Three-component reactions of aromatic amines, 1,3-dicarbonyl compounds, and α-bromoacetaldehyde acetal to access N-(hetero)aryl-4,5-unsubstituted pyrroles

• Wenbo Huang,
• Kaimei Wang,
• Ping Liu,
• Minghao Li,
• Shaoyong Ke and
• Yanlong Gu

Beilstein J. Org. Chem. 2020, 16, 2920–2928, doi:10.3762/bjoc.16.241

• -bromoacetaldehyde acetal by using aluminum(III) chloride as a Lewis acid catalyst through [1 + 2 + 2] annulation. This new versatile methodology provides a wide scope for the synthesis of different functional N-(hetero)aryl-4,5-unsubstituted pyrrole scaffolds, which can be further derived to access multisubstituted

• under the conditions; the obtained results are listed in Table 1. The mixture was heated in 1,4-dioxane at 80 °C. No reaction occurred in the absence of the catalyst (Table 1, entry 1); however, in the presence of the strong Lewis acid Bi(OTf)3, the expected product 4a was obtained in 36% yield after 6

Selective and reversible 1,3-dipolar cycloaddition of 6-aryl-1,5-diazabicyclo[3.1.0]hexanes with 1,3-diphenylprop-2-en-1-ones under microwave irradiation

• Alexander P. Molchanov,
• Mariia M. Efremova,
• Mariya A. Kryukova and
• Mikhail A. Kuznetsov

Beilstein J. Org. Chem. 2020, 16, 2679–2686, doi:10.3762/bjoc.16.218

• that the Lewis acid-catalyzed reaction of diaziridines with donor–acceptor cyclopropanes and aziridines affords the perhydropyridazine or triazine derivatives, respectively, in good yields [31][32][33]. The use of microwave irradiation in organic synthesis complies with the principles of green

Recent developments in enantioselective photocatalysis

• Callum Prentice,
• James Morrisson,
• Andrew D. Smith and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2020, 16, 2363–2441, doi:10.3762/bjoc.16.197

• desired products 267 or 268 in moderate yields and enantioselectivities (3 examples, up to 75:25 er for 267 and 2 examples, up to 68:32 er for 268). Lewis acid catalysis Lewis acids have been known for decades to activate carbonyl compounds through the formation of coordination complexes that increases

• likely operates via a radical chain mechanism. Initiation begins with the reductive quenching of the photocatalyst using iPr2NEt as a sacrificial reductant to give [Ru]•−, which then reduces the Lewis acid-coordinated enone 271 to give alkyl radical 271•. In the presence of a second enone 270 and chiral

• chiral ligand L3 (Scheme 44a) [109]. The putative mechanism proceeds via a reductive quenching cycle to give nucleophilic α-amino radicals 277•, which can add to the β-position of Lewis acid complex 280 to give the α-carbonyl radical 280•. Instead of a cyclisation, this radical is then reduced by the

Hierarchically assembled helicates as reaction platform – from stoichiometric Diels–Alder reactions to enamine catalysis

• David Van Craen,
• Jenny Begall,
• Johannes Großkurth,
• Leonard Himmel,
• Oliver Linnenberg,
• Elisabeth Isaak and
• Markus Albrecht

Beilstein J. Org. Chem. 2020, 16, 2338–2345, doi:10.3762/bjoc.16.195

• auxiliary, Lewis acid or catalyst. In the previously reported system two different induction pathways were conceivable: (1) A chiral ligand is located close to the diene and controls the stereochemistry of the cycloaddition. (2) The chiral ligand controls the helicity of the helicate (ΔΔ or ΛΛ) and the

Efficient [(NHC)Au(NTf₂)]-catalyzed hydrohydrazidation of terminal and internal alkynes

• Maximillian Heidrich and
• Herbert Plenio

Beilstein J. Org. Chem. 2020, 16, 2080–2086, doi:10.3762/bjoc.16.175

• (Table 2). The obvious consequence being a decrease in the substrate conversion. This, however, could be compensated to some extent by longer reaction times. Based on this observation catalyst decomposition appeared to be negligible and it seemed, that the role of gold is primarily that of a Lewis acid

Reactions of 3-aryl-1-(trifluoromethyl)prop-2-yn-1-iminium salts with 1,3-dienes and styrenes

• Thomas Schneider,
• Michael Keim,
• Bianca Seitz and
• Gerhard Maas

Beilstein J. Org. Chem. 2020, 16, 2064–2072, doi:10.3762/bjoc.16.173

• with cyclic enol ethers [49] and of other very electrophilic alkynes (i.e., Lewis acid-activated acetylenic esters [50], 1-(trifluoroacetyl)-3-haloacetylenes [44] and 4-chloro-2-oxobut-3-ynoic esters [51][52][53] with unactivated alkenes (including cyclohexene [51], which did not react with 1a). For

