Copper catalysis: a constantly evolving field

• Elena Fernández and
• Jaesook Yun

Beilstein J. Org. Chem. 2025, 21, 1477–1479, doi:10.3762/bjoc.21.109

• community in that it elegantly reviews recent advances in allylation reactions of copper-catalyzed asymmetric allylic substitution reactions of chiral secondary alkylcopper species [5]. In summary, the contribution includes stereospecific transmetalations of organolithium and -boron compounds, copper

Oxetanes: formation, reactivity and total syntheses of natural products

• Peter Gabko,
• Martin Kalník and
• Maroš Bella

Beilstein J. Org. Chem. 2025, 21, 1324–1373, doi:10.3762/bjoc.21.101

Recent advances in allylation of chiral secondary alkylcopper species

• Minjae Kim,
• Gwanggyun Kim,
• Doyoon Kim,
• Jun Hee Lee and
• Seung Hwan Cho

Beilstein J. Org. Chem. 2025, 21, 639–658, doi:10.3762/bjoc.21.51

• transmetalation of organolithium and organoboron compounds, copper hydride catalysis, and enantiotopic-group-selective transformations of 1,1-diborylalkanes. Detailed mechanistic insights into stereochemical control and current challenges in this field are also discussed. Keywords: allylic substitution; chiral

• nucleophiles 5 that have conjugate acids with pKa values greater than 25 such as organolithium, organomagnesium, organozinc, and organozirconium reagents. This crucial distinction effectively expanded the scope of allylic substitution reactions beyond traditional boundaries. The evolution of copper-catalyzed

• organolithium species and the other employing chiral organoboron compounds. Copper-mediated stereospecific coupling of chiral organolithium species with allylic electrophiles In the organolithium approach, a breakthrough was achieved by Knochel and co-workers through carefully controlled reaction conditions

Efficient synthesis of fluorinated triphenylenes with enhanced arene–perfluoroarene interactions in columnar mesophases

• Yang Chen,
• Jiao He,
• Hang Lin,
• Hai-Feng Wang,
• Ping Hu,
• Bi-Qin Wang,
• Ke-Qing Zhao and
• Bertrand Donnio

Beilstein J. Org. Chem. 2024, 20, 3263–3273, doi:10.3762/bjoc.20.270

• organolithium derivatives 2,2'-dilithio-4,4',5,5'-tetraalkoxy-1,1'-biphenyl (2Li-BPn). In a continuation of this study, aiming at testing the limits of the reaction and providing a large diversity of structures, a structurally related series of compounds is reported here, namely 1,2,4-trifluoro-6,7,10,11

• red-shift of the emission peak. Keywords: arene–perfluoroarene interaction; decafluorobiphenyl; fluorinated triphenylene; fluoroarene nucleophilic substitution; organolithium; Introduction Non-covalent arene–fluoroarene intermolecular interactions [1][2] are drawing increasing attention due to their

• variety of triphenylene derivatives (Figure 1) [44][45][46][47] based on the nucleophilic substitution of various electrophilic perfluoroarenes, including C6F2H4, C6F6, C10F8, and C6F5-Ph, by nucleophilic organolithium reagents. e.g., 2,2’-dilithio-4,4’,5,5’-tetrakis(alkoxy)-1,1’-biphenyls, 2Li-BPn

gem-Difluorovinyl and trifluorovinyl Michael acceptors in the synthesis of α,β-unsaturated fluorinated and nonfluorinated amides

• Monika Bilska-Markowska,
• Marcin Kaźmierczak,
• Wojciech Jankowski and
• Marcin Hoffmann

Beilstein J. Org. Chem. 2024, 20, 2946–2953, doi:10.3762/bjoc.20.247

• using organolithium reagents (Scheme 1), revealing new avenues in fluorinated unsaturated amide synthesis, which are present in numerous natural products, pharmaceuticals, and polymers [34][35][36][37][38]. The obtained α,β-unsaturated amides may represent promising structural motifs for further

Multicomponent synthesis of α-branched amines using organozinc reagents generated from alkyl bromides

