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

• benzaldehyde. A nickel-catalyzed procedure gives the dipyridyl intermediate 7 [13]. This is easily oxidized to the diketone 8 and reaction of this substance with 2-lithiopyridine gives the precursor 9. The diol 9 is a substrate with six ionizable groups. Upon ionization in superacidic CF3SO3H (triflic acid

• observed from the superacid-promoted reaction of diol 9. This suggests outside deprotonation – and formation of ion 21 – does not occur. The preference for inside deprotonation may be understood to be a consequence of charge–charge repulsive effects. In the case of 21, the five cationic charges are on

• , 123.3, 123.6, 124.2, 128.3, 131.9, 136.4, 138.1, 149.7, 154.4; low-resolution ESIMS m/z: 487 [M + 1], 397, 353, 320, 319, 279, 244; high-resolution CIMS m/z: [M + 1], calcd for C34H23N4, 487.1923; found, 487.1917. Superelectrophilic species. Synthesis of diol substrate 9. Isolated yields of products

Borylation and rearrangement of alkynyloxiranes: a stereospecific route to substituted α-enynes

• Ruben Pomar Fuentespina,
• José Angel Garcia de la Cruz,
• Gabriel Durin,
• Victor Mamane,
• Jean-Marc Weibel and
• Patrick Pale

Beilstein J. Org. Chem. 2019, 15, 1416–1424, doi:10.3762/bjoc.15.141

• B could be envisaged with the large pinacol substituent facing the small oxirane ring and thus placing the migrating group antiparallel to the adjacent oxiranyl C–O bond. This may explain the role of the diol substituent on the reaction efficacy (see Table 1). Upon migration and oxirane ring opening

Electrophilic oligodeoxynucleotide synthesis using dM-Dmoc for amino protection

• Shahien Shahsavari,
• Dhananjani N. A. M. Eriyagama,
• Bhaskar Halami,
• Vagarshak Begoyan,
• Marina Tanasova,
• Jinsen Chen and
• Shiyue Fang

Beilstein J. Org. Chem. 2019, 15, 1116–1128, doi:10.3762/bjoc.15.108

• incorporating electrophilic groups, we also needed phosphoramidite monomers 26a–c, which contained the sensitive functionalities ester, α-chloroacetamide and thioester, respectively (Figure 2). The synthesis of 26b,c has been reported [40]. Scheme 3 shows the synthesis of 26a. The required 1,2-diol 28 was

Catalytic asymmetric oxo-Diels–Alder reactions with chiral atropisomeric biphenyl diols

• Chi-Tung Yeung,
• Wesley Ting Kwok Chan,
• Wai-Sum Lo,
• Ga-Lai Law and
• Wing-Tak Wong

Beilstein J. Org. Chem. 2019, 15, 955–962, doi:10.3762/bjoc.15.92

• acid catalysts for over three decades [15][16][17][18][19][20][21][22][23][24][25][26]. Comparatively, interest in the utilization of metal-free organocatalytic oxo-DA reactions began to grow only after Rawal’s group reported a ground-breaking contribution in using a diol molecule, TADDOL, as a

• groups of the TADDOL and the carbonyl oxygen of the aldehyde was proposed to be a crucial factor for the success of this organocatalyst in the reaction. Two years later, they reported another efficient diol-based hydrogen bonding organocatalyst, BAMOL, for catalyzing the same oxo-DA reactions with a

• atropselectivities; (b) different relative spatial arrangement of the CF3- and phenyl-substituents. Torsional angle of biphenyl rings is 104.55(22). Chiral biphenyl diol organocatalysts 1–6. Synthesis of 3. Synthesis of 4. Synthesis of 6. Catalytic asymmetric oxo-DA reactions with stereolabile chiral biphenyl diols

A chemoenzymatic synthesis of ceramide trafficking inhibitor HPA-12

• Seema V. Kanojia,
• Sucheta Chatterjee,
• Subrata Chattopadhyay and
• Dibakar Goswami

Beilstein J. Org. Chem. 2019, 15, 490–496, doi:10.3762/bjoc.15.42

• (S)-4 with benzyl bromide (BnBr) and Bu4NI in the presence of NaH produced compound 6 (Scheme 2). This was subjected to asymmetric dihydroxylation (ADH) using AD mix-β [K2OsO2(OH)4 and (DHQD)2-PHAL]. The reaction proceeded predominantly from the α-face, resulting in the formation of the 1,3-anti diol

• 7a and 1,3-syn diol 7b in a 91:9 ratio (based on the isolated yields of 7a and 7b, separated by column chromatography). Previously the ADH reaction of a homologue of 6, bearing a methyl substitution and a hydroxy group (instead of benzyloxy group) with AD mix-β also produced the corresponding α

• -alcohol [53]. However, unlike in our case, the reaction proceeded with poor diastereoselectivity irrespective of the dihydroxylating agent used. To confirm the 1,3-anti diol stereochemistry of 7a, it was debenzylated using DDQ/CH2Cl2–H2O to furnish the trihydroxy compound 7a'. The 1H and 13C NMR spectra

Aqueous olefin metathesis: recent developments and applications

• Valerio Sabatino and
• Thomas R. Ward

Beilstein J. Org. Chem. 2019, 15, 445–468, doi:10.3762/bjoc.15.39

• obtained with artificial metathase ArM 1 using purified Sav samples. RCM activities of catalyst 66 and ArM 3 with substrates 67, 52 and 21. RCM of N,N-diallyltoluenesulfonamide (21) with ArM 4. Selected RCM results of N,N-diallyltoluenesulfonamide (21) and diol 64. ROMP of 7-oxonorbornene derivative 13

Syntheses and chemical properties of β-nicotinamide riboside and its analogues and derivatives

• Mikhail V. Makarov and
• Marie E. Migaud

Beilstein J. Org. Chem. 2019, 15, 401–430, doi:10.3762/bjoc.15.36

• more concentrated alkaline conditions (5 N KOH) as a result of a pyridinium ring opening–closure process [57]. It was also shown that the ionization of a diol fragment of NAD+ under alkaline conditions plays a very important role in the dissociative cleavage of the glycosyl bond of the “northern

Sigmatropic rearrangements of cyclopropenylcarbinol derivatives. Access to diversely substituted alkylidenecyclopropanes

• Guillaume Ernouf,
• Jean-Louis Brayer,
• Christophe Meyer and
• Janine Cossy

Beilstein J. Org. Chem. 2019, 15, 333–350, doi:10.3762/bjoc.15.29

• . The reduction of ester 76 with LiAlH4 and oxidative cleavage of the resulting 1,2-diol with NaIO4 delivered the highly substituted gem-difluorocyclopropanecarboxaldehyde 77 (72%) possessing a quaternary stereocenter (Scheme 26) [65]. Other examples of post-functionalization involve iodolactonization

Synthesis of nonracemic hydroxyglutamic acids

• Dorota G. Piotrowska,
• Iwona E. Głowacka,
• Andrzej E. Wróblewski and
• Liwia Lubowiecka

Beilstein J. Org. Chem. 2019, 15, 236–255, doi:10.3762/bjoc.15.22

• )-5 which after O-benzylation provided an inseparable 1:3 mixture of compounds 8a and 8b. A six-carbon chain was shortened by a diol formation–diol cleavage sequence followed by aldehyde oxidation and esterification to give 9a and 9b after chromatographic separation. They were transformed into (2S,3R

• give acid 16. To complete the synthesis of di-tert-butyl ester of (2R,3S)-2 compound 16 was first transformed into the ester and later deprotected to the diol 17 which was selectively oxidized, again esterified and finally the phenylsulfonyl group was removed electrochemically (Scheme 4) [52]. The

• derived from D- or L-tartaric acids can be used as starting materials in syntheses of enantiomers of 3,4-dihydroxyglutamic acids since they contain a vicinal diol fragment of the known stereochemistry. To demonstrate this strategy cyclic imides 106a (R = TBDMS) and 106b (R = Ac) readily prepared from L

First synthesis of cryptands with sucrose scaffold

• Patrycja Sokołowska,
• Michał Kowalski and
• Sławomir Jarosz

Beilstein J. Org. Chem. 2019, 15, 210–217, doi:10.3762/bjoc.15.20

• sucrose scaffold (e.g., 4) can be also prepared successfully [15][16]. All macrocyclic derivatives, shown in Figure 1, were prepared from hexa-O-benzylsucrose 3 by a connection of the terminal positions of glucose (C6) and fructose (C6’) units. Results and Discussion Diol 3 may be also used as a starting

• Figure 2) is, however, problematic, because of steric hindrance. The approach shown on route b (Figure 2), in which the terminal positions are elongated to avoid these difficulties, seems to be more feasible. Diol 3 was, thus, extended at both terminal positions by five atoms by reaction with bis(2

• connected to the nitrogen atoms (-CH2N units), and thus this observation confirms the presence of the crown-unit 8 in the structure. Although the first approach to sucrose cryptands was very successful, the strategy based on sucrose diol 3 has several limitations. First of all, the cavity in cryptand 11 is

Unexpected loss of stereoselectivity in glycosylation reactions during the synthesis of chondroitin sulfate oligosaccharides

• Teresa Mena-Barragán,
• José L. de Paz and
• Pedro M. Nieto

Beilstein J. Org. Chem. 2019, 15, 137–144, doi:10.3762/bjoc.15.14

• selective formation of the β(1→4) linkage in the [2 + 2] coupling. Cleavage of the anomeric 4-methoxyphenyl group followed by treatment with trichloroacetonitrile and DBU gave glycosyl donor 1 in high yield. For the synthesis of acceptor 2, diol 6 was selectively acylated at position 6 using 1.1 equiv of

Systematic synthetic study of four diastereomerically distinct limonene-1,2-diols and their corresponding cyclic carbonates

• Hiroshi Morikawa,
• Jun-ichi Yamaguchi,
• Shun-ichi Sugimura,
• Masato Minamoto,
• Yuuta Gorou,
• Hisatoyo Morinaga and
• Suguru Motokucho

Beilstein J. Org. Chem. 2019, 15, 130–136, doi:10.3762/bjoc.15.13

• )-limonene-derived diol and its corresponding five-membered cyclic carbonate were prepared. The diol (cyclic carbonate) comprises four diastereomers based on the stereochemical configuration of the diol (and cyclic carbonate) moiety. By choosing the appropriate starting compounds (trans- and cis-limonene

• their characteristic signals. Keywords: cyclic carbonate; diastereomer; diol; limonene; NMR; Introduction (R)-Limonene (LM) is a naturally occurring terpene, and therefore a very attractive and renewable resource [1]. Its derivatives have versatilely and widely been studied [1][2][3][4]. Otherwise

• corresponding LMdiol 2d [27]. Notably, the structure of 2d was confirmed by X-ray analysis. It has been reported that reduction of the 5CC moiety with LAH gives the corresponding diol with the same stereochemical configuration at the carbon atoms as of the original 5CC moiety [28][29]. Such a reduction with LAH

Synthesis, biophysical properties, and RNase H activity of 6’-difluoro[4.3.0]bicyclo-DNA

• Sibylle Frei,
• Adam K. Katolik and
• Christian J. Leumann

Beilstein J. Org. Chem. 2019, 15, 79–88, doi:10.3762/bjoc.15.9

• inseparable mixture of two diiodo-substituted products was unveiled. The major product was the bicyclic gem-diol 4 and the minor one the corresponding ketone 3. We hypothesize that the α,α-difluoroketone 3 was formed through a cyclopropane ring-opening followed by the addition of the electrophilic iodine in

• accordance to what was reported by the Dilman group [40]. The α,α-difluoroketone 3 rapidly underwent hydration in a reversible way to form the gem-diol 4. The stereochemistry of compound 4 could be assessed indicating the selective formation of the β-nucleoside with the addition of the iