(Bio)isosteres of ortho- and meta-substituted benzenes

• H. Erik Diepers and
• Johannes C. L. Walker

Beilstein J. Org. Chem. 2024, 20, 859–890, doi:10.3762/bjoc.20.78

• substrate. Employing Lewis acid catalysis Deng and co-workers reported an alternative pathway to indole-derived BCHs. Polysubstituted BCHs were accessed by nucleophilic addition of the indole to the activated bicyclobutane followed by a Mannich cyclisation [81]. The synthesis of wide variety of tri- and

SOMOphilic alkyne vs radical-polar crossover approaches: The full story of the azido-alkynylation of alkenes

• Julien Borrel and
• Jerome Waser

Beilstein J. Org. Chem. 2024, 20, 701–713, doi:10.3762/bjoc.20.64

• -2. Finally, nucleophilic addition of the alkynyl-trifluoroborate onto the benzylic carbocation would afford homopropargylic azide 4 [45]. Conclusion In summary, an azido-alkynylation of styrenes to access homopropargylic azides was developed. The reaction was initially investigated using EBX

Palladium-catalyzed three-component radical-polar crossover carboamination of 1,3-dienes or allenes with diazo esters and amines

• Geng-Xin Liu,
• Xiao-Ting Jie,
• Ge-Jun Niu,
• Li-Sheng Yang,
• Xing-Lin Li,
• Jian Luo and
• Wen-Hao Hu

Beilstein J. Org. Chem. 2024, 20, 661–671, doi:10.3762/bjoc.20.59

• alkene followed by a nucleophilic addition, is unknown (Scheme 1b, bottom). The radical-polar crossover strategy has been steadily emerging in synthetic organic chemistry during the last few years [43][44][45][46]. This strategy allows complex chemicals to be assembled with high step economy that would

• 7 and 8 were produced in high yields through LiAlH4 conditions or nucleophilic addition of methylmagnesium bromide. Moreover, product 4a could be easily transformed to unsaturated ε-amino amide 9 in total 76% yield. Likewise, Weinreb amide 10 was produced and further transformed into ketone 11 in 84

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

• radical-polar crossover affords cation 27 that delivers functionalized product 31 upon nucleophilic addition. The Doyle and Knowles groups reported the use of NHPI esters as radical precursors in the context of a radical redox annulation method [48] (Scheme 8A). This transformation occurs through an

• aromatic ring, forming intermediate 41, which was then oxidized to cation 42, thereby completing the photocatalytic cycle. The reaction proceeded by regioselective nucleophilic addition of H2O, accompanied by the loss of MeOH to deliver spirocycle 43. Notably, the dearomative spirocyclization of biaryl

• forming an iminium intermediate 101. Finally, nucleophilic addition of phthalimide anion 102 afforded the amination product 103. Bosque and Bach reported the use of 3-acetoxyquinuclidine (q-Ac) as a catalytic donor for the activation of TCNHPI esters derived from α-amino acids [72] (Scheme 20). Treatment

Copper-catalyzed multicomponent reaction of β-trifluoromethyl β-diazo esters enabling the synthesis of β-trifluoromethyl N,N-diacyl-β-amino esters

• Youlong Du,
• Haibo Mei,
• Ata Makarem,
• Ramin Javahershenas,
• Vadim A. Soloshonok and
• Jianlin Han

Beilstein J. Org. Chem. 2024, 20, 212–219, doi:10.3762/bjoc.20.21

• reacts with the copper catalyst generating the Cu-carbene intermediate B, which undergoes nucleophilic attack by acetonitrile to form the intermediate C. Subsequently, nucleophilic addition of benzoic acid to intermediate C affords the acetimidic anhydride D with the release of CuI catalyst for the next

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

• careful review of the product structure it was revealed that the purported dibenzodiazepine products were, in fact, diarylimines, which resulted from a nucleophilic addition of the aniline reagents to the aldimine substrates, followed by elimination of an tosylamine product. This was one of the principle

Aldiminium and 1,2,3-triazolium dithiocarboxylate zwitterions derived from cyclic (alkyl)(amino) and mesoionic carbenes