• Baptiste Leroux,
• Alexis Beaufils,
• Federico Banchini,
• Olivier Jackowski,
• Alejandro Perez-Luna,
• Fabrice Chemla,
• Marc Presset and
• Erwan Le Gall

Beilstein J. Org. Chem. 2024, 20, 2834–2839, doi:10.3762/bjoc.20.239

• organolithium reagents, thus limiting functional-group tolerance [11][12][13]. By contrast, heteroleptic (mixed) alkylzinc species (i.e., RZnX) are readily available and can typically be prepared from alkyl halides by direct insertion of metallic zinc into the carbon–halogen bond [14][15][16][17][18][19][20][21

Synthetic applications of the Cannizzaro reaction

• Bhaskar Chatterjee,
• Dhananjoy Mondal and
• Smritilekha Bera

Beilstein J. Org. Chem. 2024, 20, 1376–1395, doi:10.3762/bjoc.20.120

• scaffolds Burroughs et al. developed an intramolecular Cannizzaro-based cascade synthesis for the construction of 8-membered cycloocta-2,5-dienones [91]. The initial formation of the organolithium species 82 formed by acetylide addition to the ortho-substituted bromoaldehyde 81, was subjected to halogen

(E,Z)-1,1,1,4,4,4-Hexafluorobut-2-enes: hydrofluoroolefins halogenation/dehydrohalogenation cascade to reach new fluorinated allene

• Nataliia V. Kirij,
• Andrey A. Filatov,
• Yurii L. Yagupolskii,
• Sheng Peng and
• Lee Sprague

Beilstein J. Org. Chem. 2024, 20, 452–459, doi:10.3762/bjoc.20.40

• continues to be relevant. One of the methods for the synthesis of allenes was based on the interaction of bromoolefins with organolithium compounds, followed by the elimination of lithium fluoride [29][30][31]. It was logical to assume that in our case a similar reaction of the Grignard reagent 12 with

Beyond n-dopants for organic semiconductors: use of bibenzo[d]imidazoles in UV-promoted dehalogenation reactions of organic halides

• Kan Tang,
• Megan R. Brown,
• Chad Risko,
• Melissa K. Gish,
• Garry Rumbles,
• Phuc H. Pham,
• Oana R. Luca,
• Stephen Barlow and
• Seth R. Marder

Beilstein J. Org. Chem. 2023, 19, 1912–1922, doi:10.3762/bjoc.19.142

• bibenzyls being the dominant products. These reaction conditions represent an alternative metal-free approach to the conventional synthesis of bibenzyls through the reaction of Grignard or organolithium reagents with benzyl halides, or to the use of highly active metal reagents [33][34][35][36] or metal

Application of N-heterocyclic carbene–Cu(I) complexes as catalysts in organic synthesis: a review

• Nosheen Beig,
• Varsha Goyal and
• Raj K. Bansal

Beilstein J. Org. Chem. 2023, 19, 1408–1442, doi:10.3762/bjoc.19.102

• selective method for the synthesis of a wide range of organic compounds [55][56]. Organometallic reagents, such as organolithium, organomagnesium, and organozinc reagents are commonly used in conjugate addition reactions. 2.2.1 Reaction with Grignard reagents: Organomagnesium reagents, such as Grignard

• , have also been employed in conjugate addition reactions. These reagents are less reactive than organolithium and Grignard reagents but can still add to a range of α,β-unsaturated carbonyl compounds, including enones, acrylates, and imines. In 2011 Sakaguchi and co-worker [64] accomplished the conjugate

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

• diastereomers were detected (Scheme 9A). Furthermore, the authors have also demonstrated a four-component coupling reaction: by simply increasing the amount of the organolithium reagent (2.05 equiv) used for the activation of the Zn enolate, β-hydroxyketones 40 were gained via 1,2-addition of the zincate

Modern flow chemistry – prospect and advantage

• Philipp Heretsch

Beilstein J. Org. Chem. 2023, 19, 33–35, doi:10.3762/bjoc.19.3

• mass transfer of continuous flow reactors. The generation of organolithium species in the presence of carbonyl compounds and their reaction has been facilitated by the extremely fast mixing of reagents and almost instantaneous heat transfer (i.e., cooling) in specifically designed microreactors [5

