Total syntheses of highly oxidative Ryania diterpenoids facilitated by innovations in synthetic strategies

• Zhi-Qi Cao,
• Jin-Bao Qiao and
• Yu-Ming Zhao

Beilstein J. Org. Chem. 2025, 21, 2553–2570, doi:10.3762/bjoc.21.198

• , achieved the total synthesis of anhydroryanodol (10) and a formal synthesis of ryanodol (4) through a key low-valent titanium-mediated intramolecular stereoselective coupling of alkynes with 1,3-dicarbonyl compounds [52] (Scheme 9). To construct the oxygenated fused-ring system with contiguous

The application of desymmetric enantioselective reduction of cyclic 1,3-dicarbonyl compounds in the total synthesis of terpenoid and alkaloid natural products

• Dong-Xing Tan and
• Fu-She Han

Beilstein J. Org. Chem. 2025, 21, 2085–2102, doi:10.3762/bjoc.21.164

• The desymmetric enantioselective reduction of cyclic 1,3-dicarbonyl compounds is a powerful tool for the construction of ring systems bearing multiple stereocenters including all-carbon quaternary stereocenters, which are widely useful chiral building blocks for the total synthesis of structurally

• synthesized utilizing a desymmetric enantioselective reduction strategy of cyclic 1,3-dicarbonyl compounds as a key transformation. This review will summarize the application of this strategy in the total synthesis of terpenoid and alkaloid natural products from the year 2016 to 2025. We first focus on the

• synthesis of several terpenoids and alkaloids through the desymmetric enantioselective reduction of five-membered cyclic 1,3-dicarbonyl compounds. Subsequently, the utilization of six-membered cyclic 1,3-dicarbonyl compounds for the synthesis of some terpenoids natural products is described. Keywords

General method for the synthesis of enaminones via photocatalysis

• Paula Pérez-Ramos,
• Raquel G. Soengas and
• Humberto Rodríguez-Solla

Beilstein J. Org. Chem. 2025, 21, 1535–1543, doi:10.3762/bjoc.21.116

• condensation of 1,3-dicarbonyl compounds with amines [30]. While this approach is simple and straightforward, it often leads to a mixture of constitutional isomers in which the two different α-positions of the ketone have been functionalized. Therefore, the development of novel methods for the synthesis of

Recent advances in oxidative radical difunctionalization of N-arylacrylamides enabled by carbon radical reagents

• Jiangfei Chen,
• Yi-Lin Qu,
• Ming Yuan,
• Xiang-Mei Wu,
• Heng-Pei Jiang,
• Ying Fu and
• Shengrong Guo

Beilstein J. Org. Chem. 2025, 21, 1207–1271, doi:10.3762/bjoc.21.98

• without the need for external oxidants. In 2018, Xu’s group reported an electrochemical dehydrogenative cyclization of 1,3-dicarbonyl compounds (Scheme 11) [8]. The study focused on the electrochemical dehydrogenative cyclization of 1,3-dicarbonyl compounds through intramolecular C(sp3)–H/C(sp2)–H cross

• different alkyl substituents at the α-position of the 1,3-dicarbonyl compounds, including functionalized alkyl chains with alkenyl, alkynyl, and aryl groups, all of which were compatible with the reaction conditions. Interestingly, when α-alkylmalonic esters were employed instead of malonate amide moieties

Recent advances in synthetic approaches for bioactive cinnamic acid derivatives

• Betty A. Kustiana,
• Galuh Widiyarti and
• Teni Ernawati

Beilstein J. Org. Chem. 2025, 21, 1031–1086, doi:10.3762/bjoc.21.85

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

• reaction works very well for a wide variety of functional groups and substitution patterns in the aryl methyl ketone substrate, affording the desired heterocycle with good yields. Even heteroaryl methyl ketone and 1,3-dicarbonyl compounds work very well under these reaction conditions, leading to more

