Transformation of the cyclohexane ring to the cyclopentane fragment of biologically active compounds

• Natalya Akhmetdinova,
• Ilgiz Biktagirov and
• Liliya Kh. Faizullina

Beilstein J. Org. Chem. 2025, 21, 2416–2446, doi:10.3762/bjoc.21.185

• contraction of six-membered cycles in the synthesis of functionalized cyclopentane/enones, which are biologically active compounds. The main synthetic methods of ring contraction (ozonolysis–aldol condensation, ozonolysis–Dieckmann reaction, Baeyer–Villiger cleavage–Dieckmann reaction) and rearrangements

• cyclohexane/ene ring contraction. The structure of the review includes examples of simple transformations (ozonolysis–aldol condensation, ozonolysis–Dieckmann reaction, and Baeyer–Villiger cleavage–Dieckmann reaction) and rearrangements (photochemical, benzil, semi-pinacol, Wolff, Meinwald, Wagner–Meerwein

• aldol condensation of the resulting dialdehyde. This strategy is widely used at the key stage in the formation of a cyclopentane ring in the synthesis of various building blocks, including echinopine A (3) [10][11][12] (Scheme 1). The ozonolysis–cyclization sequence was used by Alvarez-Manzaneda et al

C2 to C6 biobased carbonyl platforms for fine chemistry

• Jingjing Jiang,
• Muhammad Noman Haider Tariq,
• Florence Popowycz,
• Yanlong Gu and
• Yves Queneau

Beilstein J. Org. Chem. 2025, 21, 2103–2172, doi:10.3762/bjoc.21.165

• -proline as a catalyst (Scheme 25) [100]. The C–C-bond formation between biomass-based feedstock by aldol condensation reactions of furfural with 1-hydroxyacetone has been reported by Subrahmanyam and co-workers (Scheme 26) [101]. C4 biobased carbonyl platforms Acetoin Acetoin is a very important C4

• of Lewis acid–base bifunctional catalyst (Zr-β zeolite and K2CO3) in the Meerwein–Ponndorf–Verley reduction of a concentrated furfural solution (17.3–80.5 wt % in ethanol) combined with in situ cross-aldol condensation with acetaldehyde and crotonization. Ethanol was used as hydrogen donor for the

• , or methylcyclopentadiene upon additional aldol condensation with in situ generated formaldehyde, both highly useful intermediates for the production of high-energy-density rocket fuels and polymers [204]. Conversion of CPN to hydrocarbons: CPN can be used as a precursor to produce high-octane diesel

Bioinspired total syntheses of natural products: a personal adventure

• Zhengyi Qin,
• Yuting Yang,
• Nuran Yan,
• Xinyu Liang,
• Zhiyu Zhang,
• Yaxuan Duan,
• Huilin Li and
• Xuegong She

Beilstein J. Org. Chem. 2025, 21, 2048–2061, doi:10.3762/bjoc.21.160

• aldehyde followed by base-promoted aldol condensation reaction successfully provided tabertinggine. This approach achieved the first total synthesis of tabertinggine in only ten steps and capable of supplying enough material for the following skeletal diversifications. With sufficient tabertinggine in hand

Azide–alkyne cycloaddition (click) reaction in biomass-derived solvent Cyrene^TM under one-pot conditions

• Zoltán Medgyesi and
• László T. Mika

Beilstein J. Org. Chem. 2025, 21, 1544–1551, doi:10.3762/bjoc.21.117

• successfully introduced into homogeneous [26][27][28][29] and heterogeneous [30][31] carbon–carbon and carbon–heteroatom bond-forming protocols. Although its reactive carbonyl group could limit its application when a strong base (aldol condensation [29]) or amines (potential Schiff-base formation) are present

• , a wide range of organic reactions, e.g., urea and amide formation [32][33], amide coupling [34], aldol condensation [35], C–H difluoromethylation [36], aromatic substitution [37], and MOFs synthesis [38] were demonstrated in CyreneTM. Very recently, Fasano and Citarella first reported a CuAAC

