Enantioselective synthesis of β-aryl-γ-lactam derivatives via Heck–Matsuda desymmetrization of N-protected 2,5-dihydro-1H-pyrroles

• Arnaldo G. de Oliveira Jr.,
• Martí F. Wang,
• Rafaela C. Carmona,
• Danilo M. Lustosa,
• Sergei A. Gorbatov and
• Carlos R. D. Correia

Beilstein J. Org. Chem. 2024, 20, 940–949, doi:10.3762/bjoc.20.84

• -containing electron-withdrawing groups such as methyl ester and ketone did not show much of an effect in the outcome of the reaction, providing compounds 4bd and 4be in high yields and good er. On the other hand, product 4bq was obtained in a higher yield but with a lower er. The p-halogen-containing

Direct synthesis of acyl fluorides from carboxylic acids using benzothiazolium reagents

• Lilian M. Maas,
• Alex Haswell,
• Rory Hughes and
• Matthew N. Hopkinson

Beilstein J. Org. Chem. 2024, 20, 921–930, doi:10.3762/bjoc.20.82

• - or meta-positions all reacted smoothly with 4a to afford the corresponding benzylamides 5a–c in very good isolated yields up to 81%. Electron-donating and -withdrawing groups at the para-position were well tolerated (5d–f), including halogen substituents that could serve as handles for follow-up

(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

• synthesis of some 1,5-BCHeps, including 134b, was also possible on mmol scale. Through derivatization of iodine-substituted 1,5-BCHeps 134f and 134g, an even larger number of 1,5-BCHeps were accessed (Scheme 14B) [27][47]. For example, lithium–halogen exchange was used to prepare acids 135f–g and boronic

• ]. A wide variety of 1,2,3-BCPs bearing substituents in the bridge position were reported by Measom and co-workers in their study on the lithium–halogen exchange of 2-bromo-1,2,3-BCPs [78]. Larger bridged bicyclic structures such as bicyclo[2.1.1]hexane offer multiple different exit vectors for

Ortho-ester-substituted diaryliodonium salts enabled regioselective arylocyclization of naphthols toward 3,4-benzocoumarins

• Ke Jiang,
• Cheng Pan,
• Limin Wang,
• Hao-Yang Wang and
• Jianwei Han

Beilstein J. Org. Chem. 2024, 20, 841–851, doi:10.3762/bjoc.20.76

• generally moderate to good yields of 22–83% (Table 2, entries 1–17). These substituents included halogen (Br), methyl, phenyl, aldehyde, ester, and methoxy groups, all of which were compatible with the reaction conditions. Notably, compounds 3ab, 3ah, 3aj, 3am and 3ap bearing bromine are very useful modules

Skeletal rearrangement of 6,8-dioxabicyclo[3.2.1]octan-4-ols promoted by thionyl chloride or Appel conditions

• Martyn Jevric,
• Julian Klepp,
• Johannes Puschnig,
• Oscar Lamb,
• Christopher J. Sumby and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2024, 20, 823–829, doi:10.3762/bjoc.20.74

• work, which suggests a stepwise migration of oxygen from C5 to C4, followed by addition of the halogen nucleophile. Furthermore, if the halogen was involved in the transition state via the σ* orbital (avoiding intermediate 27), the opposite configuration would result at C2 in the products. The single

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

• . An halogen-substituted styrene could be azido-alkynylated to afford 4g in 71% yield. Electron-poor aryls are expected to destabilize the carbocation intermediate formed during the reaction. Nevertheless, 4h possessing a para ester could be obtained, albeit with a decreased yield. Homopropargylic

Synthesis and biological profile of 2,3-dihydro[1,3]thiazolo[4,5-b]pyridines, a novel class of acyl-ACP thioesterase inhibitors

• Jens Frackenpohl,
• David M. Barber,
• Guido Bojack,
• Birgit Bollenbach-Wahl,
• Ralf Braun,
• Rahel Getachew,
• Sabine Hohmann,
• Kwang-Yoon Ko,
• Karoline Kurowski,
• Bernd Laber,
• Rebecca L. Mattison,
• Thomas Müller,
• Anna M. Reingruber,
• Dirk Schmutzler and
• Andrea Svejda

Beilstein J. Org. Chem. 2024, 20, 540–551, doi:10.3762/bjoc.20.46

• to afford thiazolopyridines 12a–c in good yield. This allowed us to circumvent the previously employed alkylation–oxidation–reduction sequences (Scheme 2) [12]. Thereupon, we recognized that we could introduce two halogen atoms in the halogenation step and carry one through to the end of the

• (ALOMY_R, also known as slender foxtail or black twitch) and ryegrass (LOLSS_R). Remarkably, 2,3-dihydro[1,3]thiazolo[4,5-b]pyridine 7b turned out to be superior to market standards (i.e., 1 and 2 in wheat) in terms of overall efficacy and resistance breaking potential. Halogen-free target compound 7c also

Synthesis of 2,2-difluoro-1,3-diketone and 2,2-difluoro-1,3-ketoester derivatives using fluorine gas

