Hypervalent organoiodine compounds: from reagents to valuable building blocks in synthesis

• Gwendal Grelier,
• Benjamin Darses and
• Philippe Dauban

Beilstein J. Org. Chem. 2018, 14, 1508–1528, doi:10.3762/bjoc.14.128

• and PhI(OCOt-Bu)2. These λ3-iodanes have been widely used in atom-transfer reactions, particularly for the generation of metal-bound nitrenes that are highly active species for the aziridination of alkenes and the direct amination of benzylic, allylic or tertiary C(sp3)–H bonds [80][81][82][83][84][85

• ) [108]. The overall process affords complex nitrogen-containing compounds 92 with very good yields and complete stereocontrol starting from benzylic, allylic and adamantyl substrates. In addition, the preparation of substituted [bis(acyloxy)iodo]arenes following the reaction of iodoarenes with sodium

[3 + 2]-Cycloaddition reaction of sydnones with alkynes

• Veronika Hladíková,
• Jiří Váňa and
• Jiří Hanusek

Beilstein J. Org. Chem. 2018, 14, 1317–1348, doi:10.3762/bjoc.14.113

• absence of light. Depending on the temperature, a new reaction pathway involving benzylic group migration, CO2 extrusion and final cycloaddition was proposed (Scheme 4). Kinetics and mechanism of thermal cycloaddition The kinetics and reaction mechanism of the thermal cycloaddition between 4-methyl-3

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

• ortho-1,3-dithianylaryl(aryl)methanols leading to ortho-1,3-dithianylaryl(aryl)methanes using the ZnI2-Na(CN)BH3 reductive system (Scheme 1). The use of zinc iodide is critical in this system. It was used for the first time in dichloroethane by Lau et al. to reduce aryl ketones, aldehydes, benzylic

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

• Scheme 7. The acid-catalyzed cleavage of the oxo-bridge of 34 gives benzylic carbocation 35. Consequently, after deprotonation and dehydration, chloro benzotropilium cation 37 undergoes hydrolysis to give 4,5-benzotropone (11) in aqueous reaction media. Using o-xylylene dibromide (38) as starting

• benzotropylium ion 45. Secondly, 11 is obtained in 18% yield after benzylic bromination of 42 with NBS, followed by in situ elimination reaction of the labile bromide 43 mediated by t-BuOK (Scheme 9). Palladium-catalyzed C–C bond-formation reactions such as Heck and Sonogashira couplings are employed in a wide

• compound that ionizes in liquid SO2 to the cation 134b. Treatment of cations with nucleophiles that are preferably added to the benzylic position (C-5 or C-9) yielded chloro- and bromo-5H-benzo[7]annulenes 136–143. According to Hückel molecular orbital (HMO) calculations, this observed regiochemistry is

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

• benzylic C–H bonds under mild conditions. The unique radical species, generated by the homolytic cleavage of the labile I(III)–Br bond of the in situ-formed bromo-λ3-iodane, initiated benzylic carboxylation with a high degree of selectivity for the secondary benzylic position. Keywords: carboxylic acids

• ][8]. Benzylic oxidation is of particular interest because it is a convenient direct approach to arylcarbonyl compounds; it has a long history of research and development, and thus is included among the well-investigated C(sp3)–H transformations [9][10][11][12]. To widen the scope, recent studies and

• reaction systems have been further elaborated to include elegant C–H coupling methodologies. Several important researches that provide a new benzylic C–H coupling strategy have been reported over the past few years, involving the promising catalytic activities of metal complexes [13][14]. On the other hand

An overview of recent advances in duplex DNA recognition by small molecules

• Sayantan Bhaduri,
• Nihar Ranjan and
• Dev P. Arya

Beilstein J. Org. Chem. 2018, 14, 1051–1086, doi:10.3762/bjoc.14.93

• cell lines by interacting non-covalently with the minor groove of the double helical ct-DNA [97]. Barker et al. have designed a series of novel di- and triaryl benzamide MGBs differing in the polar side chain, bonding and substitution patterns and functionalization of benzylic substituents and

• 35 with a bulky OTBDMS benzylic substituent was found to be the most active agent with (IC50 5.0 μM) followed by conjugate 36 with a chloro substituent (IC50 9.9 μM). Drozdowska et al. reported a series of distamycin analogues 37–41 (Figure 9) as potential minor groove binders and their minor groove

Hypervalent iodine(III)-mediated decarboxylative acetoxylation at tertiary and benzylic carbon centers

