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

Hypervalent iodine-mediated intramolecular alkene halocyclisation

• Charu Bansal,
• Oliver Ruggles,
• Albert C. Rowett and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 3113–3133, doi:10.3762/bjoc.20.258

• tetrahydrofurans 25 and tetrahydropyrans 26. Unsaturated carboxylic acids 24 was also cyclised to form 5-membered fluorinated lactones 27. The mechanisms proposed for the cyclisation of unsaturated alcohols and carboxylic acids both proceed first through the activation of the alkene by the iodane (Scheme 11). The

• -dimethylbenziodoxole (12) as an oxidant with AgBF4 and 4 Å molecular sieves to prevent water competing with fluoride as the nucleophile, a range of unsaturated carboxylic acids were successfully cyclised to fluorinated lactones 27 in good yields. The authors proposed a mechanism for fluorolactonization (Scheme 14

• of unsaturated alcohols and carboxylic acids to make tetrahydrofurans, fluoromethyl-γ-lactones and tetrahydropyrans. The ratio of stereoisomers is shown in parentheses. Oxyfluorination of unsaturated alcohols. Synthesis and mechanism of fluoro-benzoxazepines. Intramolecular fluorocyclisation of

Transition-metal-free decarbonylation–oxidation of 3-arylbenzofuran-2(3H)-ones: access to 2-hydroxybenzophenones

• Bhaskar B. Dhotare,
• Seema V. Kanojia,
• Chahna K. Sakhiya,
• Amey Wadawale and
• Dibakar Goswami

Beilstein J. Org. Chem. 2024, 20, 2655–2667, doi:10.3762/bjoc.20.223

• lactones are limited. Both photochemical decarboxylation methods reported for α,γ-butyrolactone [16] and γ-butyrolactones [17] yielded the products in very poor to moderate yields (Figure 2a and 2b). Recently, a transition-metal-free decarboxylation of α,β-unsaturated aromatic lactones was reported for the

• ) is the solar intensity spectrum; Abs(λ) is the experimental absorbance values at corresponding wavelength. The values of [EE(λ) × I(λ)] are constants as shown in Table 3 [9]. Some 2-hydroxybenzophenone derivatives with varied activities. Decarbonylation–oxidation of lactones. The ORTEP view of the

Natural resorcylic lactones derived from alternariol

• Joachim Podlech

Beilstein J. Org. Chem. 2024, 20, 2171–2207, doi:10.3762/bjoc.20.187

• Joachim Podlech Karlsruhe Institute of Technology (KIT), Institute of Organic Chemistry, Kaiserstraße 12, 76131 Karlsruhe, Germany 10.3762/bjoc.20.187 Abstract In this overview, naturally occurring resorcylic lactones biosynthetically derived from alternariol and almost exclusively produced by

• interesting biological activities. Keywords: biosynthesis; fungal metabolites; polyketides; resorcylic lactones; total synthesis; Introduction Alternariol and some of its derivatives are ubiquitous as fungal metabolites present in infested plants and in food and feed, but similarly in soil, in wallpapers

• . Derivatives formed through metabolization in the human body (or in animals) are only covered if the respective metabolites were similarly identified as natural products. A thorough survey of the literature revealed (at now) 127 natural products to be classified as natural resorcylic lactones derived from

Chiral bifunctional sulfide-catalyzed enantioselective bromolactonizations of α- and β-substituted 5-hexenoic acids

• Sao Sumida,
• Ken Okuno,
• Taiki Mori,
• Yasuaki Furuya and
• Seiji Shirakawa

Beilstein J. Org. Chem. 2024, 20, 1794–1799, doi:10.3762/bjoc.20.158

• ; enantioselectivity; halogenation; lactones; organocatalysis; Introduction Catalytic asymmetric halolactonizations of alkenoic acids are powerful methods for the preparation of important chiral lactones in enantioenriched forms [1][2][3][4][5][6][7][8][9][10][11]. A wide variety of chiral catalysts have been applied

• -hexenoic acids 2, β-substituted substrates 2j–n were submitted to the present catalytic system. As a result of these asymmetric reactions, β,β-dialkyl-δ-valerolactones 3j–k and β-spiro-δ-lactones 3l–n were obtained in good levels of enantioselectivity. The reaction of 2-allylbenzoic acid 2o as a related

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

• preparing spiro α-methylene-β-lactones from different steroidal propargylic alcohols [13]. The procedure involves a one-pot Pd-catalyzed cyclocarbonylation of alkynols using 5 mol % of Pd(CH3CN)2Cl2 as a catalyst precursor and 30 mol % of 2-(dibutyl)phosphine-1-(2,6-diisopropylphenyl)-1H-imidazole as

