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

• , different alkylamines with various functional groups were evaluated under the optimized conditions, successfully delivering the corresponding 1,4-difunctionalized products in moderate to excellent yields (4a–k, 35–84%) with high regioselectivity. Some simple secondary amines including cyclic amines 3a, 3c

• next turned to evaluate the scope of 1,3-dienes. Although the regioselectivity control of allylic substitution can be attributed to many factors, it is agreed that steric hindrance generally is the primary factor affecting the regioselectivity of nucleophilic attack [54][55][56][57]. Monoalkyl

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

• regioselectivity. Comparision of previous work with this work. The effects of substituent groups on the [4 + 2] annulation reaction. Reaction conditions: 1 (1.0 mmol), 2 (1.5 mmol), Et3N (2.0 mmol), MeCN (10.0 mL), 25 °C, 2.0 h. Gram-scale synthesis of 3aa. The transformation of 3aa. The reaction mechanism of the

Unveiling the regioselectivity of rhodium(I)-catalyzed [2 + 2 + 2] cycloaddition reactions for open-cage C₇₀ production

• Cristina Castanyer,
• Anna Pla-Quintana,
• Anna Roglans,
• Albert Artigas and
• Miquel Solà

Beilstein J. Org. Chem. 2024, 20, 272–279, doi:10.3762/bjoc.20.28

• holds significant promise for applications in the fields of medicinal chemistry, materials science, and photovoltaics. In this study, we investigate the regioselectivity of the rhodium(I)-catalyzed [2 + 2 + 2] cycloaddition reactions between diynes and C70 as a novel procedure for generating C70 bis

• (fulleroid) derivatives. The aim is to shed light on the regioselectivity of the process through both experimental and computational approaches. In addition, the photooxidation of one of the C–C double bonds in the synthesized bis(fulleroids) affords open-cage C70 derivatives having a 12-membered ring

• explore, both experimentally and computationally, the Rh-catalyzed intermolecular [2 + 2 + 2] cycloaddition reaction between diynes and C70 as a new procedure to generate C70 bis(fulleroids). We are particularly interested in the analysis of the regioselectivity of this [2 + 2 + 2] cycloaddition. Results

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

• regioselectivity. Significant advancements in the synthesis of arylthianthrenium salts have prompted a growing interest in their utilization as versatile precursors for the conversion of C–H bonds in arenes into C–C/X bonds through transition-metal-catalyzed cross-coupling processes [12][13][14][15][16][17][18][19

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

• , employing activated and unactivated alkyl bromides as the halogenation reagents without additional external oxidants. This method features outstanding site selectivity, broad substrate scope, and excellent yields. Keywords: aminoquinolines; C–H bromination; copper catalysis; regioselectivity; Introduction

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

• in the form of degraded fragments), affording the TCBD products. A distinguishing feature of the [2 + 2] CA–RE reaction involving electron-rich alkynes and DCFs is the alternation of regioselectivity, which is contingent upon the specific substituents incorporated onto the cyclopentadienyl moiety of

Controlling the reactivity of La@C₈₂ by reduction: reaction of the La@C₈₂ anion with alkyl halide with high regioselectivity

• Yutaka Maeda,
• Saeka Akita,
• Mitsuaki Suzuki,
• Michio Yamada,
• Takeshi Akasaka,
• Kaoru Kobayashi and
• Shigeru Nagase

Beilstein J. Org. Chem. 2023, 19, 1858–1866, doi:10.3762/bjoc.19.138

• , such as alkyl halides. In this study, the thermal reaction of the La@C2v-C82 anion with benzyl bromide derivatives 1 at 110 °C afforded single-bonded adducts 2–5 with high regioselectivity. The products were characterized by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry

• benzyl bromide under photolytic conditions affords eight monoadducts [19]. Therefore, one-electron reduction and the subsequent thermal reaction of La@C2v-C82 were effective for its functionalization in terms of both regioselectivity and reactivity compared to the thermal and photoreactions of La@C2v-C82

• afforded the corresponding single-bonded adducts 2–5 with high regioselectivity. One-electron reduction of La@C2v-C82 increased its reactivity during thermal reaction relative to that of neutral La@C2v-C82. Structural analysis of the two major products indicated that the characteristic absorption features

N-Boc-α-diazo glutarimide as efficient reagent for assembling N-heterocycle-glutarimide diads via Rh(II)-catalyzed N–H insertion reaction

• Grigory Kantin,
• Pavel Golubev,
• Alexander Sapegin,
• Alexander Bunev and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2023, 19, 1841–1848, doi:10.3762/bjoc.19.136

