Heterogeneous photocatalysis in flow chemical reactors

• Christopher G. Thomson,
• Ai-Lan Lee and
• Filipe Vilela

Beilstein J. Org. Chem. 2020, 16, 1495–1549, doi:10.3762/bjoc.16.125

• photocatalyst for the reduction of aryl halides [193]. The material could undergo consecutive photoinduced electron transfers (ConPET) in which the material enters an excited state and is reduced by a sacrificial electron donor (NEt3). The resulting Zn-PDI radical anion then undergoes a second photon absorption

• to achieve a superreducing electronic excited state capable of reducing stable aryl halides (Figure 14) [193]. More recently, PDI self-assemblies have been reported as efficient HPCats for the hydrogen evolution reaction [194] and degradation of phenol [192]. Another important material design applied

Recent synthesis of thietanes

• Jiaxi Xu

Beilstein J. Org. Chem. 2020, 16, 1357–1410, doi:10.3762/bjoc.16.116

• , or disulfonates of alkane-1,3-diols with sodium sulfide. The intramolecular substitution of 3-mercaptoalkyl halides or sulfonates is a similar strategy for the preparation of thietanes [12][13][14]. Alternatively, inter- and intramolecular photochemical [2 + 2] cycloadditions (thia-Paternò–Büchi

Disposable cartridge concept for the on-demand synthesis of turbo Grignards, Knochel–Hauser amides, and magnesium alkoxides

• Mateo Berton,
• Kevin Sheehan,
• Andrea Adamo and
• D. Tyler McQuade

Beilstein J. Org. Chem. 2020, 16, 1343–1356, doi:10.3762/bjoc.16.115

• combined with a solution-phase reagent, including: (1) copper(I) oxide to produce N-heterocyclic carbene–Cu(I) complexes for use as catalysts [13]; (2) proline to perform proline-based catalytic reactions [14]; (3) zinc powder to produce organozinc halides in tandem with Negishi couplings [15]; (4) zinc

• conversion because the neutralization can alter the aggregation states, producing a significant batch-to-batch variability. The direct insertion of magnesium metal into organic halides is the most common method used to prepare Grignard reagents but present difficulties: (1) sluggish reactions with ordinary

• use a practical system with a broad range of substrates [40][41][42]. The Alcázar group reported the generation and subsequent use of Grignard reagents [40]. In 2018, the Loren group extended the scope of the organozinc reagents made in flow to aryl and tertiary alkyl halides by the in situ formation

Photocatalysis with organic dyes: facile access to reactive intermediates for synthesis

• Stephanie G. E. Amos,
• Marion Garreau,
• Luca Buzzetti and
• Jerome Waser

Beilstein J. Org. Chem. 2020, 16, 1163–1187, doi:10.3762/bjoc.16.103

• fragmentation of the reduced intermediates. Due to their availability and their attitude to undergo reductive fragmentations, alkyl halides have been extensively used as C(sp3) radicals sources. Recently, Dell’Amico and co-workers reported a new class of naphthochromenone-based organic dyes, which, due to the

• wide redox window (E = 3.22 eV, +1.65 V/−1.77 V), can be exploited as photocatalysts for various transformations, including the reductive dehalogenation of benzylic halides (Scheme 7) [52]. In this protocol, the excited state photocatalyst OD18 can generate C(sp3) radicals through the reductive

• cleavage of various benzyl halides 7.1 (I, Br, Cl). The radical is then intercepted by an H atom donor (Hantzsch ester), which delivers the corresponding toluene derivative 7.2. Other organic dyes can promote the reductive fragmentation of alkyl halides. For instance, König and Zeitler demonstrated that a

Palladium-catalyzed regio- and stereoselective synthesis of aryl and 3-indolyl-substituted 4-methylene-3,4-dihydroisoquinolin-1(2H)-ones

• Valeria Nori,
• Antonio Arcadi,
• Armando Carlone,
• Fabio Marinelli and
• Marco Chiarini

