Reductive opening of a cyclopropane ring in the Ni(II) coordination environment: a route to functionalized dehydroalanine and cysteine derivatives

• Oleg A. Levitskiy,
• Olga I. Aglamazova,
• Yuri K. Grishin and
• Tatiana V. Magdesieva

Beilstein J. Org. Chem. 2022, 18, 1166–1176, doi:10.3762/bjoc.18.121

• construction of complex multifunctional molecules [3][4][5][6][7][8]. Recently, we elaborated a versatile electrochemical approach for the stereoselective functionalization of a side chain of amino acids involved in the Ni(II) chiral coordination environment [9][10][11][12][13][14][15]. A combination of redox

• provides targeted pharmacophoric properties of the bio-active molecule [23] but also opens a route to its further functionalization, being a building block with wide variety of reactivity. A donor–acceptor cyclopropane concept suggested in the 1980s [24] became extremely popular in the recent decade [25

• recently, two publications from the Werz group appeared concerning anodic activation of donor–acceptor cyclopropanes followed by their functionalization with arenes [43] or yielding oxy-ketones or 1,2-dioxanes [44]; the latter process was inspired by a previous report of Buriez [45]. The anodic

Morita–Baylis–Hillman reaction of 3-formyl-9H-pyrido[3,4-b]indoles and fluorescence studies of the products

• Nisha Devi and
• Virender Singh

Beilstein J. Org. Chem. 2022, 18, 926–934, doi:10.3762/bjoc.18.92

• functionalization of the β-carboline framework. Accordingly, 3-formyl-9H-β-carbolines 6a–e were subjected to MBH reaction with acrylonitrile A and various acrylates B–E under neat conditions in the presence of DABCO as depicted in Scheme 2. All the products were furnished smoothly in 27–72% yield. During this study

• -pyrido[3,4-b]indole derivatives for the C-3 functionalization by application of the MBH reaction to generate C-3-substituted β-carboline MBH adducts. It was revealed from spectroscopic analysis that few derivatives underwent MBH reaction as well as Michael addition reaction to form type 8 compounds

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

Synthesis of odorants in flow and their applications in perfumery

• Merlin Kleoff,
• Paul Kiler and
• Philipp Heretsch

Beilstein J. Org. Chem. 2022, 18, 754–768, doi:10.3762/bjoc.18.76

• review, we give an overview of selected methods for the synthesis of odorants in flow, including heterogeneously catalyzed reactions, gas reactions, and photochemical C–H functionalization processes. After a brief introduction on types of odorants, the presented odorant syntheses are ordered according to

Heteroleptic metallosupramolecular aggregates/complexation for supramolecular catalysis

• Prodip Howlader and
• Michael Schmittel

Beilstein J. Org. Chem. 2022, 18, 597–630, doi:10.3762/bjoc.18.62

• illustrates the opportunities in running enantioselective catalysis in mixed-ligand frameworks. Instead of constructing supramolecular catalysts by functionalization of the linker units, a different approach can be adopted where a catalytically active molecule is encapsulated inside a confined space, as

Bioinspired tetraamino-bisthiourea chiral macrocycles in catalyzing decarboxylative Mannich reactions

• Hao Guo,
• Yu-Fei Ao,
• De-Xian Wang and
• Qi-Qiang Wang

Beilstein J. Org. Chem. 2022, 18, 486–496, doi:10.3762/bjoc.18.51

• was commonly introduced through in-situ, noncovalent inclusion/encapsulation in the cavity or by covalent, post-functionalization of the macrocyclic scaffold. The encapsulated catalytic group could occupy the space for substrate entering, or has a risk to be squeezed out of the cavity under complex

Tosylhydrazine-promoted self-conjugate reduction–Michael/aldol reaction of 3-phenacylideneoxindoles towards dispirocyclopentanebisoxindole derivatives

• Sayan Pramanik and
• Chhanda Mukhopadhyay

Beilstein J. Org. Chem. 2022, 18, 469–478, doi:10.3762/bjoc.18.49

• substitutions on the indoline ring could be unambiguously converted into the corresponding products (Scheme 2, Scheme 3). Halo-substituted indolines (5-Cl, 5-Br) were found to furnish the desired products in good yields (70–80%) which provided possibilities of further functionalization. In addition, the

Synthesis of 3,4,5-trisubstituted isoxazoles in water via a [3 + 2]-cycloaddition of nitrile oxides and 1,3-diketones, β-ketoesters, or β-ketoamides

