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

• catalyst using 2-arylpyridines (Scheme 15). Earlier reports described the propenylation took place on the ortho-position of the phenyl ring [76][77], whereas this group achieved the propenylation of the pyridine moiety. The authors screened different allyl halides and Ru complexes as catalysts. With the

• alkenylated product 109 (Scheme 21b). Arylation C-2 Arylation Owing to the remarkable role of aromatic C–H arylation reactions in organic synthesis abundant methods have been reported for aromatic C–H arylations using different arylating coupling partners, such as for instance, aryl halides. In 2014, using

• groups used Pd(OAc)2 as catalyst with 1,10-phenanthroline as ligand. The group of Yu used aryl halides 137 as coupling partner, whereas the group of Tan utilized aryl tosylates 142 as coupling partner (Scheme 26). The Yu group also applied the developed protocol for the synthesis of the drug molecule

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

• thioethers from aryl halides and triflates through palladium catalysis [50][51]. Scheme 10 provides a retrosynthesis of amination in the synthesis of dibenzo[b,f]azepine 45 as an example. Arnold et al. [30] reported an excellent method for the convergent synthesis of variable sized dibenzo-fused heterocycles

• . Among these, Heck reaction conditions allowed for the coupling of aryl acrylates 50 to aryl halides 48 and 49, followed by intramolecular Pd-catalysed amination or etherification to give C-10 carboxylates of dibenzo[b,f]azepine 55 and dibenz[b,f]oxepine 54 in good yield (Scheme 11). However, no ring

• , whereafter Buchwald–Hartwig amination afford the various diarylazepines. A three-component one-pot process allowed for a second in situ Buchwald–Hartwig amination of the diarylazepine with aryl or benzyl halides to give the respective N-aryl and N-benzylazepine derivatives 83 and 84 (Scheme 16). 3.2 Mizoroki

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

• enolate-trapping tandem sequence using various vinylsilanes 33 (Scheme 8B), allyl halides 35, and benzyl bromide (37) (Scheme 8C) [36]. Although the asymmetric conjugate addition step routinely provided excellent selectivity (93–96% ee), only a moderate to good diastereomeric ratio was achieved

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

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

• favoring reactivity with various types of substrates, ranging from halides to carbonyls and alkenes/alkynes. It is comprehensible that this reagent attracted early interest in natural product synthesis and more precisely on medium-sized ring formation. 4.1 SmI2-mediated Barbier-type ring annulation towards

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

• ] and to a lesser extent, alkyl halides [42][44]. Accordingly, we first investigated the CROP of MeOx in DLG with a targeted degree of polymerization (DP) of 50 and 100 using methyl trifluoromethanesulfonate, also commonly referred to as methyl triflate (MeOTf) at 60 °C, 90 °C, and 120 °C. These first

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

• could afford satisfying coupling yields by a suitable variation of the nature of the leaving group. In 2008, Cahiez reported an iron-catalyzed alkenylation of organomagnesium reagents with enol phosphates as electrophiles, instead of alkenyl halides [19]. In this case, when reactive enol phosphates

• ) as a co-solvent. Nevertheless, capitalizing on these results, Cahiez further developed this iron-catalyzed cross coupling reaction with dienol phosphates as electrophiles, which are thermally more stable than dienyl halides [20]. It was found that when dienol phosphates were used as electrophiles

• allow the use of alkenyl halides as cross-coupling partners in the absence of NMP. A remarkable feature of the alkyl–dienyl cross-coupling reactions displayed in Scheme 4 is the implication of α,ω-difunctionalized Grignard reagents, bearing a magnesium alkoxide moiety at the end of the chain. Magnesium

Revisiting the bromination of 3β-hydroxycholest-5-ene with CBr₄/PPh₃ and the subsequent azidolysis of the resulting bromide, disparity in stereochemical behavior

• Christian Schumacher,
• Jas S. Ward,
• Kari Rissanen,
• Carsten Bolm and
• Mohamed Ramadan El Sayed Aly

