Synthesis of new condensed naphthoquinone, pyran and pyrimidine furancarboxylates

• Kirill A. Gomonov,
• Vasilii V. Pelipko,
• Igor A. Litvinov,
• Ilya A. Pilipenko,
• Anna M. Stepanova,
• Nikolai A. Lapatin,
• Ruslan I. Baichurin and
• Sergei V. Makarenko

Beilstein J. Org. Chem. 2025, 21, 340–347, doi:10.3762/bjoc.21.24

• furoamines [20][21], as well as by the interaction of pyrimidinols with α-halocarbonyl compounds [22], nitroalkenes [23] or gem-chloronitroalkenes [21][24][25] (Scheme 2). At the same time, the construction of furan-containing pyranopyrans and pyranochromenes in the literature is represented only by the

• reactions of 4-hydroxy-7-methyl-2H,5H-pyrano[4,3-b]pyran-2,5-dione and 4-hydroxy-2H,5H-pyrano[3,2-c]chromene-2,5-dione with ethynylbenzene [26] (Scheme 3). The possibility of the formation of substituted furan structures is shown by the example of the reaction of nitroalkenes with aliphatic CH acids [27

Cu(OTf)₂-catalyzed multicomponent reactions

• Sara Colombo,
• Camilla Loro,
• Egle M. Beccalli,
• Gianluigi Broggini and
• Marta Papis

Beilstein J. Org. Chem. 2025, 21, 122–145, doi:10.3762/bjoc.21.7

• process by using α-diazoketones, nitroalkenes and primary amines, in the presence of air as oxidant. The mechanism involved the formation of α-ketocarbene XXVI from α-diazoketone, able to react with the amine affording imine XXV after copper-catalyzed oxidative dehydrogenation. The subsequent [3 + 2

Recent advances in organocatalytic atroposelective reactions

• Henrich Szabados and
• Radovan Šebesta

Beilstein J. Org. Chem. 2025, 21, 55–121, doi:10.3762/bjoc.21.6

• are of interest and have been recently investigated by Jørgensen and co-workers. The authors employed an enantioselective aminocatalytic cycloaddition between 5H-benzo[a]pyrrolizine-3-carbaldehydes 22 and naphthyl-substituted nitroalkenes, α,β-unsaturated ketoesters, or α,β-unsaturated aldehydes 23

Facile one-pot reduction of β-nitrostyrenes to phenethylamines using sodium borohydride and copper(II) chloride

• Laura D’Andrea and
• Simon Jademyr

Beilstein J. Org. Chem. 2025, 21, 39–46, doi:10.3762/bjoc.21.4

• reduction of β-nitrostyrenes to phenethylamines, however, to date, no effective method for converting α,β-unsaturated nitroalkenes into aminoalkanes have been developed using NaBH4 as reducing agent [21][22]. The number of procedures reported in the literature regarding the reduction of β-nitrostyrenes is

• to synthesize phenethyl- and phenylisopropylamines from the corresponding nitroalkenes [15][17]. Representatively substituted β-nitrostyrene analogues were reduced via this method at 80 ˚C, including 2,5-dimethoxy-β-methyl-β-nitrostyrene (3a), precursor of amphetamines, and 2,5-dimethoxy-β

Synthesis of spiroindolenines through a one-pot multistep process mediated by visible light

• Francesco Gambuti,
• Jacopo Pizzorno,
• Chiara Lambruschini,
• Renata Riva and
• Lisa Moni

Beilstein J. Org. Chem. 2024, 20, 2722–2731, doi:10.3762/bjoc.20.230

• the acid-catalyzed [4 + 1] cycloaddition of commercially available substrates, as indoles and nitroalkenes to give spiro-isoxazoles (Scheme 1c), but acceptable yields were obtained just using nitrostyrenes [13][14]. Despite these examples, the highly efficient construction of structurally diverse

Stereoselective mechanochemical synthesis of thiomalonate Michael adducts via iminium catalysis by chiral primary amines

• Michał Błauciak,
• Dominika Andrzejczyk,
• Błażej Dziuk and
• Rafał Kowalczyk

Beilstein J. Org. Chem. 2024, 20, 2313–2322, doi:10.3762/bjoc.20.198

• nitroalkenes or guanidine-mediated addition of bisthiomalonates to maleimides, cyclic enones, and acyclic 1,4-dicarbonylbutenes, albeit at low temperatures and with relatively long reaction times, further limited to a narrow scope of thioesters (Scheme 1) [31]. Recently, we described a cinchona-squaramide

Catalysing (organo-)catalysis: Trends in the application of machine learning to enantioselective organocatalysis

• Stefan P. Schmid,
• Leon Schlosser,
• Frank Glorius and
• Kjell Jorner

Beilstein J. Org. Chem. 2024, 20, 2280–2304, doi:10.3762/bjoc.20.196

• enantioselective formation of N,S-acetals catalysed by CPAs. To represent the catalysts, the authors developed the average steric occupancy (ASO) descriptors, a representation inspired by CoMFA [104][105][106], which recently also was applied in the selectivity prediction of aldehydes to nitroalkenes [68]. In ASO

• [107] (Figure 11B). Werth and Sigman [127] investigated multiple nucleophilic additions to nitroalkenes, catalysed by bifunctional hydrogen bond donors, observing good correlations to new bi-functional donors, new nucleophiles, new electrophiles and even similar cascade-type reactions. In the authors

Diastereoselective synthesis of highly substituted cyclohexanones and tetrahydrochromene-4-ones via conjugate addition of curcumins to arylidenemalonates

• Deepa Nair,
• Abhishek Tiwari,
• Banamali Laha and
• Irishi N. N. Namboothiri

Beilstein J. Org. Chem. 2024, 20, 2016–2023, doi:10.3762/bjoc.20.177

• double Michael addition of γ,δ-unsaturated-β-keto esters or Nazarov reagents with suitable acceptors such as nitroalkenes or alkylideneazalactones [7][8][9][10]. From the perspective of an active methylene containing organic moiety, curcumin and its analogs serve as inexpensive and readily available

• –acceptor with nitroalkenes, resulting in multi-substituted cyclohexanones through a cascade inter–intramolecular double Michael addition process with high diastereoselectivity [26][27]. Subsequently, the enantioselective versions of the above reaction and a similar diastereoselective cascade Michael

• ]. Other groups have also investigated the Michael donor–acceptor reactivity of curcumins [25]. For instance, a quinine-thiourea catalyzed Michael addition of curcumins to nitroalkenes reported by Ye et al. stopped at the single Michael addition stage [35]. In the subsequent year, Yan et al. demonstrated a

Carbonylative synthesis and functionalization of indoles

• Alex De Salvo,
• Raffaella Mancuso and
• Xiao-Feng Wu

Beilstein J. Org. Chem. 2024, 20, 973–1000, doi:10.3762/bjoc.20.87

• isolated product was an indol-3-one derivative (Scheme 14). Another example for the synthesis of 3-substituted indoles was described by Hsieh and Dong [35]. They synthesized 3-arylindoles by palladium-catalyzed C–H bond amination via reduction of nitroalkenes using carbon monoxide as reducing agent. The

• palladium-catalyzed reductive N-heteroannulation. Synthesis of 3-arylindoles by palladium-catalyzed C–H bond amination via reduction of nitroalkenes. Synthesis of 2,2′-bi-1H-indoles, 2,3′-bi-1H-indoles, 3,3′-bi-1H-indoles, indolo[3,2-b]indoles, indolo[2,3-b]indoles, and 4,4′-diaza-3,3′-bi-1H-indole. Pd

Acetaldehyde in the Enders triple cascade reaction via acetaldehyde dimethyl acetal

• Alessandro Brusa,
• Debora Iapadre,
• Maria Edith Casacchia,
• Alessio Carioscia,
• Giuliana Giorgianni,
• Giandomenico Magagnano,
• Fabio Pesciaioli and
• Armando Carlone

Beilstein J. Org. Chem. 2023, 19, 1243–1250, doi:10.3762/bjoc.19.92

• because of its high reactivity. Herein, we report the Enders-type cascade reaction using acetaldehyde dimethyl acetal, as a masked form of acetaldehyde. This strategy directly converts acetaldehyde, nitroalkenes and enals into stereochemically dense cyclohexenals in good yield and excellent

• increasing structural and stereochemical complexity starting from readily available substrates. The scope of the process was shown to be successful with aliphatic aldehydes 2, aromatic nitroalkenes 3, and both aromatic and aliphatic unsaturated aldehydes 4. Given our recent interest in the use of a surrogate

• . Although the scope is limited to aromatic nitroalkenes and enals, the yields are good considering the complexity of the domino process that involves highly reactive partners, and the ees are consistently very high. Finally, albeit there is low diastereocontrol, the diastereomers can be easily separated by

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

• the trapping of metal enolates by Michael reactions with nitroalkenes 122 and disulfonyl ethylenes 124 (Scheme 31) [67]. The conjugate additions of dialkylzinc, Grignard, and trialkylaluminum reagents to cyclic enones 121 were realized using previously established chiral phosphoramidite, carbene or

New advances in asymmetric organocatalysis

• Radovan Šebesta

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

• possibilities in combination of covalent and noncovalent activation, our group designed and synthesized N-sulfinylpyrrolidine-containing ureas and thioureas and applied them in Michael additions of aldehydes to heterocycle containing nitroalkenes [25]. Dubey and Chowdhury showed that 1,4-conjugate additions of

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

• to synthesise indoloquinolizidines [5]. Moreover, six-membered and five-membered cyclic 1,3-diketones have been investigated in reactions with acetates of nitroalkenes [6], cyanoacrylates and benzylidene malononitriles [7], ortho-hydroxy-benzhydryl alcohols [8], α,β-unsaturated pyrazolamides [9] and

Solvent-free synthesis of enantioenriched β-silyl nitroalkanes under organocatalytic conditions

• Akhil K. Dubey and
• Raghunath Chowdhury

Beilstein J. Org. Chem. 2021, 17, 2642–2649, doi:10.3762/bjoc.17.177

• -nitrosilanes through a Cu(II)–chiral bipyridine complex catalyzed enantioselective silyl transfer reaction to nitroalkenes using Suginome’s silylboron reagent (Scheme 1a) [28]. Recently, we have reported the synthesis of chiral β-nitrosilanes via an organocatalytic conjugate addition of nitromethane to β

N-Sulfinylpyrrolidine-containing ureas and thioureas as bifunctional organocatalysts

• Viera Poláčková,
• Dominika Krištofíková,
• Boglárka Némethová,
• Renata Górová,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2021, 17, 2629–2641, doi:10.3762/bjoc.17.176

• Michael additions of aldehydes to nitroalkenes both under solvent-free conditions and in solution. The N-sulfinylurea catalyst was more efficient than the corresponding thiourea. For some substrates, enantioselectivities reached 98% ee. The stereogenic center on the sulfur did not have a considerable

• aldehydes and hydrogen-bond activation of nitroalkenes. Keywords: asymmetric organocatalysis; hydrogen bond; Michael addition; pyrrolidine; thiourea; urea; Introduction Asymmetric organocatalysis became one of the strategic ways for the efficient synthesis of chiral compounds [1]. Bifunctional catalysis

• -sulfinylurea as bifunctional organocatalyst [23]. The enantio- and diastereoselective addition of Meldrum’s acids to nitroalkenes via N-sulfinylurea catalysis gave products that were readily converted to pharmaceutically relevant compounds [24][25]. A sulfinylurea organocatalyst catalyzed a highly selective

Nitroalkene reduction in deep eutectic solvents promoted by BH₃NH₃

• Chiara Faverio,
• Monica Fiorenza Boselli,
• Patricia Camarero Gonzalez,
• Alessandra Puglisi and
• Maurizio Benaglia

Beilstein J. Org. Chem. 2021, 17, 1041–1047, doi:10.3762/bjoc.17.83

• nitroalkanes, valuable precursors of amines. A variety of nitrostyrenes and alkyl-substituted nitroalkenes, including α- and β-substituted nitroolefins, were chemoselectively reduced to the nitroalkanes, with an atom economy-oriented, simple and convenient experimental procedure. A reliable and easily

• ammonia borane in the chemoselective reduction of a variety of nitrostyrenes and alkyl-substituted nitroalkenes to the corresponding nitroalkanes, without any catalyst or additive [13]. We thought that the combination of an atom economic, very convenient and inexpensive reagent such as BH3NH3 in bio-based

• (entries 6 and 8, Table 1). Therefore, DES mixture B (ChCl/gly 1:2) and glycerol were selected as reaction media of choice to further investigate the reduction of nitroalkenes mediated by ammonia borane. Both solvent systems represent promising alternatives, green solvents for organic reactions; glycerol

Synthesis of imidazo[1,5-a]pyridines via cyclocondensation of 2-(aminomethyl)pyridines with electrophilically activated nitroalkanes

• Dmitrii A. Aksenov,
• Nikolai A. Arutiunov,
• Vladimir V. Maliuga,
• Alexander V. Aksenov and
• Michael Rubin

Beilstein J. Org. Chem. 2020, 16, 2903–2910, doi:10.3762/bjoc.16.239

• Within the last few years, we have developed and implemented a number of novel synthetic methodologies in our laboratories, involving acid-mediated cascade transformations of nitroalkenes and nitroalkanes, which target materials science and medicinal chemistry applications. It was demonstrated that upon

