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

• , the terminal alkene remains intact during this process, and the initial protonation proceeds with full stereocontrol, rendering this transformation both highly chemo- and diastereoselective. From the cyclization result, it is presumed that the higher nucleophilicity of the alkyne functionality over

• total synthesis of cephalotaxine. Similarly, diastereoselective reduction of 25 with KBH4 followed by alane reduction provided another alkaloid cephalezomine H. Collective total syntheses of Cephalotaxus alkaloids The cyclopentane ring in most Cephalotaxus alkaloids is characterized by the highest

Harnessing tethered nitreniums for diastereoselective amino-sulfonoxylation of alkenes

• Shyam Sathyamoorthi,
• Appasaheb K. Nirpal,
• Dnyaneshwar A. Gorve and
• Steven P. Kelley

Beilstein J. Org. Chem. 2025, 21, 947–954, doi:10.3762/bjoc.21.78

• ring was opened in a diastereoselective (SN2 type) and exo-selective manner by a trifluoroacetate anion. The trifluoroacetate anion was conveniently derived from (bis(trifluoroacetoxy)iodo)benzene (PIFA), which was used as the stoichiometric oxidant in the reaction. Overall, this amounted to a highly

• regioselective, diastereoselective, and metal-free protocol for alkene amino-hydroxylation, which compared favorably to prior art in this area [25][26][27][28][29][30][31][32]. Naturally, we wondered if other O-nucleophiles were competent in the ring-opening of the aziridinium intermediate. Indeed, almost all

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

Cu–Bpin-mediated dimerization of 4,4-dichloro-2-butenoic acid derivatives enables the synthesis of densely functionalized cyclopropanes

• Patricia Gómez-Roibás,
• Andrea Chaves-Pouso and
• Martín Fañanás-Mastral

Beilstein J. Org. Chem. 2025, 21, 877–883, doi:10.3762/bjoc.21.71

• ). We have studied this reaction and now report a catalytic methodology for the diastereoselective synthesis of these dimeric structures. The high degree of functionalization present in these molecules, which feature two ester groups, an aliphatic gem-dichloride and a dichloroalkene unit, offers ample

• opportunities for further functionalization. This is illustrated by their chemo- and diastereoselective conversion into densely functionalized cyclopropanes (Scheme 1c). Results and Discussion Based on our preliminary result, we started our study by exploring the reaction between ethyl 4,4-dichloro-2-butenoate

• mechanism for the copper-catalyzed diastereoselective dimerization of 4,4-dichoro-2-butenoic acid derivatives (Scheme 4). Initially, the LCu–pin complex generated through reaction between LCu–Ot-Bu and B2pin2 undergoes coordination and regioselective insertion into 1 giving rise to β-borylated organocopper

Copper-catalyzed domino cyclization of anilines and cyclobutanone oxime: a scalable and versatile route to spirotetrahydroquinoline derivatives

• Qingqing Jiang,
• Xinyi Lei,
• Pan Gao and
• Yu Yuan

Beilstein J. Org. Chem. 2025, 21, 749–754, doi:10.3762/bjoc.21.58

• azetidinones, enabling the efficient and enantioselective synthesis of tetrahydroquinoline-fused azetidines with three contiguous stereocenters in a single step [23]. Later, Tanaka, Nagashima, and their co-workers established a chemo-, regio-, and diastereoselective dearomative transformation of quinolines

Recent advances in allylation of chiral secondary alkylcopper species

• Minjae Kim,
• Gwanggyun Kim,
• Doyoon Kim,
• Jun Hee Lee and
• Seung Hwan Cho

Beilstein J. Org. Chem. 2025, 21, 639–658, doi:10.3762/bjoc.21.51

• approach focused on the diastereoselective formation of homoallylic boronic esters 36 through a carefully controlled sequence of hydrocupration and allylic substitution [39]. Through optimization studies, Yun found that CuCl with the Walphos ligand (L2) in Et2O provided optimal results, delivering the

• traditional crotyl addition to acetaldehyde. This methodology represents the first example of highly enantio- and diastereoselective copper-catalyzed allylic substitution that controls vicinal stereogenic centers. DFT calculations revealed that the high enantioselectivity (98:2 er) originates from a face