Beilstein J. Org. Chem. 2023, 19, 91–99, doi:10.3762/bjoc.19.9

• ·OEt2 [12]. All of those results confirmed the involvement of regio- and stereospecific i-steroid and retro-i-steroid rearrangements. Later, tetrabutylammonium halides were used as cost effective and stable alternatives of TMS-based reagents [15]. Treatment of compound 4 (Scheme 1) with NaN3 in

NaI/PPh₃-catalyzed visible-light-mediated decarboxylative radical cascade cyclization of N-arylacrylamides for the efficient synthesis of quaternary oxindoles

• Dan Liu,
• Yue Zhao and
• Frederic W. Patureau

Beilstein J. Org. Chem. 2023, 19, 57–65, doi:10.3762/bjoc.19.5

• /cyclization cascades from acrylamides for the synthesis of oxindoles [39][40][41]. The radicals are typically generated from alkyl halides [42][43][44], carboxylic acids [45][46][47], simple alkanes [48], alkylboronic acids [49], isocyanides [50], or other [51][52][53]. In this context, the group of Fu

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

• aryl halides and trialkyl phosphites [23]. Some of the most studied C–P coupling reactions involving aryl substrates are those employing catalysts, which are required in order to lower the energy barrier of the reaction and overcome the poor reactivity between aryl halides and trialkyl phosphites [24

Dissecting Mechanochemistry III

• Lars Borchardt and
• José G. Hernández

Beilstein J. Org. Chem. 2022, 18, 1454–1456, doi:10.3762/bjoc.18.150

• halides as substrates in multiple reactions. For instance, within this Thematic Issue, the synthetic relevance of aryl halides was evidenced during the development of a protocol for the solid-state palladium-catalyzed borylation reported by Kubota, Ito, and co-workers (Scheme 2) [6]. Moreover, Štrbac and

• . Mechanochemical palladium-catalyzed borylation protocol of aryl halides. 1,2-Debromination of polycyclic imides, followed by in situ trapping of the dienophile by several dienes. Synthesis of g-h-PCN from sodium phosphide and trichloroheptazine mediated by mechanochemistry. Mechanochemical intra- and

Lewis acid-catalyzed Pudovik reaction–phospha-Brook rearrangement sequence to access phosphoric esters

• Jin Yang,
• Dang-Wei Qian and
• Shang-Dong Yang

Beilstein J. Org. Chem. 2022, 18, 1188–1194, doi:10.3762/bjoc.18.123

• with highly air-sensitive and hazardous phosphorus halides, with the assistance of a suitable base [19][20][21][22][23][24]. As an alternative pathway, the phospha-Brook rearrangement [25][26][27][28][29][30] represents a green approach to phosphoric esters since it uses α-hydroxyphosphonates, which

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

• light-mediated carbon–heteroatom cross-couplings of sodium sulfinates, carboxylic acids and sulphonamides with aryl halides (Figure 2) [28]. Although recyclable, batch reactions are characterized by long reaction times (24 h). Here, we present a detailed investigation of a continuous-flow strategy for

A versatile way for the synthesis of monomethylamines by reduction of N-substituted carbonylimidazoles with the NaBH₄/I₂ system

• Lin Chen,
• Xuan Zhou,
• Zhiyong Chen,
• Changxu Wang,
• Shunjie Wang and
• Hanbing Teng

Beilstein J. Org. Chem. 2022, 18, 1032–1039, doi:10.3762/bjoc.18.104

• chemicals, agrochemicals, pharmaceuticals and dyes [1][2][3][4]. Traditional methods for the preparation of N-methylamines involve the direct methylation of amines by using methyl halides [5][6][7], dimethyl sulfate [8], diazomethane [9], methyl triflate [10][11] or dimethyl carbonate [12][13][14][15] as

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

• requires the use of a solid acid catalyst [52], apart from the use of high-cost, high-end milling equipment which limits to laboratory scale only. Therefore, developing an operationally simple, environmentally benign protocol, potentially useful for the batch-scale synthesis of aryl halides is highly

