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

• which, after MMS formation, this reactive species is subsequently captured by the stabilized Cu(II) enolate of the ketone, to provide an α,β-unsaturated ketone intermediate F. This compound condenses with the aniline component to give an imine G that follows a cyclization and aromatization cascade

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

• the presence of Cu/TBHP. The cyclohexyl radical C attacks at the α-carbon of α,β-unsaturated ketone D generating a benzylic radical E. Finally, a radical cross-coupling between B and benzylic radical E furnish the formation of cycloalkyl–peroxy product 106. The acid-catalyzed radical additions of

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

• similar to a Michaelis–Arbuzov reaction, yielding an α,β-unsaturated ketone 97. The domino sequence concludes by cyclocondensation of intermediate 97 with phenylhydrazine, ultimately affording fully substituted pyrazoles 96 after the elimination of dimethyl phosphonate (Scheme 34) [117]. β-Thioalkyl-α,β

• hindrances. α,β-Unsaturated ketones embedded and tethered in chromene systems 58 were successfully employed in a pseudo-five-component reaction with hydrazine in boiling acetic acid to give the corresponding 4-acylpyrazolinylpyrazoles 59 (Scheme 17) [76]. The Michael addition–cyclocondensation of the α,β

• -unsaturated ketone with hydrazine and acetic acid forms a 1-acylpyrazoline, while the chromene moiety and hydrazine form the pyrazole nucleus by ring opening/ring closing cyclocondensation. Upon oxidation with DDQ, the pyrazolylpyrazoline products can be readily converted into the corresponding bispyrazoles

Primary amine-catalyzed enantioselective 1,4-Michael addition reaction of pyrazolin-5-ones to α,β-unsaturated ketones

• Pooja Goyal,
• Akhil K. Dubey,
• Raghunath Chowdhury and
• Amey Wadawale

Beilstein J. Org. Chem. 2024, 20, 1518–1526, doi:10.3762/bjoc.20.136

• -withdrawing, or electron-donating group at the para-position of the benzene ring were compatible and led to the corresponding products 3ba–fa in good to excellent yields (72–97%) and enantioselectivities (90–95% ee). The α,β-unsaturated ketone 1f with a strong electron-withdrawing group (cyano) in the para

• -position of the benzene ring, was found to be more reactive as the reaction was completed within 4 h and the desired Michael adduct 3fa was isolated in 89% yield and 92% ee. Notably, the α,β-unsaturated ketone with a substituent in the meta-position of the benzene ring was also tolerated and the desired

• product 3ga was isolated in good yield (82%) and excellent enantioselectivity (95% ee). To our delight, the α,β-unsaturated ketone with a substituent in the ortho-position of the benzene ring, led to the product 3ha in good yield (76.5%) and highest enantioselectivity (98.5% ee). Moreover, 1-naphthyl

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

• . Furthermore, β-alkylation of 1-phenyl-1-ethanol with benzylic alcohols was also studied with 2 mol % of the Mn4 pre-catalyst, 5 mol % of Cs2CO3 in t-AmOH at 135 °C for 20 h (Scheme 32). NMR studies endorsed the formation of intermediates such as aldehyde, ketone, and α,β-unsaturated ketone. The proposed

• 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

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

• . Therefore, numerous structurally distinct substrates were successfully utilized. Other than nitroolefins, Liao and co-workers have observed a side reaction of the α,β-unsaturated ketone 26 and the enolate 27 when they studied the conjugate addition of R2Zn reagents to chalcone and its derivatives (Scheme 7A

Strategies to access the [5-8] bicyclic core encountered in the sesquiterpene, diterpene and sesterterpene series

• Cécile Alleman,
• Charlène Gadais,
• Laurent Legentil and
• François-Hugues Porée

Beilstein J. Org. Chem. 2023, 19, 245–281, doi:10.3762/bjoc.19.23

• and access to cotylenin A aglycon 50. Other examples of fusicoccan derivatives are represented by alterbrassicicene D (54) and 3(11)-epoxyhypoestenone (55), recently isolated from Hypoestes verticillaris [32]. Structurally, alterbrassicicene D (54) comprises an α,β-unsaturated ketone C-ring, and a

• single hydroxy group on the central eight-membered ring and 3(11)-epoxyhypoestenone (55) shows a surprising oxa-bridge between the A and C rings, an α,β-unsaturated ketone on ring C, and an endo-alkene into the cyclooctene ring. Recently, Chen et al. reported the synthesis of the tricyclic core structure

