Preparation of a furfural-derived enantioenriched vinyloxazoline building block and exploring its reactivity

• Madara Darzina,
• Anna Lielpetere and
• Aigars Jirgensons

Beilstein J. Org. Chem. 2025, 21, 1737–1741, doi:10.3762/bjoc.21.136

• reactions. Out of these, the aza-Diels–Alder reaction with TsNCO was successful, leading to a highly diastereoselective formation of an oxazolo[3,2-c]pyrimidine derivative. Keywords: aza-Diels–Alder reaction; electrosynthesis; furfural; valinol; vinyloxazoline; Introduction The utilization of biomass as

• -6 is a good substrate for an aza-Diels–Alder reaction with tosylisocyanate (TsNCO) providing the oxazolo[3,2-c]pyrimidine derivative 7 as the only detectable diastereomer (Scheme 6) [22][23][24]. Oxazolo[3,2-c]pyrimidines are substructures in several pharmaceutically relevant compounds such as

• potent gonadotropin-releasing hormone receptor antagonists with potential application as anticancer drugs [25] and as nucleoside analogs with antiviral potency [26]. According to the reaction mechanism proposed by Elliott et al., the aza-Diels–Alder reaction of vinyloxazoline S-6 with TsNCO is a step

Formaldehyde surrogates in multicomponent reactions

• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Bernhard Westermann

Beilstein J. Org. Chem. 2025, 21, 564–595, doi:10.3762/bjoc.21.45

• such as an aza-Prins cyclization [23] and aza-Diels–Alder reaction [24], where MMS serves as direct source of the methylene (-CH2-) group (Scheme 5b). In both cases, the resulting reactive species (MMS or formaldehyde) can participate as electrophilic component in several MCRs as C1 building block

• this context, quinoline and its derivatives are privileged structures in several natural products and biologically active compounds, rendering this scaffold an important synthetic target. An attractive strategy to afford tetrahydroquinolines and quinolines is the Povarov reaction, a type of aza-Diels

• –Alder reaction between an imine and an alkene (Scheme 6). Very successfully, the multicomponent version of the Povarov reaction using aldehydes, anilines, and alkenes has been explored in a three-component cascade reaction to quinolines [28][29][30][31] (Scheme 6). Furthermore, protocols have been

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

• is plausible to assume as the key step for ring formation an aza-Diels–Alder reaction between the alkyne and the imine generated by dehydration between the aldehyde and aniline. The catalyst promotes the formation of the imine XI, while the high regioselectivity is ascribable to the favored

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

• imines; asymmetric organocatalysis; cyclization; N-heterocycles; inverse electron demand aza-Diels–Alder reaction; Introduction Nitrogen-containing heterocycles are abundant scaffolds present in natural products, biologically active compounds, pharmaceuticals, synthetic agrochemicals, and functional

• , they can be attacked by a nucleophile and undergo a 1,2-addition or conjugate addition leading to the production of allylic amines or aliphatic imines, respectively. They can also behave as C4 synthons in cycloaddition reactions such as the aza-Diels–Alder reaction, giving access to nitrogen-containing

• their structure will be described. In 2012, Wang and co-workers reported a bifunctional thiourea-catalyzed aza-Diels–Alder reaction of cyclic keto/enolate salts 1 and N-tosyl-2-methylene-but-3-enoates 2 (Scheme 1). After a screening of the reaction conditions they found that organocatalyst I, acetic

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

• methyl ester 120 in four steps (Scheme 39) [73]. The organocatalytic properties of this inherently chiral calixarene Brønsted acid was firstly examined in the aza-Diels–Alder reaction of imines bearing electron-withdrawing or electron-donating substituents 122 with Danishefsky’s diene (123, Scheme 40

Addition of dithi(ol)anylium tetrafluoroborates to α,β-unsaturated ketones

• Yu-Chieh Huang,
• An Nguyen,
• Simone Gräßle,
• Sylvia Vanderheiden,
• Nicole Jung and
• Stefan Bräse

