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

• alternative to the harsh Pummerer rearrangement. Methanol played a crucial role in achieving the desired transformation and it was suggested to promote the self-assembly of reagents 24 and 25 for the formation of 27, which allows the selective abstraction of H+ from the less sterically hindered side

Synthesis, electrochemical properties, and antioxidant activity of sterically hindered catechols with 1,3,4-oxadiazole, 1,2,4-triazole, thiazole or pyridine fragments

• Daria A. Burmistrova,
• Andrey Galustyan,
• Nadezhda P. Pomortseva,
• Kristina D. Pashaeva,
• Maxim V. Arsenyev,
• Oleg P. Demidov,
• Mikhail A. Kiskin,
• Andrey I. Poddel’sky,
• Nadezhda T. Berberova and
• Ivan V. Smolyaninov

Beilstein J. Org. Chem. 2024, 20, 2378–2391, doi:10.3762/bjoc.20.202

• , imidazole, thiadiazole, or other fragments [44][45][46][47][48]. Previously, we obtained a series of sterically hindered catechols linked through a sulfide bridge with various polar or low-polar groups [36][49][50][51] and heterocyclic fragments [52] via the Michael addition reaction. Also, we have

• maximum at λ = 412 nm which is characteristic for sterically hindered o-benzoquinones. The proposed scheme for the electrooxidation of catechols 6–9 is presented in Scheme 3. Based on the current intensities of the second anodic peaks for compounds 6–8 with a 1,3,4-oxadiazole-2-thione ring (Figure 8 for 7

• most effective antioxidants in the lipid peroxidation reaction. Conclusion Thus, we have synthesized a series of new sterically hindered catechols with thioether or thione groups containing various heterocyclic fragments with good yields of 42–80%. The interaction of 3,5-di-tert-butyl-o-benzoquinone

Asymmetric organocatalytic synthesis of chiral homoallylic amines

• Nikolay S. Kondratyev and
• Andrei V. Malkov

Beilstein J. Org. Chem. 2024, 20, 2349–2377, doi:10.3762/bjoc.20.201

• enantioselectivities for both electron-rich and electron-poor N-benzoylarylimines, aliphatic N-benzoylimines, and bulkier N-carboxyalkylimines. However, less sterically hindered N-carboxyalkyl- and N-carbamoylimines showed a significant drop in both enantioselectivity and yield. The observed enantioselectivity was

• ,β-unsaturated imines 9. However, with ethynylimines 12, the enantioselectivity dropped to a modest level. In addition, the reaction with sterically hindered tertiary allylboronates, such as the chiral (R)-α-cyclohexyl-α-methyl-allylboronate required the use of catalytic amounts of zinc tert-butoxide

• enantioselective allylation of imines was described by Ryu’s group as a part of a wider asymmetric nucleophilic addition methodology [37]. The method is based on the use of 20 mol % of sterically hindered chiral oxazaborolidinium ion (COBI) 63, that can be readily prepared from a relatively inexpensive

Heterocycle-guided synthesis of m-hetarylanilines via three-component benzannulation

• Andrey R. Galeev,
• Maksim V. Dmitriev,
• Alexander S. Novikov and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2024, 20, 2208–2216, doi:10.3762/bjoc.20.188

• -aminopyridine, provided N-hetarylaniline (3af) in moderate yield. Furthermore, it is possible to synthesize sterically hindered anilines such as arylamine 3ah, which was prepared from 2,6-di(isopropyl)aniline in 53% yield. However, in the case of an electron-deficient amine (4-trifluoromethylaniline), the

Multicomponent syntheses of pyrazoles via (3 + 2)-cyclocondensation and (3 + 2)-cycloaddition key steps

• Ignaz Betcke,
• Alissa C. Götzinger,
• Maryna M. Kornet and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2024, 20, 2024–2077, doi:10.3762/bjoc.20.178

• oxalate (9) and alkylphenones 10 through a sterically hindered Claisen condensation, producing a six-membered lithium enolate salt. Subsequent cyclocondensation with hydrazines concludes the formation of pyrazoles. However, this process could not be performed as a one-pot synthesis, as the solvent had to

The Groebke–Blackburn–Bienaymé reaction in its maturity: innovation and improvements since its 21st birthday (2019–2023)