Beilstein J. Org. Chem. 2020, 16, 1084–1091, doi:10.3762/bjoc.16.95

• -alkynyltrifluoroacetanilides. In all these procedures, the activation of the triple bond was achieved by means of a σ-organyl palladium complex, in turn generated in situ by oxidative addition of a Pd(0) species to suitable organic electrophiles (aryl and vinyl halides or triflates [35][36], alkyl halides [37], alkynyl

• halides [38], α-iodoenones [39], or by transmetalation of a Pd(II) species with boronic acids [33]. In this context, we decided to explore the use of substrates 2 in the reaction with 2-alkynyltrifluoroacetanilides 5 through a sequential cyclocarbopalladation/aminopalladation/reductive elimination process

Synthesis and anticancer activity of bis(2-arylimidazo[1,2-a]pyridin-3-yl) selenides and diselenides: the copper-catalyzed tandem C–H selenation of 2-arylimidazo[1,2-a]pyridine with selenium

• Mio Matsumura,
• Tsutomu Takahashi,
• Hikari Yamauchi,
• Shunsuke Sakuma,
• Yukako Hayashi,
• Tadashi Hyodo,
• Tohru Obata,
• Kentaro Yamaguchi,
• Yasuyuki Fujiwara and
• Shuji Yasuike

Beilstein J. Org. Chem. 2020, 16, 1075–1083, doi:10.3762/bjoc.16.94

• , and aryl halides in the presence of Na2CO3 (2 equiv) using a NiBr2/2,2-bipyridine system [31]. We also developed reactions of imidazopyridines, Se powder, and triarylbismuthanes using a CuI/1,10-phenanthroline catalytic system that did not require a base or an additive [32]. On the other hand, the

Copper-based fluorinated reagents for the synthesis of CF₂R-containing molecules (R ≠ F)

• Louise Ruyet and
• Tatiana Besset

Beilstein J. Org. Chem. 2020, 16, 1051–1065, doi:10.3762/bjoc.16.92

• difluoromethylcopper ones are less stable as demonstrated by the work of Burton in 2007 [37]. Investigations on the in situ synthesis of difluoromethylcopper from a difluoromethylcadmium source at low temperature and the study of its reactivity with various classes of compounds such as allylic halides, propargylic

• halides and tosylates, iodoalkynes and reactive alkyl halides were realized. It was established that CuCF2H readily decompose into 1,1,2,2-tetrafluoroethane and cis-difluoroethylene. From this pioneer work, attention was paid either to the design of new synthetic pathways for the synthesis of a well

• -generated copper-based reagent (19 examples, up to 80% yield, Scheme 7e). With a similar method and in the presence of 1,10-phenanthroline as a ligand, the functionalization of alkenyl halides (8 examples, up to 82% yield), allyl halides (7 examples, up to 99% yield) and benzyl bromides (6 examples, up to

Fluorinated phenylalanines: synthesis and pharmaceutical applications

• Laila F. Awad and
• Mohammed Salah Ayoup

Beilstein J. Org. Chem. 2020, 16, 1022–1050, doi:10.3762/bjoc.16.91

• reported herein different methods for their synthesis. 1.1. Negishi cross coupling of aryl halide and organozinc compounds Jackson and co-workers reported the synthesis of a range of phenylalanine derivatives via Negishi cross-coupling reactions of aryl halides and Zn homoenolates of the protected (R

• )-iodoalanine 2. The reaction was activated using Pd(0) as a catalyst. A palladium-catalyzed cross-coupling reaction between an organozinc iodide and aryl halides offers a convenient method for the direct preparation of protected fluorinated Phe analogues 3. Thus, cross coupling of the protected iodoalanine 2

• and 12b afforded ʟ-4-[sulfono(difluoromethyl)]phenylalanine derivatives 13a and 13b, respectively [39] (Scheme 3). 1.2. Alkylations of fluorinated aryl halides with a chiral auxiliary Alternatively, the coupling of the bis(dimethoxybenzyl)-protected sulfonamide 14, instead of the esters 10a and 10b