Recent total synthesis of natural products leveraging a strategy of enamide cyclization

• Chun-Yu Mi,
• Jia-Yuan Zhai and
• Xiao-Ming Zhang

Beilstein J. Org. Chem. 2025, 21, 999–1009, doi:10.3762/bjoc.21.81

• aldol condensation of 5 provided the tetracyclic α,β-unsaturated enone 6 in 57% yield. Subsequent catalytic hydrogenation using Pd/C conditions delivered the hydrogen to the alkene from the less hindered face, producing ketone 7 with high diastereoselectivity. Final reduction of both the amide and

A convergent synthetic approach to the tetracyclic core framework of khayanolide-type limonoids

• Zhiyang Zhang,
• Jialei Hu,
• Hanfeng Ding,
• Li Zhang and
• Peirong Rao

Beilstein J. Org. Chem. 2025, 21, 926–934, doi:10.3762/bjoc.21.75

• essential tertiary alcohol at C1. The β-hydroxylactone moiety (D ring) in 11 could be introduced through an intramolecular aldol condensation [35] of acetate 12. Ultimately, the preparation of 12 could be traced back to aldehyde 14 through 1,2-Grignard addition with an organomagnesium reagent [36] prepared

Synthesis, structure, ionochromic and cytotoxic properties of new 2-(indolin-2-yl)-1,3-tropolones

• Yurii A. Sayapin,
• Eugeny A. Gusakov,
• Inna O. Tupaeva,
• Alexander D. Dubonosov,
• Igor V. Dorogan,
• Valery V. Tkachev,
• Anna S. Goncharova,
• Gennady V. Shilov,
• Natalia S. Kuznetsova,
• Svetlana Y. Filippova,
• Tatyana A. Krasnikova,
• Yanis A. Boumber,
• Alexey Y. Maksimov,
• Sergey M. Aldoshin and
• Vladimir I. Minkin

Beilstein J. Org. Chem. 2025, 21, 358–368, doi:10.3762/bjoc.21.26

• ). As shown in Scheme 2, in the initial step, the aldol condensation of 2,3,3-trimethylindolenine 2 with o-chloranil (3) leads to the intermediate compounds, 6-(2-hetarylmethylene)-6-hydroxy-2,4-cyclohexadien-1-ones 4. Such intermediates were isolated preparatively and structurally characterized in the

Three-component reactions of conjugated dienes, CH acids and formaldehyde under diffusion mixing conditions

• Dmitry E. Shybanov,
• Maxim E. Kukushkin,
• Eugene V. Babaev,
• Nikolai V. Zyk and
• Elena K. Beloglazkina

Beilstein J. Org. Chem. 2025, 21, 262–269, doi:10.3762/bjoc.21.18

• main reaction products. Keywords: aldol condensation; [4 + 2]-cycloaddition; diffusion mixing; formaldehyde; Knoevenagel condensation; three-component reactions; Introduction Formaldehyde is a reactive electrophilic reagent widely used as a C1 building block in multicomponent reactions [1][2][3]. Its

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

• process was inspired by the biocatalytic synthesis of aromatic polyketides by polyketide synthase from poly β-carbonyl substrates. Pyrrolidine-based organocatalyst C4 was able to promote a twofold atroposelective arene-forming 6-enolendo aldol condensation (Scheme 4). Sparr also realized a central-to

N-Glycosides of indigo, indirubin, and isoindigo: blue, red, and yellow sugars and their cancerostatic activity

• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 2840–2869, doi:10.3762/bjoc.20.240

• instead of 1 h). Interestingly, in contrast to N-glycosides 41a–d, only one geometrical isomer was formed. This result is surprising, as the carbohydrate moiety is located far away from the double bond and unlikely exerts a stereochemical effect. As the aldol condensation is irreversible once the double

Syntheses and medicinal chemistry of spiro heterocyclic steroids

• Laura L. Romero-Hernández,
• Ana Isabel Ahuja-Casarín,
• Penélope Merino-Montiel,
• Sara Montiel-Smith,
• José Luis Vega-Báez and
• Jesús Sandoval-Ramírez