Recent advances in electrochemical copper catalysis for modern organic synthesis

• Yemin Kim and
• Won Jun Jang

Beilstein J. Org. Chem. 2025, 21, 155–178, doi:10.3762/bjoc.21.9

• oxidation. C–X Bond formation Cu-catalyzed electrochemical reactions have been developed for the formation of C–C, C–N, and C–X bonds. For instance, in 2013, the Kakiuchi group reported Cu-catalyzed electrochemical chlorination of 1,3-dicarbonyl compounds (Figure 13) [63]. Typical chlorination reactions are

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

• demonstrated high tolerance to functional groups and runs, under mild conditions, with electron-poor diazo derivatives such as 2-diazoacetate, 2-diazoacetonitrile, 2-diazo-1,1,1-trifluoromethane, diazoamide, and diazophosphonate. Condensation of 2-naphthol, aromatic aldehydes and acyclic 1,3-dicarbonyl

• compounds catalyzed by copper triflate under ultrasound irradiation allowed the one-pot formation of 1H-benzo[f]chromen-2-yl(phenyl)methanones (naphthopyranes) 37. The comparison with conventional method showed better yields and shorter reaction times. The suggested reaction mechanism showed the formation

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

• reaction between 1,3-dicarbonyl compounds 68 and azoalkenes 53 (Scheme 26) [48]. This methodology provides access to C1-symmetric biarylamino alcohol derivatives (NPNOL) 69 in a wide scope with good yields (45–89%) and good to excellent atroposelectivities (64–99% ee). In order to explain the reaction

• -Diels–Alder reaction of 1,3-diazadienes and 3-vinylindoles. Chiral phosphoric acid-catalyzed asymmetric Attanasi reaction between 1,3-dicarbonyl compounds and azoalkenes. Synthetic applicability of the NPNOL derivatives. Chiral phosphoric acid-catalyzed asymmetric intermolecular formal (3 + 2

Advances in radical peroxidation with hydroperoxides

• Oleg V. Bityukov,
• Pavel Yu. Serdyuchenko,
• Andrey S. Kirillov,
• Gennady I. Nikishin,
• Vera A. Vil’ and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2024, 20, 2959–3006, doi:10.3762/bjoc.20.249

• of a set of tert-butoxy and tert-butylperoxy radicals from TBHP has been demonstrated in an undivided electrochemical cell under constant current conditions (Scheme 14) [55]. Using this approach, the electrochemical peroxidation of cyclic 1,3-dicarbonyl compounds 35 with TBHP was realized to give

• cleaved to yield the ketone radical F. The subsequent addition of alkene radical F and tert-butylperoxy radical A to alkenes 113 leads to the target product 115. Cobalt-catalyzed alkylation–peroxidation of alkenes 117 with 1,3-dicarbonyl compounds 116 and TBHP was developed (Scheme 40) [97][98]. Gram

Copper-catalyzed yne-allylic substitutions: concept and recent developments

• Shuang Yang and
• Xinqiang Fang

Beilstein J. Org. Chem. 2024, 20, 2739–2775, doi:10.3762/bjoc.20.232

• chelation interaction between the enolate derived from acyclic 1,3-dicarbonyl compounds and copper (Scheme 5, 8a–j). Detailed control experiments indicate that the terminal alkyne moiety is critical and the reaction proceeds through an SN1 mechanism. An outer-sphere nucleophilic attack through copper

• ethynylethylene carbonates as the starting materials, thus completing their enantioselective formal [4 + 1] cycloadditions with cyclic 1,3-dicarbonyl compounds (Scheme 36, 34a–k). They speculated that in the reaction mechanism, the key step is the formation of the copper vinyl allenylidene intermediate from vinyl

Factors influencing the performance of organocatalysts immobilised on solid supports: A review

