Copper-catalyzed yne-allylic substitutions: concept and recent developments

• Shuang Yang and
• Xinqiang Fang

Beilstein J. Org. Chem. 2024, 20, 2739–2775, doi:10.3762/bjoc.20.232

• rearomatization In 2023, Lin and He et al. [72] achieved the challenging dearomatization of heteroarenes through d-orbital electron of the transition-metal center and thus completed the asymmetric substitutions with remote stereoselective control induced by alkynylcopper. A newly electron-rich ligand was

• structure precludes stable copper-carbonyl interaction, favoring attack from a less hindered site. Later, Qi and Xu et al. [75] achieved highly enantioselective copper-catalyzed [4 + 1] cyclization of yne-allylic esters and cyclic 1,3-dicarbonyls, achieving remote stereoselective control through copper

• stereoselective aromatization serves as a pivotal step in the transfer of central chirality to axial chirality (Scheme 52). To harness the full potential of CO2 as a renewable and abundant carbon source, He et al. [82] proposed an innovative strategy that married asymmetric yne-allylic substitution with CO2

Computational design for enantioselective CO₂ capture: asymmetric frustrated Lewis pairs in epoxide transformations

• Maxime Ferrer,
• Iñigo Iribarren,
• Tim Renningholtz,
• Ibon Alkorta and
• Cristina Trujillo

Beilstein J. Org. Chem. 2024, 20, 2668–2681, doi:10.3762/bjoc.20.224

• strategically modifying LB substituents to induce asymmetry, a stereoselective catalytic scaffold was developed, favouring one enantiomer from both epoxide enantiomers. This work advances the in silico design of FLPs, highlighting their potential as asymmetric CCU catalysts with implications for optimising

• plot analysis reveals that the best candidate is F3_NB_C5_CF3, which is the catalyst based on the 2-borylbenzenamine scaffold, with a pyrrolidine substituent on the nitrogen atom and CF3 substituents on the boron. Through strategic modification of the Lewis base substituents, a stereoselective catalyst

A review of recent advances in electrochemical and photoelectrochemical late-stage functionalization classified by anodic oxidation, cathodic reduction, and paired electrolysis

• Nian Li,
• Ruzal Sitdikov,
• Ajit Prabhakar Kale,
• Joost Steverlynck,
• Bo Li and
• Magnus Rueping

Beilstein J. Org. Chem. 2024, 20, 2500–2566, doi:10.3762/bjoc.20.214

• involves building a ring onto a preexisting system, whether cyclic or non-cyclic. The Lei group developed an electrooxidative annulation reaction that facilitates LSF [28]. A regio- and stereoselective protocol was established for the [4 + 2] annulation of indole derivatives, allowing access to highly

• mediator between the anode and the nickel-chelated enolate intermediate. Simultaneously, the amine substrate is oxidized at the anode and deprotonated to generate a nitrogen-centered radical. The desired product then is generated by the stereoselective cross-coupling of the carbon-centered radical with the

Phenylseleno trifluoromethoxylation of alkenes

• Clément Delobel,
• Armen Panossian,
• Gilles Hanquet,
• Frédéric R. Leroux,
• Fabien Toulgoat and
• Thierry Billard

Beilstein J. Org. Chem. 2024, 20, 2434–2441, doi:10.3762/bjoc.20.207

• the position of the double bond in the molecule. Notably, a longer reaction time was required for less reactive or more hindered substrates. The reaction was stereoselective as only the anti products were obtained. A good regioselectivity was generally observed, as at least 80% of the main regioisomer

Facile preparation of fluorine-containing 2,3-epoxypropanoates and their epoxy ring-opening reactions with various nucleophiles

• Yutaro Miyashita,
• Sae Someya,
• Tomoko Kawasaki-Takasuka,
• Tomohiro Agou and
• Takashi Yamazaki

