Synthesis of electrophile-tethered preQ₁ analogs for covalent attachment to preQ₁ RNA

• Laurin Flemmich and
• Ronald Micura

Beilstein J. Org. Chem. 2025, 21, 483–489, doi:10.3762/bjoc.21.35

• derivatives have been reported [22][23][24][25][26]. Among these reports, various silylation and protection strategies have been employed to address the poor solubility of preQ1 (and analogs) in organic solvents [9][22][23][25][26][27][28][29]. Herein, we report an optimized three-step protocol, free of

The scent gland composition of the Mangshan pit viper, Protobothrops mangshanensis

• Jonas Holste,
• Paul Weldon,
• Donald Boyer and
• Stefan Schulz

Beilstein J. Org. Chem. 2024, 20, 2644–2654, doi:10.3762/bjoc.20.222

• natural extract was filtered through a glass pipette plugged with Kimtech paper before GC–MS analysis and derivatization. Extract derivatization Silylation with MSTFA: An extract (100 µL) was mixed with 50 µL of N-methyl-N-(trimethylsilyl)trifluoroacetamide (MSTFA) in a 2 mL GC vial. The solution was

A review of recent advances in electrochemical and photoelectrochemical late-stage functionalization classified by anodic oxidation, cathodic reduction, and paired electrolysis

• Nian Li,
• Ruzal Sitdikov,
• Ajit Prabhakar Kale,
• Joost Steverlynck,
• Bo Li and
• Magnus Rueping

Beilstein J. Org. Chem. 2024, 20, 2500–2566, doi:10.3762/bjoc.20.214

Domino reactions of chromones with activated carbonyl compounds

• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 1256–1269, doi:10.3762/bjoc.20.108

• (silyloxy)-1,3-butadienes are highly moisture sensitive compounds which can be prepared from the corresponding 1,3-dicarbonyl dianions in two steps. For example, diene 6a is available by silylation of 2 to give silyl enol ether 5 which is subsequently deprotonated by LDA and treated with

• trimethylchlorosilane. A direct preparation of 6a by reaction of dianion 7 with trimethylchlorosilane is not possible, because the silylation occurs at the terminal carbon atom of the dianion. (2,4-Dioxobutylidene)phosphorane 8 also represents a synthetic equivalent of dianion 7 [23]. However, reactions of such

Synthesis of 1,4-azaphosphinine nucleosides and evaluation as inhibitors of human cytidine deaminase and APOBEC3A

• Maksim V. Kvach,
• Stefan Harjes,
• Harikrishnan M. Kurup,
• Geoffrey B. Jameson,
• Elena Harjes and
• Vyacheslav V. Filichev

Beilstein J. Org. Chem. 2024, 20, 1088–1098, doi:10.3762/bjoc.20.96

• experiments with human CDA (hCDA), we used deprotected nucleoside Va as a mixture of anomers and converted it to Vb through a four-step one-pot synthesis involving silylation, treatment with oxalyl chloride, ammonolysis and removal of silyl groups. Purified phosphinamide Vb was obtained as a mixture of

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

• allylation of lithium (trimethylsilyl)amides prepared in situ from the parent amines by a lithiation/silylation/lithiation sequence (Table 1). Using this protocol, α-(aminomethyl)acrylates 5 and 6 derived from benzhydrylamine and aniline were prepared in high yields (Table 1, entries 1 and 2). The procedure

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

• less-encumbered NHC–CuSiMe2Ph complexes for the silylation of aldehydes and unsaturated ketones with silylboranes were investigated in a case study. The complexes (It-Bu)CuOt-Bu (105b) and (Me2IMe)CuOt-Bu (105c) were found to be effective (pre)catalysts for the 1,2-silylation of tolualdehyde and the

• 1,4-silylation of hex-3-ene-4-one. An efficient conversion was observed in both cases and the silylated products were isolated in good yields (Scheme 37) [42]. Recently, in 2021, Cheng and Mankad reviewed NHC–Cu(I)-catalyzed carbonylative coupling reactions including the carbonylative silylation of

