Methodologies for the synthesis of quaternary carbon centers via hydroalkylation of unactivated olefins: twenty years of advances

• Thiago S. Silva and
• Fernando Coelho

Beilstein J. Org. Chem. 2021, 17, 1565–1590, doi:10.3762/bjoc.17.112

• hydroalkylation product 92e’, indicating a possible double bond isomerization under these reaction conditions. The postulated mechanism starts with the generation of an ethyl radical from BEt3. This radical then acts as a radical initiator to promote the homolytic cleavage of the carbon–halogen bond of the α-EWG

Substituted nitrogen-bridged diazocines

• Pascal Lentes,
• Jeremy Rudtke,
• Thomas Griebenow and
• Rainer Herges

Beilstein J. Org. Chem. 2021, 17, 1503–1508, doi:10.3762/bjoc.17.107

• makes them promising candidates for applications in photopharmacology. The halogen substituents allow further functionalization via cross-coupling reactions. Keywords: bridged azobenzene; diazocine; photopharmacology; photoswitch; triazocine; visible light switch; water-soluble switch; Introduction

• synthesis of CH2–NR-bridged diazocines are analogous to the previously described synthesis of CH2–NH-bridged diazocine [15]. The single Boc-protected 1,2-phenylenediamine (2, Scheme 1) is reacted with halogen-substituted 2-nitrobenzyl bromides 3 [21] forming N-benzylanilines 4, which were protected with

• half-lives of the metastable E-isomers are larger for the N-formyl diazocines 11a–c compared to the acetylated compounds 10a–c and generally, the half-lives are larger in water than in acetonitrile. Halogen atoms Br and I at the phenyl rings in 3-position as in 10a,b, and 11a,b are a good starting

Free-radical cyclization approach to polyheterocycles containing pyrrole and pyridine rings

• Ivan P. Mosiagin,
• Olesya A. Tomashenko,
• Dar’ya V. Spiridonova,
• Mikhail S. Novikov,
• Sergey P. Tunik and
• Alexander F. Khlebnikov

Beilstein J. Org. Chem. 2021, 17, 1490–1498, doi:10.3762/bjoc.17.105

• having no additional radical-sensitive substituents. The free bases can be obtained from the synthesized hydrobromides in quantitative yield by basification at room temperature. The selectivity control of intramolecular arylation was achieved by replacing the halogen: the use of 1-(2-(ortho-bromophenyl

Fritsch–Buttenberg–Wiechell rearrangement of magnesium alkylidene carbenoids leading to the formation of alkynes

• Tsutomu Kimura,
• Koto Sekiguchi,
• Akane Ando and
• Aki Imafuji

Beilstein J. Org. Chem. 2021, 17, 1352–1359, doi:10.3762/bjoc.17.94

• . Geometric isomers of magnesium alkylidene carbenoids are in equilibrium [16], and the 1,2-rearrangement occurs giving the alkynes 4 when the substituent R1 is located trans to the chloro group (Scheme 7b). An exchange of halogen atoms was observed in the reaction of a 1-chlorovinyl p-tolyl sulfoxide with

• ethylmagnesium bromide (Scheme 7c) [16]. The nucleophilic substitution of the halide on the magnesium atom with the carbenoid carbon atom having a halogen substituent is a plausible mechanism for the isomerization. The FBW rearrangement of magnesium alkylidene carbenoids was studied by using DFT calculations

• alkynes 4. a) 1,2-Rearrangement readily takes place with substrates with trans-oriented Cl-substituent to the migratable group R1. b) Formation of product 4 from geometric cis isomer is possible due to the equilibrium between magnesium alkylidene carbenoids. c) Halogen exchange between a 1-chlorovinyl p

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

Structural effects of meso-halogenation on porphyrins

• Keith J. Flanagan,
• Maximilian Paradiz Dominguez,
• Zoi Melissari,
• Hans-Georg Eckhardt,
• René M. Williams,
• Dáire Gibbons,
• Caroline Prior,
• Gemma M. Locke,
• Alina Meindl,
• Aoife A. Ryan and
• Mathias O. Senge

