Advancements in hydrochlorination of alkenes

• Daniel S. Müller

Beilstein J. Org. Chem. 2024, 20, 787–814, doi:10.3762/bjoc.20.72

• discovery by Markovnikov in 1869, who formulated the "Markovnikov rule" as follows: "Experience shows that the halide adds to the least hydrogenated carbon, that is, to the one most susceptible to the influence of other carbon units” [1][2]. In the 1960s and 1970s, various research groups conducted detailed

• chloride metal halide complexes are −6 kJ mol−1 for SnCl4, −8 kJ mol−1 for BiCl3, −9 kJ mol−1 for ZnCl2, −15 kJ mol−1 for CdCl2, −16 kJ mol−1 for FeCl3, and −41 kJ mol−1 for AlCl3. d) Addition of chloride-containing salts (e.g., LiCl) accelerate the reaction. e) Traces of water can increase the rate of the

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

• reaction of diazo compounds mediated by visible light has been reported by the group of Gevorgyan, which achieves the monofunctionalization of alkenes [52]. Inspired by these collective studies, we considered diazo compounds could be a competent activated alkyl halide equivalent to overcome the synthetic

Switchable molecular tweezers: design and applications

• Pablo Msellem,
• Maksym Dekthiarenko,
• Nihal Hadj Seyd and
• Guillaume Vives

Beilstein J. Org. Chem. 2024, 20, 504–539, doi:10.3762/bjoc.20.45

• that enables monitoring by circular dichroism. Upon the addition of Ca(II), a large increase in the binding affinity for halide ions was observed due to the folding of the receptor in a helicoidal form that enabled cooperative interaction with both urea moieties. More flexible coordination responsive

• ligands and a halide-induced ligand rearrangement (HRI) [81]. For example, when two symmetric Rh(I) complexes, one with P,O and one with P,S ligands, are subjected to the addition of halide anions, a rearrangement is observed by ligand exchange from the symmetric [Rh(P,O)2], [Rh(P,S)2] complexes to the

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

• utility is frequently restricted due to various challenges, such as RAE decomposition and a limited aryl halide scope. In recent years, the Baran lab has made progress in enhancing the practicality and applicability of electrochemically driven decarboxylative couplings involving NHPI esters and aryl

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

• , the scope of sulfonium salts was examined, as summarized in Scheme 2a. Alkylsulfonium salts substituted with a halide (F, Cl, or Br) or isocyano group at the para-position of the aryl ring (1b–e) were successfully converted into the carbon–sulfur bond formation products (3ba–fa) in moderate to good

Copper-promoted C5-selective bromination of 8-aminoquinoline amides with alkyl bromides

• Changdong Shao,
• Chen Ma,
• Li Li,
• Jingyi Liu,
• Yanan Shen,
• Chen Chen,
• Qionglin Yang,
• Tianyi Xu,
• Zhengsong Hu,
• Yuhe Kan and
• Tingting Zhang

Beilstein J. Org. Chem. 2024, 20, 155–161, doi:10.3762/bjoc.20.14

• , and aryl bromides as bromination reagents are limited. Wan and Li, respectively, demonstrated a few examples of a one-pot N-acylation and C5–H bromination of 8‑aminoquinolines using acyl bromines acting as both acyl and halide donors [25][26]. The groups of Lei and Fang independently realized the

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

• -disubstituted-1,2,3-triazole derivatives is readily achieved via the copper(I)-catalyzed [3 + 2] cycloaddition of an azide and a terminal alkyne (CuAAC) [63][64][65]. A further alkylation of the N3 position with an alkyl halide is an equally straightforward procedure that ultimately affords a large assortment

Construction of diazepine-containing spiroindolines via annulation reaction of α-halogenated N-acylhydrazones and isatin-derived MBH carbonates

• Xing Liu,
• Wenjing Shi,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2023, 19, 1923–1932, doi:10.3762/bjoc.19.143

• ylide B. Thirdly, the intermediate C is formed by the nucleophilic substitution of a halide ion in substrate 1 by the allylic ylide B. Then, Michael addition of the amino group to the C=C bond results in the cyclic intermediate D. Finally, the spiro[indoline-3,5'-[1,2]diazepine] 3 is produced by the

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

• several other benzyl halides (1b–e), an alkyl halide 2, and several aryl halides (3a–f). Again GC–MS was used to identify and quantify the products; the necessary authentic samples were mostly commercially available, but the R2 products from 1b and 1c were not, although well-known in the literature (for

• the main products are those in which the halide is replaced by a hydrogen atom. The more easily reduced benzyl halides examined (1b and 1c) are dehalogenated by (N-DMBI)2 in the dark, and with (N-DMBI)2 and UV irradiation are quantitatively dehalogenated in 2–6 h with the corresponding substituted