• alkyl halides (Scheme 38) [53]. Carbonylative silylation of unactivated alkyl halides was achieved by using the commercially available Si nucleophile PhMe2Si-Bpin in the presence of IPrCuCl complex 106 as catalyst (Scheme 38). This allowed to obtain alkyl-substituted acylsilanes 107 in high yields from

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

Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles

• Péter Kisszékelyi and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44

• all possess helpful and, to an extent, specific reactivity characteristics. Interesting boron and silicon enolates can be generated by asymmetric conjugate boration [16], or silylation [17]. From several potentially catalytically active transition metals, copper combines beneficial properties for both

• enolate intermediate with benzaldehyde (51) and methyl bromoacetate (181) (Scheme 46). At about the same time, Riant and co-workers investigated the chiral auxiliary-assisted Cu-catalyzed tandem silylation/aldol reaction between enoyloxazolidinones and different aromatic aldehydes [89]. In the case of

• silylation/aldol cyclization sequence where the diastereoselectivity of the reaction is determined by the Si nucleophile used [90]. Using Me2PhSiZnX·2LiX in combination with ligand L21 leads to the trans adduct, while Me2PhSiBpin together with L30 provides the cis product. Consequently, the authors have

C3-Alkylation of furfural derivatives by continuous flow homogeneous catalysis

• Grédy Kiala Kinkutu,
• Catherine Louis,
• Myriam Roy,
• Juliette Blanchard and
• Julie Oble

Beilstein J. Org. Chem. 2023, 19, 582–592, doi:10.3762/bjoc.19.43

• changing the redox state of the aldehyde function, we have developed a number of directed Ru(0)-catalyzed C3-functionalizations of furfurylimines, such as alkylation [21], arylation [22], alkenylation [23] and acylation [24], as well as an Ir-catalyzed directed C3-silylation (Scheme 1a) [25]. These batch

Combretastatins D series and analogues: from isolation, synthetic challenges and biological activities

• Jorge de Lima Neto and
• Paulo Henrique Menezes

Beilstein J. Org. Chem. 2023, 19, 399–427, doi:10.3762/bjoc.19.31

• yield diol 72. The 3R,4S configuration of compound 72 was expected based on Pettit’s work [16][17] and the optical purity of the obtained product was more than 95% by 1H NMR using [Eu(hfc)3] as a chiral shift reagent. Subsequent silylation followed by ester hydrolysis and removal of the pivaloyl group

Preparation of β-cyclodextrin-based dimers with selectively methylated rims and their use for solubilization of tetracene

• Konstantin Lebedinskiy,
• Volodymyr Lobaz and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2022, 18, 1596–1606, doi:10.3762/bjoc.18.170

• according to the published procedure (Scheme 1) [26] with some modifications to achieve better results. We started with silylation of 6-azido-β-CD, using imidazole/DMF base/solvent mixture instead of pyridine, which gave higher yields and lower reaction time. Also, we found the recrystallization from the

A study of the DIBAL-promoted selective debenzylation of α-cyclodextrin protected with two different benzyl groups

• Naser-Abdul Yousefi,
• Morten L. Zimmermann and
• Mikael Bols

Beilstein J. Org. Chem. 2022, 18, 1553–1559, doi:10.3762/bjoc.18.165

• temperature control during the acetolysis step. The silylation method requires careful drying of 1 before the silylation but is otherwise experimentally simple. Hexol 6 was then DCB-protected using 2,4-dichlorobenzyl chloride and sodium hydride in DMSO. As self-condensation of the alkylating agent is possible

An alternative C–P cross-coupling route for the synthesis of novel V-shaped aryldiphosphonic acids

• Stephen J. I. Shearan,
• Enrico Andreoli and
• Marco Taddei

Beilstein J. Org. Chem. 2022, 18, 1518–1523, doi:10.3762/bjoc.18.160

• three novel aryl diphosphonate esters which were subsequently transformed to phosphonic acids through silylation and hydrolysis. Keywords: arylphosphonic acids; cross-coupling reaction; phosphonate esters; transition-metal catalysis; Introduction Phosphonates and phosphonic acids are a very

• mmol), 4.0 g (12.2 mmol) or 3.0 g (7.4 mmol) of substrate. Once the phosphonate esters had been successfully obtained and characterized by 1H, 31P, 13C NMR and mass spectrometry (see experimental section and Supporting Information File 1), they were then subjected to silylation and subsequent