• Alexander S. Hampton,
• David R. W. Hodgson,
• Graham McDougald,
• Linhua Wang and
• Graham Sandford

Beilstein J. Org. Chem. 2024, 20, 460–469, doi:10.3762/bjoc.20.41

• difluoromethylene units. To meet the demands of synthetic chemists within the life science discovery and manufacturing arenas, many fluorination methods have been developed over the years to introduce difluoromethylene groups into organic systems. Approaches using nucleophilic fluorination include halogen exchange

Green and sustainable approaches for the Friedel–Crafts reaction between aldehydes and indoles

• Periklis X. Kolagkis,
• Eirini M. Galathri and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2024, 20, 379–426, doi:10.3762/bjoc.20.36

• . Finally, another nucleophilic attack by a second molecule of indole to IV is occurring, forming the desired BIM 12, while simultaneously releasing the catalyst, rendering it available for another catalytic cycle [80]. Halogen bonding processes Recently, halogen bonding (XB) interactions have emerged as an

• electron-withdrawing substituents. The reaction mechanism is based on the activation of the carbonyl group by molecular I2, through the formation of a halogen bond, which lowers the LUMO of the carbonyl moiety, increasing its electrophilicity, and thus allowing the addition of the indole group (Scheme 7

• reaction of aldehydes and ketones with indole [93][94]. Bidentate halogen-bond donors are efficient catalysts, since they can form two halogen bonds with each substrate, instead of just one. Thus, compounds 24, 25 and 26 were screened for their catalytic activity with 26 emerging as the optimum choice

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

• (Me, t-Bu, OMe; 2c–e) and electron-withdrawing groups (Cl and CF3; 2f, and 2g) at the para-position of the aryl ring of thiophenols were well tolerated, furnishing the desired products (3ac–ag) in good yields. The reaction yield remains unaffected by the position of halogen substituents (2h–j), and

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

• groups, including alkyl (4a–e), halogen (4h–l), and phenyl (4m), were all suitable substrates for this reaction. However, the benzoic acid with ortho-substituent did not afford the expected product (4f) mainly due to the steric hindrance effect. Notably, substrates with electron-withdrawing groups (4h–l

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

• important auxiliary group for the proximal C–H activation with the efforts of Daugulis [5] and others [6]. Results from medical research indicated that the introduction of halogen atoms into quinoline motifs has positive effects on their bioactivities, such as antimalarial, antitumor, and so on [7

• , the synthesis of important C5-halogenated products gained particular attention since Stahl et al. reported the first chlorination example using LiCl as the halogen source [10]. Following this pioneering work, elegant strategies for the C5–H bromination of the quinoline ring employing simple inorganic

• and organic bromine-containing compounds such as Br2, CuBr, CuBr2, LiBr, NaBr, KBr, HBr, NH4Br, and tetrabutylammonium bromide (TBAB) as halogen sources have been realized (Scheme 1, reaction 1) [11][12][13][14][15][16][17][18][19][20]. Another category of extensively used bromination reagents are

Synthesis of N-acyl carbazoles, phenoxazines and acridines from cyclic diaryliodonium salts

• Nils Clamor,
• Mattis Damrath,
• Thomas J. Kuczmera,
• Daniel Duvinage and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2024, 20, 12–16, doi:10.3762/bjoc.20.2

• , this new method creates two C–N bonds simultaneously based on a mono-halogenated starting material, thus allowing heterocycle formation with diminished halogen waste. Keywords: carbazoles; heteroaromatics; iodanes; metal-catalyzed; one-pot reaction; Introduction N-Acyl carbazoles are effective

• of two equivalents of halogen salt waste. Their substitution with iodolium salts will be more sustainable since it reduces these unproductive halogenide salts by half. Due to our recent activity in the field of synthesis and applications of 5- and 6-membered cyclic iodonium salts, we searched for an

Biphenylene-containing polycyclic conjugated compounds

• Cagatay Dengiz

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

• subjecting α,α,α′,α′-tetrabromo-o-xylene (16) to t-BuOK to anhydrous conditions, biphenylene derivative 17 was obtained with a yield of 69% (Scheme 3). In the final step of the synthesis, a halogen–lithium exchange was carried out, followed by treatment with MeOH, resulting in a 79% yield of benzo[b

• , resulting in the formation of compound 75. Further transformation through lithium–halogen exchange, followed by reaction with Me3SiCl, yielded bis(trimethylsilylated) intermediate 76 in a 90% yield. By utilizing the conditions outlined in the prior investigation [49], compound 76 was subjected to a reaction

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

• cyclized product 16 in 75% yield. These results suggest that these Heck cyclizations are quite sensitive to the identity of the alkene substituent that is cis to the halogen. We were also interested in engaging vinyl iodide 17 in a 7-exo-trig cyclization to form 18. Z-Iodoalkene 17 appeared to react

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

• complex (deactivator, X–Mtz+1/L, typically X–CuII/L) to accumulate. When the accumulation reaches a certain level, the deactivator interacts with the active radical chain species (Pn·), so that the radical chain species gets into the dormant state (PnX) via a halogen atom transfer process. This is the

