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

• reaction was further optimized using salicylaldehyde (1a), β-nitrostyrene (2a) and benzyl azide (3a) as model substrates (see Supporting Information File 1, pages S4–S8 for full description of the optimization study). The optimized conditions for the one-pot three-component reaction were determined to be 1

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

• the new chiral amino-substituted thioureas [33][39]. For this, the Michael addition reaction of acetylacetone (8) to β-nitrostyrene (7a) was chosen as the model reaction to evaluate the efficiency of compounds 1–4 as chiral organocatalysts (Table 1, entries 1–4). From Table 1, it can be seen that the

• nitrostyrene 7a lacking substituents has minimal steric hindrance and tends to bind with the calixarene cavity by supramolecular host–guest interactions which could further improve the enantioselectivity. In addition, electronic effects of the substituents on the aromatic ring showed a significant influence on

• the groups present on the aromatic ring. We propose the following plausible synergistic catalytic mechanism (Scheme 3). First, the two oxygen atoms of the nitro group in the nitrostyrene are activated through double hydrogen bonding with the thiourea group, while the benzene ring is held by a

Recent advances in hypervalent iodine(III)-catalyzed functionalization of alkenes

• Xiang Li,
• Pinhong Chen and
• Guosheng Liu

Beilstein J. Org. Chem. 2018, 14, 1813–1825, doi:10.3762/bjoc.14.154

• -deficient unsaturated carbonyl compounds (Scheme 13). In general, terminal alkenes were found to undergo 1,2-difluorination 42a–c. The reaction of internal alkenes usually afforded the syn-difluorination products 42d and 42e. However, the opposite result was observed in the reaction of the o-nitrostyrene

Aminomethylation/hydrogenolysis as an alternative to direct methylation of metalated isoquinolines – a novel total synthesis of the alkaloid 7-hydroxy-6-methoxy-1-methylisoquinoline

• Benedikt C. Melzer,
• Jan G. Felber and
• Franz Bracher

Beilstein J. Org. Chem. 2018, 14, 130–134, doi:10.3762/bjoc.14.8

• -benzyloxyphenethylamine, which gave the 7-O-benzyl derivative of alkaloid 1 in 27% yield. The required precursor is available from commercially available precursor 2 via a nitrostyrene intermediate in three steps in 45% overall yield [13]. In conclusion, no efficient approach to this “simple” alkaloid 1 has yet been

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 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

Synthesis of new pyrrolidine-based organocatalysts and study of their use in the asymmetric Michael addition of aldehydes to nitroolefins

• Alejandro Castán,
• Ramón Badorrey,
• José A. Gálvez and
• María D. Díaz-de-Villegas

Beilstein J. Org. Chem. 2017, 13, 612–619, doi:10.3762/bjoc.13.59

• the reaction of trans-β-nitrostyrene with 3-phenylpropionaldehyde in order to determine the influence that the relative configuration of the pyrrolidine had on the results (Table 1). The reaction was initially carried out at room temperature in the presence of 10 mol % of the catalyst and using CH2Cl2

• trans-β-nitrostyrene and 3-phenylpropionaldehyde promoted by OC4 (Table 4). When thioureas were used as additives the reaction was performed in toluene in order to improve the solubility. The addition of benzoic or acetic acid increased the reactivity and anti-enantioselectivity but it was detrimental

• were less reactive and the reaction temperature had to be increased. Linear aliphatic aldehydes reacted with β-nitrostyrene to provide the Michael adducts in good yields when the reaction was conducted at room temperature. The diastereoselectivity was moderate to good (dr = 79:21–95:5) in favour of the

Continuous-flow synthesis of primary amines: Metal-free reduction of aliphatic and aromatic nitro derivatives with trichlorosilane

• Riccardo Porta,
• Alessandra Puglisi,
• Giacomo Colombo,
• Sergio Rossi and
• Maurizio Benaglia

