Multicomponent synthesis of α-branched amines using organozinc reagents generated from alkyl bromides

• Baptiste Leroux,
• Alexis Beaufils,
• Federico Banchini,
• Olivier Jackowski,
• Alejandro Perez-Luna,
• Fabrice Chemla,
• Marc Presset and
• Erwan Le Gall

Beilstein J. Org. Chem. 2024, 20, 2834–2839, doi:10.3762/bjoc.20.239

• bulk THF (c = 1.0 M) activated by chlorotrimethylsilane (20 mol %) and 1,2-dibromoethane (60 mol %), then alkyl bromide (10 mmol), 80 °C, 16 h. a2-MeTHF was used as solvent. Scope of the reaction. Yield of isolated product is given. Optimization of the organozinc synthesis.a Supporting Information

Multicomponent syntheses of pyrazoles via (3 + 2)-cyclocondensation and (3 + 2)-cycloaddition key steps

• Ignaz Betcke,
• Alissa C. Götzinger,
• Maryna M. Kornet and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2024, 20, 2024–2077, doi:10.3762/bjoc.20.178

Visible-light-induced nickel-catalyzed α-hydroxytrifluoroethylation of alkyl carboxylic acids: Access to trifluoromethyl alkyl acyloins

• Feng Chen,
• Xiu-Hua Xu,
• Zeng-Hao Chen,
• Yue Chen and
• Feng-Ling Qing

Beilstein J. Org. Chem. 2023, 19, 1372–1378, doi:10.3762/bjoc.19.98

• the synthesis of trifluoromethyl aromatic acyloins. Maekawa’s group [24] developed a tandem reaction of the reductive coupling between arylaldehydes and ethyl trifluoroacetate in the presence of magnesium and chlorotrimethylsilane, followed by desilylation to produce the trifluoromethyl aromatic

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

• with the alkylation of the racemic thioglycerol with bromooctadecane in the presence of potassium hydroxide. Then, the protection of the primary alcohol was achieved either with trityl chloride or with dimethyl-tert-butylchlorosilane. The authors also attempted to use chlorotrimethylsilane but the

Electroreductive coupling of 2-acylbenzoates with α,β-unsaturated carbonyl compounds: density functional theory study on product selectivity

• Naoki Kise and
• Toshihiko Sakurai

Beilstein J. Org. Chem. 2022, 18, 956–962, doi:10.3762/bjoc.18.95

• studied using DFT calculations. Keywords: 2-acylbenzoates; chlorotrimethylsilane; 3-(3-cyanoethyl)phthalides; 2-cyanonaphthalen-1-ols; electroductive coupling; Introduction The electroreductive coupling between carbon–heteroatom and carbon–carbon double bonds is one of the promising methods for carbon

• –carbon bond formation [1][2][3][4]. Recently, we reported the electroreductive coupling of phthalic anhydrides with α,β-unsaturated carbonyl compounds in the presence of chlorotrimethylsilane (TMSCl) and subsequent treatment with 1 M HCl to give 1,4-dihydroxynaphthalenes and 2-methyl-2,3

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

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

• the further application of compound 2o in a cyclization reaction. Upon the treatment of 2o with zinc and chlorotrimethylsilane (TMSCl), the intramolecular 1,4-addition reaction of 2o proceeded to give the 2,2-gem-difluorochromane 3 in low yield (Scheme 3). Next, we moved on consideration of the

• C8H6BrClF2O, 269.9259, 271.9238; found, 269.9264, 271.9233. 4-Benzoylmethyl-3-chloro-2,2-difluorochromane (3): To a solution of 2o (210.8 mg, 0.53 mmol) in THF (2.6 mL) was added zinc (42.1 mg, 0.64 mmol) and chlorotrimethylsilane (133 μL, 1.05 mmol) at 0 °C. After stirring for 40 min, the reaction mixture

Ring-closing metathesis of prochiral oxaenediynes to racemic 4-alkenyl-2-alkynyl-3,6-dihydro-2H-pyrans