• Nedra Touj,
• François Mazars,
• Guillermo Zaragoza and
• Lionel Delaude

Beilstein J. Org. Chem. 2023, 19, 1947–1956, doi:10.3762/bjoc.19.145

• CACTUS, Campus Vida, 15782 Santiago de Compostela, Spain 10.3762/bjoc.19.145 Abstract The synthesis of zwitterionic dithiocarboxylate adducts was achieved by deprotonating various aldiminium or 1,2,3-triazolium salts with a strong base, followed by the nucleophilic addition of the in situ-generated

• carbenes with a strong base, followed by their nucleophilic addition onto carbon disulfide. The nine products obtained were characterized by 1H and 13C NMR spectroscopy, FTIR spectroscopy, HR–ESI mass spectrometry, and elemental analysis. Moreover, the molecular structures of two CAAC·CS2 and two MIC·CS2

Trifluoromethylated hydrazones and acylhydrazones as potent nitrogen-containing fluorinated building blocks

• Zhang Dongxu

Beilstein J. Org. Chem. 2023, 19, 1741–1754, doi:10.3762/bjoc.19.127

• building blocks [91] (Scheme 14). Inspired by previous accounts and this work [92][93], Hu et al. explored 1,2- nucleophilic addition reactions of trifluoromethylated acylhydrazones with organometallic reagents for the synthesis of trifluorinated homoallylic acylhydrazines [94][95][96][97][98

• . [3 + 2] Cycloadditions of difluoromethylated hydrazonoyl halides. Preparation and early applications of trifluoromethylated acylhydrazones. 1,2-Nucleophilic addition reactions of trifluoromethylated acylhydrazones. Cascade oxidation/cyclization reactions of trifluoromethylated homoallylic

Morpholine-mediated defluorinative cycloaddition of gem-difluoroalkenes and organic azides

• Tzu-Yu Huang,
• Mario Djugovski,
• Sweta Adhikari,
• Destinee L. Manning and
• Sudeshna Roy

Beilstein J. Org. Chem. 2023, 19, 1545–1554, doi:10.3762/bjoc.19.111

• cycloaddition or addition–elimination reactions with 1,3-dipoles and gem-difluoroalkenes is largely unexplored and the only report of a cycloaddition is with 2-fluoroindolizines (Figure 1A) via a β-fluoride elimination in an SNV (nucleophilic vinylic substitution)-like transformation [9]. Nucleophilic addition

• morpholine protons was determined to be 2.3 Å (H1↔Ha), 2.6 Å (H1↔Ha′), and 4.5 Å (H1↔Hb), 4.7 Å (H1↔Hb′) (see Supporting Information File 1, regioisomer study, section 9, for more details). Based on these experiments and literature reports [28][33], we propose a base-mediated nucleophilic addition

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

• . Intramolecular nucleophilic addition of the phenoxy ring of 12 to the activated C–C triple bond afforded intermediate III, followed by deprotonation to deliver product 13 (Scheme 9). When substrate 12 had an OMe group on the phenoxy ring, ipso sulfenylcyclization, or sulfenylation of the phenoxy ring occurred

Synthesis of ether lipids: natural compounds and analogues

• Marco Antônio G. B. Gomes,
• Alicia Bauduin,
• Chloé Le Roux,
• Romain Fouinneteau,
• Wilfried Berthe,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2023, 19, 1299–1369, doi:10.3762/bjoc.19.96

• reducing agent produced 30.2. The mesylation of 30.2 followed by the nucleophilic addition of N-methyloctacedylamine produced 30.3. The debenzylation of 30.3 to produce 30.4 followed by the installation of the phosphocholine moiety by using the chlorophosphate 30.5 yield 30.6 (BN52211). The replacement of

• polyunsaturated analogues, the reaction started with the metalation of tert-butyl methyl ether according to the conditions reported by Corey and Eckrich [140], followed by the nucleophilic addition on unsaturated or polyunsaturated aldehyde to produce, as an example, 31.5. Then, the alkylation of the secondary

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

• copper is to activate the 1,3-dicarbonyl compounds through complexation that leads to a highly diastereoselective nucleophilic addition. Scheidt et al. reported an enantioselective Cu-catalyzed intramolecular cross-dehydrogenative coupling approach to substituted tetrahydropyrans with excellent yields

Selective construction of dispiro[indoline-3,2'-quinoline-3',3''-indoline] and dispiro[indoline-3,2'-pyrrole-3',3''-indoline] via three-component reaction

