Synthesis of a sucrose-based macrocycle with unsymmetrical monosaccharides "arms"

• Karolina Tiara,
• Mykhaylo A. Potopnyk and
• Sławomir Jarosz

Beilstein J. Org. Chem. 2018, 14, 634–641, doi:10.3762/bjoc.14.50

• = 10.6 Hz, J15,16 = 17.2 Hz, 1H, H-15), 5.76 (d, J1,2 = 3.3 Hz, 1H, H-1), 5.30 (d, J16,15 = 17.2 Hz, 1H, H-16), 5.21 (d, J16,15 = 10.6 Hz, 1H, H-16), 4.79 (d, J = 11.1 Hz, 1H, benzylic H), 4.77–4.71 (m, H-14, 3H, 2 × benzylic H), 4.63 (d, J = 11.8 Hz, 1H, benzylic H), 4.62 (d, J = 11.4 Hz, 1H, benzylic H

• ), 4.56 (d, J = 11.9 Hz, 1H, benzylic H), 4.50 (d, J = 11.8 Hz, 1H, benzylic H), 4.46 (d, J = 10.8 Hz, 1H, benzylic H), 4.43 (d, J = 11.8 Hz, 1H, benzylic H), 4.42–4.37 (m, H-3’, 4H, 3 × benzylic H), 4.23 (dd, J4’,5’ = 5.9 Hz, J4’,3’ = 6.2 Hz, 1H, H-4’), 4.19 (m, 1H, H-5), 4.07 (dd, J5’,6’ = 11.7 Hz, J5

• = 10.4 Hz, J15,16 = 17.3 Hz, 1H, H-15), 5.52 (d, J1,2 = 3.0 Hz, 1H, H-1), 5.36 (d, J16,15 = 17.3 Hz, 1H, H-16), 5.28 (d, J16,15 = 10.4 Hz, 1H, H-16), 4.81 (m, H-14, 3H, 2 × benzylic H), 4.70 (d, J = 11.6 Hz, 1H, benzylic H), 4.66–4.57 (m, 4H, 4 × benzylic H), 4.52–4.48 (m, 3H, 3 × benzylic H), 4.42–4.38

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

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

• on its benzylic carbon atom. Rueping et al. recently performed reactions between aza-o-QMs in situ generated from α-substituted ortho-amino benzyl alcohols 48 and substituted indoles catalysed by N-triflylphosphoramides (NTPAs) [85]. (Scheme 6) The process provided new C-2 and C-3-functionalized

Functionalization of N-arylglycine esters: electrocatalytic access to C–C bonds mediated by n-Bu₄NI

• Mi-Hai Luo,
• Yang-Ye Jiang,
• Kun Xu,
• Yong-Guo Liu,
• Bao-Guo Sun and
• Cheng-Chu Zeng

Beilstein J. Org. Chem. 2018, 14, 499–505, doi:10.3762/bjoc.14.35

• emerged as an versatile and powerful strategy for forming new C–C bonds in organic chemistry due to its step and atom economic characteristic as well as avoiding the prefunctionalization of substrates [1][2][3][4][5]. Most of the CDC reactions occur between the benzylic C–H bonds and α-C–H bonds adjacent

The selective electrochemical fluorination of S-alkyl benzothioate and its derivatives

• Shunsuke Kuribayashi,
• Tomoyuki Kurioka,
• Shinsuke Inagi,
• Ho-Jung Lu,
• Biing-Jiun Uang and
• Toshio Fuchigami

Beilstein J. Org. Chem. 2018, 14, 389–396, doi:10.3762/bjoc.14.27

• electron transfer generates the benzylic cationic intermediate A, which affords the benzylic fluorinated product. It is known that benzylic fluorinated compounds are known to be generally prone to lose a fluoride anion [26]. On the other hand, intermediate A may undergo also elimination of a β-proton due

• (Scheme 2). We next also carried out the anodic fluorination of a cyclic benzothioate namely benzothiophenone 1l. In this case, the fluorination took place predominantly at the benzylic position to afford the fluorinated product 2l in 60% isolated yield (Scheme 3). With this substrate, neither C–S bond

