Recent advances in total synthesis of illisimonin A

• Juan Huang and
• Ming Yang

Beilstein J. Org. Chem. 2025, 21, 2571–2583, doi:10.3762/bjoc.21.199

• rearrangement. Finally, a White–Chen C–H oxidation [33][34][35] was employed to install the lactone ring, thereby completing the synthesis. The synthesis began with commercially available compound 19 and known compound 20 (Scheme 2). These were joined via an intermolecular aldol reaction to give adduct 21

• cation were consistent with earlier reports [2][26], though the configurations of the intermediates were clearly delineated. The authors proposed that dicarbonyl compound 50 serves as the key intermediate diverging to all Illicium sesquiterpenes, with a retro-Dieckmann condensation and aldol reaction

• triflate formation followed by a palladium-catalyzed coupling reaction with AlMe3. The carbonyl group at C8, required for the subsequent aldol reaction, was introduced by enolate oxidation followed by Jones oxidation. Hydrolysis of the ketal at C11 afforded ketoester 64. A TBD (1,5,7-triazabicyclo[4.4.0

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

• pericyclic reactions [31][32][33][34][35][36][37][38][39][40][41][42][43][44], to control the formation of the crucial C5 chiral center precisely. Subsequent oxidative cleavage of the carbon–carbon double bond introduced in the Diels–Alder reaction, followed by an intramolecular aldol reaction, efficiently

• bond, and a subsequent transannular aldol reaction efficiently assembles the B and C rings, yielding the ABC tricyclic core 16. Further manipulations included the introduction of a methyl group at C9, adjustments of the oxidation state, and the installation of a mesylate group at C10, leading to

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

• intramolecular aldol reaction (recyclization or rearrangement). This method is applicable to triterpenoids, such as tirucallane, ursane, oleanane and dammarane types (pathway A), as well as for triterpenoids of the ursane and dammarane types (pathway B) [27]. In [28], a convenient method for ring contraction is

Synthetic study toward vibralactone

• Liang Shi,
• Jiayi Song,
• Yiqing Li,
• Jia-Chen Li,
• Shuqi Li,
• Li Ren,
• Zhi-Yun Liu and
• Hong-Dong Hao

Beilstein J. Org. Chem. 2025, 21, 2376–2382, doi:10.3762/bjoc.21.182

• and ClpP2 and it could be utilized as a probe to study the activity and structure of the ClpP1P2 complex from Listeria monocytogenes [25]. Previously, Snider and co-worker reported the first total synthesis of vibralactone (6) employing Birch reductive alkylation, intramolecular aldol reaction and

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

• -Hydroxypropanal (3-HPO) and 2,3-dihydroxypropanal (2,3-HPO) Xu et al. reported the cross-aldol reaction of formaldehyde and acetaldehyde for the synthesis of 3-hydroxypropanal and further reduction to 1,3-propanediol (PDO). The reaction was promoted by X-5Mg/SiO2 and Mg/SiO2 (X = Mn, Co, Ni, Fe) catalysts

• kinetics studies, the cross-aldol reaction of formaldehyde and acetaldehyde gives a higher yield of 3-HPO than the self-aldol reaction of acetaldehyde. Moreover, Raney nickel was applied successfully for the conversion of 3-HPO to 1,3-PDO with good yield and about 90% conversion rate of 3-HPO (Scheme 13

• rehydration into levulinic acid (Scheme 70, route b1). It is now preferred considering raw material costs, process efficiency and market demand. Alternatively, C6 monosaccharides can also be fermented to produce pyruvic acid and acetaldehyde, which combine by an aldol reaction and lead to levulinic acid by

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

• cyclization of tryptamine 26a with keto-diester intermediate 27 followed with a lactamization reaction in one-pot to access the γ-lactam moiety in product 28a, which was obtained after Boc protection. Base-promoted aldol reaction of lactam 28a with aldehyde 29 gave rise to alcohol 30a, which subsequently

Asymmetric total synthesis of tricyclic prostaglandin D2 metabolite methyl ester via oxidative radical cyclization

• Miao Xiao,
• Liuyang Pu,
• Qiaoli Shang,
• Lei Zhu and
• Jun Huang

Beilstein J. Org. Chem. 2025, 21, 1964–1972, doi:10.3762/bjoc.21.152

• -keto ester 15 [24]. The β-keto ester 15 was expected to be derived from compounds 16 and 17 via an asymmetric aldol reaction [25]. The first phase of the synthesis required the efficient preparation of compound 14, for which a transition-metal-mediated oxidative radical cyclization of β-keto ester 15

Enantioselective desymmetrization strategy of prochiral 1,3-diols in natural product synthesis

