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

• CH2Cl2 using 20 equiv of α-methylstyrene. However, the yield of 4 did not increase. The cathodic reduction of perfluoroalkyl halide generates radical and/or anionic species in general [24]. In order to generate radical species selectively, indirect cathodic reduction using various mediators has been

Synthesis of sulfur karrikin bioisosteres as potential neuroprotectives

• Martin Pošta,
• Václav Zima,
• Lenka Poštová Slavětínská,
• Marika Matoušová and
• Petr Beier

Beilstein J. Org. Chem. 2022, 18, 549–554, doi:10.3762/bjoc.18.57

• (LiHMDS), followed by the addition of an alkyl halide. Application of this method to 8 provided the target molecule 21 in good yield (Scheme 4). It has to be mentioned that the metalation proceeds exclusively at C7, and thus cannot be used for the preparation of 20 via alkylation at C5. Our attempt to

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

• monoreduced to the corresponding alkyl halide 21 as major product, together with minor alkane product that arose from the reaction outside the cavitand (Figure 6b). Experiments also indicated that the binding of the guests with the hosts must show high affinities (KA > 1.2 × 103 M−1) to make sure the

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

• reaction between an aryl/vinyl halide (Cl, Br, I, OTf) and a terminal alkyne in the presence of a Cu(I) co-catalyst under basic conditions to form a Csp2–Csp bond generating an arylalkyne is known as the Sonogashira (Sonogashira–Hagihara) coupling [1] and has become an important C–C bond-forming reaction

• cross-coupling reactions Homogeneous green protocols Tsai et al. discussed an efficient, simple and environmentally friendly method for the coupling of arylynols 3 with an aryl halide [21]. This strategy discloses a one pot reaction catalyzed by FeCl3 in an aqueous medium associated with the cationic

• iodides showed good to excellent yields when coupled with phenylacetylene. The proposed mechanism is similar to the standard palladium-catalyzed Sonogashira reaction with the steps involving oxidative addition of the aryl/vinyl halide followed by transmetallation, and reductive elimination. The mechanism

New advances in asymmetric organocatalysis

• Radovan Šebesta

Beilstein J. Org. Chem. 2022, 18, 240–242, doi:10.3762/bjoc.18.28

• by a review article devoted to aza-Michael reactions of amines and amides [17]. The evolution of the understanding of noncovalent activation modes led to the realization that anion-binding is a critical feature in many transformations. Halide anions are highly relevant and widely occurring within

Asymmetric organocatalytic Michael addition of cyclopentane-1,2-dione to alkylidene oxindole

• Estelle Silm,
• Ivar Järving and
• Tõnis Kanger

Beilstein J. Org. Chem. 2022, 18, 167–173, doi:10.3762/bjoc.18.18

• substituted oxindoles with an E-configuration of the double bond. The results are presented in Scheme 2. Both electron-withdrawing (Scheme 2, 3f–h) and electron-donating groups (Scheme 2, 3m,n) at the phenyl ring of the benzylidene moiety were tolerated. The position of the halide at the aromatic ring did not

Ready access to 7,8-dihydroindolo[2,3-d][1]benzazepine-6(5H)-one scaffold and analogues via early-stage Fischer ring-closure reaction

• Irina Kuznetcova,
• Felix Bacher,
• Daniel Vegh,
• Hsiang-Yu Chuang and
• Vladimir B. Arion

Beilstein J. Org. Chem. 2022, 18, 143–151, doi:10.3762/bjoc.18.15

• From a retrosynthetic point of view, we followed three main pathways, in order to accomplish the synthesis of scaffold C. The first retrosynthetic route (a) started with an alkyl halide precursor, which was expected to afford scaffold C after ring-closure reaction at position 2 of the indole ring [23

• to accomplish organotin-mediated cyclization [23] of 9 led to a complex mixture of compounds, in which we have not identified the desired product. Therefore, we did not further pursue this route. Attempts to perform cyclization via intramolecular alkyl halide Heck reaction [26] also failed. This is

• most likely a result of the relatively high lability of the CH2 protons in the alkyl halide moiety of the starting molecule, which might lead to enolization instead of oxidative addition of palladium under strongly basic conditions needed in this type of reaction. Thus, we came to the conclusion that

Mechanistic studies of the solvolysis of alkanesulfonyl and arenesulfonyl halides

• Malcolm J. D’Souza and
• Dennis N. Kevill

Beilstein J. Org. Chem. 2022, 18, 120–132, doi:10.3762/bjoc.18.13

• at least four orders of magnitude slower than the chloride as regards the solvolytic replacement of the halogen present in the benzenesulfonyl halide. For the reactions of the fluoride in 20% dioxane at 91 °C, the m-nitro derivative was shown to be subject to a strong nucleophilic catalysis by

