A switchable [2]rotaxane with two active alkenyl groups

• Xiu-Li Zheng,
• Rong-Rong Tao,
• Rui-Rui Gu,
• Wen-Zhi Wang and
• Da-Hui Qu

Beilstein J. Org. Chem. 2018, 14, 2074–2081, doi:10.3762/bjoc.14.181

• trifluoroacetic acid were added to reprotonate the -NH- moiety, the 1H NMR spectrum restored to the initial state, showing that the macrocyclic compound 9 moved back to the DBA recognition site. Therefore, the reversible shuttling movement of DB24C8 moiety along the thread between two recognition sites driven by

A self-assembled photoresponsive gel consisting of chiral nanofibers

• Lei Zou,
• Dan Han,
• Zhiyi Yuan,
• Dongdong Chang and
• Xiang Ma

Beilstein J. Org. Chem. 2018, 14, 1994–2001, doi:10.3762/bjoc.14.174

• , 28.17, 27.07, 25.09; HRMS m/z: [M + H]+ calcd for C34H36N7O4+, 606.2829; found, 606.2830. Synthesis of compound 3 Compound 2 was easily prepared according to a literature method [45]. Five mL of trifluoroacetic acid was dropped into a 25 mL CH2Cl2 solution of compound 1 (1.0 g, 1.65 mmol), then the

• mixture was stirred at room temperature for 2 h under an Ar atmosphere. Evaporation of the resulting red solution was performed under reduced pressure, and small amounts of CH2Cl2 was frequently added to the bottle until the trifluoroacetic acid was removed entirely. The resulting yellow solid was added

Diazirine-functionalized mannosides for photoaffinity labeling: trouble with FimH

• Femke Beiroth,
• Tomas Koudelka,
• Thorsten Overath,
• Stefan D. Knight,
• Andreas Tholey and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2018, 14, 1890–1900, doi:10.3762/bjoc.14.163

• the squaric acid monoester 10 employing squaric acid diester 9. The monoester 10 was reacted with N-Boc-ethylendiamine to obtain the squaric acid diamide 11. Then removal of the Boc protecting group with trifluoroacetic acid followed by peptide coupling with the diazirine 8 led to target molecule 4

• . Subsequently, the solution was irradiated under ice cooling with a medium pressure mercury vapor lamp for 10 min. Afterwards, 50 µL double distilled water were added and 2 µL of this solution given to 20 µL of a 0.1% trifluoroacetic acid (TFA) solution, desalted with a C18 µZipTip and spotted on a MALDI-plate

• from p-nitrophenyl α-D-mannopyranoside (1), which was first reduced to the corresponding amine 6 [26][27] by catalytic hydrogenation (Scheme 1). HATU-mediated peptide coupling with Boc-protected glycine under basic conditions led to 7. After removal of the Boc protecting group using trifluoroacetic

Recent advances in hypervalent iodine(III)-catalyzed functionalization of alkenes

• Xiang Li,
• Pinhong Chen and
• Guosheng Liu

Beilstein J. Org. Chem. 2018, 14, 1813–1825, doi:10.3762/bjoc.14.154

• chiral hypervalent iodine catalyst [47][48]. Additionally, mCPBA and trifluoroacetic acid were utilized as terminal oxidants and activators, respectively. This reaction provided a series of 4-oxyisochroman-1-ones, which are found in natural products and bioactive polyketide metabolites. For example, the

Synthesis of spirocyclic scaffolds using hypervalent iodine reagents

• Fateh V. Singh,
• Priyanka B. Kole,
• Saeesh R. Mangaonkar and
• Samata E. Shetgaonkar

Beilstein J. Org. Chem. 2018, 14, 1778–1805, doi:10.3762/bjoc.14.152

•  24). Additionally, trifluoroacetic acid (TFA) was used as an additive in the reaction. In 2015, Wang’s group [97] reported an iodine(III)-mediated approach for the intermolecular spirocyclization of amides 72 with sulfonylhydrazides 73 to spirolactams 75. In this method, functionalized amides 72

• systems. In 2015, Jain and Ciufolini [124] developed PIDA-mediated spirocyclization of 2-naphtholic sulfonamides 124 to spiropyrrolidine derivatives 125. The spirocyclization reactions were carried out by treating N-sulfonamide substrates 124 with (diacetoxyiodo)benzene (15) in trifluoroacetic acid (TFA