• C–H insertion to produce the spiro-β-lactone was accomplished by simply exposing the diazo derivative to 440 nm blue LEDs (Kessil lamp) at 50 °C, that favored the formation of a singlet carbene that reacted selectively by insertion into the C(3)–H bond. Spiro-lactones 14 were obtained in 80% yield

• assays demonstrated that the γ-spirolactone 20 inhibited the activity of 17β-hydroxysteroid dehydrogenase type 2 (17β-HSD2) with an IC50 value of 0.35 µM. In 2004, the same research group reported the synthesis of similar spiro-γ-lactones from 17α- and 17β-allylestradiols (not substituted at C-7). The

Polymer degrading marine Microbulbifer bacteria: an un(der)utilized source of chemical and biocatalytic novelty

• Weimao Zhong and
• Vinayak Agarwal

Beilstein J. Org. Chem. 2024, 20, 1635–1651, doi:10.3762/bjoc.20.146

• fundamentally signaling molecules and enzymatic modification of AQs by Microbulbifer could represent a mechanism of ecological cross-talk among marine microbiomes. Enzymatic halogenation of other signaling molecules, such as that of acyl homoserine lactones, has been postulated to modulate bacterial

Stability trends in carbocation intermediates stemming from germacrene A and hedycaryol

• Naziha Tarannam,
• Prashant Kumar Gupta,
• Shani Zev and
• Dan Thomas Major

Beilstein J. Org. Chem. 2024, 20, 1189–1197, doi:10.3762/bjoc.20.101

• microbes, in the form of alcohols, ketones, lactones, and glycosides, and of these various forms, the oxo derivatives in particular have strong aroma and biological activity. Interestingly, in addition to being used routinely as flavorings and aromatic agents, sesquiterpene oxo derivatives also have

Enantioselective synthesis of β-aryl-γ-lactam derivatives via Heck–Matsuda desymmetrization of N-protected 2,5-dihydro-1H-pyrroles

• Arnaldo G. de Oliveira Jr.,
• Martí F. Wang,
• Rafaela C. Carmona,
• Danilo M. Lustosa,
• Sergei A. Gorbatov and
• Carlos R. D. Correia

Beilstein J. Org. Chem. 2024, 20, 940–949, doi:10.3762/bjoc.20.84

• , key five-membered olefins bearing heteroatoms can provide direct access to chiral sulfones, sulfoxides, phosphine oxides [8], phthalides, isochromanones, and lactones [9] in a very efficient and convenient manner. Despite our previous results in this area, the desymmetrization of 2,5-dihydro-1H

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

• , and TBHP acting as both an oxidant and a radical initiator. In 2015, Wang et al. reported the synthesis of quinoline lactones by the double oxidative dehydrogenation (DOD) reaction between glycine derivatives and tetrahydrofuran using the FeCl2/HCl/TBHP system (Scheme 19) [80]. This practical coupling

Synthesis of medium and large phostams, phostones, and phostines

• Jiaxi Xu

Beilstein J. Org. Chem. 2023, 19, 687–699, doi:10.3762/bjoc.19.50

• /bjoc.19.50 Abstract Phostams, phostones, and phostines are a series of 1,2-azaphosphaheterocycle and 1,2-oxaphosphaheterocycle 2-oxide derivatives. They are phosphorus analogues of lactams and lactones and important biologically active compounds. The strategies for the synthesis of medium and large

• chemical synthesis of macrocyclic lactones which are the key structural motifs in some biologically active compounds, 14-methyl-2-phenoxy-1-oxa-2-phosphacyclotetradecane 2-oxide (74) was synthesized as the hapten from phenyl hydrogen (12-hydroxytridecyl)phosphonate (73) via Mitsunobu reaction. The

• Phostam, phostone, and phostine derivatives are important 1,2-aza/oxaphosphaheterocyclic compounds and phosphorus analogues of lactams and lactones. They show important biological activities. Medium and large phostam, phostone, and phostine derivatives are important biologically active compounds. Several

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

• ring, while flavylium triflate and 2,4,6-triphenylpyrylium tetrafluoroborate were not compatible with our reaction conditions. Heterodonor ferrocenyl phosphane–carbene ligands efficiently promote the conjugate addition of Grignard reagents to α,β-unsaturated lactones [58]. Building on this knowledge

