Asymmetric Mannich reaction of aromatic imines with malonates in the presence of multifunctional catalysts

• Kadri Kriis,
• Harry Martõnov,
• Annette Miller,
• Mia Peterson,
• Ivar Järving and
• Tõnis Kanger

Beilstein J. Org. Chem. 2026, 22, 151–157, doi:10.3762/bjoc.22.8

• enolized carbonyl compound to an imine derived from an aldehyde or ketone and an amine, has been known for more than hundred years [1] and it has become an important method for creating C–C bonds [2][3][4]. The obtained Mannich bases exhibit a broad spectrum of biological activities [5][6] and have also

Total synthesis of natural products based on hydrogenation of aromatic rings

• Haoxiang Wu and
• Xiangbing Qi

Beilstein J. Org. Chem. 2026, 22, 88–122, doi:10.3762/bjoc.22.4

• tetrahydropyridine and completed the synthesis of (±)-LSD (Scheme 10) [74][75]. In the synthesis of (±)-dihydrolysergic acid, Boger and co-workers constructed the tetracyclic core via an inverse-electron demand Diels–Alder cycloaddition between an enamine derived from ketone 88 and triazine, giving pyridine 90 in 75

• . After obtaining 104, the unsaturated ketone was stereoselectively reduced to a specifically oriented hydroxy group using a Luche reduction, which was then protected with acetic anhydride to yield 105. Compound 105 then gave rise to the tertiary alcohol 106 in the presence of zinc powder and ammonium

• spontaneously underwent an intramolecular cycloaddition to yield the highly rigid [2.2.2]-bridged ring skeleton in ketone 116. Finally, nominine was generated via a two-step sequence comprising a Wittig reaction followed by tert-butyl peroxide/selenium dioxide-mediated allylic oxidation, thereby completing

Advances in Zr-mediated radical transformations and applications to total synthesis

• Hiroshige Ogawa and
• Hugh Nakamura

Beilstein J. Org. Chem. 2026, 22, 71–87, doi:10.3762/bjoc.22.3

• Schwartz’s reagent to furnish product 4d. In 2017, Kishi et al. reported a radical-based ketone synthesis employing zirconocene and a nickel catalyst (Scheme 2A) [9]. Traditional anion-based ketone syntheses (e.g., Grignard or RLi reagents) are often unsuitable for complex molecules due to the strongly basic

• conditions required. As an alternative, dithiane-based ketone synthesis has long been used, but it suffers from drawbacks in terms of step economy [10][11]. To address these limitations, the authors developed a radical-based one-pot ketone synthesis that proceeds under mild conditions. When thioester 11 and

• alkyl iodide 10 were subjected to nickel catalysis in the presence of zirconocene dichloride and zinc dust, intermolecular coupling occurred to afford ketone 12 in good yields. This reaction was applicable to substrates bearing β-alkoxy substituents, which are typically problematic under anionic

Synthesis and applications of alkenyl chlorides (vinyl chlorides): a review

• Daniel S. Müller

Beilstein J. Org. Chem. 2026, 22, 1–63, doi:10.3762/bjoc.22.1

• Synthesis of Acetylenes” [29] which discusses the preparation of alkenyl chlorides via ketone chlorination using PCl5 (Figure 3A). The synthesis of β-chlorovinyl ketones was later reviewed by Poland and Benson in 1966 (Figure 3B) [30]. More recently, Morandi and co-workers summarized transition-metal

• group in the α-position (e.g., aldehyde, ketone, sulfone, nitro) is beyond the scope of this review. In 2011, Guinchard and Roulland reviewed Pd-catalyzed cross-couplings of 1,1-dichloroalkenes and boron-chlorination reactions in the context of natural product synthesis (Figure 3C) [33]. Takai’s

• 1875, Louis Henry extended this transformation to ketone 4 (Scheme 1B) [46]. Exposure to PCl5 gave a mixture of chlorinated intermediates described as 5 and 6, which, upon prolonged treatment with ethanolic KOH, underwent elimination to afford allene 7. Henry also observed that thermal treatment of the

Competitive cyclization of ethyl trifluoroacetoacetate and methyl ketones with 1,3-diamino-2-propanol into hydrogenated oxazolo- and pyrimido-condensed pyridones