• Md Imran Hossain,
• Md Imdadul H. Khan,
• Seong Jong Kim and
• Hoang V. Le

Beilstein J. Org. Chem. 2022, 18, 446–458, doi:10.3762/bjoc.18.47

• oxide and strained alkenes has been used to achieve the high-density functionalization of oligodeoxyribonucleotides [29]. However, the alkenes need to be highly strained in order for this reaction to occur without the need for an additional metal catalyst. As an alternative to the mild acidic conditions

Menadione: a platform and a target to valuable compounds synthesis

• Acácio S. de Souza,
• Ruan Carlos B. Ribeiro,
• Dora C. S. Costa,
• Fernanda P. Pauli,
• David R. Pinho,
• Matheus G. de Moraes,
• Fernando de C. da Silva,
• Luana da S. M. Forezi and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 381–419, doi:10.3762/bjoc.18.43

• studies developed by Naturale’s group, α-, β-, and γ-amino acids of linear and branched chains were used, as well as different amine protection groups (Table 5). The results revealed that the functionalization of naphthoquinones by a radical addition of decarboxylated α-, β- and γ-N-protected amino acids

Borylated norbornadiene derivatives: Synthesis and application in Pd-catalyzed Suzuki–Miyaura coupling reactions

• Robin Schulte and
• Heiko Ihmels

Beilstein J. Org. Chem. 2022, 18, 368–373, doi:10.3762/bjoc.18.41

• because the parent system does not operate in the spectrum of the sunlight. Therefore, the efficient and purposeful functionalization of the norbornadiene scaffold is an important and challenging task in this field. Specifically, earlier approaches for the synthesis of norbornadiene derivatives are mainly

Synthesis of 5-unsubstituted dihydropyrimidinone-4-carboxylates from deep eutectic mixtures

• Sangram Gore,
• Sundarababu Baskaran and
• Burkhard König

Beilstein J. Org. Chem. 2022, 18, 331–336, doi:10.3762/bjoc.18.37

• at the C4 position allow versatile further functionalization and are biologically interesting DHPMs [17][18][19][20][21], we envisioned an environmentally benign cyclocondensation protocol using low melting mixtures as a green reaction medium. We have established low melting mixtures [28][29][30][31

Site-selective reactions mediated by molecular containers

• Rui Wang and
• Yang Yu

Beilstein J. Org. Chem. 2022, 18, 309–324, doi:10.3762/bjoc.18.35

• functionalization of C–H bonds brings reaction economy and effectiveness. However, owing to the rifeness of the reactivity-similar C–H bonds, it is hard to achieve discriminate control over the product site-selectivity. In nature, the site-selective oxidation of C–H bonds is facilitated by enzymes with the donor

• diterpenoid substrates have four C–C double bonds with a trisubstituted terminal one. Functionalization of these structures would result in mixtures of products derived from each potential alkene group without site-selectivity. The cage host A was proved to recognize organic molecules in water and pre

• terminal was exposed to the aqueous solution and the more hydrophobic olefin terminal was buried deep in the cavitand hence protected from the further functionalization. This methodology could be expanded generally to the systems of converting symmetrical hydrophobic guests to unsymmetrical, amphiphilic

Iridium-catalyzed hydroacylation reactions of C1-substituted oxabenzonorbornadienes with salicylaldehyde: an experimental and computational study

• Angel Ho,
• Austin Pounder,
• Krish Valluru,
• Leanne D. Chen and
• William Tam

Beilstein J. Org. Chem. 2022, 18, 251–261, doi:10.3762/bjoc.18.30

• revolutionized the modern chemist’s synthetic toolbox, prior installation of these functional groups requires a number of steps, leading to undesired side-products and reduced overall yield. An attractive alternative is the catalytic activation and subsequent functionalization of otherwise inert carbon–hydrogen

• functionalization. Over the years, several interesting transformations have been investigated such as cycloadditions 4 [18][19][20][21][22][23], dimerizations 3 [24][25][26][27], isomerizations [28][29][30][31], among other reactions that have been reported [32][33][34][35][36][37][38]. The nucleophilic ring

Chemoselective N-acylation of indoles using thioesters as acyl source

• Tianri Du,
• Xiangmu Wei,
• Honghong Xu,
• Xin Zhang,
• Ruiru Fang,
• Zheng Yuan,
• Zhi Liang and
• Yahui Li

