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

• the first reaction mode for a difunctionalization of alkenes with diazo compounds via a radical-polar crossover process. This synthetic transformation proceeds under mild reaction conditions and shows high functional group tolerance. The studies on late-stage functionalization, scale-up reactions, and

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

• on the rate than acids and bases and both the anion and cation appear to influence the reaction kinetics. A deliberate choice of salt can either significantly improve the kinetics or quench the reaction. The latter might be exploited e.g., in late-stage functionalization strategies in order to

• applicability of the reaction conditions in a late-stage functionalization of APIs, the method was carried out on albendazole, and albendazole oxide (2t) was obtained with very good yield. Flow The photochemical protocol was then transferred to a flow setup in order to obtain a scalable and thus industrially

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

• late-stage functionalization (17i and 17j) (Figure 12A). Interestingly, sodium oxalate could be used as the electron donor provided a catalytic loading of 4-cyanopyridine was added. Although the role of the latter species was not proposed by authors, it is more facile to reduce than an aryl chloride so

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

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

• late-stage functionalization strategy [51][52][53] for the synthesis of natural products [42][54][55][56][57][58][59]. The goal of this review is to highlight and discuss the recent approaches for the synthesis of fluorinated derivatives by the direct incorporation of a fluorinated group of XRF type

Strategies to access the [5-8] bicyclic core encountered in the sesquiterpene, diterpene and sesterterpene series

• Cécile Alleman,
• Charlène Gadais,
• Laurent Legentil and
• François-Hugues Porée

Beilstein J. Org. Chem. 2023, 19, 245–281, doi:10.3762/bjoc.19.23

• following criteria: position/stage of the key cyclooctane ring formation in the synthesis plan, the selectivity, and the opportunity for late-stage functionalization. Review 1 Metathesis: ring-closing metathesis and related methods The metathesis reaction, first discovered by serendipity in the 1950s, has

Redox-active molecules as organocatalysts for selective oxidative transformations – an unperceived organocatalysis field

• Elena R. Lopat’eva,
• Igor B. Krylov,
• Dmitry A. Lapshin and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2022, 18, 1672–1695, doi:10.3762/bjoc.18.179

•  32). It should be noted that other α-carbonyl CH bonds are not affected under these reaction conditions, which makes the method suitable for the late-stage functionalization of complex molecules. The method for selective remote CH-hydroxylation involving unactivated C(sp3)–H bonds employing

On drug discovery against infectious diseases and academic medicinal chemistry contributions

• Yves L. Janin

Beilstein J. Org. Chem. 2022, 18, 1355–1378, doi:10.3762/bjoc.18.141

• example of a very late stage functionalization of molecule would be the use of zinc sulfinate chemistry [297] which, as depicted here, allowed to introduce in one step a trifluoromethyl group on the hydroquinidine 47 and access the otherwise rather hard-to-get compound 48. In fact, CH functionalization is

Synthesis of α-(perfluoroalkylsulfonyl)propiophenones: a new set of reagents for the light-mediated perfluoroalkylation of aromatics

• Durbis J. Castillo-Pazos,
• Juan D. Lasso and
• Chao-Jun Li

Beilstein J. Org. Chem. 2022, 18, 788–795, doi:10.3762/bjoc.18.79

• , perfluorohexylation, and perfluorobutylation. Keywords: α-(perfluoroalkylsulfonyl)propiophenones; innate functionalization; late-stage functionalization; light-mediated perfluoroalkylation; perfluoroalkyl sulfinates; Introduction Perfluorinated compounds are a family of molecules containing a backbone where all C–H

• of these reagents as late-stage functionalization agents [26][27]. For a trend in reactivity, a more comprehensive scope of arenes and heteroarenes has been explored with the innate trifluoromethylation methodology previously reported by our group [10]. Conclusion In summary, we have successfully

• perfluoroalkylation of electron-rich aromatics, as well as in the late-stage functionalization of small molecules such as caffeine, which is of great interest in the current literature [28]. In future work, we will explore the reach and applicability of these reagents for the functionalization of compounds of

Earth-abundant 3d transition metals on the rise in catalysis

• Nikolaos Kaplaneris and
• Lutz Ackermann

Beilstein J. Org. Chem. 2022, 18, 86–88, doi:10.3762/bjoc.18.8

• , Germany 10.3762/bjoc.18.8 Keywords: C–H activation; 3d transition metals; green chemistry; late-stage functionalization; sustainability; Transition metal catalysis has emerged as a transformative platform for the assembly of increasingly complex compounds, with enabling applications to natural product

