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

• , and easily available N-cyano-N-phenyl-p-toluenesulfonamide (NCTS) as the cyanating reagent. The reaction exhibited high chemoselectivity and good functional group tolerance. The optimized conditions for the reaction were [RuCl2(p-cymene)]2 (5 mol %), AgSbF6 (20 mol %), NaOAc (20 mol %) in DCE at 120

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

• observed generating spiro succinimidetetrahydropyridine derivatives 172. To understand the chemoselectivity of the reaction, the authors performed a DFT mechanistic study. After the iminyl radical is generated it will undergo a 1,5-HAT to form the more stable alkyl radical which will add across the alkene

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

• poor chemoselectivity [40]. However, the realization of this redox-neutral aryl–aryl cross-coupling is a formidable challenge. Therefore, the discovery of efficient catalysts and ligands to achieve high stereoselectivity is a fundamental issue in catalytic asymmetric synthesis [14]. In this section, we

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

• these results, the late-stage diversification using the [Mn(t-BuPc)Cl] catalyst was applied to more complex natural compounds such as the isosteviol derivative 45 and the betulinic acid derivative 47, which underwent conversion in good and high yields and with high chemoselectivity. The functionalized

• ′-bipyrrolidine) controls the site- and chemoselectivity in the hydroxylating step of the methylene C(sp3)–H bond while milder oxidation conditions help to increase the chemoselectivity. The methylation step is accomplished using a modestly nucleophilic organoaluminium reagent (AlMe3) to activate the hemiaminal

• , operating under mild conditions without the need of directing groups, using traceless electrons as sole redox reagents, presenting high scope and chemoselectivity. The robustness of the reaction was proved by the late-stage modification of pharmaceutically relevant compounds by promoting the azidation of a

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

• tryptophan-containing peptides (Scheme 13). A wide variety of complex peptides was explored, affording glycosylated conjugates with high stereoselectivity. The free NH functional group was tolerated in the manganese catalysis protocol, suggesting that the chemoselectivity was controlled by chelation of the

• , late-stage intramolecular C–H macrocyclization was also investigated (Scheme 15). To avoid unwanted intermolecular oligomerization, the reaction was performed at a high dilution, furnishing either C- or N-terminus-alkenylated products with excellent chemoselectivity. In this macrocyclization, cyclic

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

• strategy in total synthesis can be found [82][83][84][85][86][87][88][89][90]. The reaction’s mild conditions and high chemoselectivity allowed its use even in advanced steps in a total synthesis route when diverse functional groups were present in the intermediates. Two representative examples of the

A straightforward conversion of 1,4-quinones into polycyclic pyrazoles via [3 + 2]-cycloaddition with fluorinated nitrile imines

• Greta Utecht-Jarzyńska,
• Karolina Nagła,
• Grzegorz Mlostoń,
• Heinz Heimgartner,
• Marcin Palusiak and
• Marcin Jasiński

Beilstein J. Org. Chem. 2021, 17, 1509–1517, doi:10.3762/bjoc.17.108

• 1,4-naphthoquinone (1a) and 1,4-anthraquinone (1b), which were selected as model dipolarophiles. In addition, an important issue of the work was the examination of the chemoselectivity governing the formation of five-membered rings via competitive cycloaddition of the in-situ-generated 1,3-dipoles

• -quinone methides with common nitrile imines proceeded with different chemoselectivity, and in these cases, the exocyclic C=C bond played the role of the exclusive dipolarophilic center, yielding corresponding spiropyrazoles [39][40]. This unusual selectivity in [3 + 2]-cycloadditions of less electron

Free-radical cyclization approach to polyheterocycles containing pyrrole and pyridine rings

• Ivan P. Mosiagin,
• Olesya A. Tomashenko,
• Dar’ya V. Spiridonova,
• Mikhail S. Novikov,
• Sergey P. Tunik and
• Alexander F. Khlebnikov

Beilstein J. Org. Chem. 2021, 17, 1490–1498, doi:10.3762/bjoc.17.105

• target compounds and can be performed on a gram scale. The free bases can be obtained from the synthesized hydrobromides in quantitative yield by basification at rt. The use 2/4-(ortho-bromo/iodophenyl)-substituted pyrrolylpyridinium bromides allows control over the chemoselectivity of the intramolecular

