organic transformations

• Fatemeh Doraghi,
• Seyedeh Pegah Aledavoud,
• Mehdi Ghanbarlou,
• Bagher Larijani and
• Mohammad Mahdavi

Beilstein J. Org. Chem. 2023, 19, 1471–1502, doi:10.3762/bjoc.19.106

• functional materials and indispensable synthetic intermediates in drug discovery [31][32][33]. Because of their value, constructing C–S bonds has attracted significant attention via metal-catalyzed cross-coupling reactions and metal-free C–S bond formation [34][35][36][37]. Direct sulfenylation of the C–H

• as a sulfenylating source gave the target product in 93% yield. Knochel and co-workers found that copper acetate can catalyze the cross-coupling reaction between (hetero)aryl, alkyl and benzylic zinc halides 36 with N-thiophthalimides 14 (Scheme 18) [55]. Various metal catalysts, including CrCl2

• low reactivity of these phthalimides, 10 mol % of catalyst was required. Cross-coupling reaction of sulfoximines 44 with N‑(arylthio)succinimides 1 catalyzed by a nanomaterial containing hexagonal boron nitride (h-BN) and γ-cyclodextrin-supported copper(II) acetate (h-BN@γ-CD@Cu(OAc)2) was developed

Visible-light-induced nickel-catalyzed α-hydroxytrifluoroethylation of alkyl carboxylic acids: Access to trifluoromethyl alkyl acyloins

• Feng Chen,
• Xiu-Hua Xu,
• Zeng-Hao Chen,
• Yue Chen and
• Feng-Ling Qing

Beilstein J. Org. Chem. 2023, 19, 1372–1378, doi:10.3762/bjoc.19.98

• ., Zibo 256401, China 10.3762/bjoc.19.98 Abstract A visible-light-induced nickel-catalyzed cross coupling of alkyl carboxylic acids with N-trifluoroethoxyphthalimide is described. Under purple light irradiation, an α-hydroxytrifluoroethyl radical generated from a photoactive electron donor–acceptor

• trifluoromethyl alkyl acyloins in good yields with broad substrate compatibility. The complex bioactive molecules were also compatible with this catalytic system to afford the corresponding products. Keywords: alkyl carboxylic acids; cross coupling; EDA complex; nickel catalysis; trifluoromethyl acyloins

• might be feasible. Herein, we disclose a visible-light-induced nickel-catalyzed cross-coupling of alkyl carboxylic acids with N-trifluoroethoxyphthalimide to deliver trifluoromethyl aliphatic acyloins under mild conditions (Scheme 1d). Furthermore, this platform bypasses the need for exogenous

Non-noble metal-catalyzed cross-dehydrogenation coupling (CDC) involving ether α-C(sp³)–H to construct C–C bonds

• Hui Yu and
• Feng Xu

Beilstein J. Org. Chem. 2023, 19, 1259–1288, doi:10.3762/bjoc.19.94

• become a major strategy for ether functionalization. This review covers C–H/C–H cross-coupling reactions of ether derivatives with various C–H bond substrates via non-noble metal catalysts (Fe, Cu, Co, Mn, Ni, Zn, Y, Sc, In, Ag). We discuss advances achieved in these CDC reactions and hope to attract

• interest in developing novel methodologies in this field of organic chemistry. Keywords: alkylation; cross-dehydrogenation coupling; ether; non-noble metals; Introduction Since the 1970s, organic chemists have developed many selective cross-coupling methods for the construction of C–C bonds, such as the

• , tetrahydrofuran or tetrahydropyran can smoothly react with many methyl aryl ketones to obtain the desired coupling products (Scheme 6a) [54]. The mechanism of the dehydrogenation cross-coupling reaction may undergo a radical pathway. Initially, the tert-butoxy radical produced by the dissociation of t-BuOOH may

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

Photoredox catalysis enabling decarboxylative radical cyclization of γ,γ-dimethylallyltryptophan (DMAT) derivatives: formal synthesis of 6,7-secoagroclavine

• Alessio Regni,
• Francesca Bartoccini and
• Giovanni Piersanti

Beilstein J. Org. Chem. 2023, 19, 918–927, doi:10.3762/bjoc.19.70

• )PF6 (E1/2*III/II = +1.21 V, E1/2III/II = −1.37; E1/2IV/*III = −0.89, E1/2 IV/III = +1.69 V) [74] would permit efficient radical generation and C(sp3)–C(sp3) bond formation either by challenging selective radical–radical cross-coupling or by radical addition to a π-bond, enabling a rare example of

Synthesis of aliphatic nitriles from cyclobutanone oxime mediated by sulfuryl fluoride (SO₂F₂)

• Xian-Lin Chen and
• Hua-Li Qin

Beilstein J. Org. Chem. 2023, 19, 901–908, doi:10.3762/bjoc.19.68

• Xian-Lin Chen Hua-Li Qin School of Chemistry, Chemical Engineering and Life Science, Wuhan University of Technology, 205 Luoshi Road, Wuhan, 430070, PR China 10.3762/bjoc.19.68 Abstract A SO2F2-mediated ring-opening cross-coupling of cyclobutanone oxime derivatives with alkenes was developed for