Beilstein J. Org. Chem. 2024, 20, 2421–2433, doi:10.3762/bjoc.20.206

• preparation of 2a. Moreover, the fact that only very limited examples are known for their synthetic application except for the synthesis of 4,4,4-trifluorothreonine [29][33], stereoselective ring opening with organometallic species [29], and so on [32] also stimulated our interest. In this article, we would

• successful employment of amines as nucleophiles for the epoxy ring opening in a highly stereoselective fashion, we next turned our attention to thiols. Optimization of the reaction conditions based on the ones for amines clarified the tendency that the longer reaction time and the higher temperature

• was confirmed as 2,3-anti-3,4-syn by its X-ray crystallographic analysis [49] (Figure 2) whose construction could be readily understood as the result of a highly stereoselective SN2-type epoxy ring opening of 2a, followed by the intramolecular lactone formation with the pro-R ethoxycarbonyl group

Stereoselective mechanochemical synthesis of thiomalonate Michael adducts via iminium catalysis by chiral primary amines

• Michał Błauciak,
• Dominika Andrzejczyk,
• Błażej Dziuk and
• Rafał Kowalczyk

Beilstein J. Org. Chem. 2024, 20, 2313–2322, doi:10.3762/bjoc.20.198

• significant advancement in mechanocatalysis. The stereoselective addition of bisthiomalonates 1–4 to cyclic enones and 4-chlorobenzylideneacetone proceeds stereoselectively under iminium activation conditions secured by chiral primary amines, in contrast to oxo-esters as observed in dibenzyl malonate addition

• studies by Bolm [12][13], and Juaristi et al. [14]. have significantly advanced chiral secondary amine-catalyzed stereoselective reactions under ball milling conditions, representing a widely explored activation mode in mechanochemical-mediated transformations. However, reports on chiral primary iminium

• attention. The controlled formation of C–C and C–X bonds in a stereoselective fashion has found extensive application in asymmetric synthesis. Notably, the addition of malonates has attracted significant interest, albeit primarily limited to methyl or ethyl diesters [18][19][20]. The combination of iminium

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

• considerable interest in the stereoselective synthesis of the cyclohexanone skeleton as it constitutes the core structure in many natural products and pharmaceutical drugs [1][2]. Garsubellin A with a cyclohexanone skeleton is a potent inducer of choline acetyltransferase (ChAT) and could be used for the

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

• steroidal 17-ketones were first alkylated in the presence of the lithium derivative of ethyl propiolate. After stereoselective formation of the corresponding adduct, the triple bond was chemoselectively reduced under catalytic hydrogenation using 5% palladium on charcoal. As a final step, a p

• ninhydrin. Estrone-derived dispiropyrrolidines 43, 44, and 45 were obtained in a regio- and stereoselective manner (ylide attacks by the α-steroidal face) in yields ranging from 66% to 72%. 1,3-Dipolar cyclization of azomethine ylides can also be achieved using (E)-steroidal arylidenes at C-16. In 2014, Liu

• superior results compared to phenyl-substituted compounds. Frank et al. synthesized a series of 16-spiroisoxazolines through a regio- and a highly stereoselective 1,3-dipolar cycloaddition between the double bond of the α,β-unsaturated steroidal ketone 73 and various arylnitrile oxides [45]. The reaction

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

• well as their analogs, is outlined with an emphasis on comparing these chemo-enzymatic syntheses with the corresponding natural biosynthetic pathways. Keywords: chemo-enzymatic synthesis; late-stage modification; reactive biosynthetic intermediate; regio- and stereoselective (macro)cyclization; total

• using an enzyme or at what stage in a synthesis the enzyme is employed: 1) regio- and stereoselective late-stage functionalization of core scaffolds, 2) in situ generation of highly reactive intermediates, and 3) the one-step construction of macrocyclic or fused multicyclic scaffolds via regio- and

• stereoselective cyclization reactions. This review aims to provide an overview of these approaches and parallel comparisons with original biosynthetic pathways by highlighting five examples of chemo-enzymatic total syntheses of natural products reported since 2017. The examples are the synthesis of cotylenol (1

Methyltransferases from RiPP pathways: shaping the landscape of natural product chemistry