• with olefins bearing electronic directing groups (such as aryl, boryl, or trifluoromethyl substituents) that guide regioselective hydrocupration, unactivated alkyl-substituted alkenes pose a persistent challenge. The recent breakthrough in CuH-catalyzed enantioselective and diastereoselective allylic

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

• enantio- and diastereoselective Mannich reaction of α-cyanoesters with aldimines catalyzed by chiral amines, which provided β-amino cyanoesters in excellent yield and diastereoselectivities with up to 98% ee (Figure 2a) [41]. The Mannich reaction has been also applied in the construction of contiguous

• chiral halonium salt. Conclusion In conclusion, the enantio- and diastereoselective Mannich reaction was developed by chiral halonium salt catalysis, which provided the corresponding products with contiguous chiral tetrasubstituted carbon centers in excellent yields with up to 86% ee using only 1 mol

Vinylogous functionalization of 4-alkylidene-5-aminopyrazoles with methyl trifluoropyruvates

• Judit Hostalet-Romero,
• Laura Carceller-Ferrer,
• Gonzalo Blay,
• Amparo Sanz-Marco,
• José R. Pedro and
• Carlos Vila

Beilstein J. Org. Chem. 2025, 21, 533–540, doi:10.3762/bjoc.21.41

• functionalization of 5-aminopyrazoles [26], we decided to study 4-alkenyl-5-aminopyrazoles as nucleophiles in the vinylogous addition reaction to electrophiles. Herein, we report the regioselective and diastereoselective functionalization of 4-cyclohexenyl-5-aminopyrazoles using alkyl trifluoropyruvates [27][28][29

• yield decreased, possibly due to the formation of imine B, which might be favored by the dehydration effect of the molecular sieves. Conclusion In summary, a regioselective and diastereoselective vinylogous addition reaction of 4-alkenyl-5-aminopyrazoles to alkyl trifluoropyruvate has been studied

Organocatalytic kinetic resolution of 1,5-dicarbonyl compounds through a retro-Michael reaction

• James Guevara-Pulido,
• Fernando González-Pérez,
• José M. Andrés and
• Rafael Pedrosa

Beilstein J. Org. Chem. 2025, 21, 473–482, doi:10.3762/bjoc.21.34

• to enamine E, which epimerizes at C-4 and, after hydrolysis, provides the adduct syn-(3R,4R)-1 with an initial er of 4:96. This diastereoselective epimerization phenomenon promoted by an organocatalyst has not been previously described. The study emphasizes the reversibility of some organocatalyzed

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

• (cis/trans) determined by 19F NMR analysis. Kitamura’s synthesis of 3-fluoropyrrolidines. Values in parentheses represent the cis:trans ratio. Jacobsen’s enantio- and diastereoselective protocol for the synthesis of syn-β-fluoroaziridines 15. Different HVI reagents lead to different

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

• orientation of p-nitrophenyl units, due to the shielding of the bound aldehyde substrate from the incoming diene. The catalytic inactivity of 5 demonstrated the requirement of macrocyclic character for the potential catalysts. Later in 2009, the same group reported an organocatalyzed diastereoselective aldol

4,6-Diaryl-5,5-difluoro-1,3-dioxanes as chiral dopants for liquid crystal compositions

• Maurice Médebielle,
• Peer Kirsch,
• Jérémy Merad,
• Carolina von Essen,
• Clemens Kühn and
• Andreas Ruhl

Beilstein J. Org. Chem. 2024, 20, 2940–2945, doi:10.3762/bjoc.20.246

• here preliminary results with the diastereoselective synthesis of two 4,6-diphenyl-5,5-difluoro-1,3-dioxanes (rac-3 and rac-4) and their separation into their corresponding enantiomers ((R,R)-3 and (S,S)-3; (R,R)-4 and (S,S)-4). rac-3 and rac-4 are obtained from readily available racemic 2,2-difluoro

Access to optically active tetrafluoroethylenated amines based on [1,3]-proton shift reaction

• Yuta Kabumoto,
• Eiichiro Yoshimoto,
• Bing Xiaohuan,
• Masato Morita,
• Motohiro Yasui,
• Shigeyuki Yamada and
• Tsutomu Konno

Beilstein J. Org. Chem. 2024, 20, 2776–2783, doi:10.3762/bjoc.20.233

• ]. As a diastereoselective synthesis, reductive coupling reactions of commercially available 4-bromo-3,3,4,4-tetrafluoro-1-butene and glyceraldehyde 10a, its imine derivative 11, or Garner's aldehyde 10b have been reported [23][24]. Although the diastereoselectivities were low in some cases, the

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

• in most cases. A triple Michael adduct, tetrahydrochromen-4-one, is also formed as a side product in a few cases with excellent diastereoselectivity. Keywords: arylidenemalonates; curcumins; cyclohexanones; diastereoselective synthesis; Michael reaction; tetrahydrochromenones; Introduction There is

• –acceptor with nitroalkenes, resulting in multi-substituted cyclohexanones through a cascade inter–intramolecular double Michael addition process with high diastereoselectivity [26][27]. Subsequently, the enantioselective versions of the above reaction and a similar diastereoselective cascade Michael

• addition–cyclization of curcumins with chalcones to synthesize functionalized cyclohexanones have been reported [28][29]. On the other hand, diastereoselective cascade Michael addition–cyclization of curcumins with α-bromonitroalkenes and α-halodicyclopentadienones afforded functionalized dihyrofurans [26

Harnessing unprotected deactivated amines and arylglyoxals in the Ugi reaction for the synthesis of fused complex nitrogen heterocycles

• Javier Gómez-Ayuso,
• Pablo Pertejo,
• Tomás Hermosilla,
• Israel Carreira-Barral,
• Roberto Quesada and
• María García-Valverde

Beilstein J. Org. Chem. 2024, 20, 1758–1766, doi:10.3762/bjoc.20.154

• considering the diastereoselectivity observed when enantiopure (S)-α-methylbenzylamine was used as chiral component in the two-step syntheses from amine surrogates [22], we assayed our new strategy to achieve a one-pot diastereoselective synthesis of benzodiazepinones 6 (Scheme 2, Table 2). Interestingly, the

• (right). The thermal ellipsoid plot (Olex2) is at the 40% probability level. X-ray diffraction structure of dipyrrolopiperazinone 12c. The thermal ellipsoid plot (Olex2) is at the 40 % probability level. Synthesis of benzodiazepinones 5 from anthranilic acid derivatives. Diastereoselective one-pot

• dipyrrolopiperazinones 12. Results obtained in the synthesis of benzodiazepinones 5 from anthranilic acid derivatives. Results obtained in the diastereoselective one-pot synthesis of benzodiazepinones 6. Results obtained in the synthesis of pyrrolopiperazinones 9 from pyrrole and indole carboxylic acids. Results

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

• ]. The P450 enzyme BscF is responsible for regioselective abstraction of a hydrogen at C12 and subsequent diastereoselective hydroxylation of the radical intermediate B to produce brassicicene B (10). Meanwhile, further single-electron oxidation of the intermediate B would trigger a Wagner–Meerwein-type

• and subsequent oxidation yielded aldehyde 18, a precursor for the intramolecular ring closure of the eight-membered ring. Upon treatment of 18 with BF3·Et2O, diastereoselective Prins cyclization of 18 proceeded to generate secondary alcohol 19. Subsequent one-pot treatment with (n-Bu)4NF·HF resulted

• evolution using site-saturation mutagenesis targeting the putative active sites L110 and Y112, led to the variant MoBsc9 Y112M, which substantially improved the enzymatic conversion into 22, achieving an isolated yield of up to 67%. Diastereoselective reduction of the C8 ketone was then achieved using the

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

• -Cannizzaro reaction in the construction of the spiro-β-lactone ring while targeting the spiro-β-lactone-γ-lactam ring of oxazolomycin and lazollamycin [88]. Proceeding towards the requisite fragment they envisaged a series of crucial diastereoselective transformations arriving at the precursor 69 to the

Advancements in hydrochlorination of alkenes

• Daniel S. Müller

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

• -workers [22][23]. Recently, Jacobsen reported asymmetric Prins cyclizations with HCl solutions [24]. Hence, all the described hydrochlorinations are racemic or diastereoselective reactions. Review Polar hydrochlorination reactions To comprehend polar hydrochlorination reactions, a solid understanding of

Mechanisms for radical reactions initiating from N-hydroxyphthalimide esters

• Carlos R. Azpilcueta-Nicolas and
• Jean-Philip Lumb

Beilstein J. Org. Chem. 2024, 20, 346–378, doi:10.3762/bjoc.20.35

• ]. Two decades later, in 2012 the Overman group demonstrated the utility of this transformation in the total synthesis of (–)-aplyviolene, involving the diastereoselective coupling of a tertiary radical and an enone acceptor [38]. Further developments of this chemistry resulted in the general use of NHPI

• co-workers devised a diastereoselective Ni-catalyzed decarboxylative arylation as a crucial step in the synthesis of (–)-cajanusine [118] (Scheme 37A). Likewise, the Baran lab employed Ni-catalyzed decarboxylative couplings of RAEs to form two strategic C–C bonds in the synthesis of higginsianin A

Synthesis of spiropyridazine-benzosultams by the [4 + 2] annulation reaction of 3-substituted benzoisothiazole 1,1-dioxides with 1,2-diaza-1,3-dienes

• Wenqing Hao,
• Long Wang,
• Jinlei Zhang,
• Dawei Teng and
• Guorui Cao

Beilstein J. Org. Chem. 2024, 20, 280–286, doi:10.3762/bjoc.20.29

• . Inspired by the potential biological activity of pyridazines and in continuation of our work on the synthesis of spirobenzosultams [31][32][33], we herein report a highly diastereoselective route for the synthesis of spiropyridazine-benzosultams through [4 + 2] annulation reactions of 3-substituted

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

• other derivatives in good yields [37] (Scheme 1). Later, Wu et al. described a diastereoselective 1,3-dipolar cycloaddition of trifluoroacetaldehyde hydrazones with α,β-ethenyl ketones to obtain polysubstituted pyrazolidines and pyrazolines. These reactions were carried out under two different sets of

Decarboxylative 1,3-dipolar cycloaddition of amino acids for the synthesis of heterocyclic compounds

• Xiaofeng Zhang,
• Xiaoming Ma and
• Wei Zhang

Beilstein J. Org. Chem. 2023, 19, 1677–1693, doi:10.3762/bjoc.19.123

• diastereoselective synthesis of bis[spirooxindole-pyrrolizidine]s. Stepwise synthesis of triazolobenzodiazepine 21a. One-pot synthesis of triazolobenzodiazepines. One-pot synthesis of tetrahydropyrroloquinazolines. One-pot synthesis of tetrahydropyrrolobenzodiazepines. Stepwise synthesis of pyrrolo[2,1-a

N-Sulfenylsuccinimide/phthalimide: an alternative sulfenylating reagent in organic transformations

• Fatemeh Doraghi,
• Seyedeh Pegah Aledavoud,
• Mehdi Ghanbarlou,
• Bagher Larijani and
• Mohammad Mahdavi

Beilstein J. Org. Chem. 2023, 19, 1471–1502, doi:10.3762/bjoc.19.106

• N-thiosuccinimides 1 as the sulfur source was reported by Gao and Liu et al. (Scheme 14) [52]. Highly regio- and diastereoselective β-sulfonylamino sulfides 26 were obtained from alkenes 9, N-thiosuccinimides 1, and sulfonamides 25 in the presence of 20 mol % BF3·Et2O. While the transformation in

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

• tricyclic chromane nucleus from 8-hydroxyisochromanes and 1,3-dicarbonyl compounds in the presence of Cu(OTf)2 and T+BF4− (Scheme 7b) [57]. The strategy has a wide range of applications and is highly diastereoselective, making it an attractive strategy for synthesizing related natural products. The role of

• copper is to activate the 1,3-dicarbonyl compounds through complexation that leads to a highly diastereoselective nucleophilic addition. Scheidt et al. reported an enantioselective Cu-catalyzed intramolecular cross-dehydrogenative coupling approach to substituted tetrahydropyrans with excellent yields