One-pot and metal-free synthesis of 3-arylated-4-nitrophenols via polyfunctionalized cyclohexanones from β-nitrostyrenes

• Haruyasu Asahara,
• Minami Hiraishi and
• Nagatoshi Nishiwaki

Beilstein J. Org. Chem. 2020, 16, 1830–1836, doi:10.3762/bjoc.16.150

• method toward the preparation of 3-arylated-4-nitrophenols. On the other hand, nitroalkenes possess an electron-deficient double bond, and hence, they serve as an excellent Michael acceptor and dienophile [12][13][14][15][16][17][18][19]. When β-nitrostyrene (1, Ar = Ph) is subjected to the Diels–Alder

• nitrophenol 5a. This protocol was also applicable to other nitroalkenes, 1b–f, to afford the corresponding 3-arylated-4-nitrophenols 5b–f. This reaction could be conducted in one pot without using any transition-metal reagent. Since the starting nitroalkenes were prepared by the condensation of a (hetero)aryl

• solid was recrystalized with a mixed solvent (hexane/dichloromethane 10:1) to afford nitrostyrene 1a [24] (1.99 g, 12.2 mmol, 76%) as yellow needles. The other nitroalkenes 1b–f [25][26][27][28][29] were prepared in the same way. One-pot Diels–Alder reaction of nitrostyrene 1a and Danishefsky’s diene (2

Synthesis of non-racemic 4-nitro-2-sulfonylbutan-1-ones via Ni(II)-catalyzed asymmetric Michael reaction of β-ketosulfones

• Alexander N. Reznikov,
• Anastasiya E. Sibiryakova,
• Marat R. Baimuratov,
• Eugene V. Golovin,
• Victor B. Rybakov and
• Yuri N. Klimochkin

Beilstein J. Org. Chem. 2019, 15, 1289–1297, doi:10.3762/bjoc.15.127

• nitroalkenes in the presence of Ni(II) complexes with various chiral vicinal diamines was studied. This reaction provides convenient access to non-racemic 4-nitro-2-sulfonylbutan-1-ones with two stereocenters with high yield and excellent enantioselectivity (up to 99%). It has been established that the

• ; Michael addition; nickel complexes; nitroalkenes; Introduction Sulfones are widely used in organic synthesis, particularly, in various reactions of C–C and C=C-bond formation [1][2][3][4]. The use of sulfones in Julia–Kocienski [1] and Ramberg–Bäcklund reactions [2] made this class of compounds

• reactions. Thus, ketonitrosulfones were obtained with good enantiomeric excesses via asymmetric addition of α-nitrosulfones to enones in the presence of organocatalysts [41]. Asymmetric addition of β-ketosulfones to nitroalkenes was implemented using various organocatalysts [42]. The reaction of

Assembly of fully substituted triazolochromenes via a novel multicomponent reaction or mechanochemical synthesis

• Robby Vroemans,
• Yenthel Verhaegen,
• My Tran Thi Dieu and
• Wim Dehaen

Beilstein J. Org. Chem. 2018, 14, 2689–2697, doi:10.3762/bjoc.14.246

• .14.246 Abstract A new metal-free one-pot three-component procedure towards fully substituted triazolochromenes has been developed, starting from commercially available materials. Salicylaldehydes and nitroalkenes were reacted under solvent-free conditions, followed by a 1,3-dipolar cycloaddition of the

• assembly of triazole-fused (hetero)cycles [24][33][34][35][36][37][38][39][40][41][42], we opted to develop a new one-pot two-step three-component reaction starting from salicylaldehydes, nitroalkenes and organic azides, without isolation of the intermediate 3-nitrochromenes, in a regioselective manner and

• study using various salicylaldehydes, nitroalkenes and organic azides. Solid salicylaldehydes gave diminished yields in the one-pot three-component protocol, hence a two-step mechanochemical approach was developed offering higher yields and resulting in a complementary route for solid salicylaldehydes

Asymmetric Michael addition reactions catalyzed by calix[4]thiourea cyclohexanediamine derivatives

• Zheng-Yi Li,
• Hong-Xiao Tong,
• Yuan Chen,
• Hong-Kui Su,
• Tangxin Xiao,
• Xiao-Qiang Sun and
• Leyong Wang