Controlling the reactivity of La@C₈₂ by reduction: reaction of the La@C₈₂ anion with alkyl halide with high regioselectivity

• Yutaka Maeda,
• Saeka Akita,
• Mitsuaki Suzuki,
• Michio Yamada,
• Takeshi Akasaka,
• Kaoru Kobayashi and
• Shigeru Nagase

Beilstein J. Org. Chem. 2023, 19, 1858–1866, doi:10.3762/bjoc.19.138

N-Boc-α-diazo glutarimide as efficient reagent for assembling N-heterocycle-glutarimide diads via Rh(II)-catalyzed N–H insertion reaction

• Grigory Kantin,
• Pavel Golubev,
• Alexander Sapegin,
• Alexander Bunev and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2023, 19, 1841–1848, doi:10.3762/bjoc.19.136

• with a diazo reagent under neutral conditions may give rise to a separate regioisomer which is different from the product obtained by reaction with an alkyl halide under basic conditions. Recently, we designed a thalidomide analogue 1a in which the phthalimide moiety was replaced with benzotriazole

Tying a knot between crown ethers and porphyrins

• Maksym Matviyishyn and
• Bartosz Szyszko

Beilstein J. Org. Chem. 2023, 19, 1630–1650, doi:10.3762/bjoc.19.120

• ]. The CsF binding led to a supramolecular self-assembly process, inducing a sandwich host–guest complex formation in the solid state (Scheme 2). It was established that fluoride is preferred over any other halide anions. The binding of the ion pairs was observed in highly polar solvent media, but in the

Synthesis of 7-azabicyclo[4.3.1]decane ring systems from tricarbonyl(tropone)iron via intramolecular Heck reactions

• Aaron H. Shoemaker,
• Elizabeth A. Foker,
• Elena P. Uttaro,
• Sarah K. Beitel and
• Daniel R. Griffith

Beilstein J. Org. Chem. 2023, 19, 1615–1619, doi:10.3762/bjoc.19.118

• the same substitution pattern as substrate 7 tend to give poor yields in similar intramolecular Heck reactions [20]. Moreover, it was found that substrates on which the halide is cis to an additional methyl substituent (used to forge the ethylidene-substituted polycycle common to many alkaloids) often

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

• ATRP relies on the establishment of a reversible activation/deactivation equilibrium reaction between an alkyl halide or halide-like initiator (RX) and a radical species (R·) [43]. During the activation process, the organohalides quickly lose their terminal halogen atoms in the presence of the liganded

• photoredox catalyst mediated by light to overcome the challenge of metal contamination in the precipitated polymers [58]. After the ATRP reaction, a reactive chain end retains as a stable alkyl halide moiety. Therefore, ATRP is particularly suitable for the synthesis of polymers with complex architectures

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

• in the presence of TEMPO, followed by insertion of an isocyanide molecule 166 or other nucleophiles 161 (Scheme 72) [102]. By studying the spectroscopic evidence, the authors found that both sulfenyl halide 165 and N-sulfenylsuccinimide 1 intermediates were involved in the reaction. Removal of TEMPO

• as a radical initiator from the reaction mixture did not result in product formation so, it seems that the reaction moved through a radical route for the formation of sulfenyl halide I, and N-sulfenylsuccinimide II. The use of azobisisobutyronitrile (AIBN) instead of TEMPO also resulted in 85% yield

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

• ). The complexes were obtained in high yields (>95%). The copper complexes were air and moisture-stable as solids but decomposed in chlorinated solvents after several days. It may be mentioned that Cu(I) halide and pseudohalide complexes with NHCs Me2L, Et2L and AdL were prepared from direct reaction of

Radical ligand transfer: a general strategy for radical functionalization

• David T. Nemoto Jr,
• Kang-Jie Bian,
• Shih-Chieh Kao and
• Julian G. West

Beilstein J. Org. Chem. 2023, 19, 1225–1233, doi:10.3762/bjoc.19.90

• . Similar RLT “rebound” steps have been implicated in non-heme oxygenase and halogenase enzymes as well [16][17][18][19], hinting that this strategy might be general; however, enzymatic examples outside of hydroxo and halide ligand transfer are scarce. Groves’ initial discovery of the radical rebound

• (XAT) from the alkyl halide reagent and further oxidation of the transient radical to a carbocation by radical polar crossover (RPC), providing two mechanistic pathways to form the ATRA products [32]. While powerful, this approach is inherently incompatible with introducing alternative functionality

• instead of the halide included in the alkyl halide reagent, limiting the ability to form different difunctionalization products. Taking inspiration from Groves’ bio-inspired manganese tetradentate manganese catalysts, we found we could instead functionalize the transient alkyl radical via RLT from a

Exploring the role of halogen bonding in iodonium ylides: insights into unexpected reactivity and reaction control