• Cristina Martini,
• Muhammad Idham Darussalam Mardjan and
• Andrea Basso

Beilstein J. Org. Chem. 2024, 20, 1839–1879, doi:10.3762/bjoc.20.162

• aliphatic aldehydes showed a higher variability (50–98%) and in some cases also the classic Ugi adducts were observed. Regarding the isocyanide, excellent yields were achieved for all tested reagents, such as aromatic, aliphatic, and sterically hindered ones. Problems were only observed using a morpholine

pKalculator: A pK_a predictor for C–H bonds

• Rasmus M. Borup,
• Nicolai Ree and
• Jan H. Jensen

Beilstein J. Org. Chem. 2024, 20, 1614–1622, doi:10.3762/bjoc.20.144

• ] and experimentally validated their approach using six pharmaceutical intermediates from medicinal chemistry programs. In the article, they state that ”Iridium catalysts ligated by bipyridine ligands catalyze the borylation of the aryl C–H bonds that are most acidic and least sterically hindered…”[45

• that the site with the lowest QM-computed pKa value is sterically hindered compared to the experimentally observed site of borylation. The ML model predicts three borylation sites correctly, but, in the case of compound 5, there are two additional sites with low pKa values. One failure is for compound

Synthesis of 2-benzyl N-substituted anilines via imine condensation–isoaromatization of (E)-2-arylidene-3-cyclohexenones and primary amines

• Lu Li,
• Na Li,
• Xiao-Tian Mo,
• Ming-Wei Yuan,
• Lin Jiang and
• Ming-Long Yuan

Beilstein J. Org. Chem. 2024, 20, 1468–1475, doi:10.3762/bjoc.20.130

• good yields. The electronic properties of the substituents, irrespective of their positions on benzylamines, displayed no substantial disparity on the reaction outcomes, leading to the formation of 4ab–ap in 50–80% yields. Both the heteroarylmethylamines and sterically hindered α-methylbenzylamine

Generation of alkyl and acyl radicals by visible-light photoredox catalysis: direct activation of C–O bonds in organic transformations

• Mithu Roy,
• Bitan Sardar,
• Itu Mallick and
• Dipankar Srimani

Beilstein J. Org. Chem. 2024, 20, 1348–1375, doi:10.3762/bjoc.20.119

• of electron-rich phosphoranyl radicals, which were more prone to oxidation before undergoing β-scission. The deoxygenation process of secondary benzylic alcohols occurred with decreased efficiency (i.e., 62m and 62n, 30 and 47%), in line with the slower addition of a more sterically hindered alcohol

Oxidative hydrolysis of aliphatic bromoalkenes: scope study and reactivity insights

• Amol P. Jadhav and
• Claude Y. Legault

Beilstein J. Org. Chem. 2024, 20, 1286–1291, doi:10.3762/bjoc.20.111

• bromoalkenes as substrates delivering dialkyl α-bromoketones which are highly sought-after synthons in heterocycle synthesis and medicinal chemistry, thus overcoming the limitations of previous methods. The reaction accommodates sterically hindered bromoalkenes as substrates, leading to the corresponding α

Stability trends in carbocation intermediates stemming from germacrene A and hedycaryol

• Naziha Tarannam,
• Prashant Kumar Gupta,
• Shani Zev and
• Dan Thomas Major

Beilstein J. Org. Chem. 2024, 20, 1189–1197, doi:10.3762/bjoc.20.101

• and Figure S2 in Supporting Information File 1), e.g., carbocations A-OH and C-OH are more stable than B-OH and D-OH, and this can be explained by the more sterically hindered geometries of B-OH and D-OH compared to that of A-OH and C-OH. However, when inspecting the Gibbs free energy of F-OH and H-OH

Auxiliary strategy for the general and practical synthesis of diaryliodonium(III) salts with diverse organocarboxylate counterions

• Naoki Miyamoto,
• Daichi Koseki,
• Kohei Sumida,
• Elghareeb E. Elboray,
• Naoko Takenaga,
• Ravi Kumar and
• Toshifumi Dohi

Beilstein J. Org. Chem. 2024, 20, 1020–1028, doi:10.3762/bjoc.20.90

• sterically hindered aryl(TMP)iodonium(III) carboxylates by combining the broad substrate scope of (hetero)aryl iodine(III) and carboxylic acids under mild conditions. Results and Discussion In the synthesis of diaryliodonium(III) salts and their application in arylation reactions, it is highly desirable to