β-Hydroxy sulfides and their syntheses

• Mokgethwa B. Marakalala,
• Edwin M. Mmutlane and
• Henok H. Kinfe

Beilstein J. Org. Chem. 2018, 14, 1668–1692, doi:10.3762/bjoc.14.143

• hydrolyzes in the work-up to provide the β-hydroxy sulfide 15 as shown in Scheme 32 [68]. The protocol is a supplement to the lead(IV)-promoted addition of disulfides to alkenes in dichloromethane–trifluoroacetic acid to give, after hydrolysis, products of hydroxysulfination of simple diaryl and dialkyl

Design and biological characterization of novel cell-penetrating peptides preferentially targeting cell nuclei and subnuclear regions

• Anja Gronewold,
• Mareike Horn and
• Ines Neundorf

Beilstein J. Org. Chem. 2018, 14, 1378–1388, doi:10.3762/bjoc.14.116

• (Marktredwitz, Germany). Other chemicals and consumables including 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate (HATU), N,N-diisopropylethylamine (DIPEA), acetonitrile (ACN), and trifluoroacetic acid (TFA), dimethylformamide (DMF), N-methylpyrrolidine (NMP

• rt as described previously [20]. CF-polymers were cleaved by treatment with 20% piperidine for 45 min. The successful coupling was verified by a Kaiser test [43]. To cleave the peptides from the resin, a mixture of triisopropylsilane (TIS), H2O and concentrated trifluoroacetic acid (TFA) (1:1:38 v/v

Novel unit B cryptophycin analogues as payloads for targeted therapy

• Eduard Figueras,
• Adina Borbély,
• Mohamed Ismail,
• Marcel Frese and
• Norbert Sewald

Beilstein J. Org. Chem. 2018, 14, 1281–1286, doi:10.3762/bjoc.14.109

• modified unit B (13 or 14), affording the according linear cryptophycins 18 and 19 in acceptable yields (51–59%). Compounds 18 and 19 were treated with trifluoroacetic acid for simultaneous Boc and t-Bu removal, which also cleaved the dioxolane ring. Subsequently, macrolactamization was performed under

A selective removal of the secondary hydroxy group from ortho-dithioacetal-substituted diarylmethanols

• Anna Czarnecka,
• Emilia Kowalska,
• Agnieszka Bodzioch,
• Joanna Skalik,
• Marek Koprowski,
• Krzysztof Owsianik and
• Piotr Bałczewski

Beilstein J. Org. Chem. 2018, 14, 1229–1237, doi:10.3762/bjoc.14.105

• was observed instead [23]. Diarylmethanes were also obtained in the Friedel–Crafts reactions of arenes with primary benzyl alcohols, aryl acetals, and benzyl esters [1]. Benzyl fluorides (in 1,1,1,3,3,3-hexafluoroisopropanol in the presence of a catalytic amount of trifluoroacetic acid [24]) as well

One hundred years of benzotropone chemistry

• Arif Dastan,
• Haydar Kilic and
• Nurullah Saracoglu

Beilstein J. Org. Chem. 2018, 14, 1120–1180, doi:10.3762/bjoc.14.98

Iodine(III)-mediated halogenations of acyclic monoterpenoids

• Laure Peilleron,
• Tatyana D. Grayfer,
• Joëlle Dubois,
• Robert H. Dodd and
• Kevin Cariou

Beilstein J. Org. Chem. 2018, 14, 1103–1111, doi:10.3762/bjoc.14.96

• 3 is not so straightforward. For instance, submitting 1a to NBS in the presence of trifluoroacetic acid led to a complex mixture of products, the major one being allylic bromide 6a’. For X = I, the steric bulk would preclude the formation of the vicinal diiodide and only pathway a would thus be

Selective carboxylation of reactive benzylic C–H bonds by a hypervalent iodine(III)/inorganic bromide oxidation system

• Toshifumi Dohi,
• Shohei Ueda,
• Kosuke Iwasaki,
• Yusuke Tsunoda,
• Koji Morimoto and
• Yasuyuki Kita

Beilstein J. Org. Chem. 2018, 14, 1087–1094, doi:10.3762/bjoc.14.94

• addition, it was revealed that more acidic benzoic acids were also suitable substrates for our method. However, even more acidic acids, such as trifluoroacetic acid and methanesulfonic acid, were not effectively introduced by our benzylic C–H carboxylation procedures. We believe that the reaction mechanism

Methyl isocyanide as a convertible functional group for the synthesis of spirocyclic oxindole γ-lactams via post-Ugi-4CR/transamidation/cyclization in a one-pot, three-step sequence