Beilstein J. Org. Chem. 2016, 12, 2614–2619, doi:10.3762/bjoc.12.257

• obtained in quantitative yield as a clean product with no need for purification. We also investigated the continuous-flow reduction of nitro ester 5, which can be conveniently prepared in one step through the organocatalyzed addition of diethyl malonate to trans-β-nitrostyrene promoted by a chiral thiourea

1H-Imidazol-4(5H)-ones and thiazol-4(5H)-ones as emerging pronucleophiles in asymmetric catalysis

• Antonia Mielgo and
• Claudio Palomo

Beilstein J. Org. Chem. 2016, 12, 918–936, doi:10.3762/bjoc.12.90

• demonstrated to be either less reactive and/or less stereoselective in their addition reaction to nitrostyrene thus affording the corresponding Michael adducts with no diastereoselectivity and/or poor enantioselectivity (Scheme 3). Useful applications of the Michael adducts coming from the Michael addition of

• doesn’t change after the addition of nitrostyrene. 1.2.2 α-Silyloxyenones as acceptors. Among Michael acceptors, simple α,β-unsaturated esters and amides still are challenging substrates in direct Michael additions and have only been employed in few successful Michael reactions, mainly due to their

• -deoxyhydroquinine (Scheme 9). These catalysts were tested in the reaction between 5-methylthiazolone 49 and nitrostyrene (Scheme 10) and after optimization catalyst C5 was found to be the optimal for this transformation. A representative selection of nitroalkenes was then evaluated in the presence of catalyst C5

Stereoselective amine-thiourea-catalysed sulfa-Michael/nitroaldol cascade approach to 3,4,5-substituted tetrahydrothiophenes bearing a quaternary stereocenter

• Sara Meninno,
• Chiara Volpe,
• Giorgio Della Sala,
• Amedeo Capobianco and
• Alessandra Lattanzi

Beilstein J. Org. Chem. 2016, 12, 643–647, doi:10.3762/bjoc.12.63

• diastereoisomeric tetrahydrothiophenes were observed when using tertiary amines such Et3N, DBU or TMG [21][22]. At the outset, the sulfa-Michael/nitroaldol reaction was studied by reacting trans-β-nitrostyrene, (E)-1-phenyl-2-nitropropene and (E)-1-phenyl-2-nitrobutene in toluene at room temperature with 1,4

• -dithiane-2,5-diol as precursor of mercaptoacetaldehyde, using 10 mol % loading of different bifunctional organocatalysts (Scheme 1, Table 1). In the case of trans-β-nitrostyrene (1), a mixture of diastereoisomers 5 and 6 were rapidly formed, irrespective of the catalyst used, with a poor level of diastereo

Supported bifunctional thioureas as recoverable and reusable catalysts for enantioselective nitro-Michael reactions

• José M. Andrés,
• Miriam Ceballos,
• Alicia Maestro,
• Isabel Sanz and
• Rafael Pedrosa

Beilstein J. Org. Chem. 2016, 12, 628–635, doi:10.3762/bjoc.12.61

• bifunctional thioureas on sulfonylpolystyrene resins has been studied in the nitro-Michael addition of different nucleophiles to trans-β-nitrostyrene derivatives. The activity of the catalysts depends on the length of the tether linking the chiral thiourea to the polymer. The best results were obtained with

• first tested in the reaction of trans-nitrostyrene (1a) with diethyl malonate (2a), leading to the enantioenriched addition product 4aa with a single stereocenter. In order to the creation of two tertiary-quaternary contiguous stereocenters (5aa) we also used ethyl 2-oxocyclopentanecarboxylate (3a) as

• conditions, supported catalyst V, which differs from IV in the substitution pattern of the sulfonamide, was the best catalyst for the addition of both 2a and 3a to nitrostyrene, yielding products 4aa and 5aa, respectively, in much better yield maintaining the stereoselectivity in shorter reaction time