• Svetlana O. Kushch,
• Marina V. Goryaeva,
• Yanina V. Burgart,
• Marina A. Ezhikova,
• Mikhail I. Kodess,
• Pavel A. Slepukhin,
• Alexandrina S. Volobueva,
• Vladimir V. Zarubaev and
• Victor I. Saloutin

Beilstein J. Org. Chem. 2025, 21, 2716–2729, doi:10.3762/bjoc.21.209

• -trifluoroacetoacetate and methyl ketones enables the synthesis to be carried out for octahydropyrido[1,2-a]pyrimidin-6-ones and hexahydrooxazolo[3,2-a]pyridin-5-ones, the preferential formation of which depends on the substituent in the methyl ketone component. Dual acid–base catalysis of the reactions with alkyl

• intermediate is aldol A, which is formed from 3-oxo ester 1 and methyl ketone 2 under the catalysis of amine 3 [24][25][29]. Therefore, we suggest that the formation of octahydropyrido[1,2-a]pyrimidinones 4 and hexahydrooxazolo[3,2-a]pyridones 5 proceeds via the initial formation of aldol A, which then reacts

• [24], which showed an increase in the diastereoselectivity in synthesis of octahydropyrido[1,2-a]pyrimidinones in the three-component reaction of ethyl trifluoroacetoacetate and 1,3-diaminopropane with methyl ketones with an increase in the volume of substituent in the ketone component. Unlike the

Mechanistic insights into hydroxy(tosyloxy)iodobenzene-mediated ditosyloxylation of chalcones: a DFT study

• Jai Parkash,
• Sangeeta Saini,
• Vaishali Saini,
• Omkar Bains and
• Raj Kamal

Beilstein J. Org. Chem. 2025, 21, 2703–2715, doi:10.3762/bjoc.21.208

• -ditosyloxy ketones. It is found that the mechanism for the formation of α,β-ditosyloxy ketone involves only electrophilic addition of HTIB, and the mechanism is the same for all studied chalcones, irrespective of whether an electron-donating or electron-withdrawing substituent is present on the aryl ring

• para-substituents studied are -OCH3, -SCH3, -Cl and -NO2. The electron-donating groups are -OCH3 and -SCH3, while the remaining two are electron-withdrawing groups with relative power of -Cl < -NO2. Note, the formation of β,β-ditosyloxy ketone from chalcone (Scheme 1) with X = -OCH3 is already

• discussed in reference [34]. Therefore, here for X = -OCH3 only those results for β,β-ditosyloxy ketone formation are presented which are required for comparison with the other para-substituents. Formation of β,β-ditosyloxy ketones Depending on the nature of the para-substituent present on the aryl ring

Recent advancements in the synthesis of Veratrum alkaloids

• Morwenna Mögel,
• David Berger and
• Philipp Heretsch

Beilstein J. Org. Chem. 2025, 21, 2657–2693, doi:10.3762/bjoc.21.206

• 3-position, a copper-mediated C–H activation of position 12 and subsequent protection of the introduced hydroxy moiety to give compound 25 (Scheme 6). Installation of the lactone moiety in 22 was carried out in a three-step sequence via a 1,2-addition of organocerium reagent 26 to the ketone

• metathesis for closing the D-ring (Scheme 7). For the left-hand fragment including the A-, B-, and C-ring, the synthesis started from commercially available (S)-Wieland–Miescher ketone (34), which can also be synthesized via a three-step sequence (Scheme 8). To access 35, several protecting group

• –halogen exchange in the ABC-fragment 38 followed by 1,2-addition to the ketone moiety in the F-ring fragment 42. Protection group manipulations allowed for the union of both fragments to advanced intermediate 43 in three steps in 42%, setting the stage for the key cyclization reactions in this sequence

Synthesis of new tetra- and pentacyclic, methylenedioxy- and ethylenedioxy-substituted derivatives of the dibenzo[c,f][1,2]thiazepine ring system

• Gábor Berecz,
• András Dancsó,
• Mária Tóthné Lauritz,
• Loránd Kiss,
• Gyula Simig and
• Balázs Volk

Beilstein J. Org. Chem. 2025, 21, 2645–2656, doi:10.3762/bjoc.21.205

• removal of the acetyl group by intramolecular dehydrative thioetherification [3] to the bridged molecule 26. As regards the synthesis of compound 27, reduction of ketone 28 with NaBH4 (33), chlorination with SOCl2 (34) and treatment with 2-bromoethanol afforded 2-bromoethoxy derivative 35, which was

• cyclized to target compound 27 by intramolecular N-alkylation reaction. Structures of compounds 25, 26 and 27 have also been confirmed by single-crystal X-ray diffraction (Figure 5). Next, we synthesized some derivatives of new tetracyclic ketone 8 in a way that is already routinely used (Scheme 6

Visible-light-driven NHC and organophotoredox dual catalysis for the synthesis of carbonyl compounds

• Vasudevan Dhayalan

Beilstein J. Org. Chem. 2025, 21, 2584–2603, doi:10.3762/bjoc.21.200

• , particularly the synergistic combination of N-heterocyclic carbenes (NHCs) with organic photocatalysts, has opened new avenues in molecular construction, particularly for the novel, practical preparation of carbonyl group-containing compounds [13][14][15][16]. These ubiquitous ketone, ester, and amide

• production of ketone scaffolds, including drug moieties. The organocatalyzed acylation proceeds with excellent site selectivity and broad functional group tolerance of alkanes such as F, Cl, Br, I, CN, CF3, Me, and OMe. The reaction was achieved between acyl fluoride 4 and highly substituted alkane 7 in the

• presence of NHC (20 mol %), 4CzIPN (2 mol %) under mild conditions, producing corresponding unsymmetrical ketone derivatives 8 in up to 95% yield. An Ir-based photocatalyst was initially selected because its excited state is a strong oxidant (E1/2[Ir*III/II] = +1.21 V). Although 4-ethylanisole exhibits a

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

• , which was subsequently subjected to a one-pot desilylation to afford 24. Reduction of both the ester and ketone functionalities in 24, followed by selective protection of the primary alcohol and re-oxidation of the secondary alcohol to ketone, furnished compound 25 in three steps. The ketone in 25 was

• substructure hidden inside the natural product’s cage-like ring system, Kalesse’s group chose to construct this architecture first using a tandem Nazarov/ene cyclization [36]. The cis-pentalene was subsequently assembled via a Ti(III)-mediated epoxide–ketone coupling reaction. Starting from the known

• , deprotonation, and intramolecular addition to ketone. Treatment of the silacycle with MeMgCl cleaved the Si–O bond and subsequent intramolecular nucleophilic substitution of the chloride with the adjacent hydroxy group yielded TMS-epoxide 41. Protonic acid-mediated opening of the TMS-epoxide, accompanied by TES

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

• diastereoselective reduction of the C3 ketone, the acyl pyrrole group was introduced to yield 81. During acyl pyrrole installation, excess KHMDS enolized the lactone to suppress lactone-C3 hydroxy transesterification. However, α-chlorination of the ester carbonyl was unavoidable. Finally, reductive dechlorination

• material. Key transformations included regioselective and stereoselective alkene epoxidation, organoselenium-mediated reductive cleavage of the α,β-epoxy ketone, and a hydroxy-directed stereospecific Mukaiyama hydration. These operations successfully introduced the C6 and C10 oxidation states, enabling the

• oxidation with freshly prepared trifluoroperacetic acid in n-pentane converted 111 to bis-epoxide 112 with excellent stereoselectivity and yield. Subjecting 112 to oxidation and organoselenium-mediated regioselective α,β-epoxy ketone opening, followed by intramolecular transesterification and elimination

Rapid access to the core of malayamycin A by intramolecular dipolar cycloaddition

• Yilin Liu,
• Yuchen Yang,
• Chen Yang,
• Sha-Hua Huang,
• Jian Jin and
• Ran Hong

Beilstein J. Org. Chem. 2025, 21, 2542–2547, doi:10.3762/bjoc.21.196

• details). The following reductive cleavage of the N–O bond was carried out by Mo(CO)6 in refluxing CH3CN [39]. Subsequent oxidation of the resulting secondary alcohol with Dess–Martin periodinane (DMP) [40] afforded methyl ketone 20 in 53% yield for 2 steps. Moreover, the minor isomer 19b also underwent