Syn-selective silicon Mukaiyama-type aldol reactions of (pentafluoro-λ⁶-sulfanyl)acetic acid esters with aldehydes

• Anna-Lena Dreier,
• Andrej V. Matsnev,
• Joseph S. Thrasher and
• Günter Haufe

Beilstein J. Org. Chem. 2018, 14, 373–380, doi:10.3762/bjoc.14.25

• under liberation of a chloride. For the formed oxonium ion, two conformers A and B are possible due to free rotation around the single bond neighboring the SF5 group and the former benzylic carbon atom (Scheme 4). Due to the possible repulsive interaction of the SF5 group with the quinoid ring in

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

• aryl halides in the past years. In contrast, successful examples of copper-catalyzed trifluoromethylation of alkyl halides are quite limited. In 2011, the group of Shibata [25] firstly reported the copper-mediated chemoselective trifluoromethylation at the benzylic position with shelf-stable

• corresponding analogues from primary propargylic chlorides (Scheme 14), while the trifluoromethylated allenes can be obtained from reactions of secondary propargylic chlorides. Moreover, in 2014, the primary and secondary benzylic chlorides [28] were investigated under similar conditions, which proceeded

• smoothly to give the corresponding trifluoromethylated products in high yields (Scheme 15). But applicable substrates were limited to benzylic chlorides bearing electron-donating groups. The methodology described by the group of Nishibayashi could provide an efficient strategy for the synthesis of CF3

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

• C–F activation of benzylic fluorides for nucleophilic substitutions and Friedel–Crafts reactions, using a range of hydrogen bond donors such as water, triols or hexafluoroisopropanol (HFIP) as the activators. This study examines the stereointegrity of the C–F activation reaction through the use of

• demonstrated that both associative and dissociative pathways operate to varying degrees, according to the nature of the nucleophile and the hydrogen bond donor. Keywords: benzylic fluorides; C–F activation; chiral liquid crystal; 2H NMR; PBLG; stereochemistry; Introduction The C–F bond is the strongest

• synthesis by capitalizing on the low reactivity of the C–F bond. Paquin et al. have published extensively on non-metal based methods for benzylic C–F bond activation [3][4][5][6][7]. The reactivity relies on protic activation driven by the capacity of organic fluoride to form hydrogen bonds [8][9

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

• . The reaction was found to be suitable for a series of steric and electronic different styrenes. However, aliphatic alkenes did not give the desired product. The author’s explain this observation by a lower stability of the free carbon-centred alkyl radical intermediate, compared to benzylic substrates

The photodecarboxylative addition of carboxylates to phthalimides as a key-step in the synthesis of biologically active 3-arylmethylene-2,3-dihydro-1H-isoindolin-1-ones

• Ommid Anamimoghadam,
• Saira Mumtaz,
• Anke Nietsch,
• Gaetano Saya,
• Cherie A. Motti,
• Jun Wang,
• Peter C. Junk,
• Ashfaq Mahmood Qureshi and
• Michael Oelgemöller

Beilstein J. Org. Chem. 2017, 13, 2833–2841, doi:10.3762/bjoc.13.275

• and subsequent column chromatography. All compounds 3 showed a characteristic pair of doublets between 3 and 4 ppm with a large geminal 2J coupling of 12–16 Hz for the benzylic methylene group (-CH2Ar) in their 1H NMR spectra and a singlet at 90 ± 3 ppm for the newly formed tertiary alcohol (C–OH) in

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation. Part 1: Use of CF₃SO₂Na

• Hélène Guyon,
• Hélène Chachignon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2764–2799, doi:10.3762/bjoc.13.272

Ring-size-selective construction of fluorine-containing carbocycles via intramolecular iodoarylation of 1,1-difluoro-1-alkenes

• Takeshi Fujita,
• Ryo Kinoshita,
• Tsuyoshi Takanohashi,
• Naoto Suzuki and
• Junji Ichikawa