• Kensuke Kiyokawa,
• Daichi Okumatsu and
• Satoshi Minakata

Beilstein J. Org. Chem. 2018, 14, 1046–1050, doi:10.3762/bjoc.14.92

• I2 in a CH2Cl2/AcOH mixed solvent is reported. The reaction was successfully applied to two types of carboxylic acids containing an α-quaternary and a benzylic carbon center under mild reaction conditions. The resulting acetates were readily converted into the corresponding alcohols by hydrolysis

• solvent (Scheme 1). In subsequent experiments, the method was also found to be applicable to the reaction of benzylic carboxylic acids. The acetates that were produced in the reaction were readily converted into the corresponding alcohols by hydrolysis. Results and Discussion We started our investigation

• lower than that of a non-cyclic 2i. Using this protocol, 1-adamantanecarboxylic acid was smoothly transformed into the corresponding acetate 2k. In addition to the reaction with respect to tertiary carbon centers, the present method was successfully applied to benzylic carboxylic acid derivatives. For

Hypervalent iodine-guided electrophilic substitution: para-selective substitution across aryl iodonium compounds with benzyl groups

• Cyrus Mowdawalla,
• Faiz Ahmed,
• Tian Li,
• Kiet Pham,
• Loma Dave,
• Grace Kim and
• I. F. Dempsey Hyatt

Beilstein J. Org. Chem. 2018, 14, 1039–1045, doi:10.3762/bjoc.14.91

• thus we propose a concerted mechanism. The mechanism speculated in Scheme 3 shows a concerted demetallation of the metalloid as the C–C bond is forming. Before the transmetallation of the metalloid group, an interruptive process could be occurring that provides an orbital overlap at the benzylic

• intramolecular attack on a benzylic methylene with the hypernucleofuge attached (6). The mechanism in Scheme 4 shows the transmetallation occuring instead of being interrupted as in Scheme 3. The combination of both mechanisms (Scheme 3 and Scheme 4) explains how substitution ortho to the iodine (para to the

2-Iodo-N-isopropyl-5-methoxybenzamide as a highly reactive and environmentally benign catalyst for alcohol oxidation

• Takayuki Yakura,
• Tomoya Fujiwara,
• Akihiro Yamada and
• Hisanori Nambu

Beilstein J. Org. Chem. 2018, 14, 971–978, doi:10.3762/bjoc.14.82

• -OMe < 5-OAc < 5-Cl < H, 4-OMe < 5-Me < 5-OMe. The oxidation of various benzylic and aliphatic alcohols using a catalytic amount of the most reactive 5-methoxy derivative successfully resulted in moderate to excellent yields of the corresponding carbonyl compounds. The high reactivity of the 5-methoxy

• derivative at room temperature is a result of the rapid generation of the pentavalent species from the trivalent species during the reaction. 5-Methoxy-2-iodobenzamide would be an efficient and environmentally benign catalyst for the oxidation of alcohols, especially benzylic alcohols. Keywords: hypervalent

• . The secondary benzylic alcohols 14b–e were oxidized with 17 in much shorter reaction times than those oxidized with 13 to give the corresponding ketones 15b–e in good to excellent yields (Table 2, entries 1–4). Oxidation of the aliphatic secondary alcohol 14f with 17 required a slightly longer

Enantioselective dioxytosylation of styrenes using lactate-based chiral hypervalent iodine(III)

• Morifumi Fujita,
• Koki Miura and
• Takashi Sugimura

Beilstein J. Org. Chem. 2018, 14, 659–663, doi:10.3762/bjoc.14.53

• proceed via an SN2 reaction of a cyclic intermediate such as I1, judging from the syn selectivity of the dioxytosylation [52][53]. The attack of the tosylate ion on I1 possibly takes place at the benzylic position or at the methylene carbon atom. The positive charge of I1 may be stabilized by the aryl

• group and localized at the benzylic position. This may allow the preferential formation of I3 from I1. If I2 was the major intermediate in the pathway leading to 3, the stereochemical purity of 3 would have decreased owing to the facile elimination of the iodonium group [54] at the benzylic position of

• planar structure of the benzylic cation. Thus, the tosylate ion may act as an effective nucleophile for the SN2 reaction of I1. The stereoface-differentiation in the dioxytosylation reaction using the lactate-derived aryl-λ3-iodanes is similar to that in preceding reactions [14], which include the

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