The aminoindanol core as a key scaffold in bifunctional organocatalysts

• Isaac G. Sonsona,
• Eugenia Marqués-López and
• Raquel P. Herrera

Beilstein J. Org. Chem. 2016, 12, 505–523, doi:10.3762/bjoc.12.50

• to explain the sense of the asymmetric induction observed in the reaction, some experiments with structurally modified catalysts (4' and 4'') were carried out. The results obtained using indole (2a) and β-nitrostyrene (3a) supported the importance of the hydroxy group, since low yield and selectivity

• catalyst, in its Z form, which is stabilized due to an intramolecular hydrogen bond (Scheme 14). In 2012, Dong and co-workers studied the catalytic activity of several β-amino alcohol-based squaramide organocatalysts involved in the Michael addition of acetylacetone (36a) to β-nitrostyrene (3a) in

• dichloromethane at 15 °C (Scheme 15) [48]. Although high yields were obtained in all cases, the best enantioselectivity was provided by the bifunctional cis-aminoindanol-based squaramide 43. Under these conditions, several 1,3-dicarbonyl compounds 36 reacted with many different nitrostyrene derivatives 3 with

(Thio)urea-mediated synthesis of functionalized six-membered rings with multiple chiral centers

• Giorgos Koutoulogenis,
• Nikolaos Kaplaneris and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2016, 12, 462–495, doi:10.3762/bjoc.12.48

• substrates were tested and the products were isolated in good yields, moderate diasteroselectivities and excellent enantioselectivities. To expand the utility of the developed process, Zhao and co-workers performed the reaction with trans-β-nitrostyrene in gram scale isolating the desired product in 74

• tandem Michael addition of γ,δ-unsaturated-β-ketoesters 114 to trans-β-nitrostyrene 115 which produced tetrasubstituted cyclohexenols 116 and 117 utilizing Takemoto’s catalyst 77 (Scheme 37) [56]. In a paper that described in more detail the transformation, the authors showed that the substitution of the

Organocatalytic and enantioselective Michael reaction between α-nitroesters and nitroalkenes. Syn/anti-selectivity control using catalysts with the same absolute backbone chirality

• Jose I. Martínez,
• Uxue Uria,
• Maria Muñiz,
• Efraím Reyes,
• Luisa Carrillo and
• Jose L. Vicario

Beilstein J. Org. Chem. 2015, 11, 2577–2583, doi:10.3762/bjoc.11.277

• . Results and Discussion We started our work by first applying the conditions optimized for our recently reported cascade process to the reaction between ethyl 2-nitropropanoate (1a) and β-nitrostyrene (2a). As it can be seen in Scheme 2, the use of catalyst 4 led to the formation of the syn-diastereoisomer

• the cases studied. In particular, when the reaction was conducted using nitrostyrene derivatives as Michael acceptors, the corresponding adducts 3a–k were isolated cleanly, in high yields, diastereo- and enantioselectivities regardless the electronic nature of the aromatic substituent of the

• nitrostyrene reagent. Indeed, the reaction using nitrostyrenes containing electron-donating groups at any of the position of the aryl ring led to the formation of the corresponding adducts (syn-3a–f) in excellent yield, good diastereoselectivities and enantiomeric excesses over 95% (Table 1, entries 2–6). When

Cathodic hydrodimerization of nitroolefins

• Michael Weßling and
• Hans J. Schäfer

Beilstein J. Org. Chem. 2015, 11, 1163–1174, doi:10.3762/bjoc.11.131

• in [6][7][8]. There have been reports on the reductive dimerization of nitro alkenes prior to 1991. 1,4-Dinitro-2,3-diphenylbutane (3) has been obtained in less than 20% yield in the catalytic hydrogenation of β-nitrostyrene (4) [11]. Hydrodimerization of 4 was observed in enzymatic reduction [12