• Amarendar Reddy Maddirala and
• Peter R. Andreana

Beilstein J. Org. Chem. 2018, 14, 875–883, doi:10.3762/bjoc.14.74

• noticeable amounts of starting material were visible by TLC. Upon completion of the reaction, methanol was evaporated under reduced pressure and the crude Ugi products, without any purification, dissolved in a CH2Cl2 and trifluoroacetic acid mixture (1:1, 2 mL) and subsequently stirred at room temperature

• . The reaction was allowed to stir until no noticeable amounts of starting material were visible using TLC. Upon completion of the reaction, methanol was evaporated under reduced pressure and the crude Ugi products, without any purification, was dissolved in a CH2Cl2 and trifluoroacetic acid mixture (1

Synthesis and in vitro biochemical evaluation of oxime bond-linked daunorubicin–GnRH-III conjugates developed for targeted drug delivery

• Sabine Schuster,
• Beáta Biri-Kovács,
• Bálint Szeder,
• Viktor Farkas,
• László Buday,
• Zsuzsanna Szabó,
• Gábor Halmos and
• Gábor Mező

Beilstein J. Org. Chem. 2018, 14, 756–771, doi:10.3762/bjoc.14.64

• -hydroxybenzotriazole hydrate (HOBt), N,N’-diisopropylcarbodiimide (DIC), triisopropylsilane (TIS), piperidine, 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), trifluoroacetic acid (TFA), diisopropylethylamine (DIPEA), acetic anhydride (Ac2O), methanol (MeOH), n-butyric anhydride and solvent for HPLC (acetonitrile (ACN

Diastereoselective auxiliary- and catalyst-controlled intramolecular aza-Michael reaction for the elaboration of enantioenriched 3-substituted isoindolinones. Application to the synthesis of a new pazinaclone analogue

• Romain Sallio,
• Stéphane Lebrun,
• Frédéric Capet,
• Francine Agbossou-Niedercorn,
• Christophe Michon and
• Eric Deniau

Beilstein J. Org. Chem. 2018, 14, 593–602, doi:10.3762/bjoc.14.46

• treatment with trifluoroacetic acid to provide in-situ the corresponding benzoic acids 14a–e and 15. The direct coupling of these functionalized carboxylic acids with chiral benzylic primary amines, (R) or (S)-16 (NH2-CH(Me)Ph) and (R)-17 (NH2CH(Me)p-MeO-C6H4), afforded the required parent amides 6a–d, 7a–e

• crystallization (70% yield, >96% de). Lactam (2R,3S)-25 bearing a α-methyl-para-methoxyphenyl chiral auxiliary was then deprotected with trifluoroacetic acid at room temperature to deliver the NH-free isoindolinone (3S)-26 (76% yield, 98% ee) which is a key building block in the synthesis of benzodiazepine

Mannich base-connected syntheses mediated by ortho-quinone methides

• Petra Barta,
• Ferenc Fülöp and
• István Szatmári

Beilstein J. Org. Chem. 2018, 14, 560–575, doi:10.3762/bjoc.14.43

• ortho-amidoalkylation of phenols in which a tandem Knoevenagel condensation occurs through o-QM followed by the formation of an unstable oxazine intermediate [64]. Later, the same research group published a similar reaction extended by various lactams carried out in trifluoroacetic acid in water [65

Synthesis and stability of strongly acidic benzamide derivatives

• Frederik Diness,
• Niels J. Bjerrum and
• Mikael Begtrup

Beilstein J. Org. Chem. 2018, 14, 523–530, doi:10.3762/bjoc.14.38

• ) or trifluoroacetic acid (3) are not readily modified, and changing substituents on these acids will heavily impact their pKa value (Figure 1). In contrast, halogenated benzoic acid derivatives are easily functionalized through cross-coupling [4][5] or nucleophilic aromatic substitution reactions

• )benzimidamides (also termed benzamidines) have been generated, but only one report describes their syntheses [10]. The N-triflylbenzamides are stronger acids than any of the carboxylic acids, including trifluoroacetic acid (3). The N,N’-bis(triflyl)benzimidamides are very strong organic acids, much stronger than

Recent developments in the asymmetric Reformatsky-type reaction

• Hélène Pellissier

Beilstein J. Org. Chem. 2018, 14, 325–344, doi:10.3762/bjoc.14.21

• Zn-mediated aza-Reformatsky reaction [30]. Synthesis of a precursor of sacubitril through a Zn-mediated aza-Reformatsky reaction [31]. Synthesis of epothilone D through a Cr(II)-mediated Reformatsky reaction. TFA = trifluoroacetic acid [32]. Synthesis of β-hydroxy-α-methyl-δ-trichloromethyl-δ