• Viola Kolaříková,
• Markéta Rybáčková,
• Martin Svoboda and
• Jaroslav Kvíčala

Beilstein J. Org. Chem. 2020, 16, 2757–2768, doi:10.3762/bjoc.16.226

• compounds by substituting the terminal acetylenic hydrogens in the parent oxaenediyne 2a by treatment with butyllithium and methyl chloroformate or chlorotrimethylsilane (Scheme 10). The target disubstituted products 2e and 2f were formed in acceptable to good yields, with the complete disubstitution being

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 of choice for phosphonate ester cleavage, compared with its more and less reactive analogs, iodotrimethylsilane (ITMS) [11][12] and chlorotrimethylsilane (CTMS) [13], respectively. While being one of the most popular methods for the deprotection of organophosphorus esters, the McKenna reaction may

N-(1-Phenylethyl)aziridine-2-carboxylate esters in the synthesis of biologically relevant compounds

• Iwona E. Głowacka,
• Aleksandra Trocha,
• Andrzej E. Wróblewski and
• Dorota G. Piotrowska

Beilstein J. Org. Chem. 2019, 15, 1722–1757, doi:10.3762/bjoc.15.168

Selenophene-containing heterotriacenes by a C–Se coupling/cyclization reaction

• Pierre-Olivier Schwartz,
• Sebastian Förtsch,
• Astrid Vogt,
• Elena Mena-Osteritz and
• Peter Bäuerle

Beilstein J. Org. Chem. 2019, 15, 1379–1393, doi:10.3762/bjoc.15.138

• B3LYP and CAMB3LYP functional and 6-31++(d,p) basis-set [56]. Materials Iodine, zinc(II) chloride, copper(II) chloride, potassium hydroxide, chlorotrimethylsilane, copper(I) iodide, and potassium phosphate were purchased from Merck. Diisopropylamine, bis(dibenzylideneacetone)palladium(0

• was stirred at −78 °C for 45 min. Chlorotrimethylsilane (2 mL, 16 mmol) was added and the mixture was stirred for one more hour. Then, another portion of n-BuLi (1.6 M, 10 mL, 16 mmol) was added. After stirring for one hour at −78 °C, a solution of elemental iodine (3.8 g, 15 mmol) in THF (8 mL) was

Steroid diversification by multicomponent reactions

• Leslie Reguera,
• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Daniel G. Rivera

Beilstein J. Org. Chem. 2019, 15, 1236–1256, doi:10.3762/bjoc.15.121

• based on the use of 17-ketosteroids and chlorotrimethylsilane (TMSCl) as catalyst, which enables the formation of the nucleophilic enolate that attacks either benzaldehyde or its urea imine derivative [39]. Varied ketosteroids were employed, including methylestrone 39, dehydroepiandrosterone acetate and

Phosphonic acid: preparation and applications

• Charlotte M. Sevrain,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2017, 13, 2186–2213, doi:10.3762/bjoc.13.219

• work of Pohjala et al. [162] (Figure 15B) The authors showed that the diphosphonate 40 featuring both phenyl and alkyl substituents treated with chlorotrimethylsilane and sodium iodide in CH3CN yielded, after methanolysis and treatment with NaOH, compound 41 resulting from the hydrolysis of the diethyl

• disilylated phosphonate. The same reaction is also observed with the use of iodotrimethylsilane (Me3SiI) [168]. However, with chlorotrimethylsilane the reaction is not really efficient as indicated in the initial work of McKenna since only a partial conversion was observed after several days of reaction

• . Nevertheless, the use of a mixture of chlorotrimethylsilane with NaI in acetonitrile can be used to achieve the silylation of dialkyl phosphonates that can be then transformed in phosphonic acids after hydrolysis or methanolysis. Following these experimental conditions, the efficacy is likely explained by the

New approaches to organocatalysis based on C–H and C–X bonding for electrophilic substrate activation

• Pavel Nagorny and
• Zhankui Sun

Beilstein J. Org. Chem. 2016, 12, 2834–2848, doi:10.3762/bjoc.12.283

• followed by anion exchange. The resultant oxocarbenium/tetraphenylborate ion pair undergoes a nucleophilic attack by silyl ketene acetal, which is followed by scavenging the trimethylsilyl cation with a chloride anion to result in chlorotrimethylsilane and the product. Mechanistic studies were conducted to