Beilstein J. Org. Chem. 2018, 14, 1901–1907, doi:10.3762/bjoc.14.164

• convenience and good stereoselectivity [5][6]. Accordingly, different versions of this reaction have been extensively studied. Notably, the Michael addition reaction of 1,3-dicarbonyl compounds to conjugated nitroalkenes is very important for the synthesis of chiral nitro carbonyl compounds, such as bioactive

• Michael addition reactions of acetylacetone and aromatic nitroalkenes. Results and Discussion Synthesis of catalysts The chemical structures and synthetic pathways for catalysts are shown in Scheme 1 and Scheme 2, respectively. A series of upper rim-functionalized calix[4]arene-based cyclohexanediamine

Recent applications of chiral calixarenes in asymmetric catalysis

• Mustafa Durmaz,
• Erkan Halay and
• Selahattin Bozkurt

Beilstein J. Org. Chem. 2018, 14, 1389–1412, doi:10.3762/bjoc.14.117

• 48 with nitroalkenes 49 (Scheme 13). The asymmetric Michael addition in the presence of 10–15 mol % of the macrocyclic catalysts 47a/47b afforded both enantiomers of the products 50 in high yields (up to 95%) and in high to excellent enantioselectivities (up to 99% ee). In order to confirm the role

• addition of 48 with 49 catalyzed by 47a and 47b. Enantioselective Michael addition of 51 to 52 catalyzed by calix[4]arene thioureas. Synthesis of calix[4]arene-based tertiary amine–thioureas 54–56. Asymmetric Michael addition of 34 and 57 to nitroalkenes 49 catalyzed by 54b. Synthesis of p-tert-butylcalix

Investigations towards the stereoselective organocatalyzed Michael addition of dimethyl malonate to a racemic nitroalkene: possible route to the 4-methylpregabalin core structure

• Denisa Vargová,
• Rastislav Baran and
• Radovan Šebesta

Beilstein J. Org. Chem. 2018, 14, 553–559, doi:10.3762/bjoc.14.42

• and pregabalin [9][10]. Later, hydrogen-bonding activation proved to be more general for obtaining Michael adducts via the addition of 1,3-dicarbonyl compounds to nitroalkenes. Chiral thioureas and squaramides, particularly those with the bifunctional mode of action, served as excellent catalysts in

• successful Michael additions to nitroalkenes in aqueous media [20][21], we have also tested the Michael addition of dimethyl malonate to nitroalkene 6 in brine. For this experiment, we have employed the more lipophilic organocatalyst C4, but the desired adduct 7 was formed only in small amount (14

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation and chlorination. Part 2: Use of CF₃SO₂Cl

• Hélène Chachignon,
• Hélène Guyon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2800–2818, doi:10.3762/bjoc.13.273

• -nitroalkenes with trifluoromethanesulfonyl chloride [39]. They found out that in the presence of the photocatalyst Eosin Y, under visible-light irradiation, such substrates could be selectively converted into (E)-1-trifluoromethylalkenes in moderate to good yields (Scheme 30). A plausible mechanism for this

• -nitroalkenes because of the lower stability of the radical intermediate 38 generated. The variation of stability of this species also explained the higher yields obtained with β-nitrostyrene derivatives substituted by electron-withdrawing groups. Trifluoromethylation of alkynes: o-Azidoarylalkynes also proved

• trifluoromethylation of (hetero)arenes under photoredox catalysis. Direct C–H trifluoromethylation of five- and six-membered ring (hetero)arenes using heterogeneous catalysis. Trifluoromethylation of terminal olefins. Trifluoromethylation of enamides. (E)-Selective trifluoromethylation of β-nitroalkenes under

Conjugated nitrosoalkenes as Michael acceptors in carbon–carbon bond forming reactions: a review and perspective

• Yaroslav D. Boyko,
• Valentin S. Dorokhov,
• Alexey Yu. Sukhorukov and
• Sema L. Ioffe

Beilstein J. Org. Chem. 2017, 13, 2214–2234, doi:10.3762/bjoc.13.220

• particular focus on recent developments in this methodology and its use in total synthesis. Keywords: carbon–carbon bond formation; Michael addition; nitrosoalkenes; oximes; total synthesis; Introduction Conjugated nitrosoalkenes (NSA) are close analogs of α-nitroalkenes, which are important Michael

• acceptors in organic synthesis [1][2][3][4][5]. Unlike the parent α-nitroalkenes, α-nitrosoalkenes are unstable species usually generated in situ, and their synthetic potential has been studied in significantly less detail [6][7]. Because of relatively short lifetimes of α-nitrosoalkenes, conjugate addition