• displays a similar backbone as asteriscanolide (2), with an α,β-unsaturated ketone on the eight-membered ring, fused with a γ-butyrolactone and a cyclopentane, onto which a cyclopropane is also grafted [48]. The total synthesis of (±)-naupliolide (97) reported by Ito et al. constituted another example of

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

• derived from biomass pyrolysis, due to its reactive functionality, and the chirality which derives from glucose [4][5][6][7]. Reactions of 1 where the α,β-unsaturated ketone participates as an electrophile are usually completely diastereoselective, as the approach of the nucleophile is controlled by the

• approximate 90° dihedral angle. Conclusion This work has described a novel reaction of a cyclic biomass-derived α,β-unsaturated ketone with aromatic aldehydes. The ready availability of levoglucosenone in large quantities from biomass could make compounds such as 5 of interest for green chiral materials

Anti-inflammatory aromadendrane- and cadinane-type sesquiterpenoids from the South China Sea sponge Acanthella cavernosa

• Shou-Mao Shen,
• Qing Yang,
• Yi Zang,
• Jia Li,
• Xueting Liu and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2022, 18, 916–925, doi:10.3762/bjoc.18.91

• configuration determination of natural products with stereogenic centers near the chromophore groups [20], was applied, since there is an α,β-unsaturated ketone chromophore nearby C-5 and C-2 in compound (+)-1. Thus, the theoretical ECD spectrum of (+)-1 was calculated by the DFT calculation method at the b3lyp

• MeCN at 4 °C in the present study. Compound (+)-1 was obtained as an optically active colorless oil. Its molecular formula was deduced to be C15H22O2 on the basis of HRESIMS [quasi-molecular ion peak at m/z 235.1700 ([M + H]+, calcd for 235.1693)]. The IR spectrum displayed an absorption band of an α,β

• -unsaturated ketone group (1644 cm−1), as additionally supported by the UV absorption at λmax 245 nm (log ε 3.8). Careful analysis of the NMR spectra of (+)-1 (Table 1 and Figures S8–S13 in Supporting Information File 1) showed a close similarity with those of co-occurring 2 [12][13][14], indicating compound

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

• -phenylethylidene)indolin-2-one (1j) in acetonitrile with Et3N catalyst under refluxing conditions, and isolated the corresponding saturated ketone 1-methyl-3-(2-oxo-2-phenylethyl)indolin-2-one (4j) in 60% yield, which results from reduction of the double bond of α,β-unsaturated ketone (Scheme 5). The structure of

Regioselective synthesis of methyl 5-(N-Boc-cycloaminyl)-1,2-oxazole-4-carboxylates as new amino acid-like building blocks

• Jolita Bruzgulienė,
• Greta Račkauskienė,
• Aurimas Bieliauskas,
• Vaida Milišiūnaitė,
• Miglė Dagilienė,
• Gita Matulevičiūtė,
• Vytas Martynaitis,
• Sonata Krikštolaitytė,
• Frank A. Sløk and
• Algirdas Šačkus

Beilstein J. Org. Chem. 2022, 18, 102–109, doi:10.3762/bjoc.18.11

• -oxazoles are: the 1,3-dipolar cycloaddition of alkenes and alkynes with nitrile oxides, and the reaction of a three-carbon atom component, such as a α,β-unsaturated ketone or a 1,3-diketone with hydroxylamine hydrochloride [33]. Recently, Rosa et al. reported a useful procedure for the synthesis of various

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

• of carbamates, sulfonamides and acetamides 13 bearing an α,β-unsaturated ketone to synthesize a series of 2-substituted five- and six-membered heterocycles in good yields (up to 99%) and excellent enantioselectivity (92–97.5% ee) (Table 3). As in an earlier case [29], several acids were tested as co

Strategies for the synthesis of brevipolides

• Yudhi D. Kurniawan and
• A'liyatur Rosyidah

Beilstein J. Org. Chem. 2021, 17, 2399–2416, doi:10.3762/bjoc.17.157

• -promoted double bond migration. The cyclopropyl functionality in 46 can be assembled from the reaction of sulfur ylide and the α,β-unsaturated ketone 47, which in turn can be realized from the cross metathesis between commercially available ethyl vinyl ketone (48) and the C2-symmetrical diene-diol 49. The