Controlling the stereochemistry in 2-oxo-aldehyde-derived Ugi adducts through the cinchona alkaloid-promoted electrophilic fluorination

• Yuqing Wang,
• Gaigai Wang,
• Anatoly A. Peshkov,
• Ruwei Yao,
• Muhammad Hasan,
• Manzoor Zaman,
• Chao Liu,
• Stepan Kashtanov,
• Olga P. Pereshivko and
• Vsevolod A. Peshkov

Beilstein J. Org. Chem. 2020, 16, 1963–1973, doi:10.3762/bjoc.16.163

• stereocontrol was achieved with the aid of different Lewis acid promoters bearing chiral ligands, while the most recent and at the same time the most general procedure developed by Liu, Tan and co-workers relied on the stereoinduction by a chiral phosphoric acid (Table 1) [40]. In the standard Ugi four

Selective preparation of tetrasubstituted fluoroalkenes by fluorine-directed oxetane ring-opening reactions

• Clément Q. Fontenelle,
• Thibault Thierry,
• Romain Laporte,
• Emmanuel Pfund and
• Thierry Lequeux

Beilstein J. Org. Chem. 2020, 16, 1936–1946, doi:10.3762/bjoc.16.160

• already reported in the literature from oxetane-containing α,β-unsaturated carbonyl derivatives through a Lewis acid-catalyzed rearrangement [31]. When the previous conditions (HBr/AcOH) were tried (3.5 h, 0 °C to 20 °C), hydroxymethyllactone 14 (87%, Table 4, entry 1) was the main product with traces of

When metal-catalyzed C–H functionalization meets visible-light photocatalysis

• Lucas Guillemard and
• Joanna Wencel-Delord

Beilstein J. Org. Chem. 2020, 16, 1754–1804, doi:10.3762/bjoc.16.147

• catalysis with a second catalytic system has sparked significant interest from the scientific community. Accordingly, numerous unprecedented reactions involving photoredox catalysis in synergy with other activation modes including Brønsted/Lewis acid catalysis, organocatalysis, enzymatic biocatalysis, or

Pauson–Khand reaction of fluorinated compounds

• Jorge Escorihuela,
• Daniel M. Sedgwick,
• Alberto Llobat,
• Mercedes Medio-Simón,
• Pablo Barrio and
• Santos Fustero

Beilstein J. Org. Chem. 2020, 16, 1662–1682, doi:10.3762/bjoc.16.138

• concomitant detrifluoromethylation. Furthermore, the Lewis acid-mediated retro Diels–Alder reaction was carried out uneventfully on product 61, affording the corresponding cyclopentenone 62 in moderate yield (Scheme 33). In order to rationalize the unexpected loss of the trifluoromethyl group upon

• conjugated addition of trimethylaluminum to form 66, followed by Lewis acid-mediated retro Diels–Alder reaction (Scheme 38). In another study by Riera and co-workers, they studied the influence of the olefin counterpart on the regioselectivity of the reaction [79]. Two olefins other than norbornadiene were

Azidophosphonium salt-directed chemoselective synthesis of (E)/(Z)-cinnamyl-1H-triazoles and regiospecific access to bromomethylcoumarins from Morita–Baylis–Hillman adducts

• Soundararajan Karthikeyan,
• Radha Krishnan Shobana,
• Kamarajapurathu Raju Subimol,
• J. Helen Ratna Monica and
• Ayyanoth Karthik Krishna Kumar

Beilstein J. Org. Chem. 2020, 16, 1579–1587, doi:10.3762/bjoc.16.130

• -acetals [39], which branded them as promising motifs. The above reports and the Lewis acid character of quaternary phosphonium salts (QPS) [40][41][42][43][44][45][46][47][48] qualifies them as reliable catalysts for the proposed methodology. The most elaborate process in the proposed methodology is the

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

• to fuse samarium oxide nanoparticles to TiO2 and ceria (CeO2) as a bifunctional heterogeneous photoredox Lewis acid catalyst for reductive cyclisation reactions, previously reported with ruthenium transition metal complex photocatalysts [157]. Both electrochemical and photochemical deposition

Synthesis of 3-substituted isoxazolidin-4-ols using hydroboration–oxidation reactions of 4,5-unsubstituted 2,3-dihydroisoxazoles

• Lívia Dikošová,
• Júlia Laceková,
• Ondrej Záborský and
• Róbert Fischer

Beilstein J. Org. Chem. 2020, 16, 1313–1319, doi:10.3762/bjoc.16.112

• readily obtained through the reductive cleavage of benzoylated isoxazolidines, employing the Lewis acid-catalyzed SN reaction with triethylsilane as the hydride source (Scheme 1). For this reason, the benzoates 6a and 6b were readily prepared from the corresponding 2,3-dihydroisoxazoles 5a and 5b