Beilstein J. Org. Chem. 2021, 17, 1149–1170, doi:10.3762/bjoc.17.88

• we were able to deduce the impact a meso halogen has on a porphyrin, for example, meso-halogenation is dependent on the type of alternate substituents present when forming supramolecular assemblies. Furthermore, we have designed a method to predict the conformation of halogenated porphyrins, without

• ‘guests’ within the crystal lattice, through hydrogen-bonding and van der Waals forces. Thereafter, research over the crystal engineering of porphyrins has focused on the noncovalent interactions, such as hydrogen bonds and halogen bonds, or metal coordination interactions [2][3][4][5][6][7][8][9][10][11

• architecture based on C–I···N and C–I···π interactions was formed through halogen bonding in the lattice of self-assembly of meso-tetraarylporphyrins [7]. In recent years there has been a strong uprising interest for substituting hydrogen-bonding motifs with their halogen-bonding counterparts. This is due to

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

Manganese/bipyridine-catalyzed non-directed C(sp³)–H bromination using NBS and TMSN₃

• Kumar Sneh,
• Takeru Torigoe and
• Yoichiro Kuninobu

Beilstein J. Org. Chem. 2021, 17, 885–890, doi:10.3762/bjoc.17.74

• reaction proceeded regioselectively at the methine C(sp3)–H bond of isoamyl benzoate (1b) to give 2b in 64% yield. Isoamyl benzoates bearing halogen atoms, such as fluorine, chlorine, or bromine, on the phenyl ring were also suitable substrates and gave C(sp3)–H brominated products 2c–e in 49–60% yields

• , without any loss of the halogen substituents. Although the C(sp3)–H bromination of isobutyl benzoate 1f did not proceed at 60 °C, the corresponding C(sp3)–H brominated compound 2f was produced at higher temperature (80 °C). The C(sp3)–H bond in acetal 1g was efficiently brominated to give 2g in 79% yield

Synthetic reactions driven by electron-donor–acceptor (EDA) complexes

• Zhonglie Yang,
• Yutong Liu,
• Kun Cao,
• Xiaobin Zhang,
• Hezhong Jiang and
• Jiahong Li

Beilstein J. Org. Chem. 2021, 17, 771–799, doi:10.3762/bjoc.17.67

• spectroscopy shows that phosphono radicals could proceed throughout the reaction. A halogen bond (XB) is a noncovalent interaction formed between a halogen atom and a neutral or negatively charged Lewis base. It is a kind of weak intermolecular interaction analogous to a hydrogen bond and basically can be

• considered as a specific EDA complex [62]. In 2016, Yu and colleagues [33] employed perfluoroalkyl iodide 6 as halogen-bond donor (electron acceptor) and the organic base dibenzylamine as the halogen-bond acceptor (electron donor) to form the XB complex 8, and then a fluoroalkyl radical was given via visible

• functional-group tolerance are provided by this approach, yielding multiple indole analogues with biological activity. In 2017, Liang and Bi [56] reported a visible-light-induced three-component cyclization of ethyl acetoacetate (23), perfluoroalkyl iodides 24, and guanidine hydrochloride (25) via a halogen

Synthesis of dibenzosuberenone-based novel polycyclic π-conjugated dihydropyridazines, pyridazines and pyrroles

• Ramazan Koçak and
• Arif Daştan

Beilstein J. Org. Chem. 2021, 17, 719–729, doi:10.3762/bjoc.17.61

• , Scheme 3). The formation of 5l was also an unexpected result because there has been no precedent reported to date, in which a tetrazine acts as a halogen source in the halogenation of a double bond. Therefore, the formation of 5l constitutes the first example of this unusual behavior. In the proposed

Stereoselective syntheses of 3-aminocyclooctanetriols and halocyclooctanetriols

• Emine Salamci and
• Yunus Zozik

Beilstein J. Org. Chem. 2021, 17, 705–710, doi:10.3762/bjoc.17.59

• are also cyclitol derivatives, in which one of the hydroxy groups is replaced by a halogen. They have also attracted interest in the last decade because of their biological activities [11][19]. For instance, some brominated quercitol (cyclohexanepentol) derivatives and bromoconduritol-B act as strong

• bromo groups, while the halogen functionality was introduced to the molecule by opening of the epoxide ring with HBr(g) or HCl(g) in MeOH. Structures of some important aminocyclitols. Synthesis of cyclic sulfate 9. Synthesis of aminocyclooctanetriol 12. Synthesis of aminocyclooctanetriol 18. Synthesis

[2 + 1] Cycloaddition reactions of fullerene C₆₀ based on diazo compounds

• Yuliya N. Biglova

Beilstein J. Org. Chem. 2021, 17, 630–670, doi:10.3762/bjoc.17.55

• methylene function in halo-substituted substrates and with facilitation of bases, methanofullerenes with various structures are formed rather smoothly. It is believed that nucleophilic addition of an α-halocarbanion to C60 occurs initially, followed by intramolecular substitution of the halogen atom by an

The synthesis of chiral β-naphthyl-β-sulfanyl ketones via enantioselective sulfa-Michael reaction in the presence of a bifunctional cinchona/sulfonamide organocatalyst

• Deniz Tözendemir and
• Cihangir Tanyeli

Beilstein J. Org. Chem. 2021, 17, 494–503, doi:10.3762/bjoc.17.43

• ). The solvent effects on the SMA of the chalcone derivatives and naphthalene-1-thiol are summarized in Figure 2. This behavior might be related to the better stabilization of the transition state of the substrates containing electron-withdrawing substituents or halogen atoms with THF, or vice versa. In

Synthesis of trifluoromethyl ketones by nucleophilic trifluoromethylation of esters under a fluoroform/KHMDS/triglyme system

• Yamato Fujihira,
• Yumeng Liang,
• Makoto Ono,
• Kazuki Hirano,
• Takumi Kagawa and
• Norio Shibata

Beilstein J. Org. Chem. 2021, 17, 431–438, doi:10.3762/bjoc.17.39

• ketone 2b in only lower yield (37%). Functionalities on the benzene ring at the para-position were well-tolerated in the KHMDS/glyme system. Halogen groups, such as chloro (1c), bromo (1d), and reactive iodo (1e) substitutions were also tolerated, resulting in the corresponding trifluoromethyl aryl

• yields (45–92%). Aryl substrates with a halogen attached at the meta- and ortho-positions were also accepted to furnish the desired products (2j–m) in good yields (66–82%). Moreover, di-substituted benzoate (1n), sterically demanding methyl adamantly carboxylate (1o), and conjugated methyl ester (1p

CF₃-substituted carbocations: underexploited intermediates with great potential in modern synthetic chemistry

• Anthony J. Fernandes,
• Armen Panossian,
• Bastien Michelet,
• Agnès Martin-Mingot,
• Frédéric R. Leroux and
• Sébastien Thibaudeau

Beilstein J. Org. Chem. 2021, 17, 343–378, doi:10.3762/bjoc.17.32

• < T < −40 °C in the presence of aromatic nucleophiles, thiophenes 72-Cl and 72-Br could be converted into 74-Cl and 74-Br derivatives via a side-chain arylation reaction. When the reaction was conducted at −40 °C, the reactivity was shown to be governed by the nature of the halogen atom. For the

Synthesis of legonmycins A and B, C(7a)-hydroxylated bacterial pyrrolizidines

• Wilfred J. M. Lewis,
• David M. Shaw and
• Jeremy Robertson

Beilstein J. Org. Chem. 2021, 17, 334–342, doi:10.3762/bjoc.17.31

• α-haloketones, is well known [36][37]. The halogen-mediated oxidation of 3-acyloxypyrroles and related compounds, to give α-hydroxy-3-ketopyrroles, is not reported but oxidations that represent equivalent reactivity have been reported [38][39][40][41]. The concept was tested in an NMR experiment in

Total synthesis of decarboxyaltenusin

• Lucas Warmuth,
• Aaron Weiß,
• Marco Reinhardt,
• Anna Meschkov,
• Ute Schepers and
• Joachim Podlech

Beilstein J. Org. Chem. 2021, 17, 224–228, doi:10.3762/bjoc.17.22

• ] instead of carbon tetrachloride [22] furnished a close to quantitative yield of bromide 5a, though a prolonged reaction time of 72 h had to be accepted. The subsequent formation of boronate 6a was accomplished through a metal–halogen interchange with butyllithium and trapping with 2-isopropoxy-4,4,5,5

Tuning the solid-state emission of liquid crystalline nitro-cyanostilbene by halogen bonding

• Subrata Nath,
• Alexander Kappelt,
• Matthias Spengler,
• Bibhisan Roy,
• Jens Voskuhl and
• Michael Giese

Beilstein J. Org. Chem. 2021, 17, 124–131, doi:10.3762/bjoc.17.13

• Subrata Nath Alexander Kappelt Matthias Spengler Bibhisan Roy Jens Voskuhl Michael Giese Organic Chemistry, University of Duisburg Essen, Universitätsstraße 7, 45141 Essen, Germany 10.3762/bjoc.17.13 Abstract The first example of halogen-bonded fluorescent liquid crystals based on the interaction

• of iodofluorobenzene derivatives with nitro-cyanostilbenes is reported. The systematic variation of the fluorination degree and pattern indicates the relevance of the halogen bond strength for the induction of liquid crystalline properties. The modular self-assembly approach enables the efficient

• tuning of the fluorescence behaviour and mesomorphic properties of the assemblies. Keywords: fluorescence; halogen bonding; liquid crystal; Introduction Supramolecular chemistry has proven to be an efficient approach for the development of novel smart materials, since it relies on non-covalent

Progress in the total synthesis of inthomycins

• Bidyut Kumar Senapati

Beilstein J. Org. Chem. 2021, 17, 58–82, doi:10.3762/bjoc.17.7

• prepared stereoselectively from propargyl alcohol following the literature procedure, and the free hydroxy group was then protected as its TBDMS ether to produce 39 in 99% yield. The metal–halogen exchange of 39 followed by the Bu3SnCl quench in Et2O gave the desired stannane 40 in excellent yield (90

Recent progress in the synthesis of homotropane alkaloids adaline, euphococcinine and N-methyleuphococcinine

• Dimas J. P. Lima,
• Antonio E. G. Santana,
• Michael A. Birkett and
• Ricardo S. Porto

Beilstein J. Org. Chem. 2021, 17, 28–41, doi:10.3762/bjoc.17.4

• from the carbocupration of 85, a Grignard derivative of 1-heptyne [56]. After a lithium–halogen exchange, the corresponding vinyllithium was treated with p-menthane-3-carboxaldehyde to give the isomeric allylalcohols (−)-87a and (−)-87b in a 5:1 ratio. After chromatographic separation, (−)-adaline (1

Synthesis, crystal structures and properties of carbazole-based [6]helicenes fused with an azine ring

• Daria I. Tonkoglazova,
• Anna V. Gulevskaya,
• Konstantin A. Chistyakov and
• Olga I. Askalepova

Beilstein J. Org. Chem. 2021, 17, 11–21, doi:10.3762/bjoc.17.2

• helicenes with interesting electronic properties. Results and Discussion Synthesis In accordance with the above strategy, we first synthesized ortho-halogen alkynylazines 1a,b via the Sonogashira reaction of commercially available 2,3-dichloroquinoxaline and 2,3-dichloropyrazine with phenylacetylene using a