• Zsuzsanna Fehér,
• Dóra Richter,
• Gyula Dargó and
• József Kupai

Beilstein J. Org. Chem. 2024, 20, 2129–2142, doi:10.3762/bjoc.20.183

• cases, the support surface can even impede unwanted side reactions. Pericàs and co-workers immobilised a thiourea organocatalyst on PS (28) and applied it in the enantioselective α-amination of 1,3-dicarbonyl compounds [36]. Unlike homogeneous thioureas, catalyst 28 is not irreversibly deactivated by

Multicomponent syntheses of pyrazoles via (3 + 2)-cyclocondensation and (3 + 2)-cycloaddition key steps

• Ignaz Betcke,
• Alissa C. Götzinger,
• Maryna M. Kornet and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2024, 20, 2024–2077, doi:10.3762/bjoc.20.178

• blocks or their transformation with additional components besides hydrazines is a logical entry to MCR syntheses of pyrazoles. Therefore, 1,3-dielectrophiles encompass 1,3-dicarbonyl compounds and α,β-unsaturated carbonyl compounds, including alkenoyl and alkynoyl systems, across various oxidation states

• of the carbonyl groups and their derivatives. 1,3-Dicarbonyl compounds as key intermediates The most common and classic synthesis of ring-forming pyrazoles is the cyclocondensation of 1,3-dicarbonyl compounds with hydrazines (Knorr synthesis) [42][43]. Therefore, the in situ generation of 1,3

• -dicarbonyl compounds and their one-pot transformation pave the way for MCR syntheses of pyrazoles. 1,3-Dicarbonyl compounds can, for example, be generated in situ from enolates and carboxylic acid chlorides. They can be converted to the corresponding pyrazoles 1 in a consecutive multicomponent reaction with

Domino reactions of chromones with activated carbonyl compounds

• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 1256–1269, doi:10.3762/bjoc.20.108

• of the substituent located at carbon C3 of the chromone moiety and also on the type of nucleophile employed. Keywords: cyclizations; 1,3-dicarbonyl compounds; domino reactions; heterocycles; regioselectivity; silyl enol ethers; Introduction Domino reactions (also called cascade or tandem reactions

• ) allow for the synthesis of complex products with formation of several bonds in only one step [1][2][3][4][5]. In contrast to non-activated acetone (1a), methylene-active compounds, such as 1,3-dicarbonyl compounds, are of considerable relevance as building blocks in domino reactions (Scheme 1). For

• undergo cyclization reactions under mild conditions. In case of 1,3-diphenylacetone (4a) some activation of the methylene group is observed as well, because of benzylic stabilization. Dianions of 1,3-dicarbonyl compounds follow a different regioselectivity as compared to simple monoanions [6][7][8][9][10

Mild and efficient synthesis and base-promoted rearrangement of novel isoxazolo[4,5-b]pyridines

• Vladislav V. Nikol’skiy,
• Mikhail E. Minyaev,
• Maxim A. Bastrakov and
• Alexey M. Starosotnikov

Beilstein J. Org. Chem. 2024, 20, 1069–1075, doi:10.3762/bjoc.20.94

• for the cyclization. Alternatively (Scheme 1B), isoxazolo[4,5-b]pyridines can be constructed via intramolecular cyclization of 4-(propargylamino)isoxazoles [21] or through reactions of 4-amino-5-benzoylisoxazoles with ketones or 1,3-dicarbonyl compounds [10][13]. These and some additional examples of

1-Butyl-3-methylimidazolium tetrafluoroborate as suitable solvent for BF₃: the case of alkyne hydration. Chemistry vs electrochemistry

• Marta David,
• Elisa Galli,
• Richard C. D. Brown,
• Marta Feroci,
• Fabrizio Vetica and
• Martina Bortolami

Beilstein J. Org. Chem. 2023, 19, 1966–1981, doi:10.3762/bjoc.19.147

• -BF4 towards disubstituted alkynes containing a carbonyl group adjacent to the triple bond. This class of substrates, after water addition, yields 1,3-dicarbonyl compounds, which could yield BF2-chelates under our experimental conditions [109]. In order to study their behaviour, we decided to avoid

