Synthesis of C-glycosyl phosphonate derivatives of 4-amino-4-deoxy-α-ʟ-arabinose

• Lukáš Kerner and
• Paul Kosma

Beilstein J. Org. Chem. 2020, 16, 9–14, doi:10.3762/bjoc.16.2

• of 10, the olefinic proton was absent, whereas the 13C NMR spectrum showed downfield shifts for the anomeric carbon atom (146.48 ppm) and the adjacent ring carbon atom (133.95 ppm). Evidence from an HMBC experiment additionally indicated a correlation between the benzylic protons and the latter

Palladium-catalyzed synthesis and nucleotide pyrophosphatase inhibition of benzo[4,5]furo[3,2-b]indoles

• Hoang Huy Do,
• Saif Ullah,
• Alexander Villinger,
• Joanna Lecka,
• Jean Sévigny,
• Peter Ehlers,
• Jamshed Iqbal and
• Peter Langer

Beilstein J. Org. Chem. 2019, 15, 2830–2839, doi:10.3762/bjoc.15.276

• of the reaction of 3 was studied using different amines. The reaction of 3 with various anilines afforded products 5a–g in good to excellent yields (Table 2). No impact of the functional groups of the anilines on the yield was observed. The reactions of 3 with aliphatic or benzylic amines under our

A review of asymmetric synthetic organic electrochemistry and electrocatalysis: concepts, applications, recent developments and future directions

• Munmun Ghosh,
• Valmik S. Shinde and
• Magnus Rueping

Beilstein J. Org. Chem. 2019, 15, 2710–2746, doi:10.3762/bjoc.15.264

• asymmetric induction was proposed to be realized via a combination of chiral Lewis acid-bound radical (generated through a single-electron anodic oxidation) and benzylic radical, generated through the anodic oxidation of 95. As per the proposed catalytic cycle, initial coordination of the Lewis acid catalyst

• to 2-acylimidazole derivatives 94 generates the Lewis acid/enolate complex 100 upon deprotonation (Scheme 35). This is followed by the formation of intermediate 101 by electrolysis-induced SET oxidation. In a parallel electrochemical cycle, benzylic radical species 95 was delivered by the anodic

A toolbox of molecular photoswitches to modulate the CXCR3 chemokine receptor with light

• Xavier Gómez-Santacana,
• Sabrina M. de Munnik,
• Tamara A. M. Mocking,
• Niels J. Hauwert,
• Shanliang Sun,
• Prashanna Vijayachandran,
• Iwan J. P. de Esch,
• Henry F. Vischer,
• Maikel Wijtmans and
• Rob Leurs

Beilstein J. Org. Chem. 2019, 15, 2509–2523, doi:10.3762/bjoc.15.244

• of the inner ring with respect to the azo bond (i.e., the ortho-position with respect to the benzylic position) to afford subseries 4. This π-electron delocalization would increase the electron density of the azobenzene unit, and was also expected to have an effect on the trans–cis azobenzene

Recent advances in transition-metal-catalyzed incorporation of fluorine-containing groups

• Xiaowei Li,
• Xiaolin Shi,
• Xiangqian Li and
• Dayong Shi

Beilstein J. Org. Chem. 2019, 15, 2213–2270, doi:10.3762/bjoc.15.218

• fluoride source and PhI(OPiv)2 as a hypervalent iodine oxidant (Scheme 8). Very recently, they [44] optimized this transformation and achieved the benzylic C–H radiofluorination with no-carrier-added Ag[18F]F. This method was applied to the radiolabeling of diversely substituted 8-methylquinoline

• derivatives (Scheme 11a). This process was carried out under the strongly binding bidentate 2-(pyridine-2-yl)isopropylamine (PIP) auxiliary. A range of substrates containing both aliphatic and benzylic C(sp3)–H bonds was finally converted to the corresponding fluorinated products with excellent