Beilstein J. Org. Chem. 2024, 20, 1713–1745, doi:10.3762/bjoc.20.152

• an aldol condensation with benzaldehyde using potassium hydroxide in refluxing ethanol. The resulting enone 139 was reduced with sodium borohydride in methanol to give diastereoselectively the 17β-allylic alcohol. A successive treatment with m-CPBA in dichloromethane provided a mixture of epoxides

Chemo-enzymatic total synthesis: current approaches toward the integration of chemical and enzymatic transformations

• Ryo Tanifuji and
• Hiroki Oguri

Beilstein J. Org. Chem. 2024, 20, 1693–1712, doi:10.3762/bjoc.20.151

• on a decagram scale in five steps from (+)-limonene oxide (13), involving epoxide manipulation, oxidative cleavage, and intramolecular aldol condensation. Similarly, the right-half fragment, allyl chloride 16, was synthesized from limonene in five steps. Site-selective hydrogenation, oxidative

• Suzuki–Miyaura coupling with boronic ester 53 and O-acetylation furnished 54. The dienophile component, morachalcone A (44), was synthesized from phenol 55 in four steps including O-prenylation and subsequent Claisen rearrangement, aldol condensation with 56, and deprotection. The key chemo-enzymatic

Manganese-catalyzed C–C and C–N bond formation with alcohols via borrowing hydrogen or hydrogen auto-transfer

• Mohd Farhan Ansari,
• Atul Kumar Maurya,
• Abhishek Kumar and
• Saravanakumar Elangovan

Beilstein J. Org. Chem. 2024, 20, 1111–1166, doi:10.3762/bjoc.20.98

• formed active catalyst dehydrogenates the alcohol to generate the alkoxy complex Mn-L3-II. The liberated aldehyde undergoes aldol condensation with the ketone to afford the α,β-unsaturated ketone, followed by the selective hydrogenation with Mn-L3-III to give the desired alkylated product (Scheme 27). In

• ). The reaction proceeded via the dehydrogenation of the alcohol, aldol condensation, and hydrogenation of α,β-unsaturated ketones. In 2019, Leitner and his group introduced an outstanding cascade BH approach for the synthesis of various substituted cycloalkanes by coupling diols and secondary alcohols

• dehydrogenated secondary alcohols into ketone B and diol into aldehyde A. Further, aldol condensation occurred between the ketone and aldehyde and produced α,β-unsaturated ketone C, which was subsequently hydrogenated by complex Mn1-c, followed by allyl isomerization, which led to the formation of hydroxy ketone

Chemoenzymatic synthesis of macrocyclic peptides and polyketides via thioesterase-catalyzed macrocyclization

• Senze Qiao,
• Zhongyu Cheng and
• Fuzhuo Li

Beilstein J. Org. Chem. 2024, 20, 721–733, doi:10.3762/bjoc.20.66

• then transformed into aldehyde 31 through several protecting group adjustments and the corresponding alcohol and Ley oxidation. After the preparation of 33 using Evans syn-aldol condensation as a critical step, 34 was produced by thioester formation, desilylation, and allylic oxidation. Incubating 34

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

• the aldol condensation products. Importantly, the ability to recycle the ionic liquid in subsequent reactions was successfully demonstrated. Keywords: alkyne hydration; boron trifluoride; electrochemical synthesis; ionic liquids; Introduction Alkynes are fundamental starting materials towards more

• . Hydration of phenylacetylene 1d carried out with 3 equiv of BF3·Et2O for 5 h gave the aldol condensation product 3d (58%) in addition to acetophenone 2d with low yield (32%) (see Table S1, Supporting Information File 1). Assuming that enone 3d is formed from acetophenone, catalysed by the excess Lewis acid

• selectively obtained without the aldol condensation products. Considering 4-methylphenylacetylene (1e), the reaction carried out with 3 equiv of BF3·Et2O for 5 h gave only the condensation product 3e (70%, see Table S1, Supporting Information File 1). Reducing the amount of BF3·Et2O to 1 equiv and the