Iron-catalyzed domino coupling reactions of π-systems

• Austin Pounder and
• William Tam

Beilstein J. Org. Chem. 2021, 17, 2848–2893, doi:10.3762/bjoc.17.196

• iron-catalyzed cross-coupling reactions of alkyl halides began in 2004 when Nakamura first reported the TMEDA-mediated Fe-catalyzed cross-coupling reaction between secondary bromides with aryl Grignard reagents [52]. Since then, several reports of alkyl halide cross-coupling reactions have been

• reported [53]. In 2015, Kang and co-workers described a FeCl2-catalyzed tandem cyclization/cross-coupling reaction of alkyl iodides 1 with aryl Grignard reagents 2 to give arylmethyl-substituted pyrrolidines and tetrahydrofurans 3 in poor to excellent yield (Scheme 3) [54]. The concept of alkyl halide

• ]. The group expanded the reaction to include 1,6-dienes 24 leading to 25 via the formation of three C–C bonds through a radical cyclization/arylation cascade, like that reported by Kang et al. (Scheme 3). The authors hypothesized the alkyl halide could react with aryl iron species 27 to form the alkyl

Synthesis of a novel aminobenzene-containing hemicucurbituril and its fluorescence spectral properties with ions

• Qingkai Zeng,
• Qiumeng Long,
• Jihong Lu,
• Li Wang,
• Yuting You,
• Xiaoting Yuan,
• Qianjun Zhang,
• Qingmei Ge,
• Hang Cong and
• Mao Liu

Beilstein J. Org. Chem. 2021, 17, 2840–2847, doi:10.3762/bjoc.17.195

• important role in the cyclization, some additives were examined in combination with NaH as the base for improving the yield (Table 1, entries 6–9). For the synthesis of hemicucurbituril derivatives in a previous study, halide ions usually facilitated the cyclization [27]. However, halide ions had no effect

• on the current process (Table 1, entries 6–8). This observation could infer that the nitrobenzene-containing hemicucurbituril 9 shows no obvious affinity to halide ions such as chloride and bromide. When NaClO4 was introduced as the additive, the yield was moderately improved to 30.0% (Table 1, entry

• halide ions, especially the heavier iodide ion, to the macrocyclic sensor, slightly enhanced the fluorescence emission in CH2Cl2/CH3OH 4:1 (v/v) at 298 K, instead of quenching the fluorescence as predicted by the classic heavy-atom effect. The corresponding fluorescence enhancement efficiency of selected

Visible-light-mediated copper photocatalysis for organic syntheses

• Yajing Zhang,
• Qian Wang,
• Zongsheng Yan,
• Donglai Ma and
• Yuguang Zheng

Beilstein J. Org. Chem. 2021, 17, 2520–2542, doi:10.3762/bjoc.17.169

• complexes to photocatalysis are reported. Copper-photocatalyzed reactions, including alkene and alkyne functionalization, organic halide functionalization, and alkyl C–H functionalization that have been reported over the past 5 years, are included. Keywords: copper-photocatalyzed reactions; green chemistry

• bonds and can be applied to radical chemistry. This review discusses copper-catalyzed reactions including alkene and alkyne, organic halide, and alkyl C–H functionalization. 3. Visible-light-mediated copper-catalyzed alkene and alkyne functionalization 3.1 Olefinic C–H functionalization and allylic

• absence of organic halide, the copper salts catalyzed the hydroamination of the alkene [59]. Mechanistic studies showed that the copper–amido complex coordinated with alkenes, which then acted as a primary photocatalyst. After light irradiation, the excited alkene–copper–amido species offered a benzyl

Advances in mercury(II)-salt-mediated cyclization reactions of unsaturated bonds

• Sumana Mandal,
• Raju D. Chaudhari and
• Goutam Biswas

Beilstein J. Org. Chem. 2021, 17, 2348–2376, doi:10.3762/bjoc.17.153

• –halide complex compound 3 (Scheme 1). Review Cyclization reactions involving stoichiometric amounts of Hg(II) salts Cyclization involving alkenes (>C=C<) In 1900 and 1901, the Sand and Biilmann group had first reported the Hg(II)-mediated cyclization of allyl alcohol using Hg(II) nitrate (Hg(NO3)2) in

• selectivity of α-stereochemistry was primarily due to the strong directing effect of the neighboring benzyl ether group with the Hg(OAc)2. When cyclic mercuric halide 8 was treated with NaBH4 and oxygen (O2) in DMF oxidative demercuration takes place to give alcohol 10 in quantitative yield (Scheme 4). The

A novel methodology for the efficient synthesis of 3-monohalooxindoles by acidolysis of 3-phosphate-substituted oxindoles with haloid acids