• inert C–H bonds, alkyl bromides and -triflates: In a 2012 study, Lectka’s group [67] disclosed the catalytic fluorination of a series of aliphatic, benzylic, and allylic substrates with moderate yields. In this case, the authors employed a multicomponent catalytic system, involving Selectfluor, the

Multiple threading of a triple-calix[6]arene host

• Veronica Iuliano,
• Roberta Ciao,
• Emanuele Vignola,
• Carmen Talotta,
• Patrizia Iannece,
• Margherita De Rosa,
• Annunziata Soriente,
• Carmine Gaeta and
• Placido Neri

Beilstein J. Org. Chem. 2019, 15, 2092–2104, doi:10.3762/bjoc.15.207

• 6 in CDCl3 at 298 K at 0.95 (27H), 1.05 (54H), and 1.22 ppm (81H = 54H + 27H; accidentally isochronous) attributable to tert-butyl groups, and three singlets at 2.56, 2.80, and 3.12 ppm in a 2:1:2 ratio, attributable to OMe groups were also found. The methylene benzylic resonance of 6 was revealed

• present at 5.13 ppm and 4.96 ppm (1:2) attributable to the benzylic methylene groups of the central benzene core of 6 in 7+6 pseudo[2]rotaxane. A DOSY experiment (Figure 3, top) evidenced that the resonances in the 1H NMR spectrum of the 1:1 mixture of 6 and 7+·TFPB− in CDCl3 at 298 K all show the same

• -tetrachloroethane as internal standard, an apparent association constant of 1.01 ± 0.03 × 104 M−1 was calculated for the 7+6 pseudo[2]rotaxane. When 1 equiv of 7+·TFPB− salt was added to the 1:1 mixture of 6 and 7+·TFPB− in CDCl3 (Figure 4c), then, in addition to the benzylic resonances of the 7+6 pseudo[2]rotaxane

A review of the total syntheses of triptolide

• Xiang Zhang,
• Zaozao Xiao and
• Hongtao Xu

Beilstein J. Org. Chem. 2019, 15, 1984–1995, doi:10.3762/bjoc.15.194

• was isomerized in the presence of base and dehydrated to give diene 45. Reduction of 45 with 10% Pd/C afforded 8 in good yield (60%) after recrystallization. Benzylic oxidation of 8 (CrO3/HOAc, 45%), followed by C-14 ether cleavage (BBr3) and subsequent sodium borohydride reduction afforded 46 with

• the desired stereochemistry of the C-7 benzylic hydroxy group. Compound 46 was converted to triptonide 2 by Alder periodate reaction (NaIO4, 74%), and a sequencing m-CPBA epoxidation and basic hydrogen peroxide oxidation (H2O2/OH−) procedure (two steps, 28%). Finally, sodium borohydride reduction of 2

• isomerization of olefin 43, the benzylic oxidation of 8, the use of m-CPBA to introduce the C-9,11 epoxide and the non-stereoselective reduction of the C-14 carbonyl group using sodium borohydride, caused an unacceptable overall yield (1.6%). This pioneering work undoubtedly established the basis for the future

Metal-free mechanochemical oxidations in Ertalyte^® jars

• Andrea Porcheddu,
• Francesco Delogu,
• Lidia De Luca,
• Claudia Fattuoni and
• Evelina Colacino

Beilstein J. Org. Chem. 2019, 15, 1786–1794, doi:10.3762/bjoc.15.172

• carboxylic acid derivatives were observed in any sample. Similar results were obtained for alcohols containing an aliphatic carbon ring in their backbone, such as cyclohexylmethanol (5a). Interestingly, the oxidation reaction of benzylic alcohols proceeded smoothly to completeness in about 10 minutes even

• without need for TEMPO. The results changed significantly with benzylic alcohols decorated with an electron-withdrawing group in the aromatic ring such as 4-nitrobenzylalcohol (and 4-cyanobenzylalcohol), which required 5 mol % of TEMPO to be oxidized. Based on these experimental results, we hypothesize