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

• -dihydrobenzo[d][1,2]azaphosphole 2-oxide (55), which was further alkylated with alkyl halides in the presence of NaH, affording 1-alkyl-2-phenyl-1,3-dihydrobenzo[d][1,2]azaphosphole 2-oxides 56. Alternatively, under heating, methyl 2-aminobenzyl(phenyl)phosphinate (53) underwent a transmethylation from the O

• ]azaphosphole 2-sulfide (59). Sulfide 59 was similarly transformed to 1-alkyl-2-phenyl-1,3-dihydrobenzo[d][1,2]azaphosphole 2-sulfides 60 by treatment with alkyl halides in the presence of NaH. All 1,3-dihydrobenzo[d][1,2]azaphosphole 2-sulfides 60 were converted into the corresponding 1,3-dihydrobenzo[d][1,2

• ], the strategy is the dearomatizing anionic cyclization of diaryl-N-alkyl-N-benzylphosphinamides by treatment with sec-butyllithium followed by reactions with different electrophiles, such as water, alcohols, alkyl halides, aldehydes, etc. They first realized the dearomatizing anionic cyclization of

Cathodic generation of reactive (phenylthio)difluoromethyl species and its reactions: mechanistic aspects and synthetic applications

• Sadanobu Iwase,
• Shinsuke Inagi and
• Toshio Fuchigami

Beilstein J. Org. Chem. 2022, 18, 872–880, doi:10.3762/bjoc.18.88

• difluorocarbene adduct 5 was detected by high resolution mass spectrometry in addition to products 2, 3, and 4. As already mentioned, SmI2 is a well-known one-electron reducing reagent, and has been used to generate PhSCF2 radicals and perfluoroalkyl radicals from PhSCF2Br and perfluoroalkyl halides, respectively

• the formation of adduct 4 to some extent (from 0% to 14% yield) as shown in Table 3. Therefore, iPrOH seems to promote the radcal addition rather than reduction although the reason has not been clarified yet. Reaction mechanism Although the cathodic reduction of perfluoroalkyl halides usually involves

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

• (RSeSeR) and selanyl halides (RSeX) have been widely used as Se sources in these reactions. However, they have poor commercial availability and require complicated synthetic routes. Therefore, an alternative approach using the commercially available and easy-to-handle Se powder has attracted significant

• powder with imidazopyridine and aryl iodides or alkyl halides in the presence of Na2CO3 (2 equiv) using the NiBr2/2,2-bipyridine system to give aryl or alkyl imidazopyridinyl selenides [24]. In these reactions, aryl iodides, arylboronic acids, and alkyl halides are coupled with Se powder to form diaryl

Palladium-catalyzed solid-state borylation of aryl halides using mechanochemistry

• Koji Kubota,
• Emiru Baba,
• Tamae Seo,
• Tatsuo Ishiyama and
• Hajime Ito

Beilstein J. Org. Chem. 2022, 18, 855–862, doi:10.3762/bjoc.18.86

• , Japan 10.3762/bjoc.18.86 Abstract This study describes the solid-state palladium-catalyzed cross-coupling between aryl halides and bis(pinacolato)diboron using ball milling. The reactions were completed within 10 min for most aryl halides to afford a variety of synthetically useful arylboronates in

• organic materials, typically through Suzuki–Miyaura coupling [1][2][3][4][5][6][7]. The palladium-catalyzed boryl substitution of aryl halides with boron reagents, termed Miyaura–Ishiyama borylation, is an efficient method for synthesizing arylboronates with high functional group compatibility [8][9][10

• ][11][12][13][14]. To date, many palladium-based catalytic systems in solution for the borylation of aryl halides have been reported [8][9][10][11][12][13][14]. However, these solution-based reactions usually require long reaction times and significant amounts of dry and degassed organic solvents

An isoxazole strategy for the synthesis of 4-oxo-1,4-dihydropyridine-3-carboxylates

