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

• route commenced from (−)-pulegone. After introducing oxidation states at C6 and C10 and installing an alkynyl group at C11, oxidative cleavage of a double bond yielded the key propargylic alcohol intermediate 66. This compound underwent a 1,2-addition with alkynyl Grignard reagent 67, and the resulting

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

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

• underwent the 1,2-addition of isopropenyllithium reagent (prepared from n-BuLi/tetraisopropenyltin (67) [55]) and DMP oxidation to afford ketone 68. A three-step transformation including RCM, Mukaiyama hydration, and esterification, 68 was converted to methyl oxalate 69. Irradiation of the reaction mixture

• reduction of 72, affording the hydroxyketone 74 in 57% yield with 91% ee. Protection of the secondary alcohol in 74 followed by Beckmann rearrangement led to lactam 75. Oxidation state modifications and functional group transformations of 75 afforded ketone 76. Next, the 1,2-addition of 76 with vinyl iodine

• rings, followed by dehydration to afford pentacyclic product 125. Finally, a five-step operation including the 1,2-addition of 125 with iPrLi, PCC oxidation of the resulting tertiary alcohol, oxidative aromatization and in situ neutralization/oxidation, acid-mediated 1,6-addition with H2O, and

Fe-catalyzed efficient synthesis of 2,4- and 4-substituted quinolines via C(sp²)–C(sp²) bond scission of styrenes

• Prafull A. Jagtap,
• Manish M. Petkar,
• Vaishnavi R. Sawant and
• Bhalchandra M. Bhanage

Beilstein J. Org. Chem. 2025, 21, 1799–1807, doi:10.3762/bjoc.21.142

• during GC–MS analysis) and formaldehyde (2a′′) via C–C bond scission of styrene in the presence of FeIII/O2, possibly through a 1,2-addition of O2 to styrene [49][58][59][60]. This in-situ generated aldehyde species then undergoes condensation with the amine 1a, leading to the formation of the

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

• stage was set for the construction of the target skeleton through a 1,2-addition (Scheme 4). Preliminary trials to generate organometallic species via Li/I exchange under various conditions (n-BuLi, t-BuLi, or t-BuLi in combination with CeCl3 or MgBr2) led to rapid decomposition, likely due to inherent

Regioselective formal hydrocyanation of allenes: synthesis of β,γ-unsaturated nitriles with α-all-carbon quaternary centers

• Seeun Lim,
• Teresa Kim and
• Yunmi Lee

Beilstein J. Org. Chem. 2025, 21, 800–806, doi:10.3762/bjoc.21.63

• ]. The limited investigation of allene hydrocyanation can be attributed to the significant challenges posed by the two orthogonal π-systems in allenes. These challenges include achieving high regioselectivity and controlling (E)/(Z)-stereoselectivity, as 1,2-addition processes to allenes can generate up

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

• developed chiral halonium salts and applied them to asymmetric reactions such as vinylogous Mannich reactions of cyanomethylcoumarins 6 with isatin-derived ketimines 7 [33][35] and 1,2-addition reaction of thiols to ketimine [34], which formed the corresponding products 8 in high yields with high to

Non-covalent organocatalyzed enantioselective cyclization reactions of α,β-unsaturated imines

• Sergio Torres-Oya and
• Mercedes Zurro

Beilstein J. Org. Chem. 2024, 20, 3221–3255, doi:10.3762/bjoc.20.268

• , they can be attacked by a nucleophile and undergo a 1,2-addition or conjugate addition leading to the production of allylic amines or aliphatic imines, respectively. They can also behave as C4 synthons in cycloaddition reactions such as the aza-Diels–Alder reaction, giving access to nitrogen-containing

Synthesis of indano[60]fullerene thioketone and its application in organic solar cells

• Yong-Chang Zhai,
• Shimon Oiwa,
• Shinobu Aoyagi,
• Shohei Ohno,
• Tsubasa Mikie,
• Jun-Zhuo Wang,
• Hirofumi Amada,
• Koki Yamanaka,
• Kazuhira Miwa,
• Naoyuki Imai,
• Takeshi Igarashi,
• Itaru Osaka and
• Yutaka Matsuo