• ]. Furthermore 3 was found in the reduction of 4 with TiCl3 [13][14]. High dimer yields are reported for the reduction of several nitro olefins with the dianion of cyclooctatetraene [15]. ß-Nitrostyrene (4) has been reductively dimerized with organomanganese reagents to 3 in low yield [16]. The electrochemical

Superoxide chemistry revisited: synthesis of tetrachloro-substituted methylenenortricyclenes

• Basavaraj M. Budanur and
• Faiz Ahmed Khan

Beilstein J. Org. Chem. 2014, 10, 2531–2538, doi:10.3762/bjoc.10.264

• , entry 13) and cyclooctene (Table 1, entry 15) have furnished DA adducts in excellent yields and good diastereoselectivity ~4:1 (anti:syn) in 6–15 h. Some dienophiles such as p-nitrostyrene (Table 1, entry 5), 4-vinylpyridine (Table 1, entry 10), chlorinated styrene (Table 1, entry 12) and acrylonitrile

A tandem Mannich addition–palladium catalyzed ring-closing route toward 4-substituted-3(2H)-furanones

• Jubi John,
• Eliza Târcoveanu,
• Peter G. Jones and
• Henning Hopf

Beilstein J. Org. Chem. 2014, 10, 1462–1470, doi:10.3762/bjoc.10.150

• ][35], Pd [36], Hg [37]), etc. Lately, organo-catalyzed asymmetric routes towards 3(2H)-furanones from 4-haloacetoacetates and nitrostyrene were reported by Lu et al. [38] and Yan et al. [39]. We have recently reported on a palladium-catalyzed tandem methodology for the synthesis of 4-substituted-3(2H

New hydrogen-bonding organocatalysts: Chiral cyclophosphazanes and phosphorus amides as catalysts for asymmetric Michael additions

• Helge Klare,
• Jörg M. Neudörfl and
• Bernd Goldfuss

Beilstein J. Org. Chem. 2014, 10, 224–236, doi:10.3762/bjoc.10.18

• catalysts based on rigid cis-PV-cyclodiphosphazane amides of N1,N1-dimethylcyclohexane-1,2-diamine have been developed. Employed in the asymmetric Michael addition of 2-hydroxynaphthoquinone to β-nitrostyrene, the open-chain 9-epi-aminochinchona-based phosphorus amides show a high catalytic activity with

• . DFT computations reveal high hydrogen-bonding strengths of cyclodiphosphazane PV-amides compared to urea-based catalysts. Experimental results and computations on the enantiodetermining step with cis-cyclodiphosphazane 14a suggest a strong bidentate H-bond activation of the nitrostyrene substrate by

• defined geometry. Introducing a new motif, Shea et al. have synthesized achiral tridentate (thio)phosphorus triamides and assessed their catalytic activity relative to the established (m-(CF3)2-Ph)2thiourea [18]. In the Friedel–Crafts reaction of N-methylindole with β-nitrostyrene and the Baylis–Hillman

Synthetic scope and DFT analysis of the chiral binap–gold(I) complex-catalyzed 1,3-dipolar cycloaddition of azlactones with alkenes

• María Martín-Rodríguez,
• Luis M. Castelló,
• Carmen Nájera,
• José M. Sansano,
• Olatz Larrañaga,
• Abel de Cózar and
• Fernando P. Cossío

Beilstein J. Org. Chem. 2013, 9, 2422–2433, doi:10.3762/bjoc.9.280

• irradiation was not as effective as occurred in the reaction with NMM. For example, the purification of the crude reaction mixture of the cycloaddition of 7aa with β-nitrostyrene afforded an overall poor yield (~28%) of a complex 4:15:10 mixture of three compounds (16, 17, and 18) (Scheme 9) [44]. The desired

• -butyl acrylate. Reduction of heterocycle 7aa under different conditions. Double 1,3-DC to give polycycle 15. Reaction between 7aa and nitrostyrene. Optimization of the 1,3-dipolar cycloaddition of 5a and NPM using chiral complexes. 1,3-Dipolar cycloaddition of azlactones 5a with maleimides. Supporting