• Ziying Xiao,
• Fengshun Xu,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2023, 19, 1234–1242, doi:10.3762/bjoc.19.91

• , the nucleophilic addition of the amino anion to the carbonyl group in the of 1,3-cyclohexanedione scaffold resulted in cyclic intermediate C. Thirdly, the elimination of water from intermediate C gave the isolated product 3. In the case of the intermediate B2 with a benzoyl group, there are two kinds

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

• ). Nucleophilic addition of the amine to the acyl radical and amine-assisted intermolecular proton transfer [84] generates the α-hydroxy radical 24 from which formation of the amide 25 proceeds either via i) oxidation by [Ir2]+ and deprotonation or ii) radical chain propagation [85]. Electron-deficient, electron

The unique reactivity of 5,6-unsubstituted 1,4-dihydropyridine in the Huisgen 1,4-diploar cycloaddition and formal [2 + 2] cycloaddition

• Xiu-Yu Chen,
• Hui Zheng,
• Ying Han,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2023, 19, 982–990, doi:10.3762/bjoc.19.73

• ]. The well-known Huisgen 1,4-dipoles have a special kind of zwitterionic intermediates and are usually prepared by a nucleophilic addition of pyridine, quinoline, isoquinoline and other aza-arenes to electron-deficient alkynes [4][5][6][7][8]. The reactive Huisgen 1,4-dipoles have been widely employed

• -configured. For explaining the formation of the various cyclic compounds, a plausible reaction mechanism was proposed on the base of the previously reported works [41][42][43][44] and the present experiments (Scheme 2). Initially, the nucleophilic addition of isoquinoline to dimethyl acetylenedicarboxylate

Clauson–Kaas pyrrole synthesis using diverse catalysts: a transition from conventional to greener approach

• Dileep Kumar Singh and
• Rajesh Kumar

Beilstein J. Org. Chem. 2023, 19, 928–955, doi:10.3762/bjoc.19.71

• hydrolysis of 2,5-DMTHF (2), which provide intermediate C after the removal of methanol in the presence of CuCl2. In the next steps, nucleophilic addition reaction of amines 34 with intermediate C, dehydration, and intramolecular aromatization affords N-substituted pyrroles 35. In 2018, Patil and Kumar [70

• 52 to produce N-substituted pyrroles 53 by nucleophilic addition, subsequent expulsion of methanol, followed by dehydration and aromatization steps (Scheme 25b). The authors suggested that the acidity of DESs may play an important role in the removal of the methoxy groups, and the hydrogen-bonding

• 2,5-DMTHF (2) in the presence of iodine under MW irradiation afford intermediate A, which is converted to dialdehyde B. Finally, N-substituted pyrroles 61 are produced by nucleophilic addition of amines with dialdehyde, followed by dehydration and aromatization steps (Scheme 29b). Jafari et al. [84

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

• plays a role as an activator and is subsequently eliminated via deoxygenative elimination furnishing the C-2-functionalized pyridines 167. The reaction mechanism (Scheme 32b) involves the initial C–H-cupration of 166 producing an oxazolyl–copper intermediate 168. Nucleophilic addition followed by C–H

Sulfate radical anion-induced benzylic oxidation of N-(arylsulfonyl)benzylamines to N-arylsulfonylimines

• Joydev K. Laha,
• Pankaj Gupta and
• Amitava Hazra

Beilstein J. Org. Chem. 2023, 19, 771–777, doi:10.3762/bjoc.19.57

• their unique stability, defined reactivity, and versatility in organic synthesis [2]. Leveraging their electron-deficient nature, N-arylsulfonylimines are widely used in organic transformations including nucleophilic addition, cycloaddition, imino-aldol reaction, ene reactions, aza-Friedel–Crafts

• nucleophilic addition and as a result the corresponding cyclized product is not formed. The synthesis of these nitrogen heterocycles signifies the innate ability of in situ-generated N-arylsulfonylimines in a variety of reactions with various ortho-substituted anilines without the need for pre-isolation or

• -arylsulfonylimine 2, generated in situ from the corresponding N-(arylsulfonyl)benzylamine 1, undergoes transimination with the ortho-substituted aniline 3 to form imine 3ab via 3aa. Subsequent intramolecular nucleophilic addition in imine 3ab produces intermediate 3ac, which upon oxidation delivers the desired N