• Lihua Wei,
• Rui Yang,
• Zhifeng Shi and
• Zhiqiang Ma

Beilstein J. Org. Chem. 2025, 21, 1932–1963, doi:10.3762/bjoc.21.151

• followed by TBS protection of the free hydroxy group to give compound 89, establishing the C8 chiral center in 86% yield over two steps with 90% ee. A further 14-step sequence furnished enone 90, which underwent Evans aldol reaction with fragment 91. After triethylsilyl (TES) protection of the resulting

• ) and vinyl acetate, affording the corresponding monoacetate. Subsequent reaction with tert-butyldiphenylsilyl chloride (TBDPSCl) and imidazole provided compound 119 in 94% yield over two steps with 97% ee. Next, compound 120 was obtained in six steps from 119. A stereoselective aldol reaction installed

• , ligand 205a proved to be suitable for 2-ethylpropane-1,3-diol (204). A three-step sequence then furnished enone 207, which underwent diastereoselective aldol reaction with fragment 208 to give compound 209. Alkyne 210, prepared from 209 in six steps, underwent addition with fragment 211 to yield compound

Photoswitches beyond azobenzene: a beginner’s guide

• Michela Marcon,
• Christoph Haag and
• Burkhard König

Beilstein J. Org. Chem. 2025, 21, 1808–1853, doi:10.3762/bjoc.21.143

• Wiedbrauk and Dube [93]. Double-bond-substituted hemithioindigos 93 are synthesised by functionalising 87 with an aliphatic or aromatic 88 and subsequent intramolecular aldol reaction to 90. Treatment with SOCl2 and with the aromatic nucleophile or a cross-coupling partner of choice affords 93 (Scheme 27

Catalytic asymmetric reactions of isocyanides for constructing non-central chirality

• Jia-Yu Liao

Beilstein J. Org. Chem. 2025, 21, 1648–1660, doi:10.3762/bjoc.21.129

• L6 as the chiral catalyst, atropisomeric 3-arylpyrroles 34 were generated in 43–98% yield with 82–96% ee. Notably, two by-products 35 and 36 were observed during the reaction, resulting from the aldol reaction of isocyanoacetates with the ketone moiety in 33. The authors have also demonstrated that

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

• oxidation, the Meinwald rearrangement/aldol reaction gave rise to the bridge cyclic intermediate 35, which can finally be converted into both (−)-fortuneicyclidin A and (−)-fortuneicyclidin B. Polycyclization Cyclization/Pictet–Spengler reaction The hexahydropyrrolo[2,1-a]isoquinoline or tetrahydropyrrolo

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

• from α-iodoenone 13. Our synthesis began with the preparation of α-iodoenone 13 (Scheme 2). The α-monomethylation of cyclohexenone 15 was efficiently carried out with LDA, HMPA, and MeI [37], producing enone 16 in 78% yield. Subsequently, a diastereoselective aldol reaction between 16 and 3-furaldehyde

• % brsm). Since the newly created configuration at C30 was inconsequential, an intramolecular aldol reaction was directly carried out by treatment with LiHMDS to furnish β-hydroxylactone, which could be converted to dienone 11 through TPAP oxidation. Having secured 11, we proceeded to evaluate the pivotal

Origami with small molecules: exploiting the C–F bond as a conformational tool

• Patrick Ryan,
• Ramsha Iftikhar and
• Luke Hunter

Beilstein J. Org. Chem. 2025, 21, 680–716, doi:10.3762/bjoc.21.54

Asymmetric synthesis of β-amino cyanoesters with contiguous tetrasubstituted carbon centers by halogen-bonding catalysis with chiral halonium salt

• Yasushi Yoshida,
• Maho Aono,
• Takashi Mino and
• Masami Sakamoto

Beilstein J. Org. Chem. 2025, 21, 547–555, doi:10.3762/bjoc.21.43

• -workers developed chiral amine 1 with an electron-deficient iodine atom, which catalyzed the Mannich reaction in excellent yields and enantioselectivities [17]. In 2020, Huber and co-workers reported the bis(iodoimidazolium) 2-catalyzed Mukaiyama–aldol reaction of carbonyl compounds with enol silyl ethers

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

• 2-(indolin-2-yl)-1,3-tropolones [5]. Unlike the cross-aldol reaction of o-chloranil with methyl ketones [13][14][15], which is always accompanied by the removal of one of the chlorine atoms from the seven-membered ring, the acid-catalyzed reaction between methylene-active heterocyclic compounds and

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

• 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

• yields and enantiomeric purities. The reaction was initiated by the formation of acylazolium intermediate Int-24 that underwent a 1,6-addition with the enol form of the carbonyl substrate to give Int-25. Cyclization was realized via an intramolecular aldol reaction to Int-26 (Scheme 15). Ye and co

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

• . Then, an intramolecular aldol reaction leads to intermediate D which undergoes final protonation to produce the desired chiral product 43f. The authors proposed that the stereoselectivity of the Michael addition product would direct the stereoselectivity of the intramolecular aldol reaction. To

Advances in the use of metal-free tetrapyrrolic macrocycles as catalysts

• Mandeep K. Chahal

Beilstein J. Org. Chem. 2024, 20, 3085–3112, doi:10.3762/bjoc.20.257

• hypothesis that the reaction would work in acidic environment using catalysts insensitive to pH-induced aggregation. In the same aldol reaction, using of macrocycles 60 and 61 containing chiral secondary amine moieties provided not only good yields, but also good diastereoselectivities; chiral HPLC analysis

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

• failed under various conditions, due to decomposition by retro-aldol reaction. Interestingly, while indirubin-N-glycosides 17, thio- and selenoindirubin-N-glycosides 33 and 38 were formed as pure Z-isomers, oxoindirubin-N-glycosides 41 were formed as mixtures of E- and Z-isomers. The isolated yields of Z

• an orange solid (Scheme 29) [46]. In the first step, a base-mediated aldol reaction was carried out. The corresponding alcohol was directly used as the crude product and treated with tosyl chloride, NEt3, and DMAP (stirring for 2 h at 20 °C) to give the corresponding tosylate which was further

Catalysing (organo-)catalysis: Trends in the application of machine learning to enantioselective organocatalysis

• Stefan P. Schmid,
• Leon Schlosser,
• Frank Glorius and
• Kjell Jorner

Beilstein J. Org. Chem. 2024, 20, 2280–2304, doi:10.3762/bjoc.20.196

Selective hydrolysis of α-oxo ketene N,S-acetals in water: switchable aqueous synthesis of β-keto thioesters and β-keto amides

• Haifeng Yu,
• Wanting Zhang,
• Xuejing Cui,
• Zida Liu,
• Xifu Zhang and
• Xiaobo Zhao

Beilstein J. Org. Chem. 2024, 20, 2225–2233, doi:10.3762/bjoc.20.190

• ) [25] or β-keto esters (Scheme 1a, path 4) [26][27], the aldol reaction between aldehydes and S-ethyl acetothioate followed by oxidation with Dess–Martin periodinane (Scheme 1a, path 5) [28], the hydrolysis of α-oxo ketene dithioacetals (Scheme 1a, path 6) [29] and MgBr2·OEt2-catalyzed acylation of

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

• treatment of Alzheimer's disease [3][4]. Likewise, RL91 and BHMPC are active for selective cell growth inhibition of the resistant lines (Figure 1) [5][6]. Their synthesis mainly involves a cascade Michael–aldol reaction between enones and suitable Michael donors such as β-ketosulfones, β-diketones, or

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

• condensation of 73 and 74, followed by highly-diastereoselective vinylogous Mukaiyama aldol reaction and subsequent protecting group manipulations [81][82][83]. The separately synthesized left and right segments, 72 and 75, were then assembled via Horner–Wadsworth–Emmons (HWE) olefination to give carboxylic

pKalculator: A pK_a predictor for C–H bonds

• Rasmus M. Borup,
• Nicolai Ree and
• Jan H. Jensen

Beilstein J. Org. Chem. 2024, 20, 1614–1622, doi:10.3762/bjoc.20.144

• ML models predict the site of reaction using the lowest ML-predicted pKa value. To understand the result for the out-of-sample set, we show three different reactions in Scheme 1. The first step of the reaction shown in Scheme 1a is an aldol reaction where the deprotonation occurs at the least

• reported borylation reactions [45]. Arrow: major experimental site/prediction by SoBo; black ring: QM-computed lowest pKa + 1.5; teal filled circle: ML-predicted lowest pKa + 1.5. Predicting the reaction site for three different reactions from the out-of-sample dataset from Reaxys. (a) Aldol reaction

Synthetic applications of the Cannizzaro reaction

• Bhaskar Chatterjee,
• Dhananjoy Mondal and
• Smritilekha Bera

Beilstein J. Org. Chem. 2024, 20, 1376–1395, doi:10.3762/bjoc.20.120

• ). Huang et al. set up a clean crossed-Cannizzaro-aldol reaction strategy of isatin derivatives 88 and 90 with paraformaldehyde under microwave irradiation to furnish 3,3-disubstituted oxindole derivatives 89a–h and 91a–d [92]. The representative 3-hydroxymethyloxindole adducts with varying substituents