Sequential Diels–Alder/[3,3]-sigmatropic rearrangement reactions of β-nitrostyrene with 3-methyl-1,3-pentadiene

• Peter A. Wade,
• Alma Pipic,
• Matthias Zeller and
• Panagiota Tsetsakos

Beilstein J. Org. Chem. 2013, 9, 2137–2146, doi:10.3762/bjoc.9.251

• Peter A. Wade Alma Pipic Matthias Zeller Panagiota Tsetsakos Department of Chemistry, Drexel University, Philadelphia, PA 19104, U.S.A Department of Chemistry, Youngstown State University, Youngstown, OH, U.S.A 10.3762/bjoc.9.251 Abstract The tin(IV)-catalyzed reaction of β-nitrostyrene with (E

• formal cycloadducts of (Z)-3-methyl-1,3-pentadiene. A Friedel–Crafts alkylation product from the reaction of the diene, β-nitrostyrene, and toluene was also obtained in 10% yield. The tin(IV)-catalyzed reaction of β-nitrostyrene with (Z)-3-methyl-1,3-pentadiene in dichloromethane afforded four nitronic

• Discussion Cycloaddition studies The tin(IV) chloride-catalyzed reaction of β-nitrostyrene and an E,Z–mixture of 3-methyl-1,3-pentadiene (1a,b, 70:30, respectively) in dichloromethane solution afforded a series of six Diels–Alder nitronic ester cycloadducts, none of which heavily predominated (Table 1). Only

Diastereoselective synthesis of nitroso acetals from (S,E)-γ-aminated nitroalkenes via multicomponent [4 + 2]/[3 + 2] cycloadditions promoted by LiCl or LiClO₄

• Leandro Lara de Carvalho,
• Robert Alan Burrow and
• Vera Lúcia Patrocinio Pereira

Beilstein J. Org. Chem. 2013, 9, 838–845, doi:10.3762/bjoc.9.96

• reaction promoter. These salts were chosen in particular because of their present high recyclability, low cost, and great applicability as promoters in cycloaddition processes [12][13][14][15][16][17]. Thus, the reactions between the very reactive beta-nitrostyrene 5d, used as a model compound, and the

A versatile and efficient approach for the synthesis of chiral 1,3-nitroamines and 1,3-diamines via conjugate addition to new (S,E)-γ-aminated nitroalkenes derived from L-α-amino acids

• Vera Lúcia Patrocinio Pereira,
• André Luiz da Silva Moura,
• Daniel Pais Pires Vieira,
• Leandro Lara de Carvalho,
• Eliz Regina Bueno Torres and
• Jeronimo da Silva Costa

Beilstein J. Org. Chem. 2013, 9, 832–837, doi:10.3762/bjoc.9.95

• -nitrostyrene and its phenyl-substituted analogues, besides the heteroaromatic nitroalkenes, have been employed widely in highly enantioselective syntheses promoted by chiral metallic catalysts [33][34][35][36][37] and most recently by a great number of different chiral organocatalysts [38][39][40][41] or

Mechanochemistry assisted asymmetric organocatalysis: A sustainable approach

• Pankaj Chauhan and
• Swapandeep Singh Chimni

Beilstein J. Org. Chem. 2012, 8, 2132–2141, doi:10.3762/bjoc.8.240

• ) under ball-milling (400 rpm) to provide an easy access to Michael adducts 10 in good to high yield (63–95%) and excellent enantioselectivity (91–99% ee). The chiral squaramide IX also catalyses the Michael reaction of β-ketoesters 11 with nitrostyrene to provide Michael adducts 12 in 73–95% yield, 1.4:1

