α-(Aminomethyl)acrylates as acceptors in radical–polar crossover 1,4-additions of dialkylzincs: insights into enolate formation and trapping

• Angel Palillero-Cisneros,
• Paola G. Gordillo-Guerra,
• Fernando García-Alvarez,
• Olivier Jackowski,
• Franck Ferreira,
• Fabrice Chemla,
• Joel L. Terán and
• Alejandro Perez-Luna

Beilstein J. Org. Chem. 2023, 19, 1443–1451, doi:10.3762/bjoc.19.103

• carbonyl compounds to provide the corresponding zinc enolates (Scheme 1) [1][2]. While simple, this reaction offers attractive features: 1) it proceeds under mild conditions in the absence of any transition-metal catalyst; 2) the 1,4-addition step can be combined with condensation reactions of the zinc

Exploring the role of halogen bonding in iodonium ylides: insights into unexpected reactivity and reaction control

• Carlee A. Montgomery and
• Graham K. Murphy

Beilstein J. Org. Chem. 2023, 19, 1171–1190, doi:10.3762/bjoc.19.86

• reported by Hadjiarapoglou, Varvoglis and co-workers [107][108][109][110][111][112] and Moriarty et al. [113][114][115], who observed metal-free cycloadditions between iodonium ylides and olefins in the absence of a transition metal catalyst. These reactions proceeded under mild conditions without catalyst

• series of ylide precursors and found that when diazo compound 69 was reacted with 67 (with or without a transition-metal catalyst), no reaction occurred. Conversely, iodonium ylides 31, 70 and 71 all reacted with 67 to produce 68 in 28–81% yield. A significant improvement was realized when an ortho-ether

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

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

• to domino reactions which include at least two distinct reactions. The review is divided on the basis of the transition-metal catalyst used in the reaction and will not cover metal-free methods. The literature is covered up to and including January 2023. For reasons of clarity, newly formed bonds are

Me₃Al-mediated domino nucleophilic addition/intramolecular cyclisation of 2-(2-oxo-2-phenylethyl)benzonitriles with amines; a convenient approach for the synthesis of substituted 1-aminoisoquinolines

• Krishna M. S. Adusumalli,
• Lakshmi N. S. Konidena,
• Hima B. Gandham,
• Krishnaiah Kumari,
• Krishna R. Valluru,
• Satya K. R. Nidasanametla,
• Venkateswara R. Battula and
• Hari K. Namballa

Beilstein J. Org. Chem. 2021, 17, 2765–2772, doi:10.3762/bjoc.17.186

• the development of several approaches for the efficient construction of these heterocyclic frameworks (Scheme 1). Traditional preparations for 1-aminoisoquinolines include nucleophilic substitution of 1-haloisoquinolines with amines either employing a base [31][32][33][34][35] or a transition metal

• catalyst [36][37][38][39][40]. However, pre-functionalization of isoquinolines to the corresponding halogenated isoquinolines is the main limitation associated with these protocols as they require noxious halogenated acids for their starting materials preparation. Alternative strategies include, amination

Direct C(sp³)–H allylation of 2-alkylpyridines with Morita–Baylis–Hillman carbonates via a tandem nucleophilic substitution/aza-Cope rearrangement

• Siyu Wang,
• Lianyou Zheng,
• Shutao Wang,
• Shulin Ning,
• Zhuoqi Zhang and
• Jinbao Xiang

Beilstein J. Org. Chem. 2021, 17, 2505–2510, doi:10.3762/bjoc.17.167

• demonstrated a direct C(sp3)–H allylic alkylation reaction of 2-alkylpyridines with MBH carbonates with mild and simple operation. The process does not need either a base or a transition metal catalyst. The mechanism of this reaction was envisioned involving a tandem SN2’ type nucleophilic substitution

Catalyzed and uncatalyzed procedures for the syntheses of isomeric covalent multi-indolyl hetero non-metallides: an account

• Ranadeep Talukdar

Beilstein J. Org. Chem. 2021, 17, 2102–2122, doi:10.3762/bjoc.17.137

• could be attributed to the facile orbital interactions of the σ* orbital of silicon and the π* orbital of the butadiene unit, which overall lowers the energy of the LUMO [51][52]. Known previously with expensive transition-metal catalyst (Ru) [53], Grubbs demonstrated the first KOt-Bu-catalyzed C2–H