Transition-metal-catalyzed domino reactions of strained bicyclic alkenes

• Austin Pounder,
• Eric Neufeld,
• Peter Myler and
• William Tam

Beilstein J. Org. Chem. 2023, 19, 487–540, doi:10.3762/bjoc.19.38

• lab reported the Rh-catalyzed domino reaction of doubly bridgehead-substituted oxabicyclic alkenes 134 with secondary amine nucleophiles 135 for the synthesis of bicyclo[2.2.2]lactones 136 (Scheme 24) [70]. This reaction proceeded smoothly with a variety of secondary amine nucleophiles, including

Group 13 exchange and transborylation in catalysis

• Dominic R. Willcox and
• Stephen P. Thomas

Beilstein J. Org. Chem. 2023, 19, 325–348, doi:10.3762/bjoc.19.28

• esters, lactones, and carbonates with HBpin under microwave irradiation (Scheme 13) [57]. When HBpin and boric acid were reacted together, BH3-coordinated HBpin and O(Bpin)2 were detected by 11B NMR spectroscopy. Supported by computational analysis and single-turnover experiments, the reaction was

• reaction of enones and esters or lactones (Scheme 14) [77]. Through a series of single-turnover reactions, a mechanism was proposed (Scheme 14): H-B-9-BBN underwent 1,4-hydroboration with the enone 29, followed by B‒O/B‒H transborylation with HBpin to give an O-Bpin enolate 52 and regenerate H-B-9-BBN

• -catalysed asymmetric reduction of propargylic ketones and the proposed mechanism. H-B-9-BBN-catalysed C–F esterification of alkyl fluorides and the proposed mechanism. H-B-9-BBN-catalysed 1,4-hydroboration of enones and the proposed mechanism. Boric acid-promoted reduction of esters, lactones, and

Sequential hydrozirconation/Pd-catalyzed cross coupling of acyl chlorides towards conjugated (2E,4E)-dienones

• Benedikt Kolb,
• Daniela Silva dos Santos,
• Sanja Krause,
• Anna Zens and
• Sabine Laschat

Beilstein J. Org. Chem. 2023, 19, 176–185, doi:10.3762/bjoc.19.17

• example, the sequential hydrozirconation/carbonylation of propargylic ethers 18 reported by Donato [58] yielded α,β-unsaturated lactones 19. Beside the hydrozirconation/acylation sequence of nitriles utilizing acid chlorides published by Majoral/Floreancig [59][60], Cox revealed that terminal alkynes 16

Identification and determination of the absolute configuration of amorph-4-en-10β-ol, a cadinol-type sesquiterpene from the scent glands of the African reed frog Hyperolius cinnamomeoventris

• Angelique Ladwig,
• Markus Kroll and
• Stefan Schulz

Beilstein J. Org. Chem. 2023, 19, 167–175, doi:10.3762/bjoc.19.16

• used in chemical communication. Hyperolius cinnamomeoventris, a model species, possesses a gular gland on its vocal sac that emits chemicals, and sends visual and auditory signals during calling. Previous investigations have shown that the glandular compounds are typically macrocyclic lactones. However

• -isopropyl-1,6-dimethyl-1,2,3,4,4a,7,8,8a-octahydronaphthalen-1-ol (R-14) as part of the semiochemical mixture released by gular glands of the African reed frog Hyperolius cinnamomeoventris. This establishes the importance of sesquiterpenes for reed frogs, alongside macrocyclic lactones [2]. The total

Practical synthesis of isocoumarins via Rh(III)-catalyzed C–H activation/annulation cascade

• Qian-Ci Gao,
• Yi-Fei Li,
• Jun Xuan and
• Xiao-Qiang Hu

Beilstein J. Org. Chem. 2023, 19, 100–106, doi:10.3762/bjoc.19.10

• occurring lactones isolated from bacterial strains, molds, and plants, exhibiting a wide range of pharmacological properties such as antibacterial, antitumor, and anti-HIV activities (Scheme 1a) [1][2][3][4][5]. Fascinated by their versatile properties, researchers were prompted to develop efficient methods

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

• kinetic resolution of racemic alcohols [99] and for the oxidation of benzylic cyclic ethers to lactones [100] was demonstrated. The CuI/9-azabicyclo[3.3.1]nonane N-oxyl (ABNO) catalytic system successfully promotes the oxidative coupling of alcohols with primary amines [101] (Scheme 13). The reaction