• . Applications of this strategy range from late-stage functionalization to modern photocatalysis and electrocatalysis, with contributions from around the globe, including Brazil, China, Japan, Germany, India, and South Korea, among others. The increasing use of C–H activations in academic and industrial

Iron-catalyzed domino coupling reactions of π-systems

• Austin Pounder and
• William Tam

Beilstein J. Org. Chem. 2021, 17, 2848–2893, doi:10.3762/bjoc.17.196

• applicability in late-stage functionalization. The Bao group has since demonstrated many other carbon-centered radicals were amenable in the carboazidation reaction of alkenes including diacylperoxides [133] and aldehydes [134]. In 2021, the Bao group followed up on their previous work and developed an

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

• . The photo-electro methodology allowed the late-stage functionalization of valuable bioactive molecules, and the structures of a adapalene precursor (65) and ibuprofen derivative (66) were successfully azidated in moderate yields (Scheme 23C). Some silylated compounds like 67 have proven to be

Sustainable manganese catalysis for late-stage C–H functionalization of bioactive structural motifs

• Jongwoo Son

Beilstein J. Org. Chem. 2021, 17, 1733–1751, doi:10.3762/bjoc.17.122

• biologically active small molecules and complex peptides. Keywords: bioactive molecules; 3d transition metals; late-stage functionalization; manganese catalyst; sustainable catalysis; Introduction Manganese, a 3d transition metal, allows for a potentially ideal sustainable catalytic system because of the

• assistance. However, application of this protocol for late-stage functionalization remains challenging [96][97][98][99][100][101][102][103]. In 2021, it was revealed by the Ackermann group that manganese(I) catalysis enabled the bioorthogonal late-stage alkenylation of structurally sophisticated peptides

• -containing peptide 37g. Conclusion Metal-catalyzed late-stage functionalization has shown significant potential in the fields of medicinal chemistry, agrochemistry, and chemical biology. While transition metal catalysis has been a reliable and efficient strategy for late-stage functionalization, it suffers

Copper-mediated oxidative C−H/N−H activations with alkynes by removable hydrazides

• Feng Xiong,
• Bo Li,
• Chenrui Yang,
• Liang Zou,
• Wenbo Ma,
• Linghui Gu,
• Ruhuai Mei and
• Lutz Ackermann

Beilstein J. Org. Chem. 2021, 17, 1591–1599, doi:10.3762/bjoc.17.113

• : benzhydrazides; copper; 3-methyleneisoindolin-1-one; removable directing group; Introduction Inexpensive copper-promoted oxidative C−H activations [1][2][3][4][5][6][7][8][9][10][11] have been recognized as competent tools for the efficient assembly and late-stage functionalization of organic molecules due to

Methodologies for the synthesis of quaternary carbon centers via hydroalkylation of unactivated olefins: twenty years of advances

• Thiago S. Silva and
• Fernando Coelho

Beilstein J. Org. Chem. 2021, 17, 1565–1590, doi:10.3762/bjoc.17.112

• substrates (Scheme 2 and Scheme 4), and an external proton source (acetic acid) was required to furnish the hydroalkylated products 7 (Scheme 5A). The quaternary carbon centers were synthetized in moderate to excellent yields by this methodology, and its potential use in late-stage functionalization was

• methanol and gentle heating was necessary to optimize the formation of 75 from 74. As is usual in these Mukaiyama-like reaction conditions, the developed hydromethylation tolerated an array of functional groups and the late-stage functionalization of complex natural products (75e–g). Deuterated and other

Photosensitized direct C–H fluorination and trifluoromethylation in organic synthesis

• Shahboz Yakubov and
• Joshua P. Barham

Beilstein J. Org. Chem. 2020, 16, 2151–2192, doi:10.3762/bjoc.16.183

• of aryl triflates [29] and arylpalladium complexes [2][47], few permit a one-step transformation of unactivated C(sp3)–H bonds to C(sp3)–F bonds [1][3][36][38][48]. Such a transformation would be highly valuable for the late-stage functionalization (LSF) of complex molecules, such as those in Scheme

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

• outcome is interesting from the sophisticated molecule late-stage functionalization viewpoint. Furthermore, the quantum yield of the reaction was measured and turned out to be 6.5. This result indicated that the mechanism of this reaction involved a short radical chain process [85]. The same year, a

Functionalization of the imidazo[1,2-a]pyridine ring in α-phosphonoacrylates and α-phosphonopropionates via microwave-assisted Mizoroki–Heck reaction

• Damian Kusy,
• Agata Wojciechowska,
• Joanna Małolepsza and
• Katarzyna M. Błażewska