Beilstein J. Org. Chem. 2017, 13, 2682–2689, doi:10.3762/bjoc.13.266

• elimination from 2a, 1,2-migration of the phenyl group, and deprotonation, followed by hydrolysis of the resulting doubly activated benzylic difluoromethylene unit (Scheme 2). Neither a combination of bis(pyridine)iodonium (IPy2BF4) and trifluoromethanesulfonic acid nor a combination of I2 and silver(I

Asymmetric synthesis of propargylamines as amino acid surrogates in peptidomimetics

• Matthias Wünsch,
• David Schröder,
• Tanja Fröhr,
• Lisa Teichmann,
• Sebastian Hedwig,
• Nils Janson,
• Clara Belu,
• Jasmin Simon,
• Shari Heidemeyer,
• Philipp Holtkamp,
• Jens Rudlof,
• Lennard Klemme,
• Alessa Hinzmann,
• Beate Neumann,
• Hans-Georg Stammler and
• Norbert Sewald

Beilstein J. Org. Chem. 2017, 13, 2428–2441, doi:10.3762/bjoc.13.240

• imine 5h) after desilylation with TBAF (Table 2). As the benzylic proton of sulfinylimine 5h is quite acidic, approach II was not pursued for the synthesis of propargylamines analogous to tyrosine, histidine, tryptophan, and aspartate. Proteinogenic amino acids do not contain substituents, which

• (4b, 10%, dr 51:49). Reaction of N-sulfinylimine 5h with (trimethylsilyl)ethynyllithium. (a) GP-3 or GP-4. (b) Aqueous work-up, H2O/H+. Deprotonation in benzylic position competes with nucleophilic attack (5h/6h, 7:3). Side reactions observed in the course of the conversion of highly electrophilic

Homologated amino acids with three vicinal fluorines positioned along the backbone: development of a stereoselective synthesis

• Raju Cheerlavancha,
• Ahmed Ahmed,
• Yun Cheuk Leung,
• Aggie Lawer,
• Qing-Quan Liu,
• Marina Cagnes,
• Hee-Chan Jang,
• Xiang-Guo Hu and
• Luke Hunter

Beilstein J. Org. Chem. 2017, 13, 2316–2325, doi:10.3762/bjoc.13.228

• with the synthesis. Compound 28b was treated with DeoxoFluor at low temperature, in order to affect a deoxyfluorination of the benzylic alcohol. This reaction gave the product 31 in high yield, but unfortunately with poor stereoselectivity, presumably due to a competing SN1-type reaction mechanism [36

• to be successful. The reaction duration was another significant determinant of the yield of 43 (Table 2, entries 4−6), since the over-reduced (i.e., benzylic defluorination) product was still produced in varying amounts. The subsequent oxidation of 43 was successfully achieved using sodium

An efficient synthesis of a C₁₂-higher sugar aminoalditol

• Łukasz Szyszka,
• Anna Osuch-Kwiatkowska,
• Mykhaylo A. Potopnyk and
• Sławomir Jarosz

Beilstein J. Org. Chem. 2017, 13, 2146–2152, doi:10.3762/bjoc.13.213

• :1) to afford pure compound 4 (0.87 g, 0.7 mmol, 95%) as an oil. [α]D +12.1 (c 0.4); 1H NMR (600 MHz) δ 7.41–7.11 (m, 35H, ArH), 4.91 (d, J = 11.0, 1H, benzylic H), 4.80 (d, J = 11.5 Hz, 1H, benzylic H), 4.79 (d, J = 11.2 Hz, 1H, benzylic H), 4.80–4.67 (m, 4H, benzylic H), 4.64 (d, J = 11.6 Hz, 2H

• , benzylic H), 4.62 (d, J = 11.8 Hz, 2H, benzylic H), 4.61 (d, J = 12.2 Hz, 1H, benzylic H), 4.59 (d, J1,2 = 3.5 Hz, 1H, H-1), 4.53 (d, J = 11.5 Hz, 1H , benzylic H), 4.49 (d, J = 11.5 Hz, 1H, benzylic H), 4.42 (s, 1H, benzylic H), 4.41 (s, 1H, benzylic H), 4.39 (d, J = 11.5, 1H, benzylic H), 4.28 (d, J

