New advances in asymmetric organocatalysis II

• Radovan Šebesta

Beilstein J. Org. Chem. 2025, 21, 766–769, doi:10.3762/bjoc.21.60

• contributions in stereoselective organocatalytic transformations. The collection contains nine articles featuring various aspects of asymmetric organocatalysis. In the first contribution, Waser et al. examined how chiral phase-transfer catalysts promote β-selective additions of azlactones to allenoates. Maruoka

• ´s quaternary ammonium salts provided the corresponding substituted azlactones comprising a quaternary stereogenic center with the highest enantiomeric purity [21]. A contribution by Chowdhury and Dubey further underscored the importance of heterocyclic moieties in chiral compounds. Their article

Non-covalent organocatalyzed enantioselective cyclization reactions of α,β-unsaturated imines

• Sergio Torres-Oya and
• Mercedes Zurro

Beilstein J. Org. Chem. 2024, 20, 3221–3255, doi:10.3762/bjoc.20.268

• furnish the cycloaddition product 13a. In 2019, Xu’s group published a bifunctional squaramide-catalyzed inverse electron demand aza-Diels–Alder reaction of saccharin-derived 1-azadienes 14 and azlactones 15 [27]. This methodology enables chiral tricyclic derivatives 16 bearing a quaternary amino acid

• moiety in up to 99% yields, up to 93% ee and >20:1 dr (Scheme 5) to be obtained. In general, the steric and electronic properties of the conjugated imines had a slight effect on the enantioselectivities of the reactions. However, the authors pointed out that the azlactones with different substituents at

• azlactones through H-bond interactions with the squaramide moiety. The activated complex undergoes a [4 + 2] cyclization, through the Si-face attack of the enolate to the 1-azadiene leading to intermediate A which undergoes tautomerization and protonation to yield the chiral tricyclic derivative 16. To

Towards an asymmetric β-selective addition of azlactones to allenoates

• Behzad Nasiri,
• Ghaffar Pasdar,
• Paul Zebrowski,
• Katharina Röser,
• David Naderer and
• Mario Waser

Beilstein J. Org. Chem. 2024, 20, 1504–1509, doi:10.3762/bjoc.20.134

• , Iran 10.3762/bjoc.20.134 Abstract We herein report the asymmetric organocatalytic addition of azlactones to allenoates. Upon using chiral quaternary ammonium salt catalysts, i.e., Maruoka’s binaphthyl-based spirocyclic ammonium salts, the addition of various azlactones to allenoates proceeds in a β

• -selective manner with moderate levels of enantioselectivities (up to 83:17 er). Furthermore, the obtained products can be successfully engaged in nucleophilic ring opening reactions, thus giving highly functionalized α-amino acid derivatives. Keywords: allenoates; amino acids; azlactones; organocatalysis

• -functionalizations by reacting them with suited C- or heteroatom electrophiles. α-Amino acid-derived azlactones 1 are amongst the most commonly utilized starting materials to access more diverse chiral α,α-disubstituted amino acids (Scheme 1A) [20][21][22]. More specifically, these compounds can be engaged in a

Catalytic multi-step domino and one-pot reactions

• Svetlana B. Tsogoeva

Beilstein J. Org. Chem. 2024, 20, 254–256, doi:10.3762/bjoc.20.25

• -aminopyrazoles with azlactones under solvent-free conditions, through subsequent elimination of a benzamide molecule in a superbasic medium, is described by the Fisyuk group [13]. A further facile one-pot process toward a new series of copper(II) benzo[f]chromeno[2,3-h]quinoxalinoporphyrin analogues is described

N-Sulfenylsuccinimide/phthalimide: an alternative sulfenylating reagent in organic transformations

• Fatemeh Doraghi,
• Seyedeh Pegah Aledavoud,
• Mehdi Ghanbarlou,
• Bagher Larijani and
• Mohammad Mahdavi

Beilstein J. Org. Chem. 2023, 19, 1471–1502, doi:10.3762/bjoc.19.106

• reduction of II by silane. On the other hand, most of II were converted to intermediate III, which underwent hydride reduction to render product 140 (Scheme 61). Another organocatalysis system was disclosed by Liu and co-workers for sulfenylation of α-fluoro-β-ketoamides 143 and azlactones 145 (Scheme 62

New one-pot synthesis of 4-arylpyrazolo[3,4-b]pyridin-6-ones based on 5-aminopyrazoles and azlactones

• Vladislav Yu. Shuvalov,
• Ekaterina Yu. Vlasova,
• Tatyana Yu. Zheleznova and
• Alexander S. Fisyuk

Beilstein J. Org. Chem. 2023, 19, 1155–1160, doi:10.3762/bjoc.19.83

• Ave., 55a, 644077 Omsk, Russian Federation 10.3762/bjoc.19.83 Abstract An effective one-pot strategy was developed for the synthesis of 4-arylpyrazolo[3,4-b]pyridin-6-ones from pyrazolo[3,4-b]pyridin-6-ones, obtained by reacting 5-aminopyrazoles with 4-arylidene-2-phenyloxazol-5(4H)-ones (azlactones