Ferrocenyl-substituted tetrahydrothiophenes via formal [3 + 2]-cycloaddition reactions of ferrocenyl thioketones with donor–acceptor cyclopropanes

• Grzegorz Mlostoń,
• Mateusz Kowalczyk,
• André U. Augustin,
• Peter G. Jones and
• Daniel B. Werz

Beilstein J. Org. Chem. 2020, 16, 1288–1295, doi:10.3762/bjoc.16.109

• by means of spectroscopic methods (R = CF3). In a recent work, an alternative, efficient and useful method for the synthesis of highly functionalized tetrahydrothiophenes of type 6 was reported [9] (Scheme 2). Under Lewis acid catalysis, formal [3 + 2]-cycloadditions of aromatic and cycloaliphatic

• thioketones 8 in the presence of a Lewis acid was based on the assumption that the coordination of the catalyst by two ester groups activated the cyclopropane ring and allowed a nucleophilic attack of the C=S group on the benzylic position of the cyclopropane derivative (Scheme 4). The subsequent ring-closure

• Fc) as a single isomer. A similar reaction pathway with a zwitterionic intermediate analogous to 10, generated in the presence of a Lewis acid, was proposed for the reaction of cycloaliphatic 3-thioxo-2,2,4,4-tetramethylcyclobutanone with D–A cyclopropanes [21]. Conclusion The present study showed

Copper-catalysed alkylation of heterocyclic acceptors with organometallic reagents

• Yafei Guo and
• Syuzanna R. Harutyunyan

Beilstein J. Org. Chem. 2020, 16, 1006–1021, doi:10.3762/bjoc.16.90

• promoted the addition of Grignard reagents to N-Cbz-pyridone and N-Cbz-2,3-dihydropyridone Michael acceptors with high enantioselectivity and yield. It is worth mentioning that in copper-catalysed additions of Grignard reagents to N-Cbz-pyridone, the use of a Lewis acid (BF3·OEt2) together with the copper

• co-workers elaborated the copper-catalysed ring opening reaction of oxabicyclic alkene substrates using organolithium reagents, finding excellent anti selectivities and enantioselectivity (Scheme 12) [42]. During the optimisation studies, they discovered that when the Lewis acid BF3·OEt2 was employed

• reactivity of the heteroaromatic alkenyl substrates by Lewis acid activation in combination with readily available and highly reactive Grignard reagents and a copper catalyst bound to a chiral diphosphine ligand. Using this methodology, various chiral heteroaromatic products were obtained with high

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

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

• acid chlorides (Scheme 6) [23]. Therein, the key was the addition of a catalytic amount of iron powder as the Lewis acid to foster C–Cl bond cleavage and to access the desired products with high yields. The reaction encompassed a broad range of functional groups, including acetate, halides, and

Copper-catalyzed enantioselective conjugate addition of organometallic reagents to challenging Michael acceptors

• Delphine Pichon,
• Jennifer Morvan,
• Christophe Crévisy and
• Marc Mauduit

Beilstein J. Org. Chem. 2020, 16, 212–232, doi:10.3762/bjoc.16.24

• ]. Indeed, due to their poor reactivity compared to other Michael acceptors, catalytic asymmetric conjugate additions of organometallic reagents to N,N-dialkylenamides remained a real challenge. However, thanks to the synergistic action of the boron-based Lewis acid BF3∙Et2O, CuBr∙SMe2, and the chiral (R,S

Combination of multicomponent KA² and Pauson–Khand reactions: short synthesis of spirocyclic pyrrolocyclopentenones

• Riccardo Innocenti,
• Elena Lenci,
• Gloria Menchi and
• Andrea Trabocchi

Beilstein J. Org. Chem. 2020, 16, 200–211, doi:10.3762/bjoc.16.23

• reference set of brand-name blockbuster drugs (orange squares). Synthetic strategies for accessing pyrrolocyclopentenone derivatives, including the novel couple/pair approach that combines the KA2 and PK multicomponent reactions. L.A. = Lewis acid; PK = Pauson–Khand. Couple/pair approach using combined KA2

Synthesis, liquid crystalline behaviour and structure–property relationships of 1,3-bis(5-substituted-1,3,4-oxadiazol-2-yl)benzenes

• Afef Mabrouki,
• Malek Fouzai,
• Armand Soldera,
• Abdelkader Kriaa and
• Ahmed Hedhli

Beilstein J. Org. Chem. 2020, 16, 149–158, doi:10.3762/bjoc.16.17

• electron D–A concept may be regarded as Lewis base–Lewis acid type or charge-transfer. Based upon the above considerations, we could attribute the close proximity of fluorinated chains in conformation B to a throw space electron D–A intramolecular interaction between the perfluoroalkyl chains (electron