Synthetic reactions driven by electron-donor–acceptor (EDA) complexes

• Zhonglie Yang,
• Yutong Liu,
• Kun Cao,
• Xiaobin Zhang,
• Hezhong Jiang and
• Jiahong Li

Beilstein J. Org. Chem. 2021, 17, 771–799, doi:10.3762/bjoc.17.67

• step without any transition-metal catalyst, ligand, or photocatalyst, this method possesses a splendid application prospect. The reaction mechanism is as follows (Scheme 48): Firstly, carbon disulfide combines with N-methylaniline (134) in the presence of Cs2CO3 to form thiolate 136. Thiolate 136 is

Synthesis of legonmycins A and B, C(7a)-hydroxylated bacterial pyrrolizidines

• Wilfred J. M. Lewis,
• David M. Shaw and
• Jeremy Robertson

Beilstein J. Org. Chem. 2021, 17, 334–342, doi:10.3762/bjoc.17.31

• that Snider’s attempt to oxidize, by epoxidation, the N,O-diacetyl derivative of compound 14 was not successful. Indeed, in our own work, the use of either NBS, MCPBA, or O2 with a transition-metal catalyst also gave unpromising results in attempts to oxidize compound 17. Future work will explore

Synthesis of aryl 2-bromo-2-chloro-1,1-difluoroethyl ethers through the base-mediated reaction between phenols and halothane

• Yukiko Karuo,
• Ayaka Kametani,
• Atsushi Tarui,
• Kazuyuki Sato,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2021, 17, 89–96, doi:10.3762/bjoc.17.9

• and highly functionalized aryl 2-bromo-2-chloro-1,1-difluoroethyl ethers has been developed. This approach exhibits a broad reaction scope, a simple operation and without the need of any expensive transition-metal catalyst, highly toxic or corrosive reagents. Notably, we demonstrate the potential

When metal-catalyzed C–H functionalization meets visible-light photocatalysis

• Lucas Guillemard and
• Joanna Wencel-Delord

Beilstein J. Org. Chem. 2020, 16, 1754–1804, doi:10.3762/bjoc.16.147

• activation of one substrate, and a two-electron activation by a transition-metal catalyst of the other. The main advantage of such a system is to promote highly regioselective reactions. Indeed, while radical transformations generally suffer from selectivity issues, interception of radicals by metal

Synthesis and anticancer activity of bis(2-arylimidazo[1,2-a]pyridin-3-yl) selenides and diselenides: the copper-catalyzed tandem C–H selenation of 2-arylimidazo[1,2-a]pyridine with selenium

• Mio Matsumura,
• Tsutomu Takahashi,
• Hikari Yamauchi,
• Shunsuke Sakuma,
• Yukako Hayashi,
• Tadashi Hyodo,
• Tohru Obata,
• Kentaro Yamaguchi,
• Yasuyuki Fujiwara and
• Shuji Yasuike

Beilstein J. Org. Chem. 2020, 16, 1075–1083, doi:10.3762/bjoc.16.94

• selenium source in the presence of a transition metal catalyst, such as Cu or Ni [27][28][29][30][31][32]. In 2011, Zhou et al. reported the pioneering Cu-catalyzed C–H selenation of 2-arylimidazopyridine with diphenyl diselenide in the presence of CuI (10 mol %) [29]. Tandem reactions involving the

Aldehydes as powerful initiators for photochemical transformations

• Maria A. Theodoropoulou,
• Nikolaos F. Nikitas and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2020, 16, 833–857, doi:10.3762/bjoc.16.76

• reported a selective photoredox merger C(sp3)–H alkylation/arylation of ethers using benzaldehyde as the photoorganocatalyst and nickel as the transition metal catalyst [57]. For the coupling between (3-bromopropyl)benzene (132) and THF (131), presented in Scheme 28, NiBr2·glyme (134) was employed as the

Synthesis of benzo[d]imidazo[2,1-b]benzoselenoazoles: Cs₂CO₃-mediated cyclization of 1-(2-bromoaryl)benzimidazoles with selenium

• Mio Matsumura,
• Yuki Kitamura,
• Arisa Yamauchi,
• Yoshitaka Kanazawa,
• Yuki Murata,
• Tadashi Hyodo,
• Kentaro Yamaguchi and
• Shuji Yasuike

Beilstein J. Org. Chem. 2019, 15, 2029–2035, doi:10.3762/bjoc.15.199

• a CuI catalyst for the synthesis of benzo[b]selenophene-fused imidazo[1,2-a]pyridines occurred smoothly [15][16]. Performing these types of reactions without the addition of a transition metal catalyst is more challenging, but would alleviate the environmental burden of removing and disposing of the

• conditions for the cyclization of a chalcogen with 1-(2-bromophenyl)benzimidazole (1a). Table 1 shows the results from the screening of additives, solvents, and chalcogens. Since most of these types of reactions require a transition metal catalyst such as a copper reagent [14][15][16], the reaction between

• Figure S2 in Supporting Information File 1). Cs2CO3-mediated C(Het)–S bond formations of a heteroazole such as imidazo[1,2-a]pyridine, oxadiazole, and benzimidazole with diaryl disulfides without a transition metal catalyst have previously been developed [18][19]. The key step in these reactions is

Thiocarbonyl-enabled ferrocene C–H nitrogenation by cobalt(III) catalysis: thermal and mechanochemical

• Santhivardhana Reddy Yetra,
• Zhigao Shen,
• Hui Wang and
• Lutz Ackermann

Beilstein J. Org. Chem. 2018, 14, 1546–1553, doi:10.3762/bjoc.14.131

• motifs of powerful transition metal catalyst ligands and organocatalysts (Figure 1) [94][95][96][97]. During the preparation of this article, the use of strongly-coordinating, difficult to remove directing groups has been reported [70][71]. In sharp contrast, notable features of our approach include (i

Rhodium-catalyzed C–H functionalization of heteroarenes using indoleBX hypervalent iodine reagents

• Erwann Grenet,
• Ashis Das,
• Paola Caramenti and
• Jérôme Waser

Beilstein J. Org. Chem. 2018, 14, 1208–1214, doi:10.3762/bjoc.14.102

• nitrogen and a transition metal catalyst (reaction 1, Scheme 1A) [11][12][13][14][15][16][17][18][19]. In particular, Li and co-workers have used ethynylbenziodoxolone (EBX) hypervalent iodine reagents to achieve a regiodivergent alkynylation of the pyridinone core employing either a gold(I) or a rhodium

High-yielding continuous-flow synthesis of antimalarial drug hydroxychloroquine

• Eric Yu,
• Hari P. R. Mangunuru,
• Nakul S. Telang,
• Caleb J. Kong,
• Jenson Verghese,
• Stanley E. Gilliland III,
• Saeed Ahmad,
• Raymond N. Dominey and
• B. Frank Gupton

Beilstein J. Org. Chem. 2018, 14, 583–592, doi:10.3762/bjoc.14.45

• significant opportunity for optimization. While the recent improved route (Scheme 1b) by Li and co-workers [21] eliminates the protection–deprotection steps, its use of a complex multi-transition-metal-catalyst system to achieve direct SN2 substitution of the chlorine on 3 by amine 7, is sub-optimal [22][23

Functionalization of N-arylglycine esters: electrocatalytic access to C–C bonds mediated by n-Bu₄NI

• Mi-Hai Luo,
• Yang-Ye Jiang,
• Kun Xu,
• Yong-Guo Liu,
• Bao-Guo Sun and
• Cheng-Chu Zeng

Beilstein J. Org. Chem. 2018, 14, 499–505, doi:10.3762/bjoc.14.35

• transition metal catalyst Cu(OTf)2, Wu and co-workers achieved aerobic oxidative coupling of secondary amines with β-keto esters to form C(sp3)–C(sp3) bonds (Scheme 1) [18]. Although much advance has been made for the functionalization of glycine derivatives, most of these strategies mentioned above require

Photocatalytic formation of carbon–sulfur bonds

• Alexander Wimmer and
• Burkhard König

Beilstein J. Org. Chem. 2018, 14, 54–83, doi:10.3762/bjoc.14.4

• -dicyanobenzene) as organic photoredox catalyst and [NiCl2·dme] as transition metal catalyst in a continuous flow set-up, high yields of the coupling products were obtained in short residence times (30 min). They propose, that photoexcited 4CzIPN* generates the thiyl radical, which adds to the [NiI] complex