• ), and fluoro (1g)) groups proceeded efficiently to produce the corresponding aryl(TMP)iodonium(III) acetates 4b–g in high yields. A sterically hindered ortho-disubstituted aryl group was also well-tolerated, and the related ortho-disubstituted aryl(TMP)iodonium(III) acetate (4h) was obtained in 83

• 5b–f was explored with benzoic acid (6a) and 1,3,5-trimethoxybenzene (Scheme 5B). Iodosoarenes with electron-rich (5b, 5c, 5f), electron-deficient (5d), bromo (5e), and sterically hindered substituents (5f) were applicable to give the corresponding aryl(TMP)iodonium(III) benzoates 7ba–fa in 63–93

Synthesis and properties of 6-alkynyl-5-aryluracils

• Ruben Manuel Figueira de Abreu,
• Till Brockmann,
• Alexander Villinger,
• Peter Ehlers and
• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 898–911, doi:10.3762/bjoc.20.80

• carried out by application of the Suzuki–Miyaura cross-coupling. The optimization was carried out with 3a as the model compound (Table 1). The starting material 3a is a sterically hindered system in which the bromine is only partially accessible, due to the large residue. This could be the reason for the

SOMOphilic alkyne vs radical-polar crossover approaches: The full story of the azido-alkynylation of alkenes

• Julien Borrel and
• Jerome Waser

Beilstein J. Org. Chem. 2024, 20, 701–713, doi:10.3762/bjoc.20.64

• work [45], and will be only shortly described in a summarized form (Scheme 3). Styrene substituted with a tert-butyl at the para position afforded 4b in 78% yield. Using a styrene bearing a sterically hindered aryl afforded 4c in a similar yield. Homopropargylic azides possessing oxygen substituents

Green and sustainable approaches for the Friedel–Crafts reaction between aldehydes and indoles

• Periklis X. Kolagkis,
• Eirini M. Galathri and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2024, 20, 379–426, doi:10.3762/bjoc.20.36

• need for conventional heating (70 °C), while also requiring longer reaction times of up to 72 h for sterically hindered substrates [93][94]. A novel approach for the formation of BIMs was described, in 2020, by Herrera and co-workers, who utilized iodoalkynes as a simple halogen bond-based

• just 3 minutes [100]. With the optimum reaction conditions in hand, both aromatic and aliphatic aldehydes reached promising conversion rates of formed BIMs of 77–95%. Sterically hindered substituted aldehydes exhibited longer reaction times, while substituted indoles also showed no issue, reaching

Nucleophilic functionalization of thianthrenium salts under basic conditions

• Xinting Fan,
• Duo Zhang,
• Xiangchuan Xiu,
• Bin Xu,
• Yu Yuan,
• Feng Chen and
• Pan Gao

Beilstein J. Org. Chem. 2024, 20, 257–263, doi:10.3762/bjoc.20.26

• the resulting products (3ah–aj) can also be obtained with high efficiency. This underscores the viability of integrating this metal-free thioetherification method with other traditional cross-coupling reactions. Sterically hindered ortho-disubstituted thiophenol 2k is also compatible with this

Metal-catalyzed coupling/carbonylative cyclizations for accessing dibenzodiazepinones: an expedient route to clozapine and other drugs

• Amina Moutayakine and
• Anthony J. Burke

Beilstein J. Org. Chem. 2024, 20, 193–204, doi:10.3762/bjoc.20.19

• DMF. The reaction was performed at 130 °C, as we believed that high temperature will promote the cyclization of the sterically hindered intermediate 3a, but no DBDAP was achieved under these conditions (entry 1, Table 3). Next, Pd(OAc)2 was employed under ligand-free conditions, but again the desired

Copper-promoted C5-selective bromination of 8-aminoquinoline amides with alkyl bromides

• Changdong Shao,
• Chen Ma,
• Li Li,
• Jingyi Liu,
• Yanan Shen,
• Chen Chen,
• Qionglin Yang,
• Tianyi Xu,
• Zhengsong Hu,
• Yuhe Kan and
• Tingting Zhang

Beilstein J. Org. Chem. 2024, 20, 155–161, doi:10.3762/bjoc.20.14

• were obtained in high yields (92‒99%), which demonstrated the practical value of this methodology. Moreover, the reaction showed a good tolerance to sterically hindered substrates like trimethylbenzamide, affording the corresponding brominated product in 70% yield (3la). Also the substrate derived from

Perspectives on push–pull chromophores derived from click-type [2 + 2] cycloaddition–retroelectrocyclization reactions of electron-rich alkynes and electron-deficient alkenes