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

• proposes different disconnections. Newhouse identified a C1–C10 disconnection for a radical cyclization and a C6–C7 for an organolithium addition, allowing a convergent approach with A ring and C–D rings as key fragments. In this case, the bicyclo[3.2.1]octane is obtained by a Ni-catalyzed enolate/alkenyl

Preparation of an advanced intermediate for the synthesis of leustroducsins and phoslactomycins by heterocycloaddition

• Anaïs Rousseau,
• Guillaume Vincent and
• Cyrille Kouklovsky

Beilstein J. Org. Chem. 2022, 18, 1385–1395, doi:10.3762/bjoc.18.143

• fragment was accomplished in a stereoselective fashion through a vinyllithium intermediate. An advanced synthetic intermediate was then obtained after functional group transformation. Keywords: cycloaddition; organolithium; stereoselective; total synthesis; Introduction Leustroducsins 1a–c and

• considered the use of additives in order to make the organolithium intermediate more nucleophilic. However, no reaction was observed when ZnMe2 (which was used in the synthesis of leustroducsin B by Trost and co-workers [17]) was added; trimethylaluminum and cerium chloride also failed to promote the

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

• biomass-derived furfural and 5-methylfurfural, are converted into 3-silylated 2-furyl carbinols upon condensation with organomagnesium or organolithium reagents. The hydroxy unit of the carbinol adducts can be exploited to promote C3(sp2)–Si bond functionalization through intramolecular activation. Two

• and Discussion Synthesis of 3-silylated 2-furyl carbinols C3-silylated furfurals 1a–c and 2c are accessible from furfural or 5-methylfurfural [20], respectively, according to our previously reported protocol for selective catalytic C3 silylation [15]. The addition of organolithium [21] or Grignard

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

• inexpensive and easy to handle Se powder as the Se source. The reaction proceeded with terminal alkynes having various substitutions, such as aryl, vinyl, and alkyl groups. The obtained alkynyl imidazopyridinyl selenide was found to undergo nucleophilic substitution reaction on Se atom using organolithium

Allylic alcohols and amines by carbenoid eliminative cross-coupling using epoxides or aziridines

• Matthew J. Fleming and
• David M. Hodgson

Beilstein J. Org. Chem. 2021, 17, 2385–2389, doi:10.3762/bjoc.17.155

• , α-methoxyhexyllithium derived from stannane 7 [14][15] was reacted with terminal epoxide 5, which gave the allylic alcohol 8 (79%, E/Z = 73:27, Scheme 4). This organolithium also proved reactive with 2,2-disubstituted epoxide 9, giving allylic tertiary alcohol 10 (72%, E/Z = 82:18). A trisubstituted

N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

• reactions using organolithium and organocerium compounds. In some examples, the use of organolithium is feasible through the use of aluminum-derived additives [15]. In this study, the influence of solvents on diastereoselectivity was also observed. They found that the reactions performed in noncoordinating

• mechanism operating in reactions involving Grignard reagents in noncoordinating solvents, such as toluene and dichloromethane, while an acyclic model [43] is common in organolithium compounds in solvents such as THF. In the cyclic model, the bulky tert-butyl group occupies an equatorial position due to

A sustainable strategy for the straightforward preparation of 2H-azirines and highly functionalized NH-aziridines from vinyl azides using a single solvent flow-batch approach

• Michael Andresini,
• Leonardo Degannaro and
• Renzo Luisi

Beilstein J. Org. Chem. 2021, 17, 203–209, doi:10.3762/bjoc.17.20

• preparation of 2H-azirines and their stereoselective transformation into highly functionalized NH-aziridines, starting from vinyl azides and organolithium compounds. The protocol has been developed using cyclopentyl methyl ether (CPME) as an environmentally benign solvent, resulting into a sustainable, safe