• Maria-Paula Schröder,
• Isabel P.-M. Pfeiffer and
• Silja Mordhorst

Beilstein J. Org. Chem. 2024, 20, 1652–1670, doi:10.3762/bjoc.20.147

• within the context of ribosomally synthesised and post-translationally modified peptide (RiPP) natural products. Methyltransferases play a pivotal role in the biosynthesis of diverse natural products with unique chemical structures and bioactivities. They are highly chemo-, regio-, and stereoselective

Electrocatalytic hydrogenation of cyanoarenes, nitroarenes, quinolines, and pyridines under mild conditions with a proton-exchange membrane reactor

• Koichi Mitsudo,
• Atsushi Osaki,
• Haruka Inoue,
• Eisuke Sato,
• Naoki Shida,
• Mahito Atobe and
• Seiji Suga

Beilstein J. Org. Chem. 2024, 20, 1560–1571, doi:10.3762/bjoc.20.139

• semihydrogenation of alkynes to form Z-alkenes using a PEM reactor [31]. The Pd/C catalyst was essential for the reaction. They recently found that a PEM reactor with a Rh/C catalyst was effective for the stereoselective reduction of cyclic ketones [40]. Nagaki et al. reported the electrochemical deuteration of

Benzylic C(sp³)–H fluorination

• Alexander P. Atkins,
• Alice C. Dean and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 1527–1547, doi:10.3762/bjoc.20.137

• ; however, the methodology was only shown on secondary benzylic positions. The stereoselective benzylic monofluorination of α-amino acids was also reported by Yu and co-workers, employing a similar directing group strategy (Figure 7) [41]. The use of the monodentate directing group 2,3,5,6-tetrafluoro-4

• was effective for the stereoselective fluorination of benzylic positions ortho to aldehyde substituents (Figure 9). The choice of a bulky amino, transient, directing group dictated the stereochemical outcome and promoted the C–F reductive elimination through an inner-sphere pathway. A competitive C–O

Towards an asymmetric β-selective addition of azlactones to allenoates

• Behzad Nasiri,
• Ghaffar Pasdar,
• Paul Zebrowski,
• Katharina Röser,
• David Naderer and
• Mario Waser

Beilstein J. Org. Chem. 2024, 20, 1504–1509, doi:10.3762/bjoc.20.134

• synthesis approaches. Our group has a longstanding focus on the development of asymmetric organocatalytic methods to access non-natural chiral α- and β-AA [14][15][16][17][18][19]. Hereby we are especially interested in utilizing simple (prochiral) starting materials and carry out stereoselective α

Bismuth(III) triflate: an economical and environmentally friendly catalyst for the Nazarov reaction

• Manoel T. Rodrigues Jr.,
• Aline S. B. de Oliveira,
• Ralph C. Gomes,
• Amanda Soares Hirata,
• Lucas A. Zeoly,
• Hugo Santos,
• João Arantes,
• Catarina Sofia Mateus Reis-Silva,
• João Agostinho Machado-Neto,
• Leticia Veras Costa-Lotufo and
• Fernando Coelho

Beilstein J. Org. Chem. 2024, 20, 1167–1178, doi:10.3762/bjoc.20.99

• lilolidone nucleus [77] and by Jung in the stereoselective synthesis of podophyllotoxin derivatives (Scheme 1) [78]. Although the decarboxylation reaction of indanones has been observed and described in the literature, there are few extensive studies aimed at exploring this transformation. The only exception

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

• compound E. Cyclization occurred via dehydrogenation and intramolecular aldol condensation and in the last step hydrogen transfer provided the desired cyclic product H (Scheme 35). In 2020, Maji and Adhikari reported a phosphine-free N,N-amine–manganese complex-catalyzed stereoselective intermolecular and

Three-component N-alkenylation of azoles with alkynes and iodine(III) electrophile: synthesis of multisubstituted N-vinylazoles