Accelerating fragment-based library generation by coupling high-performance photoreactors with benchtop analysis

• Quentin Lefebvre,
• Christophe Salomé and
• Thomas C. Fessard

Beilstein J. Org. Chem. 2020, 16, 982–988, doi:10.3762/bjoc.16.87

• halides to get an insight into the specific reactivity of these building blocks. The workflow combined a powerful photoreactor with precise and reproducible conditions control with benchtop analytical tools such as TLC–MS and low-field NMR. This enabled the identification of privileged spirocyclic

Aldehydes as powerful initiators for photochemical transformations

• Maria A. Theodoropoulou,
• Nikolaos F. Nikitas and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2020, 16, 833–857, doi:10.3762/bjoc.16.76

• proceeded efficiently for a wide range of substrates in moderate to excellent yield, including various alkyl halides 93, carbon tetrachloride, 2-norbornene, cyclic alkenes, a terminal disubstituted olefin, and a terminal alkyne. The reaction mechanism was thought to proceed via energy transfer from the

• . Moreover, the excited 4-anisaldehyde (98) underwent energy transfer over the addition to the double bond of the alkene, as no Paterno–Büchi cycloadducts were observed. Furthermore, the detection of the photolysis products of the alkyl halides mentioned above indicated the presence of triplet state 4

Photocatalytic deaminative benzylation and alkylation of tetrahydroisoquinolines with N-alkylpyrydinium salts

• David Schönbauer,
• Carlo Sambiagio,
• Timothy Noël and
• Michael Schnürch

Beilstein J. Org. Chem. 2020, 16, 809–817, doi:10.3762/bjoc.16.74

• , electrophilic alkyl radicals were used in several transformations, such as electrophilic cross couplings under nickel catalysis, either with boronic acids [35] or different (aryl)halides [36][37][38]. Furthermore, visible light-promoted uncatalyzed electron transfer via the formation of electron donor–acceptor

• para-substituted product 6 was isolated in 64% yield, and the two sterically more congested products 4 and 5 gave about 10% lower yields (Scheme 2). This went in line with the similarly sterically demanding 2-methylnaphthyl product 7, which was obtained in 50% yield. Halides, such as bromo and fluoro

• substituents had a negative effect on the efficiency of the transformation, independently of their electronic effects (Scheme 3, 21–25). Still, halides, nitriles, and ester substituents were tolerated, giving a possible handle for further manipulation. However, the presence of a nitro group impeded the

Recent advances in Cu-catalyzed C(sp³)–Si and C(sp³)–B bond formation

• Balaram S. Takale,
• Ruchita R. Thakore,
• Elham Etemadi-Davan and
• Bruce H. Lipshutz

Beilstein J. Org. Chem. 2020, 16, 691–737, doi:10.3762/bjoc.16.67

• ] are common partners in a variety of important cross-coupling reactions. They are also especially valuable precursors to other functional groups such as organic halides, alcohols [5][6][7], etc. Moreover, recent drug discovery efforts have shifted towards the incorporation of these non-natural

• (Scheme 4). It should be mentioned that secondary triflates or halides are not suitable for this transformation, since they lead to products resulting from fast β-elimination. Considering this limitation, they designed alkyl triflates stabilized by a strong electron-withdrawing group (EWG) directly

• 122. Moreover, the intermediates could be trapped in the presence of electrophiles, such as aldehydes or alkyl halides to afford interesting α-substituted products 124 and 125. This phenomenon was further studied in detail on different dienones [58]. In 2013, Procter and co-workers [59] extended the

A systematic review on silica-, carbon-, and magnetic materials-supported copper species as efficient heterogeneous nanocatalysts in “click” reactions

• Pezhman Shiri and
• Jasem Aboonajmi

Beilstein J. Org. Chem. 2020, 16, 551–586, doi:10.3762/bjoc.16.52

• -functionalized silica 46 was added to the mixture, and this was heated to reflux to generate the catalyst 48. Several organic halides or epoxides, nonactivated alkynes, and sodium azide were reacted in an aqueous medium to provide triazoles or β-hydroxytriazoles using 1.0 mol % catalyst loading at 25 °C

