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

Efficient and regioselective synthesis of dihydroxy-substituted 2-aminocyclooctane-1-carboxylic acid and its bicyclic derivatives

• İlknur Polat,
• Selçuk Eşsiz,
• Uğur Bozkaya and
• Emine Salamci

Beilstein J. Org. Chem. 2022, 18, 77–85, doi:10.3762/bjoc.18.7

• -functional theory (DFT) computations were used to explain the reaction mechanism for the ring opening of the epoxide and the formation of five-membered lactones. The stereochemistry of the synthesized compounds was determined by 1D and 2D NMR spectroscopy. The configuration of methyl 6-hydroxy-9-oxo-8

A two-phase bromination process using tetraalkylammonium hydroxide for the practical synthesis of α-bromolactones from lactones

• Yuki Yamamoto,
• Akihiro Tabuchi,
• Kazumi Hosono,
• Takanori Ochi,
• Kento Yamazaki,
• Shintaro Kodama,
• Akihiro Nomoto and
• Akiya Ogawa

Beilstein J. Org. Chem. 2021, 17, 2906–2914, doi:10.3762/bjoc.17.198

• Kawai Building, 8-15,4-Chome, Nihonbashi-Honchou, Chuo-Ku, Tokyo 103-0023, Japan 10.3762/bjoc.17.198 Abstract A simple and efficient method for α-brominating lactones that affords α-bromolactones under mild conditions using tetraalkylammonium hydroxide (R4N+OH−) as a base was developed. Lactones are

• ring-opened with Br2 and a substoichiometric amount of PBr3, leading to good yields of the corresponding α-bromocarboxylic acids. Subsequent intramolecular cyclization over 1 h using a two-phase system (H2O/CHCl3) containing R4N+OH− afforded α-bromo lactones in good yields. This method can be applied

• facilitate the industrial use of α-bromolactones as important intermediates. Keywords: α-bromolactone; metal-free; one-pot operation; tetraalkylammonium hydroxide; two-phase system; Introduction Lactones are important heterocycles in the organic chemistry, materials science, and medicinal chemistry fields

Iron-catalyzed domino coupling reactions of π-systems

• Austin Pounder and
• William Tam

Beilstein J. Org. Chem. 2021, 17, 2848–2893, doi:10.3762/bjoc.17.196

• -lactones [146]. In 2020, Cai and co-workers reported a three-component intermolecular trifluoromethyl-esterification of activated alkenes 115 with NaOTf and aryl carboxylic acids 178 (Scheme 39) [147]. Notably, the use of NaOTf as a CF3 source, compared to pre-prepared trifluoromethylating agents like

Synthesis of highly substituted fluorenones via metal-free TBHP-promoted oxidative cyclization of 2-(aminomethyl)biphenyls. Application to the total synthesis of nobilone

• Ilya A. P. Jourjine,
• Lukas Zeisel,
• Jürgen Krauß and
• Franz Bracher

Beilstein J. Org. Chem. 2021, 17, 2668–2679, doi:10.3762/bjoc.17.181

• cyclic lactones [69]. The intramolecular cyclization of the acyl radical A gives the tricyclic radical species C, which then forms fluorenone (3) after abstraction of a hydrogen radical by an additional equivalent of the tert-butoxy radical. Conclusion In summary, we have demonstrated that the metal-free

Advances in mercury(II)-salt-mediated cyclization reactions of unsaturated bonds

• Sumana Mandal,
• Raju D. Chaudhari and
• Goutam Biswas

Beilstein J. Org. Chem. 2021, 17, 2348–2376, doi:10.3762/bjoc.17.153

• lactones had been synthesized from alkynoic acids via Hg(II)-salt-catalyzed cyclization reaction. For example, simple 4-pentynoic acid derivatives 137 afforded γ-methylene butyrolactones 139 in good yields via the formation of organomercural compounds 138 using catalytic mercuric oxide, mercuric acetate

Methodologies for the synthesis of quaternary carbon centers via hydroalkylation of unactivated olefins: twenty years of advances

• Thiago S. Silva and
• Fernando Coelho

Beilstein J. Org. Chem. 2021, 17, 1565–1590, doi:10.3762/bjoc.17.112

• nucleophiles beyond the usually employed dicarbonyl compounds to cyanoacetates, nitroacetates, fluoroacetates, lactones, lactams, and aromatic and heteroaromatic carbonyl compounds. The reactions were carried out at higher temperatures (120 °C) than used in the previous protocols involving more reactive

• additions [92]. Using MBH acetates 63 as substrates, olefin hydroallylation products 64 were obtained via E1cB elimination of the acetate leaving group driven by the enolate intermediate (Scheme 25B). Six-membered lactones (Scheme 25A, 65a–c) were obtained in a cascade reaction when alkenyl alcohols were

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

Recent advances in palladium-catalysed asymmetric 1,4–additions of arylboronic acids to conjugated enones and chromones

• Jan Bartáček,
• Jan Svoboda,
• Martin Kocúrik,
• Jaroslav Pochobradský,
• Alexander Čegan,
• Miloš Sedlák and
• Jiří Váňa

Beilstein J. Org. Chem. 2021, 17, 1048–1085, doi:10.3762/bjoc.17.84

• acids to 3-methyl-2-cyclohexanone catalysed by L9/Pd(TFA)2 [49]. Addition reaction of phenylboronic acid to various enones, lactones, and chromones catalysed by L9/Pd(TFA)2 [48][51]. Addition reactions of arylboronic acids to substituted chromones and N-Cbz-4-quinolones catalysed by L9/Pd(TFA)2 [51