• Jun Kikuchi,
• Roi Nakajima and
• Naohiko Yoshikai

Beilstein J. Org. Chem. 2024, 20, 891–897, doi:10.3762/bjoc.20.79

• Jun Kikuchi Roi Nakajima Naohiko Yoshikai Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba, Aramaki, Aoba-ku, Sendai 980-8578, Japan 10.3762/bjoc.20.79 Abstract A stereoselective N-alkenylation of azoles with alkynes and iodine(III) electrophile is reported. The reaction

• iodonium salts [9], which usually occurs with the retention of the stereochemistry of the vinylating agents (Scheme 1a). Nonetheless, this approach is not necessarily suited for the stereoselective preparation of densely substituted N-vinylazoles because preparing the requisite multisubstituted vinylating

• oxazolidinone-substituted ynamide also proved to undergo iodo(III)azolation in a regio- and stereoselective fashion to give the product 4ai in a moderate yield. Note that terminal alkynes such as phenylacetylene also took part in the reaction, albeit in a much-diminished yield (7% by 1H NMR; data not shown

Confirmation of the stereochemistry of spiroviolene

• Yao Kong,
• Yuanning Liu,
• Kaibiao Wang,
• Tao Wang,
• Chen Wang,
• Ben Ai,
• Hongli Jia,
• Guohui Pan,
• Min Yin and
• Zhengren Xu

Beilstein J. Org. Chem. 2024, 20, 852–858, doi:10.3762/bjoc.20.77

• stereoselective process to form complex terpene skeletons, normally with multiple stereocenters. In this context, the 3D-defined cyclization products retain the rich information of the complex cyclization process. Thus, assignment of the stereochemistry of the terpene skeleton with high confidence is crucial for

Advancements in hydrochlorination of alkenes

• Daniel S. Müller

Beilstein J. Org. Chem. 2024, 20, 787–814, doi:10.3762/bjoc.20.72

• (regioisomeric ratio) corresponds to the ratio of linear (anti-Markovnikov) and branched (Markovnikov) product. anti-Markovnikov hydrochlorinations as reported by Liu. Stereoselective hydrochlorination of 1,2-dimethylcyclohexene (29). Stereoselective hydrochlorination of octahydronaphthalene (31

• ). Stereoselective hydrochlorination of hexahydro-1H-indene (33). Hydrochlorination of cycloheptene (61). Hydrochlorination of 1-octene (63). Influence of the HCl gas pressure on the reaction yield. Control reactions for the hydrochlorination reaction of alkene 106. Optimization reactions for the hydrochlorination

Chemoenzymatic synthesis of macrocyclic peptides and polyketides via thioesterase-catalyzed macrocyclization

• Senze Qiao,
• Zhongyu Cheng and
• Fuzhuo Li

Beilstein J. Org. Chem. 2024, 20, 721–733, doi:10.3762/bjoc.20.66

• the linear predecessors. Nevertheless, this method was unable to acquire substrate derivatives, restricting the exploration of the substrate scope for TE domains. Hence, it is necessary to produce linear precursors using concise stereoselective methodologies to facilitate the investigation of

• macrolactonization, leading to the formation of tylactone (39) in 69% yield. Furthermore, the Streptomyces strain S. venezuelae DHS316 [76] performed an in vivo glycosylation resulting in M-4365 G1 (50) in 15 linear steps and 4.6% overall yield from commercial resources. With regio- and stereoselective C–H

(E,Z)-1,1,1,4,4,4-Hexafluorobut-2-enes: hydrofluoroolefins halogenation/dehydrohalogenation cascade to reach new fluorinated allene

• Nataliia V. Kirij,
• Andrey A. Filatov,
• Yurii L. Yagupolskii,
• Sheng Peng and
• Lee Sprague

Beilstein J. Org. Chem. 2024, 20, 452–459, doi:10.3762/bjoc.20.40

• significantly. One of the new and budding directions in recent years is the stereoselective olefin metathesis processes based on catalysis by complexes of molybdenum, tungsten and ruthenium [3][4][5]. The first publications have recently appeared that molybdenum complexes can catalyze cross-metathesis of butene