• regioselectivity of this reaction can be attributed to several factors, including steric hindrances to the attack of the nitrogen atom by the carbenoid. When reacting with tetrahydroquinoline (with insignificant steric shielding of the N-nucleophilic center), the product of N–H insertion 6x was obtained in good

• reaction with indazole, compound 6g, formed as a result of the attack of the carbenoid on the 2-N atom, was obtained. The regioselectivity of the reaction with 7-azaindazole was similar, however, the introduction of an additional basic nitrogen atom resulted in a significant increase in reaction time and a

• conversion of the NH-heterocycle, and the yields of target compounds 6n and 6o were slightly diminished. The single-crystal X-ray data verified the structure of product 6n. The data obtained on the regioselectivity of reactions with benzotriazoles are in agreement with those previously reported in the

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

• ). Impressively, this transformation exhibited exceptional versatility, extending beyond coumarins to encompass other nitrogen-containing heterocycles, including quinoxalinones, with remarkable C-3 regioselectivity. The findings of this study significantly expanded the synthetic toolbox for accessing

Morpholine-mediated defluorinative cycloaddition of gem-difluoroalkenes and organic azides

• Tzu-Yu Huang,
• Mario Djugovski,
• Sweta Adhikari,
• Destinee L. Manning and
• Sudeshna Roy

Beilstein J. Org. Chem. 2023, 19, 1545–1554, doi:10.3762/bjoc.19.111

• azides and gem-difluoroalkenes in the presence of morpholine generates 1,5-disubstituted-1,2,3-triazoles with a pendant C-4 morpholine moiety. The regioselectivity of the triazole formation is dictated by morpholine preferentially making the first nucleophilic attack over azide at the α-position of gem

• with an organic azide. A relatively wide range of 1,4,5-trisubstituted-1,2,3-triazoles was obtained in 30–70% yields with high regioselectivity and modest functional group tolerability. This work demonstrates that gem-difluoroalkenes can serve as versatile fluorinated building blocks in lieu of alkynes

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

• performed at room temperature, no desired product was observed, and performing the reaction at 0 °C enhanced the regioselectivity but still in low yield. By further lowering the temperature to −60 °C the yield was increased. The authors suggested a possible mechanism for this organoselenium-catalyzed

Application of N-heterocyclic carbene–Cu(I) complexes as catalysts in organic synthesis: a review

• Nosheen Beig,
• Varsha Goyal and
• Raj K. Bansal

Beilstein J. Org. Chem. 2023, 19, 1408–1442, doi:10.3762/bjoc.19.102

• reactive and difficult to isolate. The NHC–Cu complex also helps to control the regioselectivity and stereoselectivity of the reaction, which are of high importance in organic synthesis. Overall, the use of NHC–Cu complexes as catalysts for conjugate addition reactions offers a highly efficient and

• substrates and alkylboranes. Later in 2012, Hoveyda and co-worker [63] used chiral bidentate NHC–Cu complexes bearing sulfonates, which was critical to regioselectivity and resulted in high selectivity for the γ-position. Thus, allenyl-containing products were generated in up to 95% yield and 99:1 er. The

• (Scheme 61). Out of the three ligands, 154 the one incorporating a bulky trityl (–CPh3) group was found to be most effective giving the product in up to 99% yield. A low loading (2 mol %) of the catalyst was needed and the reactions occurred at rt. McQuade and co-workers observed that the regioselectivity

One-pot nucleophilic substitution–double click reactions of biazides leading to functionalized bis(1,2,3-triazole) derivatives

• Hans-Ulrich Reissig and
• Fei Yu

Beilstein J. Org. Chem. 2023, 19, 1399–1407, doi:10.3762/bjoc.19.101

• ]). Mechanistic aspects of the CuAAC have been studied in detail [16][17]. Whereas the traditional 1,3-dipolar cycloaddition (Huisgen reaction) [18][19][20] of azides and alkynes requires often – but not always – relatively harsh conditions and proceeds with moderate regioselectivity only [21], the copper

Synthesis of ether lipids: natural compounds and analogues

• Marco Antônio G. B. Gomes,
• Alicia Bauduin,
• Chloé Le Roux,
• Romain Fouinneteau,
• Wilfried Berthe,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2023, 19, 1299–1369, doi:10.3762/bjoc.19.96

• 7.2a. Interestingly, the same reaction can be achieved on the substituted glycidol 7.1b,c with a yield of 70 to 80% and a regioselectivity that depends on the substituent (100% regioselectivity for R = Ts or mNO2-Ts and 90% of regioselectivity when R is tert-butyldiphenylsilane) [83][84]. Then, 7.2a