Beilstein J. Org. Chem. 2022, 18, 89–94, doi:10.3762/bjoc.18.9

• cannabinoid (hCB1) receptor [3] (Figure 1). Indole has multiple reactive sites, and chemoselective N- or C-functionalization of indoles is a challenging and important task [4][5]. Acylation of indoles frequently takes place at the C3 position because of the relatively strong electron cloud density. As N

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

• laboratories calls for a critical analysis of these methods to enable an efficient transition of these methods. Hence, manganese-catalyzed C–H functionalization for late-stage functionalizations of biomolecules and drug-like scaffolds are summarized [8]. Likewise, 3d transition metal-catalyzed C–H

1,2-Naphthoquinone-4-sulfonic acid salts in organic synthesis

• Ruan Carlos B. Ribeiro,
• Patricia G. Ferreira,
• Amanda de A. Borges,
• Luana da S. M. Forezi,
• Fernando de Carvalho da Silva and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 53–69, doi:10.3762/bjoc.18.5

• possible to identify three alternatives for the functionalization of β-NQS with amines: a) substitution of sulfonate by secondary amines; b) substitution of sulfonate by primary amines, followed by isomerization; and c) double addition of primary amines. In addition, other nucleophiles can also be used

Recent advances and perspectives in ruthenium-catalyzed cyanation reactions

• Thaipparambil Aneeja,
• Cheriya Mukkolakkal Abdulla Afsina,
• Padinjare Veetil Saranya and
• Gopinathan Anilkumar

Beilstein J. Org. Chem. 2022, 18, 37–52, doi:10.3762/bjoc.18.4

• -up, high reproducibility and yields, lower catalyst loading, high product purity, and excellent selectivity. A visible-light-promoted Strecker-type functionalization of N-aryl-substituted tetrahydroisoquinolines under flow conditions was reported (Scheme 22) [45]. The cyanating agent utilized was

• strategy. Proposed mechanistic pathway for the cyanation of the aldimine intermediate. Strecker-type functionalization of N-aryl-substituted tetrahydroisoquinolines under flow conditions. One-pot synthesis of α-aminonitriles using RuCl3 as catalyst. Synthesis of alkyl nitriles using (Ru(TMHD)3) as the

Efficient N-arylation of 4-chloroquinazolines en route to novel 4-anilinoquinazolines as potential anticancer agents

• Rodolfo H. V. Nishimura,
• Thiago dos Santos,
• Valter E. Murie,
• Luciana C. Furtado,
• Leticia V. Costa-Lotufo and
• Giuliano C. Clososki

Beilstein J. Org. Chem. 2021, 17, 2968–2975, doi:10.3762/bjoc.17.206

• -anilinoquinazolines can be prepared from N-methylanilines under basic [14] or acidic [15][16] (Scheme 1c) conditions. Due to our interest in the functionalization of aromatic and heterocyclic compounds of medicinal relevance [21][22][23][24][25][26], we recently reported the preparation of an iodo-substituted analog

DABCO-promoted photocatalytic C–H functionalization of aldehydes

• Bruno Maia da Silva Santos,
• Mariana dos Santos Dupim,
• Cauê Paula de Souza,
• Thiago Messias Cardozo and
• Fernanda Gadini Finelli

Beilstein J. Org. Chem. 2021, 17, 2959–2967, doi:10.3762/bjoc.17.205

• differences are discussed. Keywords: C–H functionalization; DABCO; HAT; photocatalysis; Introduction The functionalization of inert C–H bonds is a goal pursued by chemists from decades, due to its ubiquity in organic molecules. This strategy also dismisses tiresome protecting groups and functional group

• accessibility, it is still underused, and has only recently started to gain attention from the synthetic community. Murphy and co-workers reported the use of the DABCO radical cation, generated by a stoichiometric oxidant (TPTA-PF6), as a hydrogen abstractor for alpha-nitrogen C–H functionalization [21] (Figure

• . Alemán and co-workers also published the use of a photogenerated DABCO radical cation in a distal β-carbonyl enantioselective C–H functionalization for the synthesis of pyrroline derivatives [26] (Figure 2d). The latter is, to the best of our knowledge, the only work reporting a direct substrate C–H bond

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

• functionalized compound (Scheme 1b). Lastly, the reaction between two C–H compounds to form a C–C bond, formally eliminating H2, hence the dehydrogenative reference (Scheme 1c). As this coupling reaction does not require functionalization prior to coupling, it shortens the synthetic route, and lowers the