Beilstein J. Org. Chem. 2024, 20, 1270–1277, doi:10.3762/bjoc.20.109

• assigned to the charge transfer band of the C=S bond in t-Bu-FIDS, which was stronger than that of the C=O bond in t-Bu-FIDO [30]. Interestingly, the maximum absorption band observed in t-Bu-FIDO at 432 nm, which is a characteristic feature of 58π-fullerene derivatives with a 1,2-addition pattern, was

• time. A single crystal of t-Bu-FIDS was grown by liquid–liquid diffusion method (CS2/EtOH). The crystal structure was successfully analyzed using synchrotron radiation at SPring-8. The crystal exhibited the orthorhombic space group (No. 61) with the D2h point group, and the structure confirmed the 1,2

• -addition pattern of t-Bu-FIDS (Figure 2a,b). The shortest π–π distance between the two fullerene molecules of t-Bu-FIDS in a unit cell was 3.14 Å, while that in t-Bu-FIDO was 2.974 Å [19]. The C=S bond length was 1.627 Å and was clearly longer than the C=O bond in t-Bu-FIDO. We consider that this longer

Palladium-catalyzed three-component radical-polar crossover carboamination of 1,3-dienes or allenes with diazo esters and amines

• Geng-Xin Liu,
• Xiao-Ting Jie,
• Ge-Jun Niu,
• Li-Sheng Yang,
• Xing-Lin Li,
• Jian Luo and
• Wen-Hao Hu

Beilstein J. Org. Chem. 2024, 20, 661–671, doi:10.3762/bjoc.20.59

• temperature (rt), the desired unsaturated ε-AA derivative 4a was obtained in 75% isolated yield (Table 1, entry 1). Isolation and NMR analysis demonstrated that this model reaction provided amino acid 4a with good E-selectivity and excellent regioselectivity (E/Z = 91:9, 1,4-/1,2-addition >20:1). Control

• -substituted dienes 2b and 2c were suitable for this MCR, affording the 1,4-addition products 4l and 4m albeit with moderate regioselectivity (1,4-/1,2-addition = 2:1). To our delight, the reactions with 2,3-disubstituted diene 2d and 1,4-disubstituted diene 2e also readily provided products 4n and 4o. In the

• case of 1,3-cyclohexadiene 2e, the amine was expected to attack the π-allyl palladium from the exo side. Considering that substituent effects might affect the regioselectivity in this MCR, we further investigated the 1,4-/1,2-addition selectivity with 1-phenyl-substituted 1,3-dienes 2f–i. Interestingly

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

• -triazolines and their derivatives via tandem 1,2-addition/cyclization reactions between trifluoromethyl acylhydrazones and cyanamide [105] (Scheme 17b). Afterwards, Hu et al. developed a method for the N-arylation and N-alkylation of trifluoromethyl acylhydrazones with diaryliodonium salts and alkyl halides

Aromatic C–H bond functionalization through organocatalyzed asymmetric intermolecular aza-Friedel–Crafts reaction: a recent update

• Anup Biswas

Beilstein J. Org. Chem. 2023, 19, 956–981, doi:10.3762/bjoc.19.72

• dehydration to generate isoxazolium cation 80 paired with a phosphate anion. This chiral phosphate is engaged in H-bonding with the free NH of the heteroarene ring to ease the stereoselective 1,2-addition to in situ generate the cationic heterocyclic scaffold 81. The reaction proceeded faster with pyrroles

• Brønsted acid to generate (N-acyl)(propargyl)imine 90 as intermediate which added to the deprotonated phosphoric acid to form phosphate ester 91 as the next intermediate through an equilibrium process. Then, 1,2-addition by the C3 position of the heteroarene ring to the acylimine intermediate afforded the

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

• diastereomers were detected (Scheme 9A). Furthermore, the authors have also demonstrated a four-component coupling reaction: by simply increasing the amount of the organolithium reagent (2.05 equiv) used for the activation of the Zn enolate, β-hydroxyketones 40 were gained via 1,2-addition of the zincate

Synthetic study toward tridachiapyrone B

• Morgan Cormier,
• Florian Hernvann and
• Michaël De Paolis

Beilstein J. Org. Chem. 2022, 18, 1741–1748, doi:10.3762/bjoc.18.183

• oxidative anionic oxy-Cope rearrangement of the tertiary alcohol arising from the 1,2-addition of a 1,3-dimethylallyl reagent to 2,5-cyclohexadienone connected to the α’-methoxy-γ-pyrone motif. Keywords: α’-methoxy-γ-pyrone; 2,5-cyclohexadienone; oxy-Cope; quaternary carbon; Robinson-type annulation