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

• benzothiazole, in which benzothiazole compounds have higher reactivity and regioselectivity than thiazole. In 2014, Lei et al. successfully realized the copper-catalyzed oxidative alkenylation of simple ethers to construct allyl ethers in the presence of di-tert-butyl peroxide and KI (Scheme 10) [60]. The

• coordinated with metal catalysts to control the selectivity and improve the reactivity in metal-catalyzed or -mediated reactions. Therefore, controlling the regioselectivity of CDC reactions by directing groups is of great interest [95][96]. Li et al. reported a cobalt-catalyzed CDC between unactivated C(sp2

Photoredox catalysis harvesting multiple photon or electrochemical energies

• Mattia Lepori,
• Simon Schmid and
• Joshua P. Barham

Beilstein J. Org. Chem. 2023, 19, 1055–1145, doi:10.3762/bjoc.19.81

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

• -ketimino esters 62 as potential electrophiles. The chiral phosphoric acid P21 catalyzed this process facilitating the formation of a quaternary stereocenter containing α-amino esters. Switching the solvent from non-polar to polar showed a regioselectivity shift to a C7 alkylation of the indole ring. The

• solvent-controlled regioselectivity switch of this aza-Friedel–Crafts reaction can be explained by the involvement of the polar solvent (acetonitrile) in the H-bonding with the catalyst thus creating a more hindered environment for a C3 alkylation, rather favoring the reaction through the less congested

• potential electrophiles, N-methoxycarbonyl-substituted aldimines 105 were explored to activate the para-carbon of the phenol derivatives catalyzed by the chiral pyrophosphoric acid Py1. The high regioselectivity was mainly caused by catalyst–substrate interactions via intermolecular H-bonding which could

Photoredox catalysis enabling decarboxylative radical cyclization of γ,γ-dimethylallyltryptophan (DMAT) derivatives: formal synthesis of 6,7-secoagroclavine

• Alessio Regni,
• Francesca Bartoccini and
• Giovanni Piersanti

Beilstein J. Org. Chem. 2023, 19, 918–927, doi:10.3762/bjoc.19.70

• -aminoalkyl radicals from free carboxylic acids of 8 and 10 under mild conditions would make the approach even more efficient and more biosimilar; nevertheless, issues regarding the regioselectivity of the ring formation could be raised, since both the 6-exo-trig and 7-endo-trig cyclization are both favorable

• preliminary conditions, albeit in low yield (35% yield) and low regioselectivity (1:1) (Table 1, entry 1). No regiocontrol was observed; but remarkably, the regioisomers exhibited distinct retention factors on silica gel, allowing 11 and 12 to be isolated separately in good yield as single trans diastereomers

• essential for product production (Table 1, entries 6 and 7), despite the fact that the removal of base did not result in a significantly reduced efficiency (Table 1, entry 5). The regioselectivity outcome was explained by the relative stability of the intermediate radicals involved, with strong evidence of

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

• dialkylpyridines with alkenes. It is to be noted that the ligands’ backbones were found to be crucial for the regioselectivity of the addition to benzylic C(sp3)–H bonds, as N-arylamine-bridged bis(phenolato) Zr complexes provided branched products whereas N-alkylamine-bridged bis(phenolato) Zr complexes provided

• regioselectivity and branched products 41 were obtained with acrylamides as coupling partners (Scheme 9, reaction conditions b). Thus, the authors demonstrated a switch in regioselectivity (linear/branched) which was controlled exclusively by the base used. During further investigations the authors found that the

• styrenes 64 using a Ni–Al bimetallic system and NHC ligand 65 through intermolecular hydroarylation with high levels of enantio- and regioselectivity in the alkylated products 66 (Scheme 13). Also, the authors performed DFT studies revealing the reaction mechanism and supported that the interaction of the

Synthesis of substituted 8H-benzo[h]pyrano[2,3-f]quinazolin-8-ones via photochemical 6π-electrocyclization of pyrimidines containing an allomaltol fragment

• Constantine V. Milyutin,
• Andrey N. Komogortsev,
• Boris V. Lichitsky,
• Mikhail E. Minyaev and
• Valeriya G. Melekhina

Beilstein J. Org. Chem. 2023, 19, 778–788, doi:10.3762/bjoc.19.58

• (Scheme 6). However, the key difference is the regioselectivity of the process and the absence of a pathway associated with the direct elimination of a water molecule and the formation of the polyaromatic compound 12. It can be assumed that for the considered system a [1,9]-H sigmatropic shift is a much