• Li Liu,
• Yue Li,
• Tiao Huang,
• Dulin Kong and
• Mingshu Wu

Beilstein J. Org. Chem. 2021, 17, 2321–2328, doi:10.3762/bjoc.17.150

• recently as precursors in Friedel–Crafts reactions of arenes [30][31] and cross-coupling reactions of arylboronic reagents [32]. However, the direct SN1 reaction of such isatin-derived 3-phosphate-substituted oxindoles by halide ions as nucleophiles has not been developed yet and remains an unsolved

• -3-yl) phosphate 2 is activated by protonation with a haloid acid. Subsequently the phosphate leaving group is eliminated to generate the carbocation intermediate III, which is then followed by rapid combination with a nucleophilic halide ion to form a 3-monohalooxindoles 3 or 4. Conclusion In

Halides as versatile anions in asymmetric anion-binding organocatalysis

• Lukas Schifferer,
• Martin Stinglhamer,
• Kirandeep Kaur and
• Olga García Macheño

Beilstein J. Org. Chem. 2021, 17, 2270–2286, doi:10.3762/bjoc.17.145

• Lukas Schifferer Martin Stinglhamer Kirandeep Kaur Olga Garcia Macheno Organic Chemistry Institute, Westfälische-Wilhelms University Münster, Correnstraße 36, 48149 Münster, Germany 10.3762/bjoc.17.145 Abstract This review intends to provide an overview on the role of halide anions in the

• a field. Thus, the use of the halide in the catalyst–anion complex as both a mere counter-anion spectator or an active nucleophile has been depicted, along with the new trends toward additional noncovalent contacts within the HB-donor catalyst and supramolecular interactions to both the anion and

• the cationic reactive species. Keywords: anion binding; asymmetric catalysis; halide anions; hydrogen donors; noncovalent interactions; Introduction Halogens and the respective anionic halides occupy an essential role in natural and chemical processes [1][2][3][4]. While in chemical syntheses

Photoredox catalysis in nickel-catalyzed C–H functionalization

• Lusina Mantry,
• Rajaram Maayuri,
• Vikash Kumar and
• Parthasarathy Gandeepan

Beilstein J. Org. Chem. 2021, 17, 2209–2259, doi:10.3762/bjoc.17.143

• authors proposed a plausible reaction mechanism to account for the mode of operation as shown in Figure 13 [87]. Here, the halide radical species generated in situ was proposed to mediate the HAT event. Considering the 'magic methyl' effect in drug candidates [88], there is a strong demand for the direct

Facile and innovative catalytic protocol for intramolecular Friedel–Crafts cyclization of Morita–Baylis–Hillman adducts: Synergistic combination of chiral (salen)chromium(III)/BF₃·OEt₂ catalysis

• Karthikeyan Soundararajan,
• Helen Ratna Monica Jeyarajan,
• Raju Subimol Kamarajapurathu and
• Karthik Krishna Kumar Ayyanoth

Beilstein J. Org. Chem. 2021, 17, 2186–2193, doi:10.3762/bjoc.17.140

• the dialkoxy and ortho-halide- substituted MBH adducts. Thereby alternative synthetic routes should be accessed to overcome the harsh reaction conditions, structural requirements and scalability issues intrinsically associated with the literature reported procedures. Hence chiral catalysts could

Constrained thermoresponsive polymers – new insights into fundamentals and applications

• Patricia Flemming,
• Alexander S. Münch,
• Andreas Fery and
• Petra Uhlmann

Beilstein J. Org. Chem. 2021, 17, 2123–2163, doi:10.3762/bjoc.17.138

• the halide anions Cl−, Br−, and I−-, respectively, UCST behavior can also be induced in polymeric ionic liquids by the addition of a suitable hydrophobic counterion, such as tetrafluoroborate BF4− [288][289]. In both cases, the critical phase transition temperature is strongly affected by the

Preparation of mono-substituted malonic acid half oxyesters (SMAHOs)

• Tania Xavier,
• Sylvie Condon,
• Christophe Pichon,
• Erwan Le Gall and
• Marc Presset

Beilstein J. Org. Chem. 2021, 17, 2085–2094, doi:10.3762/bjoc.17.135

• describing their preparation. An evaluation of different approaches has been achieved, allowing to define the best strategies to introduce diversity on both the malonic position and the ester function. A classical alkylation step of a malonate by an alkyl halide followed by a monosaponification gave access

• usually achieved by a nucleophilic substitution of an alkyl halide by the deprotonated malonate [12][13][14][15][16][17][18][19], but other strategies could be envisioned: Cu-catalyzed arylation reactions for aryl-substituted MAHOs [20][21][22][23]; Knoevenagel/reduction sequences for benzyl-substituted

• malonic position in moderate to good yields. Various primary aliphatic alkyl halides could be used (3aa, 50%; 3ab, 40%; 3ac, 75%; 3bd, 93%) and the reaction was also possible using a secondary alkyl halide (3be, 52%) with a longer reaction time. The alkylation step was obviously more efficient with