• Timur O. Zanakhov,
• Ekaterina E. Galenko,
• Mikhail S. Novikov and
• Alexander F. Khlebnikov

Beilstein J. Org. Chem. 2022, 18, 738–745, doi:10.3762/bjoc.18.74

• processes. To evaluate the scope of the disclosed reaction a set of isoxazoles 1 was prepared using approaches shown in the Scheme 3 and Scheme 4. Isoxazoles 11a–f were prepared by cycloaddition of nitrile oxides, generated from N-hydroxyimidoyl chlorides 7a–f, to propargyl halides [29], followed by the

Cs₂CO₃-Promoted reaction of tertiary bromopropargylic alcohols and phenols in DMF: a novel approach to α-phenoxyketones

• Ol'ga G. Volostnykh,
• Olesya A. Shemyakina,
• Anton V. Stepanov and
• Igor' A. Ushakov

Beilstein J. Org. Chem. 2022, 18, 420–428, doi:10.3762/bjoc.18.44

• reductive coupling of acid halides with ketones [36][37] and acetolyses of α-phenoxy-α-diazoketones [38] were also employed. Recently, F. P. Cossío et al. [39] have described a method for the preparation of benzo[b]furans by thermal heating of a dispersion of α-phenoxyketones in Al2O3. We involved the

Menadione: a platform and a target to valuable compounds synthesis

• Acácio S. de Souza,
• Ruan Carlos B. Ribeiro,
• Dora C. S. Costa,
• Fernanda P. Pauli,
• David R. Pinho,
• Matheus G. de Moraes,
• Fernando de C. da Silva,
• Luana da S. M. Forezi and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 381–419, doi:10.3762/bjoc.18.43

Synthesis of piperidine and pyrrolidine derivatives by electroreductive cyclization of imine with terminal dihaloalkanes in a flow microreactor

• Yuki Naito,
• Naoki Shida and
• Mahito Atobe

Beilstein J. Org. Chem. 2022, 18, 350–359, doi:10.3762/bjoc.18.39

• reduction of organic halides [35][36]; therefore, 1,4-dibromobutane (2a) was more easily reduced than 1 at the Ag cathode, which resulted in the recovery of a large amount of unreacted 1. Linear sweep voltammetry (LSV) experiments revealed that the reduction of 2a occurred at a lower potential than the

Site-selective reactions mediated by molecular containers

• Rui Wang and
• Yang Yu

Beilstein J. Org. Chem. 2022, 18, 309–324, doi:10.3762/bjoc.18.35

• , azides, halides and alkenes, oxidation of remote C–H bonds and alkenes, and substitution reactions involving ring-opening cyclization of epoxides, nucleophilic substitution of allylic chlorides, and hydrolysis reactions. The product selectivity is interpreted as the consequence of the space shape and

Recent developments and trends in the iron- and cobalt-catalyzed Sonogashira reactions

• Surendran Amrutha,
• Sankaran Radhika and
• Gopinathan Anilkumar

Beilstein J. Org. Chem. 2022, 18, 262–285, doi:10.3762/bjoc.18.31

• is shown in Scheme 5. Non-green protocols Nakamura et al. disclosed an Fe-catalyzed Sonogashira coupling between an alkynyl unit with primary and secondary alkyl halides (Scheme 6) [24]. They reported the coupling of an unactivated alkyl halide with the Fe catalyst can switch its chemoselectivity

• , Balla and co-workers discussed the scope of the reaction by the utilization of in-situ generated α-Fe2O3 nanoparticles with several activated and unactivated halides (Scheme 13) [30]. They also examined the effect of concentration of fluorescent aggregates of HPB, i.e., the size of the generated

• , recyclable, and selective for the coupling between aryl halides and phenylacetylene in PEG as the solvent (Scheme 22). The effect of various reaction parameters such as solvent, base, temperature, and catalyst loading was assessed by the model reaction between bromobenzene and phenylacetylene. Optimization