• Michio Yamada

Beilstein J. Org. Chem. 2024, 20, 125–154, doi:10.3762/bjoc.20.13

• , the racemization was observed at 80 °C. Torres et al. performed detailed theoretical calculations and showed that the racemization observed in 59 and 60 is caused by triplet-state photogeneration, which leads to the rotation around the sterically hindered buta-1,3-diene chiral axis [132]. In fact, the

Visible-light-induced nickel-catalyzed α-hydroxytrifluoroethylation of alkyl carboxylic acids: Access to trifluoromethyl alkyl acyloins

• Feng Chen,
• Xiu-Hua Xu,
• Zeng-Hao Chen,
• Yue Chen and
• Feng-Ling Qing

Beilstein J. Org. Chem. 2023, 19, 1372–1378, doi:10.3762/bjoc.19.98

• sterically hindered tertiary carboxylic acids were unfortunately not compatible with the reaction conditions. The structures of products 3a and 3s were unambiguously confirmed by single-crystal X-ray diffraction. Notably, the reaction of 1a could be easily scaled up to 1.0 mmol scale, affording 3a in a

Selective and scalable oxygenation of heteroatoms using the elements of nature: air, water, and light

• Damiano Diprima,
• Hannes Gemoets,
• Stefano Bonciolini and
• Koen Van Aken

Beilstein J. Org. Chem. 2023, 19, 1146–1154, doi:10.3762/bjoc.19.82

• –l) were easily and readily oxidized selectively and with good functional group tolerance. A slightly slower conversion was observed for more sterically hindered sulfides (2b–d). For the substrates where kinetics was slower (e.g., sulfides 2m and 2n which are lacking an aromatic moiety), there is the

Clauson–Kaas pyrrole synthesis using diverse catalysts: a transition from conventional to greener approach

• Dileep Kumar Singh and
• Rajesh Kumar

Beilstein J. Org. Chem. 2023, 19, 928–955, doi:10.3762/bjoc.19.71

• with electron‐donating groups (i.e., OMe, Me) reacted much faster than aniline and furnished the pyrroles in excellent yields. In addition, the reaction of more sterically hindered aniline with 2,5-dimethoxytetrahydrofuran gave moderate yields and less sterically hindered aniline gave good yields. This

• , reactions of sterically hindered anilines with 2,5-dimethoxytetrahydrofuran give moderate yields, and reactions with less sterically hindered anilines give good yields of products. The Clauson–Kaas method for the synthesis of pyrroles has a wide range of applications, including the synthesis of various

Pyridine C(sp²)–H bond functionalization under transition-metal and rare earth metal catalysis

• Haritha Sindhe,
• Malladi Mounika Reddy,
• Karthikeyan Rajkumar,
• Akshay Kamble,
• Amardeep Singh,
• Anand Kumar and
• Satyasheel Sharma

Beilstein J. Org. Chem. 2023, 19, 820–863, doi:10.3762/bjoc.19.62

Palladium-catalyzed enantioselective three-component synthesis of α-arylglycine derivatives from glyoxylic acid, sulfonamides and aryltrifluoroborates

• Bastian Jakob,
• Nico Schneider,
• Luca Gengenbach and
• Georg Manolikakes

Beilstein J. Org. Chem. 2023, 19, 719–726, doi:10.3762/bjoc.19.52

• sterically hindered arylboronic acids. Herein, we report an improved version of this palladium-catalyzed enantioselective three-component reactions using aryltrifluoroborates as replacement of the arylboronic acid building block (Scheme 1d). The broader scope of this 2nd generation protocol is exploiting a

• enantiomeric ratio of 87:13 (compared to 68% and an enantiomeric ratio of 60:40 with the boronic acid). As in the case of arylboronic acids, reactions with a sterically hindered ortho-substituted trifluoroborate furnished the arylglycine product in almost racemic form. Unfortunately, reactions with

Strategies in the synthesis of dibenzo[b,f]heteropines

• David I. H. Maier,
• Barend C. B. Bezuidenhoudt and
• Charlene Marais

Beilstein J. Org. Chem. 2023, 19, 700–718, doi:10.3762/bjoc.19.51

• yield proved to be good to excellent and sterically hindered aryl rings were tolerated. This method was applied by Huang et al. [74] to prepare a series of fluorescent compounds in excellent yield. Copper- and nickel-catalysed arylation were reported as alternatives to the Pd-catalysed arylation of 1a