Modular synthesis of 2-furyl carbinols from 3-benzyldimethylsilylfurfural platforms relying on oxygen-assisted C–Si bond functionalization

• Sebastien Curpanen,
• Per Reichert,
• Gabriele Lupidi,
• Giovanni Poli,
• Julie Oble and
• Alejandro Perez-Luna

Beilstein J. Org. Chem. 2022, 18, 1256–1263, doi:10.3762/bjoc.18.131

• -based protocol for the catalytic C3–H silylation of furfurylimines [15]. This method allows to install a C–Si bond poised for further functionalization on the furfural unit, and thereby leads to synthetic platforms useful to access elaborated furans. This prospect was demonstrated with platforms relying

• and Discussion Synthesis of 3-silylated 2-furyl carbinols C3-silylated furfurals 1a–c and 2c are accessible from furfural or 5-methylfurfural [20], respectively, according to our previously reported protocol for selective catalytic C3 silylation [15]. The addition of organolithium [21] or Grignard

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

• alkyl cation 113. Nucleophilic trapping of the carbocation provides the final product. In 2018, the Li group continued to explore Fe-catalyzed silylation cascade chemistry. Their protocol investigated the silylperoxidation of activated alkenes in good yield [107]. In 2019, Yang and co-workers described

Synthetic strategies toward 1,3-oxathiolane nucleoside analogues

• Umesh P. Aher,
• Dhananjai Srivastava,
• Girij P. Singh and
• Jayashree B. S

Beilstein J. Org. Chem. 2021, 17, 2680–2715, doi:10.3762/bjoc.17.182

• ammonolysis in methanol affords compound 1c. The silylation of 1c with TBDPSCl was carried out, and then coupling reaction with tert-Boc-Met-Leu-Phe-OH in the presence of DCC and HOBt provided compound 98. The tert-Boc protecting group was further removed in formic acid, and the resulting nucleoside peptide

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

• silylation of N-methylindole (1) with observed H2 evolution [54]. Here the di(indol-2-yl)silane (31) was found as a minor product though (Scheme 5a). The reaction has a high turnover number of 92 and it was halted in the presence of radical scavengers. However, the mechanism was unidentified, although it was

• ). A repetition of the processes leads to the bis(indol-3-yl)silanes 40. Han described a Lewis acid-promoted C3-silylation of N-protected substituted indoles by a disproportionation mechanism of the latter. He used both B(C6F5)3 and Al(C6F5)3 in the reactions (Scheme 8a and Scheme 8c) which followed a

• similar mechanism (Scheme 8b) [62][63]. The reduced form of indole, i.e., indoline 50 coordinates with the Lewis acid to form a complex which activates PhSiH3 (frustrated Lewis pair) for silylation (69, Scheme 8b). Phosphines The base-mediated syntheses of bis(indol-2-yl)phosphines 76 and 78 were

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

• efficient antibacterial compounds (Scheme 24A) [146]. In 2021, a divergent silylation of alkenes via a manganese-catalyzed C–H activation was reported by Xie et al. by using a ligand-tuned metalloradical reactivity strategy (Scheme 24B and C) [147]. Using Mn2(CO)10 as a catalyst precursor, the authors

α,γ-Dioxygenated amides via tandem Brook rearrangement/radical oxygenation reactions and their application to syntheses of γ-lactams

• Mikhail K. Klychnikov,
• Radek Pohl,
• Ivana Císařová and
• Ullrich Jahn

Beilstein J. Org. Chem. 2021, 17, 688–704, doi:10.3762/bjoc.17.58

• corresponding acyclic or cyclic allylic amines in very good yields (see Supporting Information File 1 for details). Their subsequent α-deprotonation by LDA followed by treatment with chlorotrimethylsilane at −78 °C [81] resulted in clean C-silylation of the corresponding enolate providing silylacetamides 8a–m

Recent progress in the synthesis of homotropane alkaloids adaline, euphococcinine and N-methyleuphococcinine

• Dimas J. P. Lima,
• Antonio E. G. Santana,
• Michael A. Birkett and
• Ricardo S. Porto

Beilstein J. Org. Chem. 2021, 17, 28–41, doi:10.3762/bjoc.17.4

• (1). Alternatively, the (±)-euphococcinine precursor 6 was prepared from 4, via deprotonation, silylation, and finally, silyl ether cleavage. Swern oxidation of alcohols 5 and 6 gave aldehydes 7 and 8, treated with allylmagnesium bromide, to generate secondary alcohols 9 and 10. These alcohols were

All-carbon [3 + 2] cycloaddition in natural product synthesis

• Zhuo Wang and
• Junyang Liu

Beilstein J. Org. Chem. 2020, 16, 3015–3031, doi:10.3762/bjoc.16.251

• the desired alcohol 133 in 75% yield as a single diastereomer. Allylic oxidation of freshly prepared 133 with SeO2 followed by silylation with TBSOTf/Et3N afforded enyne 134. Enyne 134 was subjected to rhodium-catalyzed intramolecular [3 + 2] cycloaddition with a catalytic amount of [Rh(cod)OH]2 to

Changed reactivity of secondary hydroxy groups in C8-modified adenosine – lessons learned from silylation

• Jennifer Frommer and
• Sabine Müller

Beilstein J. Org. Chem. 2020, 16, 2854–2861, doi:10.3762/bjoc.16.234

• conjugation of the desired moiety. A C8-alkynyl-modified adenosine derivative was synthesized, reviving an old synthetic pathway for iodination of purine nucleobases. Silylation of the C8-alkynyl-modified adenosine revealed unexpected selectivity of the two secondary sugar hydroxy groups, with the 3'-O-isomer

• charge transfer [23][24]. In the course of monomer synthesis, we encountered unexpected results regarding the reactivity and selectivity of the two secondary hydroxy groups of the adenosine derivative 7 (Scheme 1) in the silylation step, leading to non-satisfactory overall reaction yields. Therefore, the

• synthesis strategy was re-designed, allowing the preparation of building block 9 (Scheme 2) ready for use in solid-phase RNA synthesis with excellent yield. Here, we report on the selectivity problem in 2’-O-silylation of adenosine derivative 7 (Scheme 1) and the optimized synthesis strategy for the

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

• occurring during the silylation step could be usually prevented. On the other hand, the side reactions during the solvolysis step are usually obviated by the use of a buffer or weak base, which neutralize the final organophosphorus acids. Herein we mainly addressed the problems related to the silylation

• for studying the possibility of an N-alkylation by alkyl bromide, formed during the silylation step. Finally, compound 13 was included to study the possibility of a chlorine for bromine exchange reaction. The phosphonocarboxylates 8 and 9 were used to explore whether the carboxyester group could be

• phosphonate ester instead of the diethyl analogs. Even though the silylation step required longer times in case of the diisopropyl phosphonate ester [1], which may promote the formation of side products, no N-alkylated product was observed, neither for diisopropyl phosphonates 9c,d (even during 13 days), nor

Recent advances in Cu-catalyzed C(sp³)–Si and C(sp³)–B bond formation

• Balaram S. Takale,
• Ruchita R. Thakore,
• Elham Etemadi-Davan and
• Bruce H. Lipshutz

Beilstein J. Org. Chem. 2020, 16, 691–737, doi:10.3762/bjoc.16.67

• reactions are discussed. Keywords: C–B bonds; copper catalysis; C–Si bonds; enantioselective reactions; sp3 carbon functionalization; Introduction Transition-metal-catalyzed silylation and borylation are useful transformations [1], widely studied because organosilicon [2][3] and organoboron compounds [4

• the in situ-formed Cu–Si species leading ultimately to the formation of the desired C–Si bond. This process could be applied to a variety of substrates leading to the desired products 29 and 38–40 (Scheme 9) [31]. This silylation reaction was also performed on geminal dibromides 41. In such cases

• , both bromides were replaced by silyl groups. The reaction supposedly occurred partly via ionic silylation (of the first bromide), and partly via a radical pathway (silylation of the second bromide), effected by the presence of catalytic amounts of CuBr·SMe2 along with dtbpy as ligand. Whatever the