Beilstein J. Org. Chem. 2018, 14, 515–522, doi:10.3762/bjoc.14.37

• -dithioacetals [4] are of particular interest as attractive nucleophiles for the addition to halonium ions [5][6], acyl chlorides [7] and other electrophiles [8][9][10] and are broadly used as precursors for [2 + 2]-cycloaddition [11][12], (aza)-Diels–Alder reaction [13][14], and [3 + 2]-cycloaddition reactions

5-Aminopyrazole as precursor in design and synthesis of fused pyrazoloazines

• Ranjana Aggarwal and
• Suresh Kumar

Beilstein J. Org. Chem. 2018, 14, 203–242, doi:10.3762/bjoc.14.15

• CaCO-2. Lin et al. [52] developed the synthesis of pyrazolo[3,4-b]pyridine derivatives 45 via aza-Diels–Alder reaction of pyrazolylimines 43 with maleimides 44 (Scheme 8). Pyrazolylimines 43 were in turn obtained from the reaction of 5-aminopyrazole 16 with diisopropylformamide dimethyl acetal (R

Reagent-controlled regiodivergent intermolecular cyclization of 2-aminobenzothiazoles with β-ketoesters and β-ketoamides

• Irwan Iskandar Roslan,
• Kian-Hong Ng,
• Gaik-Khuan Chuah and
• Stephan Jaenicke

Beilstein J. Org. Chem. 2017, 13, 2739–2750, doi:10.3762/bjoc.13.270

• -Diels–Alder reaction [87]. Coupling between alkynoic acid and 2-aminobenzothiazole and the use of ionic liquids have also been developed [88]. Heterogeneous catalysts such as kaolin and hydrotalcites have been employed in the synthesis of benzo[4,5]thiazolo[3,2-a]pyrimidin-4-ones [89][90

• been found to be biologically active antagonists of adenosine receptors [82], inhibitors of cyclic-AMP-diphosphoesterase [83], and benzodiazepine receptor ligands [84][85]. Reported methods to access this structural motif include annulation between an aromatic amine and acid chloride [86] or via aza

New approaches to organocatalysis based on C–H and C–X bonding for electrophilic substrate activation

• Pavel Nagorny and
• Zhankui Sun

Beilstein J. Org. Chem. 2016, 12, 2834–2848, doi:10.3762/bjoc.12.283

• atoms covalently bonded to a benzylic carbon (Scheme 8). In 2016 Maruoka and Shirakawa followed up the aforementioned studies by demonstrating that tetraalkylammonium salts L5, L6, L11 and L12 as well as TBAI could activate imines toward aza-Diels–Alder reaction with Danishefsky’s diene (Scheme 9) [51

• coordinating TfO− anion did not accelerate the cycloaddition. In 2015, Takeda, Minakata and co-workers demonstrated that 2-iodoimidazolium salt L24 could serve as an efficient catalyst of the aza-Diels−Alder reaction of aldimines and Danishefsky diene (Scheme 19) [90]. Other organohalides such as

• bond-donor catalysts by Bibal and co-workers [53][54]. Tetraalkylammonium catalyst (L6)-catalyzed dearomatization of isoquinolinium salts [50]. Tetraalkylammonium catalyst L6 complexation to halogen-containing substrates [51]. Tetraalkylammonium-catalyzed aza-Diels–Alder reaction by Maruoka and co

(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

• a variety of transformations. Utilizing the primary amine-thiourea 18, an enantioselective formal aza-Diels–Alder reaction of enones 12 and 13 was reported. In this reaction the enamine is formed from the side of the methyl ketone, which is conjugated with the pre-existing double bond, providing the

• electron-rich diene, which reacts with substituted dihydroisoquinoline 14 and dihydro-β-carboline 15, so that cyclohexanone derivatives 16 and 17 will be produced, respectively (Scheme 8) [19]. Also, a cyclic derivative of 13 was utilized (not shown). This aza-Diels–Alder reaction provides products with