• washed with acetonitrile and dried before being used in “click” reactions. CuI/AK (68) furnished the desired products of the reaction of phenacyl halides (with Me, Br, and Cl substituents), benzyl halides or methyl iodide, and phenylacetylene or propargyl alcohol as substrates using a catalytic amount of

• and organic halides as well as sodium azide were stirred in a mixture of t-BuOH/H2O, 3:1, v/v as the solvent in the presence of diethylisopropylamine and SiO2–Cu. In both cases, the SiO2–Cu catalyst was filtered off and then, the triazole products were purified. In another approach, 2-pyridine

Efficient synthesis of 3,6,13,16-tetrasubstituted-tetrabenzo[a,d,j,m]coronenes by selective C–H/C–O arylations of anthraquinone derivatives

• Seiya Terai,
• Yuki Sato,
• Takuya Kochi and
• Fumitoshi Kakiuchi

Beilstein J. Org. Chem. 2020, 16, 544–550, doi:10.3762/bjoc.16.51

• groups to form biaryl frameworks. Traditionally, transition-metal-catalyzed cross-coupling reactions of aryl halides or pseudohalides with arylmetal reagents have been employed for the connection of two aryl units [5][6][7][8][9]. However, in search of more efficient synthetic routes, C–H arylation

Copper-catalyzed remote C–H arylation of polycyclic aromatic hydrocarbons (PAHs)

• Anping Luo,
• Min Zhang,
• Zhangyi Fu,
• Jingbo Lan,
• Di Wu and
• Jingsong You

Beilstein J. Org. Chem. 2020, 16, 530–536, doi:10.3762/bjoc.16.49

• it possible to introduce useful functional groups into the products through the further transformation of corresponding aryl halides. 2-Naphthyliodonium salt could react smoothly with 1a to provide 3p in 66% yield (Scheme 2, 3p). Moreover, thiophen-2-yliodonium salt could be tolerated, albeit with a

Regio- and stereoselective synthesis of new ensembles of diversely functionalized 1,3-thiaselenol-2-ylmethyl selenides by a double rearrangement reaction

• Svetlana V. Amosova,
• Andrey A. Filippov,
• Nataliya A. Makhaeva,
• Alexander I. Albanov and
• Vladimir A. Potapov

Beilstein J. Org. Chem. 2020, 16, 515–523, doi:10.3762/bjoc.16.47

• ]. Having established the synthesis of heterocycle 4 this unsaturated five-membered S,Se-containing compound was used as a starting material for the synthesis of novel ensembles of selenium heterocycles with promising biological activity. The treatment of 4 with organyl halides resulted in the efficient

• with organyl halides. Various substrates were involved in the reaction, providing the introduction of alkyl, benzyl, allyl, and 2-propynyl moieties as well as pharmacophores as 2-pyridylmethyl and 4-fluorobenzyl. A possibility for the synthesis of compounds containing two 1,3-thiaselenol-2

• 1,3-thiaselenol-2-ylmethylselenolate through reduction of the Se–Se bond with NaBH4 followed by nucleophilic substitution with alkyl halides (Scheme 11). Thus, two efficient methods for the preparation of novel 1,3-thiaselenol-2-ylmethylselanyl derivatives 6a–l from selenocyanate 4 and diselenides 8

KOt-Bu-promoted selective ring-opening N-alkylation of 2-oxazolines to access 2-aminoethyl acetates and N-substituted thiazolidinones

• Qiao Lin,
• Shiling Zhang and
• Bin Li

Beilstein J. Org. Chem. 2020, 16, 492–501, doi:10.3762/bjoc.16.44

• -dihydrothiazole with benzyl halides under basic conditions is described for the first time. The method provides a convenient and practical pathway for the synthesis of versatile 2-aminoethyl acetates and N-substituted thiazolidinones with good functional group tolerance and selectivity. KOt-Bu not only plays an