Synthesis of tetrafluorinated piperidines from nitrones via a visible-light-promoted annelation reaction

• Vyacheslav I. Supranovich,
• Igor A. Dmitriev and
• Alexander D. Dilman

Beilstein J. Org. Chem. 2020, 16, 3104–3108, doi:10.3762/bjoc.16.260

• involved in the reductive annelation reaction (Scheme 2). The process worked with nitrones containing alkyl, halogen, and electron-donating groups in the aromatic ring. With ester and cyano groups, the piperidines 3h and 3j were obtained in decreased yields, which may be tentatively attributed to a greater

An atom-economical addition of methyl azaarenes with aromatic aldehydes via benzylic C(sp³)–H bond functionalization under solvent- and catalyst-free conditions

• Divya Rohini Yennamaneni,
• Vasu Amrutham,
• Krishna Sai Gajula,
• Rammurthy Banothu,
• Murali Boosa and
• Narender Nama

Beilstein J. Org. Chem. 2020, 16, 3093–3103, doi:10.3762/bjoc.16.259

• ) gave the expected product 3c along with the dehydrated product 4c (Table 2, entry 3). Substrates containing a halogen, such as fluorine, chlorine, and bromine, were efficiently reacted to afford the products 3e–h in successively moderate yields (Table 2, entries 5–8). Notably, 3-fluorobenzaldehyde (2e

• clean process. A variety of aromatic aldehydes, including electron-donating, electron-withdrawing, as well as halogen groups was screened, affording the products in moderate to excellent yields. Azaarenes such as pyridines with various substitution patterns and a few quinolines were also reacted with

Synthesis and characterization of S,N-heterotetracenes

• Astrid Vogt,
• Florian Henne,
• Christoph Wetzel,
• Elena Mena-Osteritz and
• Peter Bäuerle

Beilstein J. Org. Chem. 2020, 16, 2636–2644, doi:10.3762/bjoc.16.214

• -dibromothienothiophene 2 [39], which was obtained from thieno[3,2-b]thiophene (1) [38], was triisopropylsilyl (TIPS)-protected by lithium-halogen exchange with n-BuLi and triisopropylsilyl chloride to give thienothiophene 3 in 69% yield. A halogen dance reaction of 3, induced by lithium diisopropylamide (LDA) at −78 °C

• , the SN4’-intermediate was directly alkylated with 2-ethylhexyl bromide and the corresponding dialkylated SN4' system was subsequently obtained by removal of the bromines by lithium–halogen exchange and acidic work-up [28]. Synthesis of S,N-heterotetracenes SN4''. In contrast to SN4’, S,N

Synthesis of novel fluorinated building blocks via halofluorination and related reactions

• Attila Márió Remete,
• Tamás T. Novák,
• Melinda Nonn,
• Matti Haukka,
• Ferenc Fülöp and
• Loránd Kiss

Beilstein J. Org. Chem. 2020, 16, 2562–2575, doi:10.3762/bjoc.16.208

• process, an alkene reacts with a halogen cation to form a halonium ion, which immediately undergoes ring opening by fluoride to form a vicinal halofluoride (see Scheme 1). The overall result is an anti-addition of the XF moiety (X = Cl, Br, I) across the double bond. Since many nucleophilic fluorine

• the absence of the reagent. It is also worth mentioning that the bromolactone (rac)-17a was surprisingly stable against lactone ring-opening: the compound remained intact after 20 hours of reflux in methanol in the presence of a catalytic amount of H2SO4. Presumably, the halogen cation attacks from

• isomeric halofluorination products can be explained by the preferred formation of the halonium ions T6a–c, respectively, since the halogen cation attacks the C=C bond of the imide 19 from the less hindered side, followed by rearrangement into the intermediates (rac)-T7a–c, respectively. For epoxides and