• was not the case, the process was poorly reproducible. On the other hand, the 1,2-addition of Grignard reagents to 5 was observed, providing thus an alternative way of grafting a side chain. As summarized in Scheme 7a, this was envisaged through a sequence encompassing the 1,2-addition of the 1,3

• 1,2-addition of a rather hindered nucleophile to a carbonyl electrophile with low reactivity. Precedents were noted though, as Carreira used this strategy for the synthesis of indoxamycine B exploiting the reactivity of 1,3-dimethylallyltitanocene species [39]. The 1,2-addition of various

A recent overview on the synthesis of 1,4,5-trisubstituted 1,2,3-triazoles

• Pezhman Shiri,
• Ali Mohammad Amani and
• Thomas Mayer-Gall

Beilstein J. Org. Chem. 2021, 17, 1600–1628, doi:10.3762/bjoc.17.114

• process displayed good regioselectivity (Scheme 10) [23]. The authors proposed that the reaction may proceed through the mechanism illustrated in Scheme 11. Initially, EDAM 24 is treated with an azide source and subsequently, the intermediate 26 is formed through 1,2-addition reaction. The intermediate 26

N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

• solvent, metal and additives in 1,2-addition reactions to N-tert-butanesulfinyl imines of organometallic compounds, different transition models have been proposed to explain the stereochemical outcomes. The cyclic model justified by the Zimmermann–Traxler transition state [40][41][42] is the typical

Synthetic approaches to bowl-shaped π-conjugated sumanene and its congeners

• Shakeel Alvi and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 2212–2259, doi:10.3762/bjoc.16.186

• parent sumanene (2). Later on, they transformed trione 40 into the corresponding exo-trimethyl derivative 44 by means of a Grignard reaction with MeMgBr via 1,2-addition (Scheme 7). The imination of monoketosumanene 38 as well as triketosumanene 40 has also been reported by these authors to obtain the

Tuneable access to indole, indolone, and cinnoline derivatives from a common 1,4-diketone Michael acceptor

• Dalel El-Marrouki,
• Sabrina Touchet,
• Abderrahmen Abdelli,
• Hédi M’Rabet,
• Mohamed Lotfi Efrit and
• Philippe C. Gros

Beilstein J. Org. Chem. 2020, 16, 1722–1731, doi:10.3762/bjoc.16.144

• % yield. We assume that the tertiary amine would interact with the protonated intermediate, and thus promoting the 1,2-addition (Scheme 6). However, for the pyridine substituent (compounds 6k and 6l), another intermediate may be involved as the shape of this diamine does not allow enough flexibility to

• , only the indolone derivative is obtained in those conditions as well (compound 7i, Scheme 7). Based on these results, we found it important to check whether the indole 6b resulted from a 1,2-addition and not from a degradation of the indolone 7b. For this purpose, the indolone 7b was refluxed overnight

• with acetic acid in toluene, under these conditions producing mainly the indole (Table 1, entry 5). The indolone 7b was found unchanged, with no trace of the indole 6b being detected (see Supporting Information File 1, chapter I), indicating that the indole was formed intramolecularly by a 1,2-addition

In silico rationalisation of selectivity and reactivity in Pd-catalysed C–H activation reactions

• Liwei Cao,
• Mikhail Kabeshov,
• Steven V. Ley and
• Alexei A. Lapkin

Beilstein J. Org. Chem. 2020, 16, 1465–1475, doi:10.3762/bjoc.16.122

• , explaining the experimental observations for C–H activation reactions, depending on the nature of a ligand (Ln) and transition metal (M) in the catalytically active species (LnM). These mechanisms include four elementary steps: oxidative addition, σ-bond metathesis, electrophilic substitution and 1,2

• -addition, respectively [15]. Even though the mechanisms are inherently different, three most important aspects should be primarily taken into account when classifying and rationalising C–H activation reactions: the proximity of C–H bond to the transition metal; the energy of C–H bond cleavage within the

Copper-catalysed alkylation of heterocyclic acceptors with organometallic reagents

• Yafei Guo and
• Syuzanna R. Harutyunyan

Beilstein J. Org. Chem. 2020, 16, 1006–1021, doi:10.3762/bjoc.16.90

• aluminium reagents and commercial alkylaluminium reagents were examined in this methodology, providing the corresponding products with a moderate yield but high enantioselectivity (Scheme 2B). In 2009, Feringa and co-workers presented the first highly enantioselective 1,2-addition of dialkylzinc reagents to

Recent advances in Cu-catalyzed C(sp³)–Si and C(sp³)–B bond formation

• Balaram S. Takale,
• Ruchita R. Thakore,
• Elham Etemadi-Davan and
• Bruce H. Lipshutz

Beilstein J. Org. Chem. 2020, 16, 691–737, doi:10.3762/bjoc.16.67

•  46). The product featuring the PhMe2Si residue at the β-location 287, however, arises by way of a 1,2-addition to an imine, formed from the same Pd(II) intermediate via elimination [84]. Oestrich and co-workers have recently demonstrated non-directed, asymmetric syn-addition-silylations of 3,3

• an appropriate electrophile led to C–C bond formation, ultimately delivering chiral tertiary alcohols. Mechanistic studies and DFT calculations showed that an in situ-formed borylcopper(I) species is responsible for the 1,2-addition (Scheme 73) [136]. C,O-Diboration of ketones 464 was explored using

Copper-catalyzed enantioselective conjugate addition of organometallic reagents to challenging Michael acceptors

• Delphine Pichon,
• Jennifer Morvan,
• Christophe Crévisy and
• Marc Mauduit

Beilstein J. Org. Chem. 2020, 16, 212–232, doi:10.3762/bjoc.16.24

• . However, as depicted in Scheme 1, due to their stronger reactivity than that of usual esters or ketones, a competitive 1,2-addition to the carbonyl function of enals could occur, leading to the corresponding alcohol as a byproduct. Moreover, even if the 1,4-addition is favored, thanks to the copper/ligand

Allylic cross-coupling using aromatic aldehydes as α-alkoxyalkyl anions

• Akihiro Yuasa,
• Kazunori Nagao and
• Hirohisa Ohmiya

Beilstein J. Org. Chem. 2020, 16, 185–189, doi:10.3762/bjoc.16.21

• aromatic aldehydes can be used as α-alkoxyalkyl anions for catalytic carbon–carbon bond formations [7][8][9]. For example, a nucleophilic α-silyloxybenzylcopper(I) species can be generated catalytically from aromatic aldehydes through the 1,2-addition of a silylcopper(I) species followed by [1,2]-Brook

• ) species B. The 1,2-addition of silylcopper(I) B to the aromatic aldehyde 1 [15][16][17][18][19] and the subsequent [1,2]-Brook rearrangement from the obtained α-silyl-substituted copper(I) alkoxide C forms the key intermediate, an α-silyloxybenzylcopper(I) species D. The transmetallation between D and an

Efficient method for propargylation of aldehydes promoted by allenylboron compounds under microwave irradiation

• Jucleiton J. R. Freitas,
• Queila P. S. B. Freitas,
• Silvia R. C. P. Andrade,
• Juliano C. R. Freitas,
• Roberta A. Oliveira and
• Paulo H. Menezes

Beilstein J. Org. Chem. 2020, 16, 168–174, doi:10.3762/bjoc.16.19

• results indicated that the substituent nature, whether electron-donating or electron-withdrawing, has no dramatic influence on the product yields. When the α,β-unsaturated aldehyde, cinnamaldehyde was used, the corresponding 1,2-addition product 2i was obtained exclusively. The chemoselectivity of the

Synthesis of 3-alkenylindoles through regioselective C–H alkenylation of indoles by a ruthenium nanocatalyst

• Abhijit Paul,
• Debnath Chatterjee,
• Srirupa Banerjee and
• Somnath Yadav

Beilstein J. Org. Chem. 2020, 16, 140–148, doi:10.3762/bjoc.16.16

• following three categories: (i) by Wittig or Doebner reaction of indoles bearing a 3-aldehyde group; (ii) by 1,4- or 1,2-addition of α,β-enones or carbonyl compounds, followed by oxidation or elimination, respectively; (iii) by Pd-catalysed oxidative coupling of indoles with activated alkenes. Several