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

• -workers developed atroposelective formation of benzothiophene-fused biaryls via formal (4 + 2) annulation [35]. The NHC catalyst C12 was the most efficient for realizing the de novo formation of a new aryl ring within the newly formed axially chiral biaryl 51 from enals 49 and 2-benzylbenzothiophene- or

• activation, atroposelective aza-Michael addition, and intramolecular aldol reaction to form the cationic intermediate Int-6. Release of the catalyst C2, reduction with NaBH4, and dehydration with acetic acid leads to the desired product 6. Recently, an organocatalytic atroposelective intramolecular (4 + 2

• ) annulation of enals with ynamides 8 to afford axially chiral 7-arylindolines 9 was reported [20]. The reaction mechanism, rationalized by DFT calculations, is believed to occur through catalyst C3 activation of the substrate 8, dehydration, and deprotonation with tautomerization leading to the enamine

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

• Mannich-type reaction of isocyanoacetates with N-(2-benzothiazolyl)imines. Enantioselective modified cinchona alkaloid-catalyzed [4 + 2] annulation of γ-butenolides and saccharin-derived 1-azadienes. Chiral tertiary amine-catalyzed [2 + 4] annulation of cyclic 1-azadiene with γ-nitro ketones. Inverse

A review of recent advances in electrochemical and photoelectrochemical late-stage functionalization classified by anodic oxidation, cathodic reduction, and paired electrolysis

• Nian Li,
• Ruzal Sitdikov,
• Ajit Prabhakar Kale,
• Joost Steverlynck,
• Bo Li and
• Magnus Rueping

Beilstein J. Org. Chem. 2024, 20, 2500–2566, doi:10.3762/bjoc.20.214

• involves building a ring onto a preexisting system, whether cyclic or non-cyclic. The Lei group developed an electrooxidative annulation reaction that facilitates LSF [28]. A regio- and stereoselective protocol was established for the [4 + 2] annulation of indole derivatives, allowing access to highly

• , due to the protonation of triticonazole, the participation of the protonated form in the overall reaction mechanism is also considered in pathway B (Scheme 21). Benzo[c][1,2]oxazines are useful scaffolds for the synthesis of natural products. In 2021, the Han group developed the electrochemical [4 + 2

• ] annulation of hydroxamic acids 54 with alkenes for approaching benzo[c][1,2]oxazines [30]. This method successfully achieved the LSF of several natural products such as lithocholic acid and estrone, affording the following benzo[c][1,2]oxazine derivatives in moderate to good yields (Scheme 22). The

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

• , curcumin showcases its Michael donor–acceptor ability in different ways, such as simple Michael addition, [4 + 2] annulation, Michael addition followed by cyclization or one-pot multicomponent reactions (MCR), etc. (Scheme 1) [25]. In 2011, our group reported the reactivity of curcumin as a Michael donor

Sustainable tandem acylation/Diels–Alder reaction toward versatile tricyclic epoxyisoindole-7-carboxylic acids in renewable green solvents

• Ayhan Yıldırım

Beilstein J. Org. Chem. 2024, 20, 1308–1319, doi:10.3762/bjoc.20.114

• + 2] annulation reactions [68][69][70]. This study was the first to evaluate the performances of sunflower seed oil (SSO), olive oil (OO), oleic acid (OA) and lauryl myristate (LM) as green solvents in the well-known intramolecular Diels–Alder furan (IMDAF) reaction between aminofuranes and maleic

• importance in intramolecular Diels–Alder reactions, the effects of solvents such as glycerol, polyethylene glycol, organic carbonates, deep eutectic solvents, supercritical CO2 and H2O have recently been extensively studied [65][66][67]. Recently, attention has also been drawn to photoinduced oxidative [4

Synthesis of spiropyridazine-benzosultams by the [4 + 2] annulation reaction of 3-substituted benzoisothiazole 1,1-dioxides with 1,2-diaza-1,3-dienes

• Wenqing Hao,
• Long Wang,
• Jinlei Zhang,
• Dawei Teng and
• Guorui Cao

Beilstein J. Org. Chem. 2024, 20, 280–286, doi:10.3762/bjoc.20.29

• developed by means of [4 + 2] annulation reaction of 3-substituted benzoisothiazole 1,1-dioxides with 1,2-diaza-1,3-dienes. This approach displays advantages such as mild reaction conditions, wide substrate range tolerance, simple operation, compatibility with gram-scale preparation. Keywords: [4 + 2

• ketimines as suitable three-carbon synthons in [3 + 2] and [3 + 3] annulations [11][12][13][14][15]. However, methods using N-sulfonyl ketimines as dienophiles in [4 + 2] annulation reactions to afford biologically important spiro compounds are still limited to date [16]. 1,2-Diaza-1,3-dienes [17][18][19

• . Inspired by the potential biological activity of pyridazines and in continuation of our work on the synthesis of spirobenzosultams [31][32][33], we herein report a highly diastereoselective route for the synthesis of spiropyridazine-benzosultams through [4 + 2] annulation reactions of 3-substituted

Recent advancements in iodide/phosphine-mediated photoredox radical reactions

• Tinglan Liu,
• Yu Zhou,
• Junhong Tang and
• Chengming Wang

Beilstein J. Org. Chem. 2023, 19, 1785–1803, doi:10.3762/bjoc.19.131

• notable advantages in terms of both step- and atom-economy. Taking inspiration from the groundbreaking work of Shang and Fu [6], Li and colleagues demonstrated an innovative approach for the photocatalytic [3 + 2] and [4 + 2] annulation of enynals 32 and γ,σ-unsaturated N-(acyloxy)phthalimides 33 (Scheme