• = 11.7 Hz, 1H, benzylic H), 4.22 (d, J5,4 = 10.3 Hz, 1H, H-5), 4.18–4.13 (m, 2H, H-7, H-8), 4.05 (dd, J9,8 = 5.8 Hz, J9,10 = 4.3 Hz, 1H, H-9), 4.01 (d, J6,7 = 9.8 Hz, 1H, H-6), 3.97 (dd, J3,4 = 9.2 Hz, J3,2 = 9.3 Hz, 1H, H-3), 3.83 (dd, J4,5 = 10.1 Hz, 1H, H-4), 3.75 (m, 1H, H-10), 3.67 (m, 1H, H-11

Intramolecular glycosylation

• Xiao G. Jia and
• Alexei V. Demchenko

Beilstein J. Org. Chem. 2017, 13, 2028–2048, doi:10.3762/bjoc.13.201

• -selectivity. With the varying anomeric stereoselectivities and yields, it was hypothesized that the benzylic methylene group may be responsible for the increased rotational freedom between the triazoyl and benzyl moieties. Investigations with o-azidobenzyl protecting groups were used to reduce the degrees of

Mechanochemical synthesis of small organic molecules

• Tapas Kumar Achar,
• Anima Bose and
• Prasenjit Mal

Beilstein J. Org. Chem. 2017, 13, 1907–1931, doi:10.3762/bjoc.13.186

• significant in organic synthesis because aryl halides are important synthons for the synthesis of many natural and non-natural products [93][94]. In 2005, Rahman and co-workers reported a pioneering solid state benzylic bromination of diquinoline derivatives via N-bromosuccinimide (NBS) [95]. In 2012, Wang

• benzylic iodination could be observed in case of alkyl benzenes. Interestingly, benzaldehyde derivatives did not lead to any over-oxidation to acids in presence of oxone. Trihaloisocyanuric acids are also used effectively for halogenations of arenes and 1,3-dicarbonyl compounds and double bond-containing

Selective enzymatic esterification of lignin model compounds in the ball mill

• Ulla Weißbach,
• Saumya Dabral,
• Laure Konnert,
• Carsten Bolm and
• José G. Hernández

Beilstein J. Org. Chem. 2017, 13, 1788–1795, doi:10.3762/bjoc.13.173

• monoacetylated derivatives, and the reactions occurred regioselectively at the primary hydroxy group of the model compounds. The regioselectivity of the reaction was further confirmed after the milling of isopropenyl acetate (2a) and the monolignol 1i, only containing a benzylic alcohol. After the standard

• addressing the centrally-located primary aliphatic hydroxyl content of lignins is still highly possible. This strategy is expected to allow the preservation of the phenolic and benzylic alcohol contents in modified lignins, in order to keep the antibacterial and antioxidant activities of this biopolymer

Oxidative dehydrogenation of C–C and C–N bonds: A convenient approach to access diverse (dihydro)heteroaromatic compounds

• Santanu Hati,
• Ulrike Holzgrabe and
• Subhabrata Sen

Beilstein J. Org. Chem. 2017, 13, 1670–1692, doi:10.3762/bjoc.13.162

• -workers in the year 2000 [26][27][28][29]. It oxidizes diverse functionalities such as amines, imines, alcohols etc. [30]. Later, it was demonstrated that IBX can also be used as a reagent for oxidative dehydrogenation of benzylic carbons in various aromatic systems via single electron transfer (SET) and

• quinazolinones. A putative mechanism involved the homolysis of DTBP to generate tert-butoxide radicals, which in turn abstracts a proton radical from the methyl(hetero)arene to facilitate the formation of a benzylic radical. The benzylic radical couples with o-aminobenzylamide to generate H. It then interacts

• yield. The proposed mechanism of this transformation is illustrated in the formation of 73. It involved oxidation of Cu(I)-(DABCO)2 by either oxygen or TEMPO to afford the Cu(II)-(DABCO)2 complex which gets coordinated with the N-atom of the substrate and TEMPO to generate an η2 complex Y. The benzylic