• domino reaction of enamines with azlactones [22][23][24][25][26][27][28][29][30]. We have previously reported a plausible mechanism of such reactions [22][25]. 1H-Pyrazol-5-amines also enter into similar transformations with azlactones in various solvents. The yields of tetrahydro-1H-pyrazolo[3,4-b

• -aminopyrazoles 1, 5, 6 and azlactones 2a–i, followed by heating the resulting intermediate in DMSO in the presence of t-BuOK. Photophysical properties of the obtained compounds were studied. Biologically active 4-arylpyrazolo[3,4-b]pyridin-6-ones. Normalized absorption and fluorescence spectra of solutions of

Recent advances in the asymmetric phosphoric acid-catalyzed synthesis of axially chiral compounds

• Alemayehu Gashaw Woldegiorgis and
• Xufeng Lin

Beilstein J. Org. Chem. 2021, 17, 2729–2764, doi:10.3762/bjoc.17.185

• -trifluoromethylpropargyl alcohol are very important for the reaction. Li and co-workers developed a chiral phosphoric acid-catalyzed asymmetric remote 1,8-conjugate addition of thiazolones 111 and azlactones 112 to propargyl alcohols 110 for the synthesis of the chiral allenes 113 and 114, respectively. In the presence of

• diastereoselectivity (10:1 to >20:1 dr). In addition, the enantioselective 1,8-conjugate addition of azlactones 112 to para-quinone methides generated in situ from propargyl alcohols 110 were carried out in the presence of 1 mol % chiral phosphoric acid CPA 7 and afforded the chiral allenes 114 in high yields (65–97

• reaction. Moreover, both electron-withdrawing and donating groups on the aromatic rings of propargyl alcohols or azlactones smoothly participated in the asymmetric 1,8-conjugate addition and afforded the corresponding chiral allenes in good yields with high enantioselectivity. The control experiments

Enantioenriched α-substituted glutamates/pyroglutamates via enantioselective cyclopropenimine-catalyzed Michael addition of amino ester imines

• Zara M. Seibel,
• Jeffrey S. Bandar and
• Tristan H. Lambert

Beilstein J. Org. Chem. 2021, 17, 2077–2084, doi:10.3762/bjoc.17.134

• achieved [31], Michael reactions with these nucleophiles have met with limited success [32][33][34][35][36][37][38][39]. In terms of enantioselective catalytic strategies, Kobayashi has reported the conjugate addition of azlactones to acrylates using a calcium pybox complex, but with enantioselectivities

Asymmetric organocatalyzed synthesis of coumarin derivatives

• Natália M. Moreira,
• Lorena S. R. Martelli and
• Arlene G. Corrêa

Beilstein J. Org. Chem. 2021, 17, 1952–1980, doi:10.3762/bjoc.17.128

• cascade synthesis of hydrocoumarin 78 mediated by squaramide catalyst with 9-amino-9-deoxy-epi-quinine moiety 73 was reported by Albrecht et al. [59]. In this transformation, the authors developed a Michael addition of azlactones to 2-hydroxychalcones 76 followed by the opening of the azlactone 77 ring to

Synthesis of esters of diaminotruxillic bis-amino acids by Pd-mediated photocycloaddition of analogs of the Kaede protein chromophore

• Esteban P. Urriolabeitia,
• Pablo Sánchez,
• Alexandra Pop,
• Cristian Silvestru,
• Eduardo Laga,
• Ana I. Jiménez and
• Carlos Cativiela

Beilstein J. Org. Chem. 2020, 16, 1111–1123, doi:10.3762/bjoc.16.98

• ortho-position of the 2,4-aryl rings in the resulting bis-amino acids can be functionalized [30]. Substrates of the (Z)-4-arylidene-2((E)-styryl)-5(4H)-oxazolone type, shown in Figure 2b, are interesting starting materials for the synthesis of new 1,3-diaminotruxillic derivatives. These azlactones are

A Brønsted base-promoted diastereoselective dimerization of azlactones

• Danielle L. J. Pinheiro,
• Gabriel M. F. Batista,
• Pedro P. de Castro,
• Leonã S. Flores,
• Gustavo F. S. Andrade and
• Giovanni W. Amarante

Beilstein J. Org. Chem. 2017, 13, 2663–2670, doi:10.3762/bjoc.13.264

• Brønsted base system for the diastereoselective dimerization of azlactones using trichloroacetate salts and acetonitrile has been developed. Desired products were obtained in good yields (60–93%) and with up to >19:1 dr after one hour of reaction. Additionally, the relative stereochemistry of the major

• analogue of streptopyrrolidine was accomplished in 65% overall yield. Keywords: azlactones; dimerization; diasteoreselective synthesis; kinetics; streptopyrrolidine analogue; Findings Azlactones have been acknowledged as a common nucleophilic reagent to introduce a quaternary carbon stereocenter in the α

• -position of α-amino acid derivatives. To this end, different catalytic transformations involving azlactones have been established [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19]. For example, our research group has explored the potential of these heterocycles in the presence of Michael