Progress and challenges in the synthesis of sequence controlled polysaccharides

• Giulio Fittolani,
• Theodore Tyrikos-Ergas,
• Denisa Vargová,
• Manishkumar A. Chaube and
• Martina Delbianco

Beilstein J. Org. Chem. 2021, 17, 1981–2025, doi:10.3762/bjoc.17.129

• oligosaccharides having multiple α-glycosidic linkages by AGA [171]. Additional strategies include the dehydrative glycosylation of glucosyl hemiacetal [172] or the halide-catalyzed in situ anomerization of glucosyl iodide donors that yielded α(1–6)-hexaglucans [173]. The halide-catalyzed in situ anomerization

Regioselective N-alkylation of the 1H-indazole scaffold; ring substituent and N-alkylating reagent effects on regioisomeric distribution

• Ryan M. Alam and
• John J. Keating

Beilstein J. Org. Chem. 2021, 17, 1939–1951, doi:10.3762/bjoc.17.127

• distribution. For example, employing C-7 NO2 or CO2Me substituted indazoles conferred excellent N-2 regioselectivity (≥ 96%). Importantly, we show that this optimized N-alkylation procedure tolerates a wide structural variety of alkylating reagents, including primary alkyl halide and secondary alkyl tosylate

• conditions A and B (Table 6). The high selectivity observed for N-1 alkylation using NaH in THF (conditions A) was mainly effective using primary halide and tosylate compounds as electrophiles. Similar to the regiospecificity observed when employing n-pentyl bromide (ratio N-1 (10):N-2 (11) > 99:1, Table 1

• amounts (< 5% isolated yield, Table 6, entries 7 and 9), due to poor conversion (< 5%, combined N-1 and N-2 (see Supporting Information File 1)). While the latter observation may be due to competing elimination of the alkyl halide under strongly basic conditions [40], the use of a secondary tosylate

A recent overview on the synthesis of 1,4,5-trisubstituted 1,2,3-triazoles

• Pezhman Shiri,
• Ali Mohammad Amani and
• Thomas Mayer-Gall

Beilstein J. Org. Chem. 2021, 17, 1600–1628, doi:10.3762/bjoc.17.114

• produce [Ru]–N3 169. Then, the resulting intermediate cyclizes with ynoate ester 170 to form metal-bound heterocyclic complex 171. This metal-bound heterocyclic complex 171 reacts with alkyl halide to produce final product 172 via a bond cleavage between ruthenium and nitrogen (Scheme 45) [66]. Cu/Ru

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

• changing the previously optimized mild reaction conditions (Scheme 6). Only traces of 10 were observed in the absence of one of the metal salts; this excluded the participation of the silver salt in the olefin activation but highlighted its usual role in the activation of the gold catalyst, namely halide

• in Fe(III)-promoted hydroalkylation/cyclization cascades (Scheme 26A) [93]. Here, the carbocyclization occurred via a SN2 mechanism between the enolate intermediate and the tethered halide (Scheme 26B). Using arylidene diones 67 as radical acceptors, spiro compounds 69 were obtained in moderate to

• good yields. Five- and six-membered rings were synthesized by this method, and the tetracyclic compounds 69i–l were obtained when isopregol halide derivatives were employed. No diastereoselectivity was observed in the five-membered cyclizations (Scheme 26A, 69e–g), whereas the six-membered ring 69h was

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

• 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

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

Prins cyclization-mediated stereoselective synthesis of tetrahydropyrans and dihydropyrans: an inspection of twenty years

• Asha Budakoti,
• Pradip Kumar Mondal,
• Prachi Verma and
• Jagadish Khamrai

Beilstein J. Org. Chem. 2021, 17, 932–963, doi:10.3762/bjoc.17.77

• -orbital at C4. These orbital stabilizations, along with the lack of 1,3-diaxial interaction experienced by the incoming nucleophile (mostly halide) leads to the preferential equatorial attack over an axial attack by the nucleophile (Scheme 3) to give all-cis-2,4,6-trisubstituted THPs. In the absence of an

• cyclization between homoallyl alcohol 118 (or using the corresponding aldehyde and allylsilyl chloride 119) and an aldehyde 120 in the presence of a catalytic amount of the mild Lewis acid In(OTf)3 and trimethylsilyl halide as an additive to produce cis-4-halo-2,6-disubstituted tetrahydropyran 121 (Scheme 28

• -trimethylsilylalkenyl cation 242 formed by the Grob-type fragmentation (Scheme 57), which was trapped by the subsequent attack of the halide anion, leading to the formation of Prins product 244. On the basis of theoretical calculations, the authors could conclude factors controlling the alkyne Prins cyclization over