• introduced by the addition of a protected propargyl alcohol to the epoxide derived from triol 109. The furan ring is formed by an acid-catalyzed intramolecular cyclization of the alcohol intermediate obtained from the Noyori reduction of α,β-unsaturated ketone 110. This compound is eventually constructed

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

All-carbon [3 + 2] cycloaddition in natural product synthesis

• Zhuo Wang and
• Junyang Liu

Beilstein J. Org. Chem. 2020, 16, 3015–3031, doi:10.3762/bjoc.16.251

• -unsaturated enone to afford conidiogenone B (171) in 32% yield upon treatment with RhCl3 in microwave. The reaction mechanism of Danheiser’s [3 + 2] annulation is shown according to the Danheiser’s proposal [74] (Scheme 13C, inset). Initial complexation of the α,β-unsaturated ketone 167 and titanium

Chiral terpene auxiliaries V: Synthesis of new chiral γ-hydroxyphosphine oxides derived from α-pinene

• Anna Kmieciak and
• Marek P. Krzemiński

Beilstein J. Org. Chem. 2019, 15, 2493–2499, doi:10.3762/bjoc.15.242

• sodium carbonate to give (+)-3-methyleneverbanone (5) in 57% yield from 3. α,β-Unsaturated ketone 5 was exclusively reduced to allylic alcohol (1R,2R,4S,5R)-3-methyleneneoisoverbanol (6), using the Luche method [24]. 1,2-Reduction of enone 5 was achieved with sodium borohydride in the presence of cerium

Synthesis and biological evaluation of truncated derivatives of abyssomicin C as antibacterial agents

• Leticia Monjas,
• Peter Fodran,
• Johanna Kollback,
• Carlo Cassani,
• Thomas Olsson,
• Maja Genheden,
• D. G. Joakim Larsson and
• Carl-Johan Wallentin

Beilstein J. Org. Chem. 2019, 15, 1468–1474, doi:10.3762/bjoc.15.147

• , which suggests a suitable level of structural truncation of compound 2. Further docking studies, using covalent docking, also showed that both atrop-O-benzyl-desmethyl-abyssomicin C and 2 can bind to the active site cysteine via a Michael addition to the α,β-unsaturated ketone, still maintaining the

Synthesis of cis-hydrindan-2,4-diones bearing an all-carbon quaternary center by a Danheiser annulation

• Gisela V. Saborit,
• Carlos Cativiela,
• Ana I. Jiménez,
• Josep Bonjoch and
• Ben Bradshaw

Beilstein J. Org. Chem. 2018, 14, 2597–2601, doi:10.3762/bjoc.14.237

• reaction of a (trimethylsilyl)allene and a suitable cyclic α,β-unsaturated ketone [30][31]. Despite the applicability of the reaction to construct five-membered rings, it has not been extensively examined [32] for the synthesis of complex natural products. As depicted in Scheme 2, the hydrindane core ring

Studies towards the synthesis of hyperireflexolide A

• G. Hari Mangeswara Rao

Beilstein J. Org. Chem. 2018, 14, 2106–2111, doi:10.3762/bjoc.14.185

• cyclopentane 5, a functionalized key intermediate, is presented. Compound 5 is involved in hydrolysis, α-allylation at C-8 and α-methylation at C-10 stereoselectively from the convex face. Then it is subjected to cross metathesis to give α,β-unsaturated ketone 11 as precursor in the total synthesis of

• conditions were unsuccessful [38], which prevented completion of the proposed synthetic sequence. Conclusion In conclusion, synthetic studies towards hyperireflexolide A, the synthetic precursor α,β-unsaturated ketone 11 was synthesized. Failure of the stereoselective epoxidation of 11 prevented completion

• of the proposed synthetic sequence. Future studies will include the stereoselective epoxidation of 11 followed by opening of the epoxide and lactonization or 1,4-nucleophilic addition to the α,β-unsaturated ketone 11 followed by epoxidation of the resulted enolate with subsequent lactonization to

An overview of recent advances in duplex DNA recognition by small molecules

• Sayantan Bhaduri,
• Nihar Ranjan and
• Dev P. Arya

Beilstein J. Org. Chem. 2018, 14, 1051–1086, doi:10.3762/bjoc.14.93

Total syntheses of the archazolids: an emerging class of novel anticancer drugs

• Stephan Scheeff and
• Dirk Menche

Beilstein J. Org. Chem. 2017, 13, 1085–1098, doi:10.3762/bjoc.13.108

• yield. For coupling with known aldehyde 66 [93] the O’Neil group chose Ba(OH)2 as base for the HWE-type reaction [94] to generate the α,β-unsaturated ketone 67 in 75% yield as a 10:1 mixture of isomers. Similar to the earlier discussed synthesis of Trauner and co-workers [43] reduction with sodium