α-(Aminomethyl)acrylates as acceptors in radical–polar crossover 1,4-additions of dialkylzincs: insights into enolate formation and trapping

• Angel Palillero-Cisneros,
• Paola G. Gordillo-Guerra,
• Fernando García-Alvarez,
• Olivier Jackowski,
• Franck Ferreira,
• Fabrice Chemla,
• Joel L. Terán and
• Alejandro Perez-Luna

Beilstein J. Org. Chem. 2023, 19, 1443–1451, doi:10.3762/bjoc.19.103

• protodemetalation to provide ultimately the 1,4-addition adduct. In the presence of carbonyl acceptors, aldol condensation occurs providing overall a tandem 1,4-addition–aldol process. When a tert-butanesulfinyl moiety is present on the nitrogen atom, these electrophilic substitution reactions occur with good

• thus the sense of chiral induction for the 1,4-addition reactions reported in Table 2. Tandem 1,4-addition–aldol condensation reactions We then went on to consider tandem 1,4-addition–aldol condensation reactions (Scheme 6), which offer the interesting prospect of generating an all-carbon quaternary

• informative. As discussed previously (Scheme 4), application of the developed protocol for 1,4-addition to 10 only yields N-benzyl-N-tert-butylsulfinamide following β-elimination. By contrast, in the presence of benzaldehyde, 1,4-addition–aldol condensation is predominant, yielding 26 in 56% yield as a 49:25

Acetaldehyde in the Enders triple cascade reaction via acetaldehyde dimethyl acetal

• Alessandro Brusa,
• Debora Iapadre,
• Maria Edith Casacchia,
• Alessio Carioscia,
• Giuliana Giorgianni,
• Giandomenico Magagnano,
• Fabio Pesciaioli and
• Armando Carlone

Beilstein J. Org. Chem. 2023, 19, 1243–1250, doi:10.3762/bjoc.19.92

• last step involves the enamine intermediate which drives an intramolecular aldol condensation to form the final product 5. In this elegant cascade process, catalyst 1 promotes three consecutive carbon–carbon bond forming steps generating four stereogenic centers with high diastereoselectivity and

Unravelling a trichloroacetic acid-catalyzed cascade access to benzo[f]chromeno[2,3-h]quinoxalinoporphyrins

• Chandra Sekhar Tekuri,
• Pargat Singh and
• Mahendra Nath

Beilstein J. Org. Chem. 2023, 19, 1216–1224, doi:10.3762/bjoc.19.89

• condensation of intermediate 17 with 2-arylidene-5,5-dimethylcyclohexane-1,3-dione 18 (formed in situ through an Aldol condensation of aldehydes with dimedone), to generate copper(II) benzo[f]chromeno[2,3-h]dihydroquinoxalinoporphyrins which on dehydration produce the desired copper(II) benzo[f]chromeno[2,3-h

Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles

• Péter Kisszékelyi and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44

• (Scheme 47B). The authors concluded that the new structure 186 is formed by intramolecular ring opening of the oxazolidine unit initiated by the hydroxy group either following the aldol condensation or during the reaction workup. In 2021, Zhang and Oestreich presented a Cu-catalyzed tandem conjugate

Rhodium-catalyzed intramolecular reductive aldol-type cyclization: Application for the synthesis of a chiral necic acid lactone

• Motoyuki Isoda,
• Kazuyuki Sato,
• Kenta Kameda,
• Kana Wakabayashi,
• Ryota Sato,
• Hideki Minami,
• Yukiko Karuo,
• Atsushi Tarui,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2022, 18, 1642–1648, doi:10.3762/bjoc.18.176

• aldol reaction is one of the most powerful tools to achieve this transformation [1][2][3][4][5][6][7][8]. In particular, the intramolecular aldol condensation is an important approach to the formation of ring systems such as cyclic β-hydroxy carbonyl products or cyclic α,β-unsaturated carbonyl products