Syntheses of 3,4- and 1,4-dihydroquinazolines from 2-aminobenzylamine

• Jimena E. Díaz,
• Silvia Ranieri,
• Nadia Gruber and
• Liliana R. Orelli

Beilstein J. Org. Chem. 2017, 13, 1470–1477, doi:10.3762/bjoc.13.145

• 5a with PPE/CHCl3 under microwave irradiation led to 1,4-dihydroquinazoline 2a, accompanied by a low percentage of a collateral product. This compound was identified as 2-methyl-1-propylquinazolin-4(1H)-one (6a) (Scheme 3, (a), R1 = Pr, R2 = Me), arising from spontaneous benzylic oxidation of 2a. An

• benzylic oxidation. In spite of this, partial oxidation during workup and purification could not be avoided accounting for the lower yields obtained for the 2-aryl derivatives 2i,j (Table 4, entries 9 and 10). The higher sensitivity of compounds 2i,j towards oxidation may be a consequence of the enhanced

• . Benzylic oxidation of 1,4-dihydroquinazolines (a) and 3,4-dihydroquinazolines (b). Selective N-acylation of 2-ABA and its derivatives. Synthesis of compounds 5. Synthesis of 3,4-dihydroquinazolines 1. Synthesis of 1,4-dihydroquinazolines 2. Supporting Information Supporting Information File 94

Strategies toward protecting group-free glycosylation through selective activation of the anomeric center

• A. Michael Downey and
• Michal Hocek

Beilstein J. Org. Chem. 2017, 13, 1239–1279, doi:10.3762/bjoc.13.123

α-Acetoxyarone synthesis via iodine-catalyzed and tert-butyl hydroperoxide-mediateded self-intermolecular oxidative coupling of aryl ketones

• Liquan Tan,
• Cui Chen and
• Weibing Liu

Beilstein J. Org. Chem. 2017, 13, 1079–1084, doi:10.3762/bjoc.13.107

• ketones from aryl ketones using I2 and tert-butyl hydroperoxide (TBHP) [16][17][18] (Scheme 1). Several oxidative cross-coupling methods have been developed for the synthesis of α-acetoxy ketones from ketone derivatives and carboxylic acids [10], benzylic alcohols [19], toluene derivatives [20][21] and

Transition-metal-free one-pot synthesis of alkynyl selenides from terminal alkynes under aerobic and sustainable conditions

• Adrián A. Heredia and
• Alicia B. Peñéñory

Beilstein J. Org. Chem. 2017, 13, 910–918, doi:10.3762/bjoc.13.92

• and tertiary alkyl halides were used, preventing formation of 5f and 5g products, and this is a limitation of the procedure reported herein (Table 3, entries 7 and 8). By employing a benzylic halide such as benzyl bromide, the expected product 5h (Table 3, entry 9) was not detected. Again, the basic

Synthesis of new pyrrolidine-based organocatalysts and study of their use in the asymmetric Michael addition of aldehydes to nitroolefins

• Alejandro Castán,
• Ramón Badorrey,
• José A. Gálvez and
• María D. Díaz-de-Villegas

Beilstein J. Org. Chem. 2017, 13, 612–619, doi:10.3762/bjoc.13.59

• of the benzylic group with molecular hydrogen using Pd(OH)2/C as a catalyst in the presence of trifluoroacetic acid, b) reprotection of the amino group as benzylcarbamate by treatment of the crude reaction mixture with benzyl chloroformate in the presence of diisopropylethylamine, c) hydrolysis of

Derivatives of the triaminoguanidinium ion, 5. Acylation of triaminoguanidines leading to symmetrical tris(acylamino)guanidines and mesoionic 1,2,4-triazolium-3-aminides

• Jan Szabo,
• Julian Greiner and
• Gerhard Maas

Beilstein J. Org. Chem. 2017, 13, 579–588, doi:10.3762/bjoc.13.57

• crystal structure of salt 8b (Figure 2) shows a nearly planar core of the molecule (the triazole ring, N4, N5, N6). One face of this core is occupied by the three benzylic substituents, leaving the other face open for the chloride anion which is held in place by two N–H···Cl hydrogen bonds, one of them