[1,3]/[1,4]-Sulfur atom migration in β-hydroxyalkylphosphine sulfides

• Katarzyna Włodarczyk,
• Piotr Borowski and
• Marek Stankevič

Beilstein J. Org. Chem. 2020, 16, 88–105, doi:10.3762/bjoc.16.11

• reaction. In the presence of a Brønsted acid, mainly [1,3]-rearrangement is observed, whereas a Lewis acid catalyzes the [1,4]-sulfur migration. To gain insight into the mechanism of these transformations, the stereochemistry of these rearrangements have been tested, along with the conduction of some

• remains to be proved for Lewis acid use. It was then decided to prepare substrates possessing double bonds at the β position (Scheme 6). It appeared that the sulfides derived from aldehydes 8 and 9 failed to undergo transformation to the corresponding alkenylphosphine sulfides when treated with a MsCl

• 2 and 3). The difference must therefore have arisen from the different C–O bond dissociation energies of the alcohols and mesylates. Assuming that the Lewis acid coordinated to either hydroxy oxygen atom or to one of the oxygen atoms of the mesyl group, the activation energies for C–O bond

Synthesis of C-glycosyl phosphonate derivatives of 4-amino-4-deoxy-α-ʟ-arabinose

• Lukáš Kerner and
• Paul Kosma

Beilstein J. Org. Chem. 2020, 16, 9–14, doi:10.3762/bjoc.16.2

• preliminary experiments, Lewis acid cleavage using BBr3, BCl3, and TiCl4, respectively, was not successful, although the latter reagent had previously been used to deprotect two benzyl groups from an allyl glycoside containing a 4-amino-4-deoxy-ʟ-arabinose residue [36]. Cleavage of the benzyl protecting

Extension of the 5-alkynyluridine side chain via C–C-bond formation in modified organometallic nucleosides using the Nicholas reaction

• Renata Kaczmarek,
• Dariusz Korczyński,
• James R. Green and
• Roman Dembinski

Beilstein J. Org. Chem. 2020, 16, 1–8, doi:10.3762/bjoc.16.1

• obtained successfully in moderate to good yields (Table 1). The reactions progressed quite slowly and required an excess amount of the Lewis acid (4–5 equiv) to proceed at a preparatively reasonable rate (Table 1, entries 1–4). These observations can be attributed to the substantial number of potentially

• nucleophile present was in slight excess relative to that of the Lewis acid, whereas limited amounts of nucleophile resulted in greater amounts of decomposition. Slightly more decomposition products were observed by TLC in reactions with ribo nucleoside 5 (Table 1, entries 4–7) than with 2'-deoxy derivative 4

SnCl₄-catalyzed solvent-free acetolysis of 2,7-anhydrosialic acid derivatives

• Kesatebrhan Haile Asressu and
• Cheng-Chung Wang

Beilstein J. Org. Chem. 2019, 15, 2990–2999, doi:10.3762/bjoc.15.295

• order to access glycans in a pure form. In line with this, various C-5-substituted 2,7-anhydrosialic acid derivatives bearing both electron-donating and -withdrawing protecting groups were synthesized and subjected to different Lewis acid-catalyzed solvent-free ring-opening reactions at room temperature

• -anhydro bridges [29][30][31]. Accordingly, ᴅ-galactosamine and ᴅ‑allosamine derivatives were synthesized via scandium(III) triflate-catalyzed ring opening of 1,6-anhydroglucosamine derivatives [29][32]. However, there is a paucity of reports on the Lewis acid-catalyzed acetolysis of the 2,7-anhydro

• the hydroxymethyl group in 10 to furnish 11 in 82% yield. After having obtained the 2,7-anhydrosialic acid derivatives 5–11, they were subjected to various Lewis acid-catalyzed ring-opening reactions. In line with this, Sc(OTf)3-, copper(II) triflate-, and SnCl4-catalyzed acetolysis of diacetylamino

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

• chiral Co(II)-(R,R)salen complex 83 in DMF saturated with CO2 resulted in the formation of 84 in a low yield but with good enantioselectivity (Scheme 31). Very recently, Meggers research group described an application of an asymmetric Lewis acid catalyst using electricity to provide a synthetic route

• towards chiral 1,4-dicarbonyls bearing tertiary and all-carbon quaternary stereocenters via oxidative cross coupling of 2-acylimidazoles 85 with silyl enol ethers 86 (Scheme 32). Chiral Rh complex 87 was exploited as a Lewis acid catalyst for the purpose of activating the substrate towards anodic

• and his group developed an electrochemical strategy for the asymmetric alkylation of 2-acylimidazole derivatives 94 with substituted para-methylphenols 95 using Ni(OAc)2 as a Lewis acid catalyst in presence of chiral diamine ligand 96 (Scheme 34) [71]. Based on their detailed mechanistic studies, the