• more preferable process compared to aromatization. The above-mentioned photochemical reaction of pyrimidines 10 allows to synthesize polycyclic products 12 (Scheme 8, method A). In this case, the yields of compounds 12 did not exceed 41%, which is associated with low regioselectivity of the process and

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

• -substituted derivatives were reported. The authors used alpha-substituted acrylates to reduce the effect of poor endo/exo regioselectivity in the intramolecular Heck reaction (cf. Scheme 19). Božinović et al. [52] reported the synthesis of symmetrical 5H-dipyridoazepines 60a and unsymmetrical 5H

• regioselectivity. A later correction to the article revised the yield from 99% to 70% and with overall poorer selectivity [59]. The correction is in line with reports of poor selectivity when performing intramolecular Heck reactions (cf. Jepsen et al. [60]). An analogous reaction pathway by Jepsen et al. [60] was

Photocatalytic sequential C–H functionalization expediting acetoxymalonylation of imidazo heterocycles

• Deepak Singh,
• Shyamal Pramanik and
• Soumitra Maity

Beilstein J. Org. Chem. 2023, 19, 666–673, doi:10.3762/bjoc.19.48

• products with excellent yields and regioselectivity, thus confirming excellent functional group tolerability. Keywords: C–H functionalization; imidazo heterocycles; photoredox; regioselective; relay catalysis; Introduction Among all N-fused heterocycles, imidazo[1,2-a]pyridines (IPs) are the prevalent

• diverse electronic properties were present in the pyridine ring of the IP moieties (4l–q). With substrates having a methyl substitution at C-7 and C-8 of the pyridine ring, the yields and regioselectivity were still excellent (4l and 4m), but reduced significantly upon introducing a halogen group onto the

Transition-metal-catalyzed domino reactions of strained bicyclic alkenes

• Austin Pounder,
• Eric Neufeld,
• Peter Myler and
• William Tam

Beilstein J. Org. Chem. 2023, 19, 487–540, doi:10.3762/bjoc.19.38

• is entirely regioselective for the formation of a 1,2,4-trisubstituted pattern. The observed regioselectivity arises from the preferential migratory insertion of the aryl group distal to the bridgehead substituent. In 2010, Ogata and Fukuzawa explored the Ni-catalyzed two- and three-component

• little effect on the reaction (32b) with reactions involving unsymmetrically substituted bicyclic alkenes demonstrating complete regioselectivity for either 1,2,3- or 1,2,4-trisubstitued products (32a, 32f). DFT calculations were used to explain the syn-1,2-substitution experimentally observed rather

• reduced yield and enantioselectivity. Bridgehead-substituted, non-benzo-fused oxabicycles, as well as azabicyclic alkenes failed to produce the desired product. When the benzo-fused moiety was unsymmetrically substituted, little regioselectivity was observed. Based on X-ray crystallographic data for their

Transition-metal-catalyzed C–H bond activation as a sustainable strategy for the synthesis of fluorinated molecules: an overview

• Louis Monsigny,
• Floriane Doche and
• Tatiana Besset

Beilstein J. Org. Chem. 2023, 19, 448–473, doi:10.3762/bjoc.19.35

• bonds did not have a significant impact on the outcome of the reaction. It should be noted that this methodology afforded the products with a high regioselectivity, and no incorporation of the SCF3 moiety on the benzylic or at the C5 position of the quinoline part of the directing group was observed

CuAAC-inspired synthesis of 1,2,3-triazole-bridged porphyrin conjugates: an overview

• Dileep Kumar Singh

Beilstein J. Org. Chem. 2023, 19, 349–379, doi:10.3762/bjoc.19.29

• yields, quick reaction times, and excellent regioselectivity, the "click" cycloaddition reaction has enabled the synthesis of several compounds with a wide range of applications in a variety of sectors, including bioconjugation [5][6] drug development [7][8], glycoscience [9][10], porphyrin chemistry [11

• azide and alkyne groups in high yield and regioselectivity without using harsh reaction conditions. In recent years, this click protocol has been successfully employed in porphyrin chemistry to synthesize various triazoloporphyrins by attaching an azide or alkyne moiety to the periphery of the porphyrin

• molecular architectures featuring 1,4-disubstituted triazole units with high yield and higher regioselectivity. The click-inspired synthesis and photophysical properties of diverse triazole-linked porphyrin conjugates are discussed in this review. This review includes a number of recent and important