Synthesis and enzymatic ketonization of the 5-(halo)-2-hydroxymuconates and 5-(halo)-2-hydroxy-2,4-pentadienoates

• Tyler M. M. Stack,
• William H. Johnson Jr. and
• Christian P. Whitman

Beilstein J. Org. Chem. 2017, 13, 1022–1031, doi:10.3762/bjoc.13.101

• in Supporting Information File 1. The approximate percentages of the components were determined by integration and are summarized in Table 3 [15]. The highly electronegative fluoride substituent in 5d prevents the detectable formation of the corresponding α,β-unsaturated ketone, 9d. Ketonization of

• ). The α,β-unsaturated ketone 9d (from 5d) is not detectable (by UV or 1H NMR spectroscopy). The steady state kinetic parameters for the Lc 4-OT-catalyzed conversion of 5b–d to the β,γ-unsaturated ketones (11b–d, respectively) were determined and compared to those for the non-halogenated species (5a to

• determined as described above. The 4-OT-catalyzed ketonization of 3a to 4a The Pp and Lc 4-OT-catalyzed conversion of 3a to the α,β-unsaturated ketone, 4a (Scheme 2) was measured by following the increase in absorbance at 236 nm [8]. The reactions were carried out in 10 mM KH2PO4 buffer (1 mL, pH 7.3

Chemical probes for competitive profiling of the quorum sensing signal synthase PqsD of Pseudomonas aeruginosa

• Michaela Prothiwa,
• Dávid Szamosvári,
• Sandra Glasmacher and
• Thomas Böttcher

Beilstein J. Org. Chem. 2016, 12, 2784–2792, doi:10.3762/bjoc.12.277

• selectively targeting the active site of an enzyme and a reporter group that allows in-gel imaging and/or affinity enrichment of target enzymes [22]. We thus synthesized a small library of chemical probes with electrophilic α-chloroacetamide, α,β-unsaturated amide, and α,β-unsaturated ketone moieties as

• α-chloroacetamide probes CA1–3 by reaction with chloroacetyl chloride (Figure 2B). The α,β-unsaturated ketone probe UK1 was synthesized via the Weinreb–Nahm amide in a Grignard reaction with vinylmagnesium bromide (Figure 2C). An overview of the small ABPP probe library is given in Figure 2D. Active

• amide probes UA1–3 and the α,β-unsaturated ketone UK1 only resulted in very weak or no labeling, all three α-chloroacetamide probes CA1–3 gave a strong fluorescent signal in the gel (Figure 3A). In order to investigate the selectivity of the probes, we constructed a PqsD C112A mutant, where the active

Synthesis and properties of fluorescent 4′-azulenyl-functionalized 2,2′:6′,2″-terpyridines

• Adrian E. Ion,
• Liliana Cristian,
• Mariana Voicescu,
• Masroor Bangesh,
• Augustin M. Madalan,
• Daniela Bala,
• Constantin Mihailciuc and
• Simona Nica

Beilstein J. Org. Chem. 2016, 12, 1812–1825, doi:10.3762/bjoc.12.171

• chemical manner, by grinding neat starting materials without the use of classical organic solvents [26]. The α,β-unsaturated ketone was formed in good yields, 72% for 2a and 70% for 2b, respectively using NaOH as base. The azulenyl-substituted chalcones are stable at room temperature for months, whereas at

• at 110 °C for 10 min in aqueous medium. In both cases, the desired α,β-unsaturated ketone 2 were isolated in similar yields (see Table 1). It is worth mentioning here that the microwave-assisted reaction was performed in aqueous medium, an environmentally benign solvent. The other advantage of this

Conjugate addition–enantioselective protonation reactions

• James P. Phelan and
• Jonathan A. Ellman

Beilstein J. Org. Chem. 2016, 12, 1203–1228, doi:10.3762/bjoc.12.116

• review, Lou and co-workers reported an additional example of conjugate addition–enantioselective protonation involving an α,β-unsaturated ketone. In the new report, a chiral primary amine catalyzed conjugate addition of a 1,3-diketone nucleophile into an in situ generated ortho-quinone methide was