• cycloalkanones using catalyst 11 [18]. The enantioselective synthesis of indolo- and benzoquinolidine compounds through aza-Diels–Alder reaction of enones with cyclic imines [19]. Enantioselective [5 + 2] cycloaddition [20]. Asymmetric synthesis of oxazine derivatives 26 [21]. Asymmetric synthesis of bicyclo

Aza-Diels–Alder reaction between N-aryl-1-oxo-1H-isoindolium ions and tert-enamides: Steric effects on reaction outcome

• Amitabh Jha,
• Ting-Yi Chou,
• Zainab ALJaroudi,
• Bobby D. Ellis and
• T. Stanley Cameron

Beilstein J. Org. Chem. 2014, 10, 848–857, doi:10.3762/bjoc.10.81

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265

• R-(+) form, the S-(−) form or the racemate leading to the conclusion that an enantioselective synthesis leading to solely S-(−)-amlodipine would be beneficial only if economically feasible [67]. An alternative strategy to this molecule begins with an interesting aza-Diels–Alder reaction between the

Asymmetric Brønsted acid-catalyzed aza-Diels–Alder reaction of cyclic C-acylimines with cyclopentadiene

• Magnus Rueping and
• Sadiya Raja

Beilstein J. Org. Chem. 2012, 8, 1819–1824, doi:10.3762/bjoc.8.208

• Magnus Rueping Sadiya Raja Institute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, D-52074 Aachen, Germany 10.3762/bjoc.8.208 Abstract A new chiral Brønsted acid-catalyzed aza-Diels–Alder reaction of cyclic C-acylimines with cyclopentadiene has been developed. The reaction provides

• optically active aza-tetracycles in good yields with high diastereo- and enantioselectivities under mild reaction conditions. Keywords: BINOL phosphate; [4 + 2] cycloaddition; Diels–Alder reaction; organocatalysis; Introduction The enantioselective aza-Diels–Alder reaction is an important method for the

• chiral Lewis acids [5][6][7][8][9][10][11][12][13][14][15][16]. Recently, chiral Brønsted acids have attracted interest as effective catalysts for a variety of asymmetric transformations involving imine electrophiles [17][18][19][20][21][22][23]. Among others, the aza-Diels–Alder reaction of imino

Imidazolinium and amidinium salts as Lewis acid organocatalysts

• Oksana Sereda,
• Nicole Clemens,
• Tatjana Heckel and
• René Wilhelm

Beilstein J. Org. Chem. 2012, 8, 1798–1803, doi:10.3762/bjoc.8.205

• the C(2) position as catalysts for the aza-Diels–Alder reaction [11][12]. These catalysts do not activate the substrate through hydrogen bonding, but instead, like other carbon-cation based catalysts, through their positive center [8][9][10][13][14][15], and belong also to the field of organocatalysis

Asymmetric aza-Diels- Alder reaction of Danishefsky's diene with imines in a chiral reaction medium

• Bruce Pégot,
• Olivier Nguyen Van Buu,
• Didier Gori and
• Giang Vo-Thanh

Beilstein J. Org. Chem. 2006, 2, No. 18, doi:10.1186/1860-5397-2-18

• Bruce Pegot Olivier Nguyen Van Buu Didier Gori Giang Vo-Thanh Laboratoire de Chimie des Procédés et Substances Naturelles, ICMMO, CNRS UMR 8182, Université Paris-Sud, 91405 Orsay Cedex, France 10.1186/1860-5397-2-18 Abstract The asymmetric aza-Diels-Alder reaction of chiral imines with

• ] ZnCl2,[5] or lanthanide triflates[6] and Brönsted acids, including HBF4 or TsOH[7] largely helped promote the reaction. Of late, catalytic asymmetric versions of the aza-Diels-Alder reaction have been explored and high stereoselectivities were reported. So far, a few catalyst systems have been quoted in

• .[29] In connection with our studies on chiral ILs and our ongoing project on asymmetric synthesis, we describe herein how chiral ILs can be used as a new chiral reaction medium in the asymmetric aza-Diels-Alder reaction between Danishefsky's diene and chiral imines. Results We have recently reported a