• of fused ketones 34, eliminating the need for transition-metal catalysts or oxidants. The technique offered a broad substrate scope, remarkable selectivity, and simple reaction conditions. A plausible mechanism had been proposed for the photocatalytic decarboxylative [3 + 2]/[4 + 2] annulation, as

• cyclization to release an active alkyl radical intermediate C. Once formed, C added to the aldehyde group via a [4 + 2] annulation, releasing the alkoxy radical intermediate D. The latter then underwent a subsequent 1,2-H atom shift to generate the alkyl radical intermediate E which was further oxidized by

Photoredox catalysis harvesting multiple photon or electrochemical energies

• Mattia Lepori,
• Simon Schmid and
• Joshua P. Barham

Beilstein J. Org. Chem. 2023, 19, 1055–1145, doi:10.3762/bjoc.19.81

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

• ][35][36]. In this context, Huang, Fu and co-workers reported carbene-catalyzed enantioselective formal [4 + 2] annulation reactions of β-silyl enones with enals and with active acetic esters (Scheme 1g) for the preparation of chiral organosilanes [34][35][36]. Very recently, during the final stage of

Prins cyclization-mediated stereoselective synthesis of tetrahydropyrans and dihydropyrans: an inspection of twenty years

• Asha Budakoti,
• Pradip Kumar Mondal,
• Prachi Verma and
• Jagadish Khamrai

Beilstein J. Org. Chem. 2021, 17, 932–963, doi:10.3762/bjoc.17.77

• and trans-2,6-DHP, respectively, was reported by a [4 + 2]-annulation strategy. The authors utilized crotylsilanes syn-170 and anti-170, respectively, with an aldehyde 171 in the presence of TMSOTf to deliver different DHPs 172 (Scheme 41) [76]. For syn-170, the reaction went via the favored boat-like

• synthesized utilizing this [4 + 2]-annulation strategy. Following the above annulation route, later, Roush's group Introduced β-hydroxyallylsilanes for the synthesis of 2,6-disubstituted DHP (Scheme 44) [82]. This strategy was further utilized for the synthesis of the C29−C45 bispyran subunit (E−F) of

• -crotylsilanes. Roush and co-workers’ [4 + 2]-annulation strategy for DHP synthesis [82]. TMSOTf-promoted annulation reaction. Dobb and co-workers’ synthesis of DHP. BiBr3-promoted tandem silyl-Prins reaction by Hinkle et al. Substrate scope of Hinkle and co-workers’ strategy. Cho and co-workers’ strategy for

Construction of highly enantioenriched spirocyclopentaneoxindoles containing four consecutive stereocenters via thiourea-catalyzed asymmetric Michael–Henry cascade reactions

• Yonglei Du,
• Jian Li,
• Kerong Chen,
• Chenglin Wu,
• Yu Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2017, 13, 1342–1349, doi:10.3762/bjoc.13.131

• effective strategies to construct biologically active spirocyclic oxindoles [65][66][67][68], we have built successfully interesting spirooxindoles via an NHC-catalyzed [4 + 2] annulation involving an oxidative γ-carbon activation of common α,β-unsaturated aldehydes [68]. Herein, we report another effective

Highly chemo-, enantio-, and diastereoselective [4 + 2] cycloaddition of 5H-thiazol-4-ones with N-itaconimides

• Shuai Qiu,
• Choon-Hong Tan and
• Zhiyong Jiang

Beilstein J. Org. Chem. 2016, 12, 2293–2297, doi:10.3762/bjoc.12.222

• ) were obtained for a series of spirocyclic 1,4-sulfur-bridged piperidinone-based succinimides. Keywords: [4 + 2] annulation; asymmetric organocatalysis; dipeptide-based Brønsted bases; 5H-thiazol-4-ones; N-itaconimides; Introduction Sulfur-containing tetrasubstituted carbon stereocenters are widely

• , herein, we report an asymmetric [4 + 2] annulation reaction of 5H-thiazol-4-ones with N-itaconimides. The method features excellent chemo-, enantio, and diastereoselectivities, thus leading to a series of chiral spirocyclic 1,4-sulfur-bridged piperidinone-based succinimides with excellent results

• excellent catalytic efficacy as demonstrated in a series of asymmetric reactions [18]. It was found that the reaction was completed after 48 hours, affording the desired [4 + 2] annulation adduct 3a in 55% yield with 64% ee. A significant amount of conjugate addition adduct led to the unsatisfactory

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

• asymmetric [3 + 2] annulations, asymmetric [4 + 2] annulations have been less studied, with only limited examples reported. In 2005, based on Kwon’s phosphine-catalyzed [4 + 2] annulation of allenoates with N-tosylimines [83], Fu and co-workers developed an asymmetric variant using the binaphthyl-based

• stereoselectivities (up to 99% ee, up to 99:1 dr) and moderate to excellent yields (42–99%). The piperidine products could be transformed conveniently into biologically important heterocyclic compounds. For example, with this asymmetric [4 + 2] annulation as the key step, using indole-2-carboxaldehyde as the starting

• material, the bridged tetracyclic framework of the Alstonia class of indole alkaloids was readily formed in high yield. This asymmetric [4 + 2] annulation was a seminal advance in the area of nucleophilic phosphine catalysis, attracting much attention toward chiral phosphine-catalyzed asymmetric reactions