Iodine-catalyzed electrophilic substitution of indoles: Synthesis of (un)symmetrical diindolylmethanes with a quaternary carbon center

• Thanigaimalai Pillaiyar,
• Masoud Sedaghati,
• Andhika B. Mahardhika,
• Lukas L. Wendt and
• Christa E. Müller

Beilstein J. Org. Chem. 2021, 17, 1464–1475, doi:10.3762/bjoc.17.102

• unsymmetrical 3,3'-diindolylmethanes (DIMs) with a quaternary carbon center has been developed via iodine-catalyzed coupling of trifluoromethyl(indolyl)phenylmethanols with indoles. In contrast to previously reported methods, the new procedure is characterized by chemoselectivity, mild conditions, high yields

Nitroalkene reduction in deep eutectic solvents promoted by BH₃NH₃

• Chiara Faverio,
• Monica Fiorenza Boselli,
• Patricia Camarero Gonzalez,
• Alessandra Puglisi and
• Maurizio Benaglia

Beilstein J. Org. Chem. 2021, 17, 1041–1047, doi:10.3762/bjoc.17.83

• , nitrocyclohexene was reduced in 60% yield in a ChCl/glycerol mixture, while 6c was obtained in similar yields in glycerol or DES B. Noteworthy, the reduction of nitrobutadiene 5d produced nitro derivative 6d in 63% yield in glycerol and 44% in DES B, with complete control of the chemoselectivity. Remarkably, the

• reduction of nitrodiene 5e, featuring an ester group, was also accomplished with complete chemoselectivity in 50% yield in DES B and in 60% yield in glycerol. The reduction of the nitro group to an amine, followed by cyclization would afford the unsaturated δ-lactam, a valuable precursor for further

• also demonstrated. A wide variety of alkyl- and aryl-substituted nitroalkenes were reduced with high chemoselectivity, including β-substituted nitroolefins, and thus paving the way to the study of innovative, sustainable and stereoselective reductive methods to synthesize enantiopure nitroalkanes

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

• synthesis of unnatural α-amino acids 129 and precise alkylation modification of peptides in the later stage (Scheme 45). Even in the presence of other amino acid residues, this protocol has excellent regio- and chemoselectivity, providing a sequence of novel corresponding dipeptides with good yield. The

Particle size effect in the mechanically assisted synthesis of β-cyclodextrin mesitylene sulfonate

• Stéphane Menuel,
• Sébastien Saitzek,
• Eric Monflier and
• Frédéric Hapiot

Beilstein J. Org. Chem. 2020, 16, 2598–2606, doi:10.3762/bjoc.16.211

• study, we found that the reactivity depended more upon diffusion phenomena in the crystalline parts of the material than on the increase in the surface area of the CD particles resulting from grinding. Keywords: beta-cyclodextrin; chemoselectivity; grinding; mechanosynthesis; reactivity; Introduction

• constituting the reaction mixture on the reactivity for the synthesis of β-CDMts under ball-milling conditions. Additionally, in the presence of a base such as KOH, we show that the chemoselectivity of the reaction is significantly altered in favor of the β-CD product mono-substituted on the primary face, thus

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

•  1. The lack of sophisticated methods for direct C(sp3)–H fluorinations is attributed to the challenges of regio- and chemoselectivity in C(sp3)–H activation. Compounds that possess several C(sp3)–H bonds will form several regioisomeric or polyfluorinated products that may be challenging to separate

• chemoselectivity. Overall, chemo- and regioselective C(sp3)–H fluorinations continue to challenge chemists. Most direct C(sp3)–H fluorinations are reported to proceed under radical pathways involving hydrogen atom transfer (HAT), although proton-coupled electron transfer (PCET) has also been reported [44][49][50

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

The McKenna reaction – avoiding side reactions in phosphonate deprotection

• Katarzyna Justyna,
• Joanna Małolepsza,
• Damian Kusy,
• Waldemar Maniukiewicz and
• Katarzyna M. Błażewska