• inaccessible (Scheme 5) [41]. We assumed the steric hinderance of the Boc protecting group might have a great impact to the reactivity of ketone. Investigation along this line is currently on the way. Conclusion In summary, we have streamlined the rapid construction of the core perhydrofuropyran skeleton of

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

• measure the significance of the β-face methyl groups. The attractive synthesis of 3-ethyl-substituted betulinic acid derivatives with high cytotoxic and anti-inflammatory activity was described by Grishko et al. [35]. The 2,3-secotriterpenic 3-ethyl-3-ketone 46 was obtained in two steps from lupane α

• -ketoxime 45 by Grignard reduction alkylation, followed by a Beckmann fragmentation of the C2–C3 bond of the intermediate 3-ethyl-substituted hydroxyimino ketone in the SOCl2-CH2Cl2 system. The introduction of a carbonyl substituent into the isopropylidene fragment of ketone 46 was achieved either by

• allylic oxidation using H2SeO3-dioxane system to form the C30 aldehyde 47, or by the ozonolytic cleavage of the double bond between C20 and C29 to produce 20-methyl-3-ethyldiketone 48 [36]. Intramolecular nitrile–anionic cyclization of ketone 46 or diketone 48 under conditions of basic catalysis proceeded

An Fe(II)-catalyzed synthesis of spiro[indoline-3,2'-pyrrolidine] derivatives

• Elizaveta V. Gradova,
• Nikita A. Ozhegov,
• Roman O. Shcherbakov,
• Alexander G. Tkachenko,
• Larisa Y. Nesterova,
• Elena Y. Mendogralo and
• Maxim G. Uchuskin

Beilstein J. Org. Chem. 2025, 21, 2383–2388, doi:10.3762/bjoc.21.183

• -unsaturated ketone; dearomatization; indole; spirocyclization; spiro[indoline-3,2'-pyrrolidine]; Introduction Spiro[indoline-3,2'-pyrrolidine] derivatives represent an important class of organic compounds found in both natural products (e.g., coerulescine [1], horsfiline [2], and elacomine [3]) and synthetic

• . For instance, an intramolecular SN2-type cyclization of β-3-indolyl ketone oximes using MsCl and Et₃N affords spiro[indoline-3,2'-pyrrolidines] (Scheme 1, path f) [13]. A subsequent Cu-catalyzed spirocyclization of β-3-indolyl ketone oxime acetates was developed. This process involves homolytic N–O

• demonstrated an Fe-catalyzed dearomatization of β-2-furyl ketone oxime acetates, yielding functionalized pyrroles [18]. Herein, we report our investigation of the Fe-catalyzed spirocyclization of β-3-indolyl ketone oxime acetates. Results and Discussion Our study commenced with the synthesis of key propan-1

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

• deprotection followed by C–H insertion. However, when attempting to remove the ketal protecting group, only decomposition of the starting material was observed. A plausible explanation for this outcome is that the β-lactone ring, located at the β-position of the methyl ketone, may undergo facile β-elimination

Comparative analysis of complanadine A total syntheses

• Reem Al-Ahmad and
• Mingji Dai

Beilstein J. Org. Chem. 2025, 21, 2334–2344, doi:10.3762/bjoc.21.178

• in four steps. Subsequent conjugate addition of the lithium anion of TMS-acetonitrile to 15, followed by careful one-pot protonation of the resulting enolate with ethyl salicylate and TMS removal with CsF, gave 16 bearing three properly arranged substituents. Grignard 1,2-addition to ketone 16

• underwent ketone release and amine-ketone condensation to form iminium ion 27. Under the same acidic conditions, enamide 26 underwent hydrolysis and tautomerization to form enol 28. Conjugate addition of enol 28 to iminium ion 27 gave 29 for the subsequent intramolecular Mannich cyclization to deliver 30

• , which continued with an amide-ketone condensation to finally produce 31 in this highly efficient one-step biomimetic cascade sequence. The secondary amine of 31 was selectively protected as a Boc carbamate and the dihydropyridone moiety was oxidized to a pyridone with Pb(OAc)4. Pyridone 32 was prepared