• and potentially automatable method for the synthesis of interesting strained compounds. Keywords: aziridines; 2H-azirines; flow chemistry; green chemistry; organolithium compounds; Introduction Since their conception in the early 1990s, Green Chemistry Principles (GCP) have been applied with

• to access aziridines with great structural variability [21]. The reaction of azirines with Grignard and organolithium reagents has been poorly investigated, and only without using green and renewable solvents [22][23]. In turn, 2H-azirines can be smoothly obtained through intramolecular cyclization

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

• flow system). We predict that with small modifications, this system could be configured to produce many different reagents. Our group is currently working on an organolithium version of this on-demand reagent approach. Experimental Turbo Grignard: isopropylmagnesium chloride–lithium chloride complex

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

• organolithium reagents 41 at 0 °C in Et2O forming mainly di-tert-butyl oxime 1f and the products of C–O coupling [86]. The reactions were performed by addition of the solution of the organometallic compound 41 in Et2O to the solution of di-tert-butyliminoxyl radical in Et2O. The product yields obtained

• employing organolithium reagents are presented below (Scheme 14). The Grignard reagents demonstrated very similar results that are omitted. Among the major C–O coupling product (oxime ether 42) small amounts of C–N coupling products (nitrones 43) were detected in the case of sterically unhindered

• organolithium reagents. Presumably, the reaction proceeds via SET from the organometallic compound and iminoxyl radical with the formation of an oxime anion and an intermediate C-centered radical. In the case of MeLi and PhLi, which correspond to the most reactive methyl and phenyl radicals, products 44 of

Copper-catalysed alkylation of heterocyclic acceptors with organometallic reagents

• Yafei Guo and
• Syuzanna R. Harutyunyan

Beilstein J. Org. Chem. 2020, 16, 1006–1021, doi:10.3762/bjoc.16.90

• heterocyclic ring, while the second part deals with acceptors in which the reacting unsaturated double bond is located outside of the heterocyclic unit (e.g., alkenyl-substituted heterocycles). The organometallics discussed in this minireview include organoaluminium, organozinc, organozirconium, organolithium

• -catalysed AAAs using Grignard, organolithium, organoaluminium, and organozirconium reagents have been reported. In 2015, Fletcher and co-workers presented the copper-catalysed AAA of racemic 3,6-dihydro-2H-pyrans using alkylzirconocenes in the presence of the Cu/L14 catalytic system (Scheme 10A) [39

• co-workers elaborated the copper-catalysed ring opening reaction of oxabicyclic alkene substrates using organolithium reagents, finding excellent anti selectivities and enantioselectivity (Scheme 12) [42]. During the optimisation studies, they discovered that when the Lewis acid BF3·OEt2 was employed

Synthesis of six-membered silacycles by borane-catalyzed double sila-Friedel–Crafts reaction

• Yafang Dong,
• Masahiko Sakai,
• Kazuto Fuji,
• Kohei Sekine and
• Yoichiro Kuninobu

Beilstein J. Org. Chem. 2020, 16, 409–414, doi:10.3762/bjoc.16.39

• in terms of the functional group tolerance and versatility of these previously reported synthetic methods due to the use of a stoichiometric amount of the organolithium reagents. In addition, despite these contributions, catalytic reaction systems have not been developed as much [26][27]. The sila

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

• where the metalated organohalogen compound is reacted with the halogen phosphine. Alternatively, the metal phosphide can be reacted with an organohalogen compound leading to the desired product. The most commonly used trans-metalation reagents are Grignard [54] or organolithium reagents [55] and other

• to the coordinating phosphorous [79]. The PTA-PPh2 ligand 76 is derived from the lithiated intermediate 75 (Scheme 14) [79]. The conversion of PTA (74) to the organolithium intermediate (PTA-Li, 75) is almost quantitative with a 90% isolated yield. However, the yield of the desired ligand PTA-PPh2 76

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

• , agrochemicals and bioactive natural products. Generally, α-alkoxyalkyl anions are presynthesized as stoichiometric organometallic reagents such as organolithium, organozinc, organocuprate, organostannane, organosilane and organoboron compounds [1][2][3][4][5][6]. Alternatively, we showed that easily available