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

• their pKa values (approximately 19 in DMSO) [19] are much higher, one exception being thioesters [20][21] and pyrazoleamides [22]. As an alternative, some specific heterocycles have been proposed as carboxylic acid surrogates. Examples of this type of heterocycles are oxazol-5-(4H)-ones (or azlactones

• be easily hydrolyzed to provide carboxylic acids or their derivatives carrying different functionalities. The most common pronucleophiles of this type are oxazol-5-(4H)-ones or azlactones (Figure 1a, X = O), which have been thoroughly investigated and reviewed [23][24][25]. On the other hand, since

• ]. The main advantages of these pronucleophiles over the previous known templates are: i) the NR group can be installed in the heterocycle previous to the asymmetric reaction, ii) they are easily deprotonated under soft enolization conditions (aromatic enolate formation), and iii) unlike azlactones and

(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

• bifunctional thiourea 57 [55]. A wide range of azlactones 112 were tested, as well as a plethora of o-hydroxychalcone derivatives 111, providing the products in good to excellent yield and good to excellent stereoselectivity (Scheme 36). The authors proposed that azlactones are deprotonated by the tertiary

Cupreines and cupreidines: an established class of bifunctional cinchona organocatalysts

• Laura A. Bryant,
• Rossana Fanelli and
• Alexander J. A. Cobb

Beilstein J. Org. Chem. 2016, 12, 429–443, doi:10.3762/bjoc.12.46

• methanol bridge, explaining the need for this as an additive within the reaction to give optimal stereoselectivities. Similarly, Xu and co-workers have used β-ICPD in the cycloaddition between isatin framework 87 and olefinic azlactones 88 to give adduct 89 (Scheme 21b) [64]. Finally, in a remarkable

A convergent, umpoled synthesis of 2-(1-amidoalkyl)pyridines

• Tarn C. Johnson and
• Stephen P. Marsden

Beilstein J. Org. Chem. 2016, 12, 1–4, doi:10.3762/bjoc.12.1

• of bioactive structures. Keywords: azlactones; pyridines; pyridine N-oxides; substitution; Introduction Pyridines constitute the most frequently observed class of heterocycles found in pharmaceutical products [1]. As such, there is significant demand for synthetic methods that enable access both to

• readily-available azlactones and pyridine N-oxides in the presence of p-toluenesulfonyl chloride as an activating agent, followed by opening of the arylated azlactone intermediate with nucleophiles such as alcohols, primary and secondary amines, and N,O-dialkylhydroxylamines [21] (Scheme 1). However, in

• methods. Given the ready availability of azlactones bearing differential functionality at C2 and C4, a wide range of 2-(1-amidoalkyl)pyridines should become available and we elected to exemplify this process. Substrate scope We first examined variation of azlactone substituents in their reaction with 4

Chiral phosphines in nucleophilic organocatalysis

• Yumei Xiao,
• Zhanhu Sun,
• Hongchao Guo and
• Ohyun Kwon

Beilstein J. Org. Chem. 2014, 10, 2089–2121, doi:10.3762/bjoc.10.218

• /alcoholysis reaction. Alkylidene azlactones, among the most widely used starting materials for the syntheses of quaternary amino acids, were cyclized with ethyl allenoate and, subsequently, alcoholyzed in situ to afford highly functionalized, optically active amino esters in moderate to good yields and with

• many have been applied in medicine and other fields. Using the axially chiral spirophosphine D1, Shi and co-workers accomplished highly regioselective, diastereoselective, and enantioselective [3 + 2] annulations of a series of alkylidene azlactones with allenoates (Scheme 18) [49]. Under mild

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

• , Universidad del País Vasco, Apdo. 1072, E-20018 San Sebastián, Spain IKERBASQUE, Basque Foundation for Science, 48011 Bilbao, Spain 10.3762/bjoc.9.280 Abstract The 1,3-dipolar cycloaddition between glycine-derived azlactones with maleimides is efficiently catalyzed by the dimeric chiral complex [(Sa

• (azlactones) are suitable heterocycles to perform this C–C bond generation based strategy affording both quaternized and non quaternized α-amino acid derivatives [2][3][4][5]. The preparation of azlactones is very simple and their reactivity is very diverse due to their functional groups [2][3][4][5]. Many

• electrophilic alkenes have not been exploited. Toste´s group published an efficient 1,3-dipolar cycloaddition (1,3-DC) between alanine, phenylalanine and allylglycine derived azlactones with maleimides and acrylates employing dimetallic (S)-Cy-Segphos(AuOBz)2 complex 1 as a catalyst (2 mol %) in the absence of

Chiral gold(I) vs chiral silver complexes as catalysts for the enantioselective synthesis of the second generation GSK-hepatitis C virus inhibitor

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

Beilstein J. Org. Chem. 2011, 7, 988–996, doi:10.3762/bjoc.7.111

• been so extensively explored. Reports of chiral transformations involving azlactones [32][33] and iminoesters 6 [34], which employed chiral diphosphines and gold(I) salts, have been published showing very good endo-diastereoselectivities and moderate to excellent enantioselectivities. However, the use