Recent advances in Norrish–Yang cyclization and dicarbonyl photoredox reactions for natural product synthesis

• Peng-Xi Luo,
• Jin-Xuan Yang,
• Shao-Min Fu and
• Bo Liu

Beilstein J. Org. Chem. 2025, 21, 2315–2333, doi:10.3762/bjoc.21.177

• congested benzofuranone-based 4,5-spirocycle [26]. Starting from Wieland–Miescher ketone (18, Scheme 4), the synthesis proceeded through a sequence of transformations: the nonconjugated carbonyl was chemoselectively protected as ketal 19; the unprotected ketone then underwent α-methylation to provide 20

• ; and subsequent conversion of the ketone in 20 to the vinyl iodide in 21 – via hydrazone formation, lithium–halogen exchange, and final nucleophilic substitution – secured the Norrish–Yang cyclization precursor 22. Following systematic optimization of reaction conditions, irradiation of 22 with 100 W

• (44) would trigger a quinone-based Norrish–Yang cyclization, enabling divergent synthesis of these meroterpenoids (or their core structures). In Yang's divergent total synthesis, Wieland–Miescher ketone (18) served as the starting material. Selective acetalization of the non-conjugated ketone in 18

Halogenated butyrolactones from the biomass-derived synthon levoglucosenone

• Johannes Puschnig,
• Martyn Jevric and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2025, 21, 2297–2301, doi:10.3762/bjoc.21.175

• [14][15]. In recent years, the chiral biomass derivatives levoglucosenone (LGO, 5) and its reduced form Cyrene® (6) have gained increased attention as platforms for drug discovery [16][17][18][19]. The bicyclic ketone 5 is the major product from the pyrolysis of acid-treated cellulose [20], while its

• monochlorination and bromination of ketone 6 via enamine 9a [31], and it was envisaged that 9a would be a suitable substrate to achieve the double halogenation using an excess of electrophilic halogen. When enamine 9a was treated with 1.0 mol equivalent of trichloroisocyanouric acid (TCCA), a reagent which can

• transfer all three chlorine atoms [32], dichlorinated ketone 10a was obtained in 88% yield following acidic workup. Similarly, treatment of enamine 9a with 3.0 equivalents of N-bromosuccinimide and acidic hydrolysis gave dibrominated material 10b in excellent yield. This procedure is attractive due to the

Enantioselective radical chemistry: a bright future ahead

• Anna C. Renner,
• Sagar S. Thorat,
• Hariharaputhiran Subramanian and
• Mukund P. Sibi

Beilstein J. Org. Chem. 2025, 21, 2283–2296, doi:10.3762/bjoc.21.174

• method for the enantioselective α-C(sp3) alkenylation of ketones containing imidazole auxiliaries (Scheme 10) [24]. The transformation was catalyzed by a chiral-at-rhodium Lewis acid 42. A variety of ketone electrophiles 40 and alkenyl trifluoroborate nucleophiles 41 were converted to the corresponding α

A chiral LC–MS strategy for stereochemical assignment of natural products sharing a 3-methylpent-4-en-2-ol moiety in their terminal structures

• Rei Suo,
• Raku Irie,
• Hinako Nakayama,
• Yuta Ishimaru,
• Yuya Akama,
• Masato Oikawa and
• Shiro Itoi

Beilstein J. Org. Chem. 2025, 21, 2243–2249, doi:10.3762/bjoc.21.171

• –MS detection of the MPO-derived fragment and to achieve a separation of four candidate stereoisomers. To this end, methylation of commercially available methyl acetoacetate (2) and subsequent reduction of the ketone carbonyl group was carried out to prepare a mixture of four stereoisomers of methyl 3

Thiadiazino-indole, thiadiazino-carbazole and benzothiadiazino-carbazole dioxides: synthesis, physicochemical and early ADME characterization of representatives of new tri-, tetra- and pentacyclic ring systems and their intermediates

• Gyöngyvér Pusztai,
• László Poszávácz,
• Anna Vincze,
• András Marton,
• Ahmed Qasim Abdulhussein,
• Judit Halász,
• András Dancsó,
• Gyula Simig,
• György Tibor Balogh and
• Balázs Volk