Efficient synthetic protocols for the preparation of common N-heterocyclic carbene precursors

• Morgan Hans,
• Jan Lorkowski,
• Albert Demonceau and
• Lionel Delaude

Beilstein J. Org. Chem. 2015, 11, 2318–2325, doi:10.3762/bjoc.11.252

• convenient to carry out the synthesis of imidazolinium salts in parallel to their imidazolium counterparts via the reduction of the diimines into diammonium salts. The critical assembly of the C2 precarbenic unit was best achieved with paraformaldehyde and chlorotrimethylsilane in the case of imidazolium

• cyclization step. In addition to the use of chloromethyl ethyl ether pioneered by Arduengo et al. [43], mixtures of paraformaldehyde and HCl in anhydrous solvents were investigated by Bantreil and Nolan [45], while Hintermann identified chlorotrimethylsilane as a convenient source of chloride counterions [44

• -diisopropylphenyl)ethylenediimine with paraformaldehyde and chlorotrimethylsilane in ethyl acetate (Scheme 7). In our hands, this procedure proved reliable and afforded typical yields of 85%. Its major drawback is the necessity to work under high dilution conditions, which implies the use of large amounts of

Deoxygenative gem-difluoroolefination of carbonyl compounds with (chlorodifluoromethyl)trimethylsilane and triphenylphosphine

• Fei Wang,
• Lingchun Li,
• Chuanfa Ni and
• Jinbo Hu

Beilstein J. Org. Chem. 2014, 10, 344–351, doi:10.3762/bjoc.10.32

• silylation of ozone-depleting-substances bromotrifluoromethane (CF3Br) [35], bromochlorodifluoromethane (CF2BrCl) [36][37], and dibromodifluoromethane (CF2Br2) [36][37] with chlorotrimethylsilane (TMSCl). In recent years, Prakash and co-workers have discovered two Freon-free methods for the synthesis of

Synthesis of nucleotide–amino acid conjugates designed for photo-CIDNP experiments by a phosphotriester approach

• Tatyana V. Abramova,
• Olga B. Morozova,
• Vladimir N. Silnikov and
• Alexandra V. Yurkovskaya

Beilstein J. Org. Chem. 2013, 9, 2898–2909, doi:10.3762/bjoc.9.326

• ; traces of buffer were removed by coevaporation with water. The last portion of water was added along with TEA (14 mL, 100 mmol). The residue was coevaporated with acetonitrile (3 × 25 mL) and Py (2 × 20 mL) and dissolved in Py (60 mL). Chlorotrimethylsilane (8.2 mL, 6 mmol) was added to the solution

Incorporation of perfluorohexyl-functionalised thiophenes into oligofluorene-truxenes: synthesis and physical properties

• Neil Thomson,
• Alexander L. Kanibolotsky,
• Joseph Cameron,
• Tell Tuttle,
• Neil J. Findlay and
• Peter J. Skabara

Beilstein J. Org. Chem. 2013, 9, 1243–1251, doi:10.3762/bjoc.9.141

• then reacted with bis(pinacolato)diboron to afford boronic ester 8. The synthetic route to 2-iodo-4-perfluorohexylthiophene (13) (Scheme 2) began with treatment of 3-bromothiophene (1) with lithium bis(trimethylsilyl)amide and chlorotrimethylsilane to afford 2-trimethylsilyl-3-bromothiophene (9

Simple synthesis of pyrrolo[3,2-e]indole-1-carbonitriles

• Adam Trawczyński,
• Robert Bujok,
• Zbigniew Wróbel and
• Krzysztof Wojciechowski

Beilstein J. Org. Chem. 2013, 9, 934–941, doi:10.3762/bjoc.9.107

• Warszawa, Poland 10.3762/bjoc.9.107 Abstract Alkylation of 5-nitroindol-4-ylacetonitriles with ethyl chloroacetate, α-halomethyl ketones, and chloroacetonitrile followed by a treatment of the products with chlorotrimethylsilane in the presence of DBU gives 1-cyanopyrrolo[3,2-e]indoles substituted in