Navigating and expanding the roadmap of natural product genome mining tools

• Friederike Biermann,
• Sebastian L. Wenski and
• Eric J. N. Helfrich

Beilstein J. Org. Chem. 2022, 18, 1656–1671, doi:10.3762/bjoc.18.178

• bioinformatic analysis of (meta-)genomes to identify gene clusters involved in the biosynthesis of NPs [3]. NPs have been shown to act as signaling metabolites (e.g., acylhomoserine lactones (1) [6]), siderophores (e.g., pyoverdines (2) [7]), virulence factors (e.g., malleicyprol (3) [8][9][10]), toxins (e.g

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

• , the synthesis of necic acid lactones such as monocrotalic acid is rare (Figure 2). Consequently, we attempted to apply the rhodium-catalyzed intramolecular reductive aldol-type reaction to the synthesis of a chiral necic acid lactone that is a part of structural component of monocrotaline. According

Synthesis of (−)-halichonic acid and (−)-halichonic acid B

• Keith P. Reber and
• Emma L. Niner

Beilstein J. Org. Chem. 2022, 18, 1629–1635, doi:10.3762/bjoc.18.174

• system found in this natural product. However, we were intrigued that a competing cyclization process also formed isomeric lactones 9 and 10 in 8% yield and 11% yield, respectively. 1H NMR analysis confirmed that compounds 9 and 10 were both trans-fused 6/5 bicycles based on the magnitude of the vicinal

• difference in the 13C NMR chemical shift of the C7-methyl group, which appears at δ = 20.7 in (−)-2 and δ = 14.5 in 11. Discussion Rationalizing the outcome of the aza-Prins reaction leading to the formation of ethyl ester 8 and isomeric lactones 9 and 10 (Scheme 2) provides an interesting exercise in

• hydrolyzed under basic conditions (Scheme 2) to form the enantiomer of halichonic acid B ((−)-2). It is interesting to note that halichonic acid B exists exclusively as an open-chain 4-hydroxycarboxylic acid even though the corresponding γ-lactones typically form spontaneously. Indeed, no lactone formation

Vicinal ketoesters – key intermediates in the total synthesis of natural products

• Marc Paul Beller and
• Ulrich Koert

Beilstein J. Org. Chem. 2022, 18, 1236–1248, doi:10.3762/bjoc.18.129

• alcohol 56, which was dehydroxylated to the diastereomeric cations VIII and IX. Friedel–Crafts reaction gave diastereomeric lactones 57 and 58. The major diastereomer 58 could be converted to the complex polyphenol (−)-hopeanol (59) in seven further steps. (+)-Camptothecin In the formal synthesis of the

New azodyrecins identified by a genome mining-directed reactivity-based screening

• Atina Rizkiya Choirunnisa,
• Kuga Arima,
• Yo Abe,
• Noritaka Kagaya,
• Kei Kudo,
• Hikaru Suenaga,
• Junko Hashimoto,
• Manabu Fujie,
• Noriyuki Satoh,
• Kazuo Shin-ya,
• Kenichi Matsuda and
• Toshiyuki Wakimoto

Beilstein J. Org. Chem. 2022, 18, 1017–1025, doi:10.3762/bjoc.18.102

• alcohols [24], methoxides [23][25][26], carboxylic acids [27], amides [28], ketones [29][30], an exo-olefin [31], and lactones [32]. Elucidating the mechanisms of structural diversification is essential when considering the synthesis of unnatural azoxides by a synthetic biology-based approach. However

First example of organocatalysis by cathodic N-heterocyclic carbene generation and accumulation using a divided electrochemical flow cell

• Daniele Rocco,
• Ana A. Folgueiras-Amador,
• Richard C. D. Brown and
• Marta Feroci

Beilstein J. Org. Chem. 2022, 18, 979–990, doi:10.3762/bjoc.18.98

• and cis γ-butyrolactones were easily separated by column chromatography. Increasing the applied charge from 0.5 F (Table 2, entry 1) to 1.0 F (Table 2, entry 2) improved the yield of both cis (2a) and trans (2b) lactones by approximately three fold. Instead, with a charge of 2.0 F the yield of 2a

Terpenoids from Glechoma hederacea var. longituba and their biological activities

• Dong Hyun Kim,
• Song Lim Ham,
• Zahra Khan,
• Sun Yeou Kim,
• Sang Un Choi,
• Chung Sub Kim and
• Kang Ro Lee

Beilstein J. Org. Chem. 2022, 18, 555–566, doi:10.3762/bjoc.18.58

• distributed in Korea, Japan, and China. This plant has been used as Korean traditional medicine for treating asthma, bronchitis, cholelithiasis, colds, and inflammation [1][2]. Previous studies have shown that G. hederacea var. longituba contains phytochemicals such as monoterpenoids, sesquiterpene lactones