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

• yields with moderate to good diastereoselectivities via Michael addition and nucleophilic addition–elimination (Scheme 17) [39]. The synthesis is a [5 + 2] annulation fashion. The reactions of 2-phenyl/alkoxy-4H-benzo[d][1,3,2]dioxaphosphinin-4-ones 82 and dialkyl 2-benzylidenemalonates 78 produced

• '-carboxylates 83 in 5–10% yield as byproducts. The major products 84 were generated via Michael addition and the nucleophilic addition–elimination of the carbanion of the generated enolate moiety, while the oxyanion of the enolate moiety attacked the phosphorus to form the byproducts 83 (Scheme 18) [40][41

• -[1,1'-binaphthalen]-2-ol (97) with n-BuLi and TMEDA followed by addition of phenylphosphonic dichloride generated a pair of diastereomeric (M,4R)-4-phenyl-5H-dinaphtho[2,1-d:1',2'-f][1,2]oxaphosphepine 4-oxides 98 and 99 in low yields and low diastereoselectivity via double nucleophilic addition

Nucleophile-induced ring contraction in pyrrolo[2,1-c][1,4]benzothiazines: access to pyrrolo[2,1-b][1,3]benzothiazoles

• Ekaterina A. Lystsova,
• Maksim V. Dmitriev,
• Andrey N. Maslivets and
• Ekaterina E. Khramtsova

Beilstein J. Org. Chem. 2023, 19, 646–657, doi:10.3762/bjoc.19.46

• direction of nucleophilic addition of alcohols to FPD species was observed earlier on the example of 5-oxa-FPDs II and was found to be reversible [33][53][54]. We isolated products 5a,b,e to study their chemical behavior in solutions. We found that when compounds 5a,b,e were dissolved in anhydrous solvents

A new oxidatively stable ligand for the chiral functionalization of amino acids in Ni(II)–Schiff base complexes

• Alena V. Dmitrieva,
• Oleg A. Levitskiy,
• Yuri K. Grishin and
• Tatiana V. Magdesieva

Beilstein J. Org. Chem. 2023, 19, 566–574, doi:10.3762/bjoc.19.41

• techniques; for details, see Supporting Information File 1); [α]D20 = 2127 (MeOH). To test the stereocontrolling efficiency of the new ligand L7 and to obtain new cysteine Ni–Schiff base derivatives (RCysNi)L7 which are of practical interest, complex (ΔAlaNi)L7 was involved in a nucleophilic addition as

• stereoselectivity level. Additionally, Schiff base derivatives of L7 have a considerably higher solubility in acetonitrile as compared to the L4-based complexes (see Table 3 and Supporting Information File 1); this makes it easier to scale-up the synthesis (e.g., for the SN2 alkylations or nucleophilic addition

Transition-metal-catalyzed domino reactions of strained bicyclic alkenes

• Austin Pounder,
• Eric Neufeld,
• Peter Myler and
• William Tam

Beilstein J. Org. Chem. 2023, 19, 487–540, doi:10.3762/bjoc.19.38

• coordinate to the bicyclic alkene forming 91. Migratory insertion of the olefin affords 92 which undergoes intramolecular nucleophilic addition followed by protodemetalation and elimination of MHP to afford 94. Base-mediated ring opening of the bridging ether generates 95 which undergoes an elimination

Investigation of cationic ring-opening polymerization of 2-oxazolines in the “green” solvent dihydrolevoglucosenone

• Solomiia Borova and
• Robert Luxenhofer

Beilstein J. Org. Chem. 2023, 19, 217–230, doi:10.3762/bjoc.19.21

• which interfere with the cationic ring-opening polymerization of 2-oxazolines (Figure 5). It has been reported that DLG can undergo keto–enol tautomerism and form enols or can participate in nucleophilic addition reactions [49]. Furthermore, it can react with water to its hydrated form, a geminal diol

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

• promotes the formal hydride transfer from the substrate, resulting in the formation of the hydroxylamine and substrate-derived iminium cation, which undergoes nucleophilic addition. Amine cation radical catalysis The single-electron oxidation of amines leads to amine cation radicals. Amine cation radicals

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

• for this facile transformation might proceed with first hydrogenation followed by the substitution of the labile triflate ester (for details, see Supporting Information File 1). Moving forward, compound 17 was further converted into alkynone 9 through DIBAL-H reduction, nucleophilic addition and Dess