Beilstein J. Org. Chem. 2020, 16, 1436–1446, doi:10.3762/bjoc.16.119

• reagent for the formation of silyl enol ethers [10]. However, these reactions often required higher temperatures (up to 100 °C) or were applicable to only certain types of functional groups, such as methoxymethyl ethers [10]. Still, BTMS, due to its balanced effectiveness and high chemoselectivity, is the

• reaction with BTMS, and underwent exchange of the chlorine substituent for bromine. This reaction can be partially circumvented by using nonpolar solvents, amines and lower temperatures. Section 5: Cleavage of the tert-butyl carboxyester group BTMS is known for its chemoselectivity and cleaves phosphonate

Distinctive reactivity of N-benzylidene-[1,1'-biphenyl]-2-amines under photoredox conditions

• Shrikant D. Tambe,
• Kwan Hong Min,
• Naeem Iqbal and
• Eun Jin Cho

Beilstein J. Org. Chem. 2020, 16, 1335–1342, doi:10.3762/bjoc.16.114

• -donating (2q and 2r) and electron-withdrawing (2s) substituents underwent the cross-coupling with excellent reactivities. We also tried the transformation with aliphatic amines other than Cy2NMe, such as TMEDA, TEA, and DIPEA. However, these reactions proceeded with a poor chemoselectivity and resulted in

Highly selective Diels–Alder and Heck arylation reactions in a divergent synthesis of isoindolo- and pyrrolo-fused polycyclic indoles from 2-formylpyrrole

• Carlos H. Escalante,
• Eder I. Martínez-Mora,
• Carlos Espinoza-Hicks,
• Alejandro A. Camacho-Dávila,
• Fernando R. Ramos-Morales,
• Francisco Delgado and
• Joaquín Tamariz

Beilstein J. Org. Chem. 2020, 16, 1320–1334, doi:10.3762/bjoc.16.113

• similar chemoselectivity has been previously observed, being explained as a consequence of the acidity of the C–H bond being cleaved [6][44]. Additional intramolecular cross-coupling reactions were carried out by utilizing dimethyl malonates 8k and 8l, which were prepared through the N-benzylation of 16c

Recent applications of porphyrins as photocatalysts in organic synthesis: batch and continuous flow approaches

• Rodrigo Costa e Silva,
• Luely Oliveira da Silva,
• Aloisio de Andrade Bartolomeu,
• Timothy John Brocksom and
• Kleber Thiago de Oliveira

Beilstein J. Org. Chem. 2020, 16, 917–955, doi:10.3762/bjoc.16.83

• porphyrins as photocatalysts under sunlight irradiation furnished the corresponding sulfoxides with high chemoselectivity (up to 100%), scalability (up to 2.6 mmol) and high yields (up to 100%) [94]. According to the authors, the protonation of the porphyrins causes a red-shift of the photosensitizer with an

Copper catalysis with redox-active ligands

• Agnideep Das,
• Yufeng Ren,
• Cheriehan Hessin and
• Marine Desage-El Murr

Beilstein J. Org. Chem. 2020, 16, 858–870, doi:10.3762/bjoc.16.77

• selectivity. Homo- and cross-coupling adducts 16a and 16b–g were obtained from the corresponding phenols (14a–e and 15a–c) as shown in the bottom of Scheme 9 with high chemoselectivity. C–N bond formation While copper complexes are at the heart of oxidative biological networks, the introduction of nitrogen is

Efficient method for propargylation of aldehydes promoted by allenylboron compounds under microwave irradiation

• Jucleiton J. R. Freitas,
• Queila P. S. B. Freitas,
• Silvia R. C. P. Andrade,
• Juliano C. R. Freitas,
• Roberta A. Oliveira and
• Paulo H. Menezes

Beilstein J. Org. Chem. 2020, 16, 168–174, doi:10.3762/bjoc.16.19

• results indicated that the substituent nature, whether electron-donating or electron-withdrawing, has no dramatic influence on the product yields. When the α,β-unsaturated aldehyde, cinnamaldehyde was used, the corresponding 1,2-addition product 2i was obtained exclusively. The chemoselectivity of the

Palladium-catalyzed Sonogashira coupling reactions in γ-valerolactone-based ionic liquids

• László Orha,
• József M. Tukacs,
• László Kollár and
• László T. Mika

Beilstein J. Org. Chem. 2019, 15, 2907–2913, doi:10.3762/bjoc.15.284

• synthesis of a wide range of functionalized organic molecules from laboratory to industrial scale [1][2][3]. Among these tools, the Pd-catalyzed coupling reactions have received substantial attention, due to the mild operation conditions, excellent functional group tolerance and chemoselectivity as well as

Synthesis of acremines A, B and F and studies on the bisacremines

• Nils Winter and
• Dirk Trauner

Beilstein J. Org. Chem. 2019, 15, 2271–2276, doi:10.3762/bjoc.15.219

• reduction conditions to afford cyclohexa-1,4-diene 13 [9]. Enantioselective Sharpless dihydroxylation proceeded in good chemoselectivity but with modest yield and optical purity (25% ee). Unfortunately, all attempts to improve the enantioselectivity of this reaction failed. We discovered, however, that at a

Cyclopropanation–ring expansion of 3-chloroindoles with α-halodiazoacetates: novel synthesis of 4-quinolone-3-carboxylic acid and norfloxacin

• Sara Peeters,
• Linn Neerbye Berntsen,
• Pål Rongved and
• Tore Bonge-Hansen

Beilstein J. Org. Chem. 2019, 15, 2156–2160, doi:10.3762/bjoc.15.212

• derived from ethyl α-halodiazoacetates (X-EDA) react readily with unprotected indoles to form ethyl 3-carboxyquinoline structures (Scheme 1) [15]. The Rh carbenes derived from X-EDAs stand out from the three other types of classified carbenoids with respect to chemoselectivity in reactions with indoles

Superelectrophilic carbocations: preparation and reactions of a substrate with six ionizable groups

• Sean H. Kennedy,
• Makafui Gasonoo and
• Douglas A. Klumpp

Beilstein J. Org. Chem. 2019, 15, 1515–1520, doi:10.3762/bjoc.15.153

• (pyridinium/benzylic carbocation) for the hexacation 14, while the ratio of charges is 4:1 (pyridinium/benzylic carbocation) for the pentacation 5. Similarly, we previously reported good chemoselectivity for trication 3 – no cyclization product observed in the presence of benzene – but poor chemoselectivity

• for the tetracation 4. The ratio of charges in these systems are consistent: a charge ratio of 2:1 shows good chemoselectivity (trication 3), while a charge ratio of 3:1 shows poor chemoselectivity (tetracation 4). As we previously reported, a reaction of tetracation 4 with benzene in CF3SO3H leads to

• superacidic CF3SO3H leads to cyclization or arylation products, depending on the presence or absence of benzene. A mechanism is proposed involving tetra-, penta-, and hexacationic reactive intermediates. Most notably, this system shows remarkably good chemoselectivity in its reaction with benzene (only

Switchable selectivity in Pd-catalyzed [3 + 2] annulations of γ-oxy-2-cycloalkenones with 3-oxoglutarates: C–C/C–C vs C–C/O–C bond formation

• Yang Liu,
• Julie Oble and
• Giovanni Poli

Beilstein J. Org. Chem. 2019, 15, 1107–1115, doi:10.3762/bjoc.15.107

• success of this bis-nucleophile/bis-electrophile [3 + 2] annulation is its well-defined step chronology in combination with the total chemoselectivity of the former step. This [3 + 2] C–C/O–C bond forming annulation protocol could be also extended to 1,3,5-triketones as well as 1,3-bis-sulfonylpropan-2

• , top reaction). The success of this bis-nucleophile/bis-electrophile [3 + 2] C–C/N–C bond-forming annulation is due to the well-defined chronology of the steps and the total chemoselectivity of the initial step (C-allylation). Another non-trivial feature of this process is that the possible undesired

• nucleophile is chemoselectivity control. Herein we disclose two chemodivergent [3 + 2] annulation reactions taking place between dialkyl-3-oxoglutarates I and α,β-unsaturated-γ-oxycarbonyl derivatives II that differ simply by the reaction temperature adopted. These methods allow the exclusive [3 + 2] C–C/C–C