• to the styrene derivative selectively to afford a metastable benzyl radical [111] which is captured by BuOO• via a radical termination process. Iron-catalyzed oxidative addition/coupling and functionalization Carbofunctionalization Moving forward, the Fe-catalyzed carbofunctionalization of alkenes

• will be discussed as a method for the formation of multiple bonds in a single step. Mechanistically, Fe-catalyzed oxidative addition and functionalization reactions proceed similarly to cross dehydrogenative couplings (vide supra); however, these reactions will result in byproducts other than the

Selective sulfonylation and isonitrilation of para-quinone methides employing TosMIC as a source of sulfonyl group or isonitrile group

• Chuanhua Qu,
• Run Huang,
• Yong Li,
• Tong Liu,
• Yuan Chen and
• Guiting Song

Beilstein J. Org. Chem. 2021, 17, 2822–2831, doi:10.3762/bjoc.17.193

• sulfones is a valuable and appealing task in synthetic chemistry. Traditionally, diarylmethyl sulfones are synthesized by transition-metal-catalyzed deoxy C–S bond-coupling reaction of sodium arylsulfinates with diarylmethanols [11], C–H functionalization of alkyl sulfones with aryl halides [12], and via a

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

• 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

Recent advances in the asymmetric phosphoric acid-catalyzed synthesis of axially chiral compounds

• Alemayehu Gashaw Woldegiorgis and
• Xufeng Lin

Beilstein J. Org. Chem. 2021, 17, 2729–2764, doi:10.3762/bjoc.17.185

• acids are widely used in stereoselective oxidative/cross-coupling of two aryl counterparts, asymmetric control of aromatic ring formation, atroposelective functionalization of biaryl compounds, and so on [17][29][30]. In this context, Akiyama (2004) described that chiral phosphoric acids (CPAs) have

• phosphoric acid-catalyzed synthesis of axially chiral compounds and to suggest that much more attention should be paid to these catalysts in order to promote asymmetric synthesis. Review 1. Enantioselective synthesis of atropisomeric biaryls Direct C–H functionalization strategies for the atroposelective

• be prepared by asymmetric C–H activation. The C–H activation or functionalization can be achieved by a metal-catalyzed chiral phosphoric acid ligand-assisted method, which offers distinct possibilities to provide various chiral biaryl compounds by changing different directing groups (DGs) [46]. Since

Ligand-dependent stereoselective Suzuki–Miyaura cross-coupling reactions of β-enamido triflates

• Tomáš Chvojka,
• Athanasios Markos,
• Svatava Voltrová,
• Radek Pohl and
• Petr Beier

Beilstein J. Org. Chem. 2021, 17, 2657–2662, doi:10.3762/bjoc.17.179

• of cytotoxic, antifungal, or antibiotic properties [10][11][12]. Modern stereoselective syntheses leading to highly substituted enamides include cross-coupling of vinyl (pseudo)halides or organoboron compounds [13], hydroamidation of alkynes [14][15][16], ynamide functionalization [17][18][19], or

Silica gel and microwave-promoted synthesis of dihydropyrrolizines and tetrahydroindolizines from enaminones

• Robin Klintworth,
• Garreth L. Morgans,
• Stefania M. Scalzullo,
• Charles B. de Koning,
• Willem A. L. van Otterlo and
• Joseph P. Michael

Beilstein J. Org. Chem. 2021, 17, 2543–2552, doi:10.3762/bjoc.17.170

• temperature and microwave power, although requiring much longer time. A possible mechanism for the cyclization is presented, and further functionalization of the newly created pyrrole ring in the dihydropyrrolizine core is described. Keywords: dihydropyrrolizines; enaminones; microwaves; silica gel

• uncommon biaryl axis with a pyrrole ring as one of the components, the pyrrole ring itself is created in an unusual manner, and further functionalization of the pyrrole ring is possible. Since both classes of azabicyclic product are well represented in compounds of pharmaceutical interest as well as in

• , 100 °C), 1–3 h. Further functionalization of dihydropyrrolizine 19a. Reagents and conditions: (i) NBS, DMF, 0 °C, 1 h, then rt, 18 h; (ii) PhB(OH)2, Pd(PPh3)4 (cat.), Na2CO3, DMF, reflux, 20 h. Optimization of the cyclization of enaminone 15a to pyrrolizine 19a. Preparation of enaminones 15a–ya, and