• to 5.3:1 dr and 91–99% ee. The solvent-free ball-milling of dimethyl malonate with nitrostyrene in the presence of IX provides the corresponding Michael adduct in 80% yield and 91% ee. However, chiral squaramide catalysed Michael addition of dicarbonyl compounds to nitroalkenes in dichloromethane by

Organocatalytic tandem Michael addition reactions: A powerful access to the enantioselective synthesis of functionalized chromenes, thiochromenes and 1,2-dihydroquinolines

• Chittaranjan Bhanja,
• Satyaban Jena,
• Sabita Nayak and
• Seetaram Mohapatra

Beilstein J. Org. Chem. 2012, 8, 1668–1694, doi:10.3762/bjoc.8.191

• , respectively, via the generation of a transient ion pair through iminium and imine intermediates. The reaction afforded the corresponding tetrahydroxanthenones 14 in excellent yields (95%) and enantioselectivities (95%) (Scheme 10). 1.2. Reaction of 2-hydroxycinnamaldehydes/2-hydroxy-β-nitrostyrene with

• for constructing highly functionalized and enantiomerically enriched tetrahydro-6H-benzo[c]chromenes with five stereogenic centers. The reaction involved a domino oxa-Michael–Michael–Michael–aldol condensation of o-hydroxy-β-nitrostyrene 15 and two equivalents of α,β-unsaturated aldehydes in the

• cascade reaction starts in an analogous manner to that previously mentioned, although the first oxa-Michael step is followed by a second Michael addition to form the chroman unit. A series of α,β-unsaturated aldehydes were reacted with the o-hydroxy-β-nitrostyrene as shown in Scheme 11. Except for the

Synthesis and evaluation of new guanidine-thiourea organocatalyst for the nitro-Michael reaction: Theoretical studies on mechanism and enantioselectivity

• Tatyana E. Shubina,
• Matthias Freund,
• Sebastian Schenker,
• Timothy Clark and
• Svetlana B. Tsogoeva

Beilstein J. Org. Chem. 2012, 8, 1485–1498, doi:10.3762/bjoc.8.168

• Organic Chemistry I, University of Erlangen-Nuremberg, Henkestraße 42, 91054, Erlangen, Germany 10.3762/bjoc.8.168 Abstract A new guanidine-thiourea organocatalyst has been developed and applied as bifunctional organocatalyst in the Michael addition reaction of diethyl malonate to trans-β-nitrostyrene

• thiourea moiety and an imidazole group [43][44] on a chiral scaffold, as asymmetric catalysts in the addition of acetone to trans-β-nitrostyrene, have also been reported [44][45][46][47]. Since guanidines [48] are stronger bases than amines and/or imidazole, we were interested in exploring whether

• . However, guanidine-thiourea 7 gave the product 10 only in racemic form and in moderate yield (62%, Scheme 2). The Michael additions of 2,4-pentanedione and diethylmalonate to trans-β-nitrostyrene were further explored (Scheme 3). The use of guanidine-thiourea 7 at 20 mol % in toluene at room temperature

A quantitative approach to nucleophilic organocatalysis

• Herbert Mayr,
• Sami Lakhdar,
• Biplab Maji and
• Armin R. Ofial

Beilstein J. Org. Chem. 2012, 8, 1458–1478, doi:10.3762/bjoc.8.166

• -nitrostyrene (E = –13.9) [85] or di-tert-butyl azodicarboxylate (E = –12.2) [86]. The less basic imidazolidinones, which yield the less nucleophilic enamines 32d and 32e, are suitable catalysts for reactions with stronger electrophiles, such as the chlorinating agent 2,3,4,5,6,6-hexachlorocyclohexan-2,4-dien-1

• of the C–C bond. The observation that β-nitrostyrene, a neutral electrophile, also reacts 102 times faster with 33– than with 36 also excludes Coulomb attraction to be the major factor for the high reactivity of 33−. On the other hand, di-tert-butyl azodicarboxylate reacts only six times faster with