• Carlee A. Montgomery and
• Graham K. Murphy

Beilstein J. Org. Chem. 2023, 19, 1171–1190, doi:10.3762/bjoc.19.86

• intermolecular processes throughout the preceding sections, and was often formed between the ylide and the intended nucleophile (e.g., alkene, amine or halide) of the reaction. However, intramolecular halogen bonding was also observed with other non-reacting Lewis bases, where it altered an ylide’s stability and

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

• electron transfer (conPET) mechanism (Figure 4C), PDI is photoexcited and reductively quenched by Et3N to form its stable, colored radical anion PDI•− that can be photoexcited again to generate an even stronger reductant; *PDI•− (*E1/2 = −1.87 V vs SCE) [34]. A SET process to the aryl halide regenerates

• -poor aryl halide substrates (Figure 11C). While trialkylamines like Et3N or DIPEA have been proven to be suitable terminal reductants in conPET chemistry [15][45][46][51][54], they may still decrease photoreductant activity via back electron transfer [56], in contrast to CO2•− which has an entropic

• mechanism follows a ‘monophotonic’ oxidative quenching (OQ) route in which [FeIII(btz)3]3+ is oxidatively quenched to [FeIV(btz)3]4+ by the alkyl halide substrate after excitation with green light. After addition of the alkyl radical to the alkene or alkyne substrate, the catalyst is regenerated by

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

• formation and a hydroxyl radical (•OH). However, it is possible to transform an alcohol into a leaving group, in the radical sense, by converting it into a halide or pseudohalide derivative [104][105]. For alcohol 8, all attempts to make a better leaving group, including phenyl sulfone derivative, to have

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

• pyridine to form aryl–Pd(II) species 140 via intermediate C. Subsequently, oxidative addition takes place in the presence of the aryl halide to give the Pd(IV) complex 141 followed by reductive elimination furnishing 3-arylpyridines 138. Almost at the same time, Yu and co-workers reported the selective Pd

• . The proposed mechanism (Scheme 29b) involves the oxidative addition of the aryl halide to the Pd(0) complex in the presence of base ligand to afford 153. Subsequently, the substitution of the halide by pyridine 1 provides the intermediate 154 which undergoes C–H activation followed by reductive

Strategies in the synthesis of dibenzo[b,f]heteropines

• David I. H. Maier,
• Barend C. B. Bezuidenhoudt and
• Charlene Marais

Beilstein J. Org. Chem. 2023, 19, 700–718, doi:10.3762/bjoc.19.51

• derivatives follow standard reactions of secondary arylamines and as such will be only briefly discussed with selected examples. Huang and Buchwald [73] reported a palladium-catalysed arylation of 1a. Treatment of 1a with aryl halide 140 or 141 gave excellent yields of N-aryldibenzo[b,f]azepines 142 (Scheme

• ) by alkylation of 1a was patented in 1997 [79]. The process involves the alkylation of iminostilbene (1a) as a critical intermediate step (Scheme 33C). The alkyl halide linker of 148 was further functionalised by reaction with piperazine derivative 149 to give opipramol (5). 6.2 C-Functionalisation

Photocatalytic sequential C–H functionalization expediting acetoxymalonylation of imidazo heterocycles

• Deepak Singh,
• Shyamal Pramanik and
• Soumitra Maity

Beilstein J. Org. Chem. 2023, 19, 666–673, doi:10.3762/bjoc.19.48

• triple role as activator of IPs, halide scavenger, and acetylating agent. Results and Discussion Optimization In the quest for the optimal reaction conditions, we started our investigations with 2-phenylimidazo[1,2-a]pyridine (1a) and diethyl bromomalonate (2a) as model substrates. Initially, the

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

• -substituents including methoxy and halide groups; however, O-acetyl ketoximes with ortho- or meta-substituents failed to react. A small number of substituted [2.2.1]diazabicyclic alkenes 130a were successfully employed, albeit with slightly lower yields. In the reaction with N-methoxybenzamides 161, the same

Combretastatins D series and analogues: from isolation, synthetic challenges and biological activities

• Jorge de Lima Neto and
• Paulo Henrique Menezes

Beilstein J. Org. Chem. 2023, 19, 399–427, doi:10.3762/bjoc.19.31

• ] between halide 37 and phenol 38 leading to the formation of diaryl ether 39, which was subjected to a regioselective iodination reaction to give compound 40. Conversion of the nitrile in compound 40 into the corresponding aldehyde 41 followed by Z-selective Still–Gennari olefination gave the cis α,β

• order to obtain higher yields in the intramolecular cyclization step, the authors also investigated the use of a strategy based on an SNAr reaction using an electron-deficient aryl halide. Thus, 4-fluoro-3-nitrobenzaldehyde (118) was subjected to the Still–Gennari reaction, to give the corresponding cis