Non-noble metal-catalyzed cross-dehydrogenation coupling (CDC) involving ether α-C(sp³)–H to construct C–C bonds

• Hui Yu and
• Feng Xu

Beilstein J. Org. Chem. 2023, 19, 1259–1288, doi:10.3762/bjoc.19.94

• tricyclic chromane nucleus from 8-hydroxyisochromanes and 1,3-dicarbonyl compounds in the presence of Cu(OTf)2 and T+BF4− (Scheme 7b) [57]. The strategy has a wide range of applications and is highly diastereoselective, making it an attractive strategy for synthesizing related natural products. The role of

• copper is to activate the 1,3-dicarbonyl compounds through complexation that leads to a highly diastereoselective nucleophilic addition. Scheidt et al. reported an enantioselective Cu-catalyzed intramolecular cross-dehydrogenative coupling approach to substituted tetrahydropyrans with excellent yields

• -dicarbonyl compounds. Rare earth-metal-catalyzed CDC reaction. Visible-light-driven CDC of cycloalkanes with benzazoles. Photoinduced alkylation of quinoline with cyclic ethers. Photocatalyzed CDC reactions between α-C(sp3)–H bonds of ethers and C(sp2)–H bonds of aromatics.

First synthesis of acylated nitrocyclopropanes

• Kento Iwai,
• Rikiya Kamidate,
• Khimiya Wada,
• Haruyasu Asahara and
• Nagatoshi Nishiwaki

Beilstein J. Org. Chem. 2023, 19, 892–900, doi:10.3762/bjoc.19.67

• nitronic acid furnishes cyclopropane 1a (method a) [1][4][12][13]. Halogenated malonate 6a [7][14][15][16][17] and nitrostyrene 7 [18] can also be used as substrates in this protocol (methods b and c, respectively). In these methods, diesters are mostly used as 1,3-dicarbonyl compounds, with acetylacetone

• quite difficult, although they would be very useful in synthetic chemistry, if available. In this study, we investigated the synthesis of nitrocyclopropanes using keto esters 3c–f and diketones 3b and 3g instead of diester 3a as the starting 1,3-dicarbonyl compounds. Results and Discussion We commenced

• ), 133.8 (CH), 135.1 (C), 137.8 (C), 167.0 (C), 192.7 (C). Although the adduct was obtained as a mixture of diastereomeric isomers (54:46), these isomers were subjected to subsequent cyclization without separation. When other 1,3-dicarbonyl compounds 3 or nitrostyrene 2b were used, the reaction was

Facile access to 3-sulfonylquinolines via Knoevenagel condensation/aza-Wittig reaction cascade involving ortho-azidobenzaldehydes and β-ketosulfonamides and sulfones

• Ksenia Malkova,
• Andrey Bubyrev,
• Stanislav Kalinin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2023, 19, 800–807, doi:10.3762/bjoc.19.60

• , the method for the synthesis of 3-acyl-substituted quinolines from o-azidobenzaldehydes and 1,3-dicarbonyl compounds was reported [70][71] (Figure 2a). A combination of Knoevenagel condensation and aza-Wittig reaction allowed to build up target products in high yields. In case of [70], the procedure

Redox-active molecules as organocatalysts for selective oxidative transformations – an unperceived organocatalysis field

• Elena R. Lopat’eva,
• Igor B. Krylov,
• Dmitry A. Lapshin and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2022, 18, 1672–1695, doi:10.3762/bjoc.18.179

• presented in Scheme 31 [136]. An enantioselective oxidation can be achieved by combining a ketone catalyst with a chiral amine [137]. The resulting chiral oxaziridine intermediate promotes the hydroxylation of CH-acidic 1,3-dicarbonyl compounds in high yields and enantioselectivities (up to 99% ee) (Scheme

Derivatives of benzo-1,4-thiazine-3-carboxylic acid and the corresponding amino acid conjugates