• benzylic alcohols 6a or 7a to afford the corresponding intermediate benzyl hypobromites 6c or 7c (Scheme 5, reaction 3). In the final step, the base deprotonates the acidic benzylic proton leading to the corresponding benzaldehyde 6b or 7b (Scheme 5, reaction 4). The oxidation of furfuryl alcohol gave

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

• NaBH4/ZnCl2 mixture (chelation controlled) gave the aziridine alcohol 20 as a major product. Reductive opening of the aziridine ring produced the amino alcohol 21 which was transformed into the substituted oxazolidin-2-one 22. Its catalytic hydrogenation effected deoxygenation at the benzylic position

• cleavage of the aziridine ring occurred regiospecifically at the N–C3 bond (benzylic position) to provide N-Boc-ᴅ-phenylalaninol ((R)-118) after saponification. When mesylation of (2S,1'R/S,1''R)-28 was followed by LiAlH4 reduction the aziridine (2R,1'R)-119 was produced from which the acetate (2R,1'R)-120

• these conditions the acetate function was also hydrolyzed the carboxy group was formed by oxidation of the hydroxymethyl residue. To complete the synthesis N- and O-benzylic protecting groups were removed during the Birch reaction. A polyoxamic structural framework was found in polyoxins, natural

A novel three-component reaction between isocyanides, alcohols or thiols and elemental sulfur: a mild, catalyst-free approach towards O-thiocarbamates and dithiocarbamates

• András György Németh,
• György Miklós Keserű and
• Péter Ábrányi-Balogh

Beilstein J. Org. Chem. 2019, 15, 1523–1533, doi:10.3762/bjoc.15.155

• , we have turned our attention to different benzylic alcohols that could be utilized to further examine the functional group tolerance of the reaction. Notably, chlorine, bromine and iodine substituents were compatible with the transformation, providing 3m, 3n, 3r and 3s in 81–89% yield. The nitrile

Superelectrophilic carbocations: preparation and reactions of a substrate with six ionizable groups

• Sean H. Kennedy,
• Makafui Gasonoo and
• Douglas A. Klumpp

Beilstein J. Org. Chem. 2019, 15, 1515–1520, doi:10.3762/bjoc.15.153

• (pyridinium/benzylic carbocation) for the hexacation 14, while the ratio of charges is 4:1 (pyridinium/benzylic carbocation) for the pentacation 5. Similarly, we previously reported good chemoselectivity for trication 3 – no cyclization product observed in the presence of benzene – but poor chemoselectivity

• arylation product is observed). This is attributed to the presence of two carbocationic sites stabilized by benzylic-type resonance. Thus, molecular structures having a very large overall charge may be viable if stabilizing groups are incorporated into the structure. Experimental General. All reactions were

Formation of an unexpected 3,3-diphenyl-3H-indazole through a facile intramolecular [2 + 3] cycloaddition of the diazo intermediate

• Andrew T. King,
• Hugh G. Hiscocks,
• Lidia Matesic,
• Mohan Bhadbhade,
• Roger Bishop and
• Alison T. Ung

Beilstein J. Org. Chem. 2019, 15, 1347–1354, doi:10.3762/bjoc.15.134

• , the spectrum showed only one benzylic proton, as a singlet at 6.82 ppm. 13C NMR and HSQC showed tertiary and quaternary resonances at 51.3 and 101.5 ppm, respectively. The first resonance is indicative of HC(Ph)2, while the one at 101.5 ppm is more likely to be the 3,3-diphenyl-substituted carbon of

• highly activated benzylic carbon and further expedited by three phenyl groups, to form the resonance stabilisation of 9 [32]. Furthermore, 8 cannot attain planarity of the methylene–benzhydryl fragment due to steric hindrance. These reactions appear to be also encouraged by the reduction of the crowding

Alkylation of lithiated dimethyl tartrate acetonide with unactivated alkyl halides and application to an asymmetric synthesis of the 2,8-dioxabicyclo[3.2.1]octane core of squalestatins/zaragozic acids

• Herman O. Sintim,
• Hamad H. Al Mamari,
• Hasanain A. A. Almohseni,
• Younes Fegheh-Hassanpour and
• David M. Hodgson

Beilstein J. Org. Chem. 2019, 15, 1194–1202, doi:10.3762/bjoc.15.116

• (e.g., 7, Scheme 2) was originally reported by Seebach and co-workers for ‘activated’ (allylic, benzylic) alkyl halides [17][18][19]. If an alkylated tartrate 9 could be accessed from a silyloxy-substituted alkyl iodide 8 and subsequently oxidised (for example via a second tartrate enolate) with

• work, which concluded that only especially reactive halides (methyl, benzylic, allylic) were feasible electrophiles; with iodoethane, 1-iodo-2-methylpropane and chloromethoxymethane no alkylation products were formed [17][18][19]. Given these rather discouraging observations in the context of our

Molecular recognition using tetralactam macrocycles with parallel aromatic sidewalls

• Dong-Hao Li and
• Bradley D. Smith

Beilstein J. Org. Chem. 2019, 15, 1086–1095, doi:10.3762/bjoc.15.105

• water is due primarily to a highly favorable enthalpic change [61]. Furthermore, tetralactam threading studies using water-soluble squaraine guests with flanking benzylic groups have produced Ka values that were close to 1011 M−1 [62]. The affinity gain is due to a guest back-folding effect where the

• affinity of the threaded squaraine is enhanced by additional contacts made by the dye’s flanking benzylic groups with the external surface of the surrounding macrocycle (Scheme 4). This type of noncovalent interaction between an encapsulated guest and the external surface of the surrounding tetralactam has

Photochemical generation of the 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) radical from caged nitroxides by near-infrared two-photon irradiation and its cytocidal effect on lung cancer cells

• Ayato Yamada,
• Manabu Abe,
• Yoshinobu Nishimura,
• Shoji Ishizaka,
• Masashi Namba,
• Taku Nakashima,
• Kiyofumi Shimoji and
• Noboru Hattori

Beilstein J. Org. Chem. 2019, 15, 863–873, doi:10.3762/bjoc.15.84

• -iodo-4-nitrobenzene (3) [68]. The TEMPO moiety was introduced at the benzylic position of 5a and 5b using the copper-catalyzed radical reaction in the presence of tert-butyl hydroperoxide (TBHP) to afford 2a and 2b in 38% and 52% yield, respectively [69]. The caged TEMPOs 2a and 2b were thermally

• , the compounds oxidized at the benzylic carbon, 6 and 7, were isolated in 15% (15%) and 56% (42%) yield in the photolysis of 2a and 2b under atmospheric conditions, respectively (Scheme 3), indicating that under degassed conditions, the photochemically generated radical pair returns to the starting

Coordination chemistry and photoswitching of dinuclear macrocyclic cadmium-, nickel-, and zinc complexes containing azobenzene carboxylato co-ligands

• Jennifer Klose,
• Tobias Severin,
• Peter Hahn,
• Alexander Jeremies,
• Jens Bergmann,
• Daniel Fuhrmann,
• Jan Griebel,
• Bernd Abel and
• Berthold Kersting

Beilstein J. Org. Chem. 2019, 15, 840–851, doi:10.3762/bjoc.15.81

• solution. Thus, the six N-methyl groups give rise to two singlets (one for the methyl protons on the benzylic nitrogen atoms (NBzCH3) and one for the methyl protons on the central amine nitrogen of the linking diethylenetriamine units (NCH3)). Note that the four aromatic protons (ArH) and the tert-butyl

• protons [C(CH3)3] appear as singlets. The remaining six signals can be assigned to the methylene protons of the linking diethylenetriamine chains (two doublets for the benzylic CH2 and four multiplets for linking CH2 groups). The 1H NMR data are indicative of a C2v symmetric structure of the [Cd2L]2