• process that usually qualifies for a definition of “click chemistry” [44]. A similar radical addition to vinyl groups takes place in ATRA despite the halogen atom transfer is mediated by a metal complex. Post-polymerization modification by ATRA was pioneered by Jérôme and co-workers [110][111]. In 2014

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

• cesium cation with the halogen atom and the activation of the Sn–O bond of the stannylene acetal via a pentacoordinated intermediate with the fluoride anion [110]. The acetylation of the secondary alcohol and the deprotection of the primary alcohol with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ

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

• paradigm with photocatalytic ATRA to enable the modular difunctionalization of alkenes under reagent control (Scheme 3). In Stephenson’s photocatalytic ATRA reports, the C–X bond in the product was proposed to be formed through both direct quenching of a transient alkyl radical by halogen atom transfer

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

• Carlee A. Montgomery Graham K. Murphy Department of Chemistry, University of Waterloo, 200 University Ave W., Waterloo, Ontario, N2L3G1, Canada 10.3762/bjoc.19.86 Abstract Halogen bonding is commonly found with iodine-containing molecules, and it arises when Lewis bases interact with iodine’s σ

• -holes. Halogen bonding and σ-holes have been encountered in numerous monovalent and hypervalent iodine-containing compounds, and in 2022 σ-holes were computationally confirmed and quantified in the iodonium ylide subset of hypervalent iodine compounds. In light of this new discovery, this article

• provides an overview of the reactions of iodonium ylides in which halogen bonding has been invoked. Herein, we summarize key discoveries and mechanistic proposals from the early iodonium ylide literature that invoked halogen bonding-type mechanisms, as well as recent reports of reactions between iodonium

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

• a halogen atom transfer (XAT) agent [101]. While yields of the monophotonic oxidative quenching route and the (biphotonic) conPET reductive quenching route were generally well comparable, the RQ route clearly benefits from a longer lifetime of the key catalytic species, shorter reaction times and

Copper-catalyzed N-arylation of amines with aryliodonium ylides in water

• Kasturi U. Nabar,
• Bhalchandra M. Bhanage and
• Sudam G. Dawande

Beilstein J. Org. Chem. 2023, 19, 1008–1014, doi:10.3762/bjoc.19.76

• –h in 57–65% yields. Also, the halogen-substituted arylamines such as p-bromo, o-bromo, p-chloro, and p-fluoroanilines reacted smoothly to produce the corresponding diarylamine products 3i–l with 65–73% yields. To identify the effect of steric hindrance we treated 2,6-dimethylaniline under optimal

Eschenmoser coupling reactions starting from primary thioamides. When do they work and when not?

• Lukáš Marek,
• Jiří Váňa,
• Jan Svoboda and
• Jiří Hanusek

Beilstein J. Org. Chem. 2023, 19, 808–819, doi:10.3762/bjoc.19.61

• reaction pathway opens that involves either the E2 or E1cB-like mechanism to give the corresponding nitrile X and thiolate IX, which can be further alkylated with an excess of α-halogen component to give a symmetrical sulfide. Only in very few cases when the starting α-thioiminium salt III contains an

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

• ). In contrast to the effect reported for NO2 and CF3 substituents by Tokmakov and Grandberg [48], electron-withdrawing halogen substituents on the aryl ring did not prevent rearrangement to dibenzo[b,f]azepine 43 [49]. The isolated yield of unsubstituted 43 was good (67%), however, substitution

• bromides and electron-withdrawing groups. The authors found that the addition of potassium iodide, and thus in situ palladium-catalysed halogen exchange, improved the yield of dibenzo[b,f]azepine 110. Unsymmetrical derivatives of 110 containing -CO2Me, -CF3, -NO2 and -CN substituents were synthesised in

• from 2-bromostyrene (116) via halogen–lithium exchange and quenching with the appropriate heteroatom source (SiR2Cl2, SnMe2Cl2, GeR2Cl2, BBr3). P-Tethered dienes were synthesised via quenching of a 2-vinylphenyl Grignard reagent with phenylphosphonic dichloride (PhPOCl2). O-Tethered dienes were

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

• the aryl ring – as electron-releasing groups (Me, OMe) showed little more reactivity than electron-withdrawing groups (CN) at the same position (4b, 4f, and 4g). Halogen-substituted IPs also followed the general reactivity trend of the respective halogens (4c–e). Excellent reactivity was found for o-F

• diverse electronic properties were present in the pyridine ring of the IP moieties (4l–q). With substrates having a methyl substitution at C-7 and C-8 of the pyridine ring, the yields and regioselectivity were still excellent (4l and 4m), but reduced significantly upon introducing a halogen group onto the

• pyridine ring. Except for the 6-bromo-substituted compound (4o), all other substrates having a halogen substituent in the pyridine ring showed reduced yields (4n, and 4p,q). The number of substituents also seemed to negatively affect the yield, as observed for products 4p and 4q, featuring two substituents

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

• array of organic synthetic transformations. Enolates are usually formed by deprotonation of the corresponding organic compound. However, other synthetic approaches for their generation exist, such as cleavage of enol ethers and esters, halogen–metal exchange, transmetalations, and conjugate additions to