Oxa-Michael-initiated cascade reactions of levoglucosenone

• Julian Klepp,
• Thomas Bousfield,
• Hugh Cummins,
• Sarah V. A.-M. Legendre,
• Jason E. Camp and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2022, 18, 1457–1462, doi:10.3762/bjoc.18.151

• yields (Table 1, entries 5 and 7). Electron-poor aromatic aldehydes including 3-nitrobenzaldehyde and 3-pyridine carboxaldehyde also afforded good yields of the expected products 5g and 5j (Table 1, entries 10 and 13). The reaction of 5-methylfurfural afforded a low yield of 7, and the aldol condensation

Synthesis of odorants in flow and their applications in perfumery

• Merlin Kleoff,
• Paul Kiler and
• Philipp Heretsch

Beilstein J. Org. Chem. 2022, 18, 754–768, doi:10.3762/bjoc.18.76

• ” and only “slightly fruity” [9]. Kappe and co-workers disclosed an access to both odorants in a two-step synthesis (Scheme 1) [24]. In the first step, 4-aryl-3-buten-2-ones 3 and 4 are prepared via aldol condensation of the corresponding aldehydes 1 and 2 and acetone in 78–90% yield with a productivity

• . For compound 6, both individual steps were combined for a two-step aldol condensation/hydrogenation flow sequence providing raspberry ketone methyl ether (6) on a gram scale in 75% overall yield. Interestingly, also alternative flow protocols for the synthesis of 4-aryl-3-buten-2-ones 3 and 4 were

• extensively in perfumes” and “soap perfumes” to introduce “jasmine-like floralcy when accompanied by more volatile chemicals of floral character”, while assisting “in fixation of the fragrance” due to its relatively high boiling point of 285 °C. It is industrially produced by an aldol condensation of heptanal

Tosylhydrazine-promoted self-conjugate reduction–Michael/aldol reaction of 3-phenacylideneoxindoles towards dispirocyclopentanebisoxindole derivatives

• Sayan Pramanik and
• Chhanda Mukhopadhyay

Beilstein J. Org. Chem. 2022, 18, 469–478, doi:10.3762/bjoc.18.49

• Michael addition with another molecule of 3-phenacylidieneoxindole to yield intermediate B. Finally, an intramolecular aldol condensation takes place between the carbanion and the carbonyl group of intermediate B towards the formation of the dispirocyclopentanebisoxindole derivative. To support the

• cyclization of two molecules of 3-phenacylideneoxindoles. In this reaction tosylhydrazine serves as reducing agent to reduce one molecule of 3-phenacylideneoxindole to 3-phenacylindolinone which, under base-catalyzed conditions, involves a sequential Michael addition/intramolecular aldol condensation with

Recent advances in organocatalytic asymmetric aza-Michael reactions of amines and amides

• Pratibha Sharma,
• Raakhi Gupta and
• Raj K. Bansal

Beilstein J. Org. Chem. 2021, 17, 2585–2610, doi:10.3762/bjoc.17.173

• occurred via an aza-Michael/aldol condensation/vinylogous Michael addition/aldol condensation sequence (Table 26) [67]. Recently, the synthesis of axially chiral 4-naphthylquinoline-3-carbaldehydes 117 has been reported via Michael/Aldol cascade reaction of alkynals 116 with N-(2-(1-naphthoyl)phenyl

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

• applied on terpenoids are abundant in the literature. As terpenoids are one of the most important odorants in the F&F industry. Schütz et al. developed an aldol condensation of citral (79, 63:37 mixture of geranial (Z)-79/neral (E)-79) with acetone to prepare ψ-Ionone or pseudoionone (80) in good yield

• process. A recent example, Gavriilidis et al. described a heterogeneous version for the synthesis of 4-(4-methoxyphenyl)butan-2-one (85) starting from 4-methoxybenzyl alcohol (84). In this case, the preparation is divided in 3 stages: oxidation, aldol condensation, and reduction (Scheme 16). The setup