Tuning the stability of alkoxyisopropyl protection groups

• Zehong Liang,
• Henna Koivikko,
• Mikko Oivanen and
• Petri Heinonen

Beilstein J. Org. Chem. 2019, 15, 746–751, doi:10.3762/bjoc.15.70

• ., 8a (Figure 2). Recently, the same kind of enol ether formation was considered in connection to an optimization of the conditions for MIP protection on secondary and benzylic hydroxy groups of mandelonitrile derivatives in a flow reactor process [9]. All of the studied acetals are stable toward basic

Selective benzylic C–H monooxygenation mediated by iodine oxides

• Kelsey B. LaMartina,
• Haley K. Kuck,
• Linda S. Oglesbee,
• Asma Al-Odaini and
• Nicholas C. Boaz

Beilstein J. Org. Chem. 2019, 15, 602–609, doi:10.3762/bjoc.15.55

• 08544 USA Permanent address: Department of Chemistry, North Central College, 30 N. Brainard Street, Naperville, IL 60540 USA; phone: +1-630-637-5187. 10.3762/bjoc.15.55 Abstract A method for the selective monooxdiation of secondary benzylic C–H bonds is described using an N-oxyl catalyst and a

• oxygenation of substrates containing secondary benzylic C–H bonds, yielding the corresponding benzylic acetates in good to moderate yield. Tertiary benzylic C–H bonds were shown to be unreactive under similar conditions, despite the weaker C–H bond. A preliminary mechanistic analysis suggests that this NHPI

• -iodate system is functioning by a radical-based mechanism where iodine generated in situ captures formed benzylic radicals. The benzylic iodide intermediate then solvolyzes to yield the product ester. Keywords: acetoxylation; benzylic; iodate; NHPI; oxidation; radical; Introduction The ability to

Study on the regioselectivity of the N-ethylation reaction of N-benzyl-4-oxo-1,4-dihydroquinoline-3-carboxamide

• Pedro N. Batalha,
• Luana da S. M. Forezi,
• Maria Clara R. Freitas,
• Nathalia M. de C. Tolentino,
• Ednilsom Orestes,
• José Walkimar de M. Carneiro,
• Fernanda da C. S. Boechat and
• Maria Cecília B. V. de Souza

Beilstein J. Org. Chem. 2019, 15, 388–400, doi:10.3762/bjoc.15.35

• HMBC spectra. In the COSY spectrum of 7, the correlations between the hydrogen of the amide group (CONH) and of the benzylic hydrogens (CONHCH2Ph) confirm again the occurrence of the alkylation in the nitrogen of the oxoquinoline nucleus (Figure 4). From the HMBC spectrum of 7 it was observed that H-2

• correlated with the carbon resonance for benzylic carbon at δ = 42.06 ppm (2JCH, Figure 5). These data also confirm the regioselectivity of the N-ethylation reaction. Furthermore, adequate crystals of compound 7 were obtained from a mixture of ethanol and DMSO, which allowed the unambiguous resolution of its

Synthesis of 1,2-divinylcyclopropanes by metal-catalyzed cyclopropanation of 1,3-dienes with cyclopropenes as vinyl carbene precursors

• Jesús González,
• Alba de la Fuente,
• María J. González,
• Laura Díez de Tejada,
• Luis A. López and
• Rubén Vicente

Beilstein J. Org. Chem. 2019, 15, 285–290, doi:10.3762/bjoc.15.25

• feasibility of an analogous reaction with 1,3-dienes preparing dienylcyclopropene 4. While treatment of 4 with ZnCl2 led to complex mixtures, likely due to the Lewis acid sensitivity of the benzylic cyclopropenylcarbinol moiety, the use of [Rh2(OAc)4] (1.0 mol %, CH2Cl2, rt) led to the tricyclic compound 5 in

Synthesis and biological activity of methylated derivatives of the Pseudomonas metabolites HHQ, HQNO and PQS

• Sven Thierbach,
• Max Wienhold,
• Susanne Fetzner and
• Ulrich Hennecke

Beilstein J. Org. Chem. 2019, 15, 187–193, doi:10.3762/bjoc.15.18

• separated from the N-methylation product by column chromatography and could be isolated in 32% yield. Surprisingly, the N-methylated product under these conditions was not NMe-HHQ (2), but instead a second methylation in the benzylic position had occurred to give N-methyl-2-(1-methylheptyl)-4(1H)-quinolone

• in the benzylic position could be observed. Instead of direct ortho-metalation, a strategy based on halogen–lithium exchange proved to be more suitable. To this end, HHQ (1) was converted into 3I-HHQ (8) following a literature procedure [21]. 3I-HHQ (8) was then methylated using the MeI/K2CO3

• conditions to give a mixture of OMe-3I-HHQ (9, 21%) and NMe-3I-HHQ (10, 24%, Scheme 3). Interestingly, in the case of 3I-HHQ (8) the ratio of N-methylation versus O-methylation was almost 1:1 and no further methylation of 10 in the benzylic position was observed. With the methylated compounds 9 and 10 in

Computational characterization of enzyme-bound thiamin diphosphate reveals a surprisingly stable tricyclic state: implications for catalysis

• Ferran Planas,
• Michael J. McLeish and
• Fahmi Himo

Beilstein J. Org. Chem. 2019, 15, 145–159, doi:10.3762/bjoc.15.15

• interchangeable (Table 1). Model E: active site of BFDC with (R)-mandelate bound In model E, in which the active site of BFDC contains the inhibitor (R)-mandelate, the hydrogen-bonding network is very similar to that of benzoylformate in model D. However, as shown in Figure 6, the benzylic hydroxy group provides

• different energies. The superposition of the AP states of the two models (see Supporting Information File 1) shows that the additional hydrogen bond provided by the benzylic hydroxy group of (R)-mandelate (vide supra) contributes significantly to this difference. Further, changing from the sp2 carbonyl

• carbon to the sp3 benzylic carbon results in a substantial movement of the substituent oxygen which also contributes to the energy difference between the models. According to Table 1 the AP/APH+ forms are the most stable states for models C and E, i.e., BFDC in the absence of ligand and in the presence

Reactions of 3-(p-substituted-phenyl)-5-chloromethyl-1,2,4-oxadiazoles with KCN leading to acetonitriles and alkanes via a non-reductive decyanation pathway

• Akın Sağırlı and
• Yaşar Dürüst

Beilstein J. Org. Chem. 2018, 14, 3011–3017, doi:10.3762/bjoc.14.280

• substitution reaction with various alkyl halides to afford mono-, di- or trialkylated acetonitriles [17]. Most recently, Strzalko and co-workers disclose mono and dialkylation of the benzylic carbon of phenylacetonitrile with a poor selectivity by benzyl and methyl halides in the presence of LiHMDS, LDA or n

Ring-closing-metathesis-based synthesis of annellated coumarins from 8-allylcoumarins

• Christiane Schultze and
• Bernd Schmidt

Beilstein J. Org. Chem. 2018, 14, 2991–2998, doi:10.3762/bjoc.14.278

• catalyze allylic and benzylic oxidation reactions through a radical mechanism [70]. To implement this tandem sequence in the synthesis of pyran-2-one-annellated coumarins 15 an isomerization of the 8-allyl substituent to a prop-1-enyl substituent was first required. When 8-allyl-7-hydroxycoumarin (8a) was

Synthesis of mono-functionalized S-diazocines via intramolecular Baeyer–Mills reactions

• Miriam Schehr,
• Daniel Hugenbusch,
• Tobias Moje,
• Christian Näther and
• Rainer Herges

Beilstein J. Org. Chem. 2018, 14, 2799–2804, doi:10.3762/bjoc.14.257

• dinitro compounds, strongly basic conditions have to be applied. Unfortunately, the benzylic position of the bridge is deprotonated under these conditions, leading to a plethora of side products. Formation of the N=N double bond by oxidation of diamines [21][22][23] cannot be applied either, because the