Progress in copper-catalyzed trifluoromethylation

• Guan-bao Li,
• Chao Zhang,
• Chun Song and
• Yu-dao Ma

Beilstein J. Org. Chem. 2018, 14, 155–181, doi:10.3762/bjoc.14.11

• economic decarboxylative trifluoromethylation reagent [Cu(phen)O2CCF3], which was prepared from readily available and inexpensive starting materials (Scheme 8). Treatment of copper tert-butoxide with phen, followed by addition of trifluoroacetic acid afforded the air-stable [Cu(phen)O2CCF3] complex, which

Stereochemical outcomes of C–F activation reactions of benzyl fluoride

• Neil S. Keddie,
• Pier Alexandre Champagne,
• Justine Desroches,
• Jean-François Paquin and
• David O'Hagan

Beilstein J. Org. Chem. 2018, 14, 106–113, doi:10.3762/bjoc.14.6

• donors, namely HFIP, in the presence or absence of trifluoroacetic acid (TFA). For both of these activators, Paquin et al. proposed a dissociative unimolecular (SN1) mechanism, whereby the strong hydrogen bond donor associates with the benzyl fluoride, leading to ionisation of the molecule, generating a

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

Aminosugar-based immunomodulator lipid A: synthetic approaches

• Alla Zamyatina

Beilstein J. Org. Chem. 2018, 14, 25–53, doi:10.3762/bjoc.14.3

Position-dependent impact of hexafluoroleucine and trifluoroisoleucine on protease digestion

• Susanne Huhmann,
• Anne-Katrin Stegemann,
• Kristin Folmert,
• Damian Klemczak,
• Johann Moschner,
• Michelle Kube and
• Beate Koksch

Beilstein J. Org. Chem. 2017, 13, 2869–2882, doi:10.3762/bjoc.13.279

• triisopropylsilane (TIS, 10% (v/v)), water (1% (v/v)), and trifluoroacetic acid (TFA) (89% (v/v)) for 3 h. The resin was washed twice with TFA (1 mL) and DCM (1 mL) and excess solvent was removed by evaporation. The crude peptide was precipitated with ice-cold diethyl ether (80 mL), and after centrifugation dried by

An efficient synthesis of 1,6-anhydro-N-acetylmuramic acid from N-acetylglucosamine

• Matthew B. Calvert,
• Christoph Mayer and
• Alexander Titz

Beilstein J. Org. Chem. 2017, 13, 2631–2636, doi:10.3762/bjoc.13.261

• ); HRMS (ESI–TOF) m/z: [M + H]+ calcd for C30H32NO7, 518.21788; found, 518.21596. 1,6-Anhydro-N-acetylmuramic acid (1) A solution of 13 (720 mg, 1.4 mmol) in chloroform (20 mL) was treated with trifluoroacetic acid (1.0 mL) at 0 °C. The reaction mixture was allowed to warm to room temperature, stirred

• mL) was treated with trifluoroacetic acid (0.1 mL) at 0 °C. The reaction mixture was allowed to warm to room temperature, stirred for 3 hours and then coevaporated with toluene (2 × 10 mL). The residue was purified by HPLC (5% acetonitrile + 0.1% formic acid, 9.5 mL/min) to provide the title

• to 90 °C, 30 min; (d) trifluoroacetic acid, CHCl3, 0 °C to rt, 3 h. Synthesis of AnhydroMurNAc and diastereomer 5. Conditions: (a) (±)-2-chloropropionic acid, NaH, dioxane, 45 °C to 90 °C, 3 h; (b) trifluoroacetic acid, CHCl3, 0 °C to rt, 3 h. Supporting Information Supporting Information File 434

Regioselective decarboxylative addition of malonic acid and its mono(thio)esters to 4-trifluoromethylpyrimidin-2(1H)-ones

• Sergii V. Melnykov,
• Andrii S. Pataman,
• Yurii V. Dmytriv,
• Svitlana V. Shishkina,
• Mykhailo V. Vovk and
• Volodymyr A. Sukach

Beilstein J. Org. Chem. 2017, 13, 2617–2625, doi:10.3762/bjoc.13.259

• )-unsubstituted products 4j and 5n,o, we utilized N1(3)-(4-methoxybenzyl) derivatives 4i, 5i, 5k in trifluoroacetic acid (TFA); the resulting cleavage of the 4-methoxybenzyl (PMB) group afforded the target compounds in good yields (see Table 2). Next we studied the decarboxylative addition of reagent 1a to model