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

• the α-position led to the desired products albeit with unsatisfactory results. The bifunctional squaramide catalyst V has two functions; firstly it deprotonates the enolic form of the azlactone through the Brønsted-base moiety, and secondly it activates the 1-azadiene and enolate form of the

• -azadienes bearing substituents at the ortho-position were tested, the enantioselectivities decreased, probably due to higher steric hindrance. The mechanism of the reaction is depicted in Scheme 7; firstly, the dual activation of the azadiene and the enol form of the azlactone through hydrogen bonding with

• the bifunctional squaramide enables a stereoselective Michael addition of the azlactone to the azadiene forming intermediate A which transforms into intermediate B, which then undergoes an intramolecular cyclization to give the desired product 20. In 2020, Ni, Song and co-workers described a

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

• transformation under asymmetric ammonium salt catalysis [35][36][37][38] and the results of these investigations are outlined in this contribution (Scheme 1C). Results and Discussion We started our investigations by testing the quaternary ammonium salt-catalyzed addition of azlactone 1a to allenoate 3a (Table 1

• be less-suited for our azlactone protocol, as exemplified for derivative C1 (Table 1, entry 9). Accordingly, we carried out our final optimization using Maruoka’s catalyst B2 (Table 1, entries 10–14). By testing different bases and lower temperatures as well as lower catalyst loadings we identified

• derivatives by means of nucleophilic azlactone-opening reactions. Gratifyingly primary amines can be easily utilized under reflux conditions to access the amide derivatives 6a and 6b straightforwardly (Scheme 3), thus demonstrating the versatility of compounds 5 to access more complex acyclic α-AA derivatives

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

• azlactone 146 skeletons. The presence of two heteroatom-bearing tetrasubstituted chiral carbon centers in a one-step fashion, avoiding the use of the heavy metal catalysts, and the performance of the reaction at ambient temperature are the prominent features of the protocol. Sahoo and co-workers found that

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

• when irradiated with UV light. Keywords: 5-aminopyrazole; azlactone; elimination; fluorescence; one-pot synthesis; pyrazolo[3,4-b]pyridin-6-one; Introduction The pyrazolo[3,4-b]pyridine scaffold is present in many biologically active compounds [1][2][3][4][5][6][7][8][9][10][11][12]. Among them, 4

• ]pyridones 3 obtained by this method vary widely [31][32][33]. Solvent-free reactions are convenient from both economic and environmental points of view. We obtained tetrahydro-1H-pyrazolo[3,4-b]pyridinone 3a by heating 5-aminopyrazole 1 with azlactone 2a in the absence of solvent at 150 °C in 62% yield

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

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

• and Mannich acceptors [20][21][22][23]. Enolate anions derived from azlactone are effective intermediates for the functionalization of α-amino acids. However, the acylation of the enolate ion by another azlactone has been less reported in the literature [24][25][26]. This transformation affords an

• azlactone dimer, which is a versatile heterocycle containing two stereogenic centers (Figure 1). Kobayashi and co-workers demonstrated the rich reactivity of azlactones conducting the dimerization reaction using strong bases as catalysts; however, higher temperatures and long reaction times were required

• diastereomer was assigned by X-ray analysis. Finally, one of the products was selectively reduced to provide a functionalized analogue of streptopyrrolidine, a marine natural product isolated from Streptomyces sp. As shown in Table 1, our studies started with the synthesis of dimer 2a using azlactone 1a in the

Synergistic chiral iminium and palladium catalysis: Highly regio- and enantioselective [3 + 2] annulation reaction of 2-vinylcyclopropanes with enals

• Haipan Zhu,
• Peile Du,
• Jianjun Li,
• Ziyang Liao,
• Guohua Liu,
• Hao Li and
• Wei Wang

Beilstein J. Org. Chem. 2016, 12, 1340–1347, doi:10.3762/bjoc.12.127

• and methyl vinyl ketone and α,β-unsaturated esters [44]. Trost and co-workers orchestrated the only example of the enantioselective reaction of D–A cyclopropanes with C=C double bonds with Meldrum’s acid and alkylidenes or azlactone alkylidenes, catalyzed by the chiral Trost Pd(0)-complexes [45

• promote these processes (Table 1, entries 3–7). Inspired by Trost’s work of Pd(0)-catalyzed annulations of D–A cyclopropanes with C=C double bonds with Meldrum’s acid and alkylidenes or azlactone alkylidenes [45], we probed the Pd2(dba)3-dppe complex for the 1,4-addition cycloaddition reaction (Table 1

(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

• transformation is initiated by a Michael addition of 158 to alkylidene azlactone 159, followed by a Mannich reaction and finally transesterification. The same year, Yuan and co-workers reported the double Michael reaction between 160 and alkylidene azlactone 161 to produce the spiro-fused cyclohexanone/5

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

• substitution of suitably-activated pyridine N-oxides by azlactone nucleophiles, followed by decarboxylative azlactone ring-opening. The synthesis obviates the need for precious metal catalysts to achieve a formal enolate arylation reaction, and constitutes a formally ‘umpoled’ approach to this valuable class

• 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

• the reaction of alanine-derived azlactone 6 with 4-methylpyridine N-oxide (7) we found that when water (in the form of 1 M HCl) was employed as a nucleophile, the product isolated was in fact the 2-(1-benzamidoethyl)-4-methylpyridine (8a), formed by facile decarboxylation of the intermediate

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

• base (Figure 1) [18][19]. This catalytic system was very effective but the reactions performed with (R)-Binap(AuOBz)2 (Figure 1) as catalyst offered a very low enantioselection, for example, a 8% ee was achieved in the 1,3-DC of alanine derived azlactone and N-phenylmaleimide (NPM). Numerous gold

• electrophilic alkenes using the bis-gold(I) complex 3 (where the gold atom:ligand ratio is 1:1, Figure 1) [25][26][27] inspired us to test it in this azlactone involved cycloaddition. Previous experience in the 1,3-DC between imino esters and electrophilic alkenes revealed that the dimeric chiral gold complex 3

• gold(I) catalyst, promoted the enantioselective reaction although with lower efficiency (Table 1, entries 17 and 18) [32]. The scope of the reaction was next surveyed. Firstly, azlactone 5a was allowed to react with several maleimides (Scheme 2, and Table 2, entries 1–10). NPM and 4