Beilstein J. Org. Chem. 2025, 21, 2220–2233, doi:10.3762/bjoc.21.169

• reaction of compounds 5a,b with ketone 8, a crude mixture of pentacyclic derivatives 10 and 11 was obtained (10a/11a = 50:50 and 10b/11b = 46:54, respectively). Under these conditions, a full conversion to the oxidized product 10 could not be reached even after long reaction times, presumably because the

• ): [M•]+ calcd for C14H14N4O2S, 302.0837; found, 302.0827. General procedure for the synthesis of hydrazones 7a–e, (E)-9a [22][23]. Method A, step 1: A suspension of 5a (100 mg, 0.416 mmol), the corresponding ketone 6a–e or 8 (1.1 equiv) and bismuth(III) nitrate pentahydrate (44.4 mg, 0.092 mmol) in

• , 1475, 1299, 1152 cm−1; HRESIMS (m/z): [M + H]+ calcd for C15H21N4O2S, 321.1385; found, 321.1377. General procedure for the synthesis of hydrazones 7f–j, (E)-9b [22][23]. A suspension of 5b (100 mg, 0.331 mmol), the corresponding ketone 6a–e or 8 (1.1 equiv) and bismuth(III) nitrate pentahydrate (35.4

Electrochemical cyclization of alkynes to construct five-membered nitrogen-heterocyclic rings

• Lifen Peng,
• Ting Wang,
• Zhiwen Yuan,
• Bin Li,
• Zilong Tang,
• Xirong Liu,
• Hui Li,
• Guofang Jiang,
• Chunling Zeng,
• Henry N. C. Wong and
• Xiao-Shui Peng

Beilstein J. Org. Chem. 2025, 21, 2173–2201, doi:10.3762/bjoc.21.166

• for this reaction was proposed. Firstly, oxidation of I− at the anode afforded I•, which abstracted a hydrogen atom from 50a to form the intermediate A with elimination of HI as a by-product. The second abstraction of a hydrogen atom generated ketone B, which then underwent 1,3-dipolar cycloaddition

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

• level of oxygen content in biomass, small molecules arising from biomass often possess a carbonyl group. This is why biobased platform molecules possessing a carbonyl group, either under the form of an aldehyde, a ketone, an acid or an ester, play a dominant role in biobased chemistry. This review aims

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

• secondary alcohol to a ketone allowed for rapid construction of bicyclic ketone 34 in high overall yield. The oxidative dehydrogenation of 34 gave α,β-unsaturated bicyclic ketone 35 smoothly. Sequential A-ring construction and functional group modifications of 35 produced the diketone 36. Subsequently, 36

• to ketone 48 via a seven-step transformation. Finally, removal of the TBS group in 48 followed by a sequential reduction and selective oxidation of allylic primary alcohol achieved the total synthesis of (−)-cyrneine A (7). The authors then moved forward to the synthesis of other target molecules

• (Scheme 3) [31][32]. Oxidation state adjustment of 48 led to the ketone 49. Starting from this common intermediate, firstly, base-promoted double bond migration and oxidation at the γ-position gave tertiary alcohol 50. Deprotection of acetyl in 50 followed by selective oxidation delivered (−)-cyrneine B

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

• be oxidized to ketone, which gives chabranol. According to this biosynthetic proposal, we thought that the Prins-triggered double cyclization would serve as a powerful method to construct the bicycle in one step, and moreover, the proposed Prins-based double cyclization needs further supporting

• , Wittig reaction with MOMPPh3Cl and LDA gave the putative methyl enol ether, which could be directly converted into 1,3-dithiane 12 with propane-1,3-dithiol. Nucleophilic addition to chiral epoxide 13 and oxidative hydrolysis of 1,3-dithiane to ketone delivered chiral β-hydroxyketone 14. Evans−Tishchenko

• reduction of ketone using SmI2 and propionaldehyde provided 15 diastereoselectively. Friedel–Crafts cyclization using trimethyl orthoformate and TMSOTf provided the cyclic acetal moiety to be oxidized with PDC, delivering the isocoumarin skeleton in 16. Chemoselective removal of the ester with the lactone