Transition-metal-free synthesis of 3-sulfenylated chromones via KIO₃-catalyzed radical C(sp²)–H sulfenylation

• Yanhui Guo,
• Shanshan Zhong,
• Li Wei and
• Jie-Ping Wan

Beilstein J. Org. Chem. 2017, 13, 2017–2022, doi:10.3762/bjoc.13.199

• protocol toward these compounds through the tandem reactions between o-hydroxyphenylenaminones and sulfonyl hydrazines. In this method, the construction of the target products is furnished via the key C–H sulfenylation without using any transition metal catalyst or oxidative additive. Results and

Mechanochemical synthesis of small organic molecules

• Tapas Kumar Achar,
• Anima Bose and
• Prasenjit Mal

Beilstein J. Org. Chem. 2017, 13, 1907–1931, doi:10.3762/bjoc.13.186

• example, a) at higher frequency (800 min−1) for 45 min lower yield with less selectivity was observed and b) using lower frequency, 200 min−1 for 8 h led to 82% of yield with high selectivity. In the traditional method of pyran synthesis the use of transition metal catalyst, corrosive acid, longer

2-Methyl-2,4-pentanediol (MPD) boosts as detergent-substitute the performance of ß-barrel hybrid catalyst for phenylacetylene polymerization

• Julia Kinzel,
• Daniel F. Sauer,
• Marco Bocola,
• Marcus Arlt,
• Tayebeh Mirzaei Garakani,
• Andreas Thiel,
• Klaus Beckerle,
• Tino Polen,
• Jun Okuda and
• Ulrich Schwaneberg

Beilstein J. Org. Chem. 2017, 13, 1498–1506, doi:10.3762/bjoc.13.148

• protein FhuA; Introduction The combination of a transition metal catalyst and a protein by either dative, supramolecular or covalent means leads to so-called artificial metalloenzymes or biohybrid catalysts [1][2]. Using a non-natural catalyst, the scope of natural enzymes can be expanded or the activity

Palladium-catalyzed ring-opening reactions of cyclopropanated 7-oxabenzonorbornadiene with alcohols

• Katrina Tait,
• Oday Alrifai,
• Rebecca Boutin,
• Jamie Haner and
• William Tam

Beilstein J. Org. Chem. 2016, 12, 2189–2196, doi:10.3762/bjoc.12.209

• type of ring-opening pathway it follows. This complements previous studies by our group involving the ring opening of cyclopropanated oxabenzonorbornadiene through the novel use of a transition metal catalyst. Using a transition metal catalyst could reveal new ring-opening pathways and provide further

Modular synthesis of the pyrimidine core of the manzacidins by divergent Tsuji–Trost coupling

• Sebastian Bretzke,
• Stephan Scheeff,
• Felicitas Vollmeyer,
• Friederike Eberhagen,
• Frank Rominger and
• Dirk Menche

Beilstein J. Org. Chem. 2016, 12, 1111–1121, doi:10.3762/bjoc.12.107

• imines, carbonyls or allene homologs. The resulting homologated nucleophile 8 may then be trapped in an intramolecular fashion by a π-allyl complex, which may concomitantly form from 6 through activation of the homoallylic functionality with a suitable transition metal catalyst. According to this concept

Cationic Pd(II)-catalyzed C–H activation/cross-coupling reactions at room temperature: synthetic and mechanistic studies

• Takashi Nishikata,
• Alexander R. Abela,
• Shenlin Huang and
• Bruce H. Lipshutz

Beilstein J. Org. Chem. 2016, 12, 1040–1064, doi:10.3762/bjoc.12.99

• ][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55][56][57][58][59][60][61][62][63][64][65][66][67][68][69][70][71], has been found to profoundly impact reactivity; (3) tuning of ligands around the transition metal catalyst center has emerged as an especially powerful

• means of enhancing and controlling reactivity in these processes [95][96][97][98][99][100][101][102][103][104][105][106][107]. A fourth approach with considerable potential, and which appears to have received considerably less attention, involves tuning the cationicity of the transition metal catalyst