• on our continuing interest in developing new transformation methodologies of oxazolines [25], herein, we report a simple KOt-Bu-promoted selective ring-opening N-alkylation of 2-methyl-2-oxazolines and 2-(methylthio)-4,5-dihydrothiazole with benzyl halides, leading to 2-aminoethyl acetates and N

• new and simple transition-metal-free selective ring-opening N-alkylation of 2-methyl-2-oxazoline or 2-(methylthio)-4,5-dihydrothiazole with benzyl halides and allyl halides under mild conditions. Various 2-aminoethyl acetates and N-substituted thiazolidinone derivatives were successfully isolated in

Recent advances in photocatalyzed reactions using well-defined copper(I) complexes

• Mingbing Zhong,
• Xavier Pannecoucke,
• Philippe Jubault and
• Thomas Poisson

Beilstein J. Org. Chem. 2020, 16, 451–481, doi:10.3762/bjoc.16.42

• ) photocatalyst (Scheme 1) [16]. The [Cu(I)(dap)2]Cl complex had a strong absorption under irradiation at 530 nm using a green LED. Different organic halides and alkenes were reacted, leading to the product by an ATRA reaction pathway with moderate to good yield at room temperature (Scheme 1). The authors

• catalysts in a similar transformation [17]. In another study, Reiser and co-workers described a related allylation process of organic halides with allyltributyltin in the presence of [Cu(I)(dap)2]Cl as the catalyst [16]. This reaction was applied to a broad range of substrates, including a para-nitrophenyl

• initial step. In early 2019, our research group reported the copper-photocatalyzed borylation of organic halides using [Cu(I)(DMEGqu)(DPEPhos)]PF6 as the photocatalyst (Scheme 26) [41]. The photocatalytic Miyaura borylation reaction was carried out using aryl iodides bearing either electron-donating or

Copper-promoted/copper-catalyzed trifluoromethylselenolation reactions

• Clément Ghiazza and
• Anis Tlili

Beilstein J. Org. Chem. 2020, 16, 305–316, doi:10.3762/bjoc.16.30

• starting materials. The group of Weng first explored the trifluoromethylselenolation of alkyl halides [13] and then propargylic chlorides and allylic bromides (Scheme 1) [14]. Overall, the reactions were performed at temperatures between 70–100 °C with an excess of the trifluoromethylselenyl source, and

• the desired corresponding products were generally obtained in very good yields. The application scope of the [(bpy)CuSeCF3]2 complex was then extended to aromatic halides for the formation of C(sp2)–SeCF3 bonds. The authors demonstrated that a very broad range of (hetero)aryl halides and vinyl halides

• trifluoromethylselenolated alkyne product could be isolated. After that, the same group studied the α-trifluoromethylselenolation of ketones and esters starting from the corresponding halides or diazoacetates (Scheme 4) [19][20]. Both methods led to the desired products with moderate to very good yields, and the reactions

Halogen-bonding-induced diverse aggregation of 4,5-diiodo-1,2,3-triazolium salts with different anions

• Xingyu Xu,
• Shiqing Huang,
• Zengyu Zhang,
• Lei Cao and
• Xiaoyu Yan

Beilstein J. Org. Chem. 2020, 16, 78–87, doi:10.3762/bjoc.16.10

• noncovalent interaction between electrophilic halides and Lewis bases or electron-rich regions [1][2]. Computational studies [3][4][5][6][7] and cyrstal architectures including XB-donors (σ-hole) such as perfluorocarbons [8][9][10][11][12], tetraiodoethylene [13], 1,2-diiodo-1,2-difluoroethene [14

• , 2-Br and 2-Cl show tetrameric aggregation of the 4,5-diiodo-1,3-dimesityl-1,2,3-triazolium moiety with four anion halides that are bridged together to form a saddle shape through XB (Figure 2). 2-I crystallizes in the tetragonal space group . The distances of I···I are 3.306(1) Å and 3.300(1) Å