• the construction of a range of δ-olefin-containing aliphatic nitriles with (E)-configuration selectivity. This new method features wide substrate scope, mild conditions, and direct N–O activation. Keywords: direct N–O activation; E-selectivity; nitrile synthesis; ring-opening cross-coupling; sulfuryl

• of novel synthetic methods and strategies toward nitrile group construction continues to be a focus for synthetic chemists. The cross-coupling reactions of C–C bonds catalyzed by transition-metal complexes play a crucial role in modern organic synthesis, as they make it feasible to synthesize complex

Pyridine C(sp²)–H bond functionalization under transition-metal and rare earth metal catalysis

• Haritha Sindhe,
• Malladi Mounika Reddy,
• Karthikeyan Rajkumar,
• Akshay Kamble,
• Amardeep Singh,
• Anand Kumar and
• Satyasheel Sharma

Beilstein J. Org. Chem. 2023, 19, 820–863, doi:10.3762/bjoc.19.62

• on subsequent deprotonation gives the branched alkylated product 4. Whereas, in case of styrene 3 a 1,2-insertion takes place possibly due to the formation of the stable benzallylic species 8, which on deprotonation gives the linear alkylated product 5. The C–H activation/C–C cross-coupling reaction

• cross-coupling of pyridine N-oxides with nonactivated secondary (2°) alkyl bromides [51]. The cross-coupling is difficult to achieve as the Pd-catalyzed SN2 process is sensitive towards the steric bulk of the secondary or tertiary alkyl electrophiles. The optimized conditions for the ortho-alkylation of

• Heck cross-coupling [69][70]. However, researchers have developed various methods for the transition-metal-catalyzed C(sp2)–H olefination using various types of alkenes as coupling partners [71][72][73]. This part of the review covers reports for the alkenylation of pyridine with terminal alkynes

Construction of hexabenzocoronene-based chiral nanographenes

• Ranran Li,
• Di Wang,
• Shengtao Li and
• Peng An

Beilstein J. Org. Chem. 2023, 19, 736–751, doi:10.3762/bjoc.19.54

• ]azepine and tetrabromothiophene-S,S-dioxide, followed by oxidative aromatization in the presence DDQ to afford compound 25 in an overall 75% yield. Suzuki−Miyaura cross-coupling reaction of compound 25 with (4-ethylphenyl)boronic acid in the presence of Pd(CH3CN)2Cl2, SPhos, and K3PO4 then furnished the

• Sonogashira cross-coupling reaction of phenylacetylene 50 and 1,4-dibromotetrafluorobenzene. The resulting bis[aryl(ethynyl)]tetrafluorobenzene 59 was able to undergo a 2-fold [4 + 2] cycloaddition reaction with cyclopentadienone 2, affording polyaromatic 60 in a 70% yield. The final step was the Scholl

• benzo[b]naphtho[2,3-f]oxepine 66 with tetrabromothiophene-S,S-dioxide in toluene followed by oxidative aromatization in the presence of DDQ afforded tetrabrominated aromatics 67 in an 81% yield. Subsequently, fourfold Suzuki–Miyaura cross-coupling of polybrominated compound 67 was performed, affording

Synthesis of medium and large phostams, phostones, and phostines

• Jiaxi Xu

Beilstein J. Org. Chem. 2023, 19, 687–699, doi:10.3762/bjoc.19.50

• ][17]. The Zn-catalyzed cross-coupling of dialkyl 2-bromo-1-methylethylphosphonates 68 and trimethylsilyl but-3-ynyl ether (69) generated dialkyl 5-hydroxy-1-methyl-3-methylenepentylphosphonates 70 in 66–73% yields under ultrasonic irradiation in THF at 45–50 °C for 45 min followed by treatment with

Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles

• Péter Kisszékelyi and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44

• , transformation to potassium trifluoroborate salt, hydrolysis, C–C cross-coupling, base-mediated elimination, radical C–B cleavage) [72]. Therefore, enantioenriched boronates are commonly applied intermediates in organometallic, medicinal, and other fields of chemistry. At the same time, some organoboronic acid

• highly beneficial scaffold which was successfully involved in diastereoselective Ni/photoredox dual-catalyzed cross-coupling reactions. Furthermore, rather than the stereoselective protonation, they have also demonstrated the successful trapping of the Cu enolate with benzaldehyde (Scheme 45B). This

Strategies to access the [5-8] bicyclic core encountered in the sesquiterpene, diterpene and sesterterpene series

• Cécile Alleman,
• Charlène Gadais,
• Laurent Legentil and
• François-Hugues Porée

Beilstein J. Org. Chem. 2023, 19, 245–281, doi:10.3762/bjoc.19.23