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

Regioselective addition of Grignard reagents to N-acylpyrazinium salts: synthesis of substituted 1,2-dihydropyrazines and Δ⁵-2-oxopiperazines

• Valentine R. St. Hilaire,
• William E. Hopkins,
• Yenteeo S. Miller,
• Srinivasa R. Dandepally and
• Alfred L. Williams

Beilstein J. Org. Chem. 2019, 15, 72–78, doi:10.3762/bjoc.15.8

• Grignard reagent to add regioselectively to give 1,2-dihydropyrazine 3a. DFT calculations support the observations that the isolated regioisomer we obtained was the result of a thermodynamically favored 1,2-addition over a 1,6-addition [9]. It has also been shown that TMS-ketene acetals add selectively to

• the two vinyl protons at C5 and C6, respectively. This result is in agreement with our observation that nucleophiles favored 1,2-addition over a 1,6-addition [9]. A formation of 1,6-dihydropyrazine was not observed. With THF identified as the optimal solvent to use, we sought to expand the scope of

• . Based on our results from the monosubstituted substrates, a 1,2-addition of the Grignard was expected to occur. When an aryl group was present on the ring, trisubstituted dihydropyrazines in good yields ranging from 78–100% were produced (Figure 1, compounds 6, 7a,b and 12). An alkyl substitution with

Molecular iodine-catalyzed one-pot multicomponent synthesis of 5-amino-4-(arylselanyl)-1H-pyrazoles

• Camila S. Pires,
• Daniela H. de Oliveira,
• Maria R. B. Pontel,
• Jean C. Kazmierczak,
• Roberta Cargnelutti,
• Diego Alves,
• Raquel G. Jacob and
• Ricardo F. Schumacher

Beilstein J. Org. Chem. 2018, 14, 2789–2798, doi:10.3762/bjoc.14.256

• could be obtained in 90% yield as depicted in Scheme 3. On the basis of previous reports [21][25] a mechanism can be proposed for this reaction as depicted in Scheme 4. Initially, we believe that arylhydrazine 2 reacts with benzoylacetonitrile 1 by a 1,2-addition reaction in the presence of iodine as

Some mechanistic aspects regarding the Suzuki–Miyaura reaction between selected ortho-substituted phenylboronic acids and 3,4,5-tribromo-2,6-dimethylpyridine

• Piotr Pomarański,
• Piotr Roszkowski,
• Jan K. Maurin,
• Armand Budzianowski and
• Zbigniew Czarnocki

Beilstein J. Org. Chem. 2018, 14, 2384–2393, doi:10.3762/bjoc.14.214

• with ortho-substituted phenylboronic acid for triaryl products. Summary of results for coupling with ortho-substituted phenylboronic acid for diaryl products. Proposed intermediates for the 1,2-addition of 5 with methoxy group. A) Oxidative addition step. B) Transmetalation step. Proposed intermediates

• for the 1,3-addition with methoxy group. A) Oxidative addition step. B) Transmetalation step. Proposed intermediates for the 1,2-addition with chlorine atom. A) Oxidative addition step. B) Transmetalation step. Proposed intermediates for the 1,3-addition with chlorine atom. A) Oxidative addition step

Bi-mediated allylation of aldehydes in [bmim][Br]: a mechanistic investigation

• Mrunesh Koli,
• Sucheta Chatterjee,
• Subrata Chattopadhyay and
• Dibakar Goswami

Beilstein J. Org. Chem. 2018, 14, 2198–2203, doi:10.3762/bjoc.14.193

• , respectively, in >86% yields (Table 2, entries 8 and 9). Allylation of the conjugated aldehyde 1k furnished the 1,2-addition product 2k exclusively, establishing chemoselectivity of the protocol (Table 2, entry 10). With the chiral substrate (R)-2,3-O-cyclohexylideneglyceraldehyde (1l), the anti-homoallylic

Hypervalent organoiodine compounds: from reagents to valuable building blocks in synthesis