Starazo triple switches – synthesis of unsymmetrical 1,3,5-tris(arylazo)benzenes

• Andreas H. Heindl and
• Hermann A. Wegner

Beilstein J. Org. Chem. 2020, 16, 22–31, doi:10.3762/bjoc.16.4

• Baeyer–Mills reactions and the other based on Pd-catalyzed coupling reactions of arylhydrazides and aryl halides, followed by oxidation, were investigated. The Pd-catalyzed route efficiently led to the target compounds, unsymmetrical tris(arylazo)benzenes. These triple switches were preliminarily

• example of such compounds are 1,3,5-tris(arylazo)benzenes – ‘starazos’ – introduced by Cho and co-workers in 2004 (Figure 1) [10]. Despite their successful synthesis, using Pd-catalyzed coupling reactions of aryl halides and arylhydrazides [11] followed by Cu(I)-mediated oxidation, the photochemical

Functionalization of the imidazo[1,2-a]pyridine ring in α-phosphonoacrylates and α-phosphonopropionates via microwave-assisted Mizoroki–Heck reaction

• Damian Kusy,
• Agata Wojciechowska,
• Joanna Małolepsza and
• Katarzyna M. Błażewska

Beilstein J. Org. Chem. 2020, 16, 15–21, doi:10.3762/bjoc.16.3

• for the 6- and 7-substituted analogs 1a–c, but no product was observed in the reaction with the 8-halogeno-imidazo[1,2-a]pyridine analog 1d [25]. As the Mizoroki–Heck reaction is sensitive to the electronic properties of the aryl halides, with electron-withdrawing substituents imparting a smaller

Diversity-oriented synthesis of spirothiazolidinediones and their biological evaluation

• Sambasivarao Kotha,
• Gaddamedi Sreevani,
• Lilya U. Dzhemileva,
• Milyausha M. Yunusbaeva,
• Usein M. Dzhemilev and
• Vladimir A. D’yakonov

Beilstein J. Org. Chem. 2019, 15, 2774–2781, doi:10.3762/bjoc.15.269

• bromide (6a) in the presence of Mo(CO)6 in acetonitrile at 90 °C under microwave irradiation (MWI) conditions to give the co-trimerized spiro derivative 8a (Scheme 2). The free NH moiety of thiazolidinedione 3 was alkylated using alkyl or aryl halides in the presence of Et3N using DCM as solvent. To our

• peaks in the carbonyl region of the 13C NMR spectrum and no third carbonyl peak (Figure 1). Finally, mass spectral (HRMS) data confirmed the molecular formula. Next, we prepared the diyne precursors and examined the [2 + 2 + 2] cyclotrimerization strategy with different propargyl halides 6 to obtain

• strategy with propargyl halides. We have also shown the synthesis of linearly fused spirocyclic alcohol derivatives of thiazolidinedione using Wilkinson’s catalyst and these compounds were tested for their anticancer activity. We have shown for the first time that the new benzyl alcohol derivatives of

A review of asymmetric synthetic organic electrochemistry and electrocatalysis: concepts, applications, recent developments and future directions

• Munmun Ghosh,
• Valmik S. Shinde and
• Magnus Rueping

Beilstein J. Org. Chem. 2019, 15, 2710–2746, doi:10.3762/bjoc.15.264

• the major diastereomers of 151a and 153a, respectively, allowed access to optically active mandelic acid esters (Scheme 49). In 1997, Durandetti’s group published a Ni-catalyzed method for the electroreductive coupling between aryl halides and α-chloropropionic acid derivatives 153 in which the

Recent advances in transition-metal-catalyzed incorporation of fluorine-containing groups

• Xiaowei Li,
• Xiaolin Shi,
• Xiangqian Li and
• Dayong Shi

Beilstein J. Org. Chem. 2019, 15, 2213–2270, doi:10.3762/bjoc.15.218

• source and behaves as a nucleophile. The electrophile, such as an alkyl chain or an aryl ring with halides or sulfonates, reacts with the fluoride source (Scheme 1a). On the other hand, in the electrophilic fluorination, the nucleophile may be a carbon anion (e.g., Grignard reagent), a compound with