• chlorotrimethylsilane–triethylamine the reaction proceeded slowly, and the starting material was completely consumed after 24 h, but the product 6a was isolated in moderate 30% yield. However, when we replaced triethylamine with a stronger base, such as DBU, the reaction was completed in 30 min, and the product was

• combination with DBU proved ineffective in this reaction giving a very low rate of conversion after 24 h. Thus, transformations of other nitriles 5b–g into pyrrolo[3,2-e]indoles 6 were performed in the DBU–chlorotrimethylsilane system, and the results are presented in Table 1. It is worth mentioning that the

Intramolecular carbenoid ylide forming reactions of 2-diazo-3-keto-4-phthalimidocarboxylic esters derived from methionine and cysteine

• Marc Enßle,
• Stefan Buck,
• Roland Werz and
• Gerhard Maas

Beilstein J. Org. Chem. 2012, 8, 433–440, doi:10.3762/bjoc.8.49

• racemisation. A sample of 8a, which was prepared from a slightly racemised sample of 6a (HPLC: 90:10 enantiomeric ratio of the derived methyl ester, which was prepared from 6a and dry methanol in the presence of excess chlorotrimethylsilane) on the latter route, had an enantiomeric ratio of 83:17. Rhodium

Photocycloaddition of aromatic and aliphatic aldehydes to isoxazoles: Cycloaddition reactivity and stability studies

• Axel G. Griesbeck,
• Marco Franke,
• Jörg Neudörfl and
• Hidehiro Kotaka

Beilstein J. Org. Chem. 2011, 7, 127–134, doi:10.3762/bjoc.7.18

• for irradiations. Trimethylsilyl ester of aci-nitroethane (1) [19]. Chlorotrimethylsilane (43.20 g, 0.4 mol, 50.5 mL) was added to nitroethane (30.0 g, 0.4 mol, 28.7 mL) and triethylamine (40.40 g, 0.4 mol, 55.6 mL) in benzene (200 mL). The mixture was stirred vigorously for 18 h at rt, filtered and

• -(trimethylsilyloxy)isoxazole (7h) [27]. To 2.72 g (25 mmol, 3.2 mL) of chlorotrimethylsilane, was added a mixture of 5 (3.22 g, 20 mmol) and hexamethyldisilazane (7.26 g, 45 mmol, 9.5 mL). The solution was heated at 120 °C for 30 min and then concentrated. The resulting product was unstable and therefore used

Synthesis of unsymmetrically substituted biaryls via sequential lithiation of dibromobiaryls using integrated microflow systems

• Aiichiro Nagaki,
• Naofumi Takabayashi,
• Yutaka Tomida and
• Jun-ichi Yoshida

Beilstein J. Org. Chem. 2009, 5, No. 16, doi:10.3762/bjoc.5.16

• iodomethane gave 2-bromo-2′-methylbiphenyl (5) in 89% yield with high selectivity. Chlorotrimethylsilane, benzaldehyde, and benzophenone were also effective as electrophiles, and the corresponding products derived from the monolithiated species were obtained selectively in high yields. These results show that

Expedient syntheses of the N-heterocyclic carbene precursor imidazolium salts IPr·HCl, IMes·HCl and IXy·HCl

• Lukas Hintermann

Beilstein J. Org. Chem. 2007, 3, No. 22, doi:10.1186/1860-5397-3-22

• -dimethylphenyl), precursors to widely used N-heterocyclic carbene (NHC) ligands and catalysts, were prepared in high yields (81%, 69% and 89%, respectively) by the reaction of 1,4-diaryl-1, 4-diazabutadienes, paraformaldehyde and chlorotrimethylsilane in dilute ethyl acetate solution. A reaction mechanism

• source of the chloride counter ion. The choice fell on chlorotrimethylsilane (TMSCl), the "silyl version" of HCl, which is easily measured and handled. The current pricing of TMSCl is 8 €/mol, as opposed to 80–100 €/mol for HCl/dioxane (4 M). The reaction optimization went as follows: Initial experiments

• condensation of 1,4-diaryl-diazabutadienes and paraformaldehyde with the following characteristics: a) chlorotrimethylsilane (TMSCl) serves as a cheap and easy to handle source of the chloride counter ion, b) ethyl acetate is the optimal reaction solvent with respect to product purity and precipitation, and c