Catalytic multi-step domino and one-pot reactions

• Svetlana B. Tsogoeva

Beilstein J. Org. Chem. 2024, 20, 254–256, doi:10.3762/bjoc.20.25

• facile stereoselective tandem reaction based on the asymmetric conjugate addition of dialkylzinc reagents to unsaturated acylimidazoles, followed by trapping of the intermediate zinc enolate with carbocations [12]. A practical one-pot synthesis of fluorescent pyrazolo[3,4-b]pyridin-6-ones by reacting 5

Comparison of glycosyl donors: a supramer approach

• Anna V. Orlova,
• Nelly N. Malysheva,
• Maria V. Panova,
• Nikita M. Podvalnyy,
• Michael G. Medvedev and
• Leonid O. Kononov

Beilstein J. Org. Chem. 2024, 20, 181–192, doi:10.3762/bjoc.20.18

• supramolecular aggregates (supramers) rather than single molecules of reacting substances that are the real reacting species [39]. This line of reasoning allowed us to explain, predict, discover a number of unusual phenomena and develop highly efficient and stereoselective glycosylation reactions with sialyl

• Table 1) rather than that of the parent molecules of sialyl donors 1 and 2. Then it is no longer surprising why at low concentration (0.05 mol·L−1) the sialyl donor 1 was 23% more stereoselective while at high concentration (0.15 mol·L−1) sialyl donor 2 was 50% more stereoselective and the relative

• stereoselective while sialyl donor 1 with a trifluoroacetyl group at O-9 became 33% less stereoselective at high concentration (0.15 mol·L−1) as compared to the results at low concentration (0.05 mol·L−1). To the best of our knowledge, traditional mechanistic reasons for the opposite influence of the increase in

A novel recyclable organocatalyst for the gram-scale enantioselective synthesis of (S)-baclofen

• Gyula Dargó,
• Dóra Erdélyi,
• Balázs Molnár,
• Péter Kisszékelyi,
• Zsófia Garádi and
• József Kupai

Beilstein J. Org. Chem. 2023, 19, 1811–1824, doi:10.3762/bjoc.19.133

• , acetonitrile, with 91–100% efficiency, and the catalyst was reused in five reaction cycles without the loss of activity and selectivity. Keywords: baclofen; catalyst recovery; lipophilic cinchona squaramide; organocatalysis; stereoselective catalysis; Introduction In today’s chemical industry, catalytic

• organocatalysts has been a major breakthrough in the realization of enantioselective transformations. Stereoselective synthesis is essential in the pharmaceutical industry, as the development of drugs often requires the production of enantiomerically pure chiral compounds [6][7][8]. The application of

• cinchona squaramide organocatalyst. Its catalytic activity and recyclability were examined in a new stereoselective synthesis of baclofen, which is used to treat muscle spasms [30]. Finally, the catalyst was easily recycled by centrifugation over five reaction cycles without significant loss of activity

Recent advancements in iodide/phosphine-mediated photoredox radical reactions

• Tinglan Liu,
• Yu Zhou,
• Junhong Tang and
• Chengming Wang

Beilstein J. Org. Chem. 2023, 19, 1785–1803, doi:10.3762/bjoc.19.131

• active natural products. The direct functionalization of C–H bonds in enamides offers a convenient and versatile approach to access a wide range of functionalized enamides. In 2021, Fu and his colleagues successfully developed a novel method for the stereoselective alkylation of enamides 14 using iodine

Trifluoromethylated hydrazones and acylhydrazones as potent nitrogen-containing fluorinated building blocks

• Zhang Dongxu

Beilstein J. Org. Chem. 2023, 19, 1741–1754, doi:10.3762/bjoc.19.127

• =N motif within hydrazones gives them both electrophilic and nucleophilic character. In 2005, Brigaud et al. developed a highly stereoselective method for the synthesis of α-trifluoromethylamines with organometallic reagents to extend the asymmetric methodologies of trifluoroacetaldehyde hydrazones