Beilstein J. Org. Chem. 2020, 16, 15–21, doi:10.3762/bjoc.16.3

• ]pyridine ring has been synthesized via the microwave-assisted Mizoroki–Heck reaction. The efficient modification of the imidazo[1,2-a]pyridine ring has been achieved as late-stage functionalization, enabling and accelerating the generation of a library of compounds from a common precursor. Keywords: α

• overrated [1]. However, as is true for many reactions, the late-stage functionalization of target compounds or their advanced intermediates is rarely an extension of reaction conditions developed for structurally simple analogs. The late-stage approach is especially desirable in the synthesis of a library

Synthesis and characterization of bis(4-amino-2-bromo-6-methoxy)azobenzene derivatives

• David Martínez-López,
• Amirhossein Babalhavaeji,
• Diego Sampedro and
• G. Andrew Woolley

Beilstein J. Org. Chem. 2019, 15, 3000–3008, doi:10.3762/bjoc.15.296

• substituent in an attempt to enhance water solubility. Late-stage functionalization of the ortho-position was carried out through a palladium(II)-catalyzed C–H activation, resulting in ortho-brominated azobenzenes [21]. Photochemical characterization Despite the morpholino substituent, compound 4 was found to

Recent advances in transition-metal-catalyzed incorporation of fluorine-containing groups

• Xiaowei Li,
• Xiaolin Shi,
• Xiangqian Li and
• Dayong Shi

Beilstein J. Org. Chem. 2019, 15, 2213–2270, doi:10.3762/bjoc.15.218

Synthesis of pyrrolidine-based hamamelitannin analogues as quorum sensing inhibitors in Staphylococcus aureus

• Jakob Bouton,
• Kristof Van Hecke,
• Reuven Rasooly and
• Serge Van Calenbergh

Beilstein J. Org. Chem. 2018, 14, 2822–2828, doi:10.3762/bjoc.14.260

• , CH2Cl2, 0 °C; l) conc. HCl, MeOH/H2O 1:1, reflux. Late stage functionalization of the pyrrolidine nitrogen. Reagents and conditions: A) (masked) aldehyde, NaBH3CN, AcOH, MeOH, 60 °C; B) MeI, DIPEA, THF, 0 °C; C) Ms-Cl, Et3N, THF, 0 °C; D) AcOH, DIPEA, HATU, DMF, rt. Supporting Information Supporting

DABCO- and DBU-promoted one-pot reaction of N-sulfonyl ketimines with Morita–Baylis–Hillman carbonates: a sequential approach to (2-hydroxyaryl)nicotinate derivatives

• Soumitra Guin,
• Raman Gupta,
• Debashis Majee and
• Sampak Samanta

Beilstein J. Org. Chem. 2018, 14, 2771–2778, doi:10.3762/bjoc.14.254

• as the requirement of high temperatures or use of strong oxidants (H2O2, oxone, K2S2O8, TBHP, PIDA, NHPI etc.) that are not much compatible with functionality, precluding late-stage functionalization. Moreover, the scope of substitution on the pyridine ring is limited which in turn hampers the

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

• method tolerates the presence of pyridine derivatives, alcohols, esters, carboxylic acids, Boc-protected amines, boronic pinacol esters and was applied to the late-stage functionalization of complex molecules. In 2016, the first metal-free photoredox-catalyzed radical thiol–yne reaction was reported by

• diaryliodonium salts reacted efficiently with alkyl and aryl thiosulfate salts to the respective sulfide and sulfoxides. A row of functional groups like for example amines, cyano groups, esters, hydroxy groups or nitro groups were highly tolerated and gave the opportunity for late-stage functionalization of

Versatile synthesis of the signaling peptide glorin

• Robert Barnett,
• Daniel Raszkowski,
• Thomas Winckler and
• Pierre Stallforth

Beilstein J. Org. Chem. 2017, 13, 247–250, doi:10.3762/bjoc.13.27

• previous syntheses is that ours allows for late-stage functionalization of the α-amino group of the glutamic acid moiety. This is particularly useful for the rapid generation of different α-amide analogues. Biological activity of glorin and glorinamide The bioactivities of synthetic glorin (1) and

Chiral cyclopentadienylruthenium sulfoxide catalysts for asymmetric redox bicycloisomerization

• Barry M. Trost,
• Michael C. Ryan and
• Meera Rao

Beilstein J. Org. Chem. 2016, 12, 1136–1152, doi:10.3762/bjoc.12.110

• tolerate many sensitive functional groups, such as free alcohols, silyl enol ethers, and ketones, which makes it an attractive metal for late stage functionalization and elaboration of complex molecules. It is thought that the origin of ruthenium’s divergent behavior stems from a difference in reaction