• Péter Kisszékelyi,
• Tibor Peňaška,
• Klára Stankovianska,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2022, 18, 1195–1202, doi:10.3762/bjoc.18.124

• 1,3-dicarbonyl compounds using a catalytic amount of hydrazine hydrate without solvent in a short reaction time (10 min) [14]. Reactions of 2-aminothiophenols with β-keto esters and β-diketones under microwave irradiation (MWI) using basic alumina as heterogeneous catalyst without solvent afforded 4H

• -benzo-1,4-thiazines in a yield of 69–85% within 6–11 min [15]. Furthermore, baker’s yeast as whole-cell biocatalyst catalyzed the reaction of 2-aminothiophenols with 1,3-dicarbonyl compounds in methanol and the corresponding 4H-benzo-1,4-thiazines were prepared in 51–82% yield. These reactions were

• significantly accelerated by ultrasonic irradiation [16]. Cyclocondensation of 1,3-dicarbonyl compounds with substituted diaryl disulfides in water in the presence of β-cyclodextrin gave 2,3-disubstituted benzo-1,4-thiazines in 70–91% yield in 50 min [17]. A highly efficient visible-light-mediated one-pot

Iron-catalyzed domino coupling reactions of π-systems

• Austin Pounder and
• William Tam

Beilstein J. Org. Chem. 2021, 17, 2848–2893, doi:10.3762/bjoc.17.196

• and 1,3-dicarbonyl compounds 84 via synergistic photoredox/iron catalysis (Scheme 14) [90]. This protocol parallels Li’s seminal report in 2007 [44]; however, under these reaction conditions, the reactive radical was propagated across an alkene before termination with the activated methylene unit

Recent advances in the syntheses of anthracene derivatives

• Giovanni S. Baviera and
• Paulo M. Donate

Beilstein J. Org. Chem. 2021, 17, 2028–2050, doi:10.3762/bjoc.17.131

• synthesize tetrahydrobenzo[a]xanthene-11-ones 184 and diazabenzo[a]anthracene-9,11-dione derivatives 185 in good yields via a multicomponent reaction (Scheme 42) [76]. This methodology was based on the cyclocondensation of aromatic aldehydes 180, β-naphthol (181), and cyclic 1,3-dicarbonyl compounds 182 or

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

• addition of cyclic 1,3‐dicarbonyl compounds, including 4-hydroxycoumarins 1, to α,β‐unsaturated enones 2 (Scheme 1). This versatile Michael reaction afforded (S)-warfarin (3a) and other Michael adducts 3 in high yields and good enantiomeric excess (ee), using (4S,5S)-4,5-diphenylimidazolidine-2-carboxylic

Development of N-F fluorinating agents and their fluorinations: Historical perspective

• Teruo Umemoto,
• Yuhao Yang and
• Gerald B. Hammond

Beilstein J. Org. Chem. 2021, 17, 1752–1813, doi:10.3762/bjoc.17.123

• ], electron-rich alkenes (entry 3) [65][66], alkyl sulfides (entry 4) [65][67], 1,3-dicarbonyl compounds [65][68], phosphonate esters (entry 5) [65], steroidal silyl enol ethers and enol acetates (entry 6) [65], pyrimidine bases and nucleosides (entry 7) [67][69], phenylalkynes (entry 8) [70], anthraquinones

• -dicarbonyl compounds using Selectfluor (16-3a) [61]. In 1995, the same group reported that Selectfluor reacted with quinuclidine to form N-fluoroquinuclidinium tetrafluoroborate in quantitative yield [62] (Scheme 35). They described this as a “transfer fluorination” since there was an intermolecular transfer

• , Grignard reagents, and aromatic compounds under mild conditions. In each case Selectfluor gave the corresponding fluorinated products in good to high yields (Scheme 34). As can be seen in Figure 3 and Figure 4, two years later (1994), Banks et al. reported mono- and difluorinations of various 1,3