• Gwendal Grelier,
• Benjamin Darses and
• Philippe Dauban

Beilstein J. Org. Chem. 2018, 14, 1508–1528, doi:10.3762/bjoc.14.128

• the conversion of allenes 20. A regioselective 1,2-addition on the internal π-bond was observed to afford the products 21, because of the presence of a heteroatom substituent that can stabilize the radical or cationic intermediate by coordination with the copper complex (Scheme 9) [42]. However, the

• complexes has led the authors to demonstrate the superior ability of cheap FeCl2 to mediate the 1,2-addition thereby allowing the formation of the trans-products 43 with complete regio- and diastereocontrol (Scheme 14). The group of Hamashima has reported that various 1,2-difunctionalizations of alkenes can

One hundred years of benzotropone chemistry

• Arif Dastan,
• Haydar Kilic and
• Nurullah Saracoglu

Beilstein J. Org. Chem. 2018, 14, 1120–1180, doi:10.3762/bjoc.14.98

• oxidized to 1-ethynylbenzotropone 150 in situ, the etheric compound 152 was obtained from the reaction of 1,2-addition product 151 with HCl (Scheme 25). c. Decarbonylation of 4,5-benzotropone (11): The mechanism for the neutral and radical-cationic decarbonylation of tropone and benzannulated tropones was

Gram-scale preparation of negative-type liquid crystals with a CF₂CF₂-carbocycle unit via an improved short-step synthetic protocol

• Tatsuya Kumon,
• Shohei Hashishita,
• Takumi Kida,
• Shigeyuki Yamada,
• Takashi Ishihara and
• Tsutomu Konno

Beilstein J. Org. Chem. 2018, 14, 148–154, doi:10.3762/bjoc.14.10

• the 1,2-addition reaction of Int-I proceeds in preference to the conjugate addition reaction, the desired octa-1,7-diene 5a should be produced in higher yield. However, no significant improvement was observed after various attempts such as employing a more nucleophilic lithium reagent instead of the

Quinone-catalyzed oxidative deformylation: synthesis of imines from amino alcohols

• Xinyun Liu,
• Johnny H. Phan,
• Benjamin J. Haugeberg,
• Shrikant S. Londhe and
• Michael D. Clift

Beilstein J. Org. Chem. 2017, 13, 2895–2901, doi:10.3762/bjoc.13.282

• resulting imines (7r−t) are hydrolyzed under the current reaction conditions. Notably, imines 7n [42][43][44][45] and 7t [46][47][48] are useful imines for diastereoselective 1,2-addition reactions. Following these substrate scope studies, we next examined the quinone-catalyzed C–C bond cleavage of

Electron-deficient pyridinium salts/thiourea cooperative catalyzed O-glycosylation via activation of O-glycosyl trichloroacetimidate donors

• Mukta Shaw,
• Yogesh Kumar,
• Rima Thakur and
• Amit Kumar

Beilstein J. Org. Chem. 2017, 13, 2385–2395, doi:10.3762/bjoc.13.236

• trichloroacetimidate donors using a synergistic catalytic system of electron-deficient pyridinium salts/aryl thiourea derivatives at room temperature is demonstrated. The acidity of the adduct formed by the 1,2-addition of alcohol to the electron-deficient pyridinium salt is increased in the presence of an aryl

• to lower acidity of the ammonium salt formed by 1,2-addition of the acceptor to the pyridinium salt. The conjugate base formed after the release of a proton from the ammonium salt may be quite stable to impart a negative charge to the acceptor oxygen. The acidity of the ammonium salt may be enhanced

• -deficient pyridinium salt/thiourea cocatalyzed glycosidation is outlined in Figure 4. It is presumed that at first electron-deficient pyridinium salt 3a undergoes 1,2-addition with the acceptor to produce ammonium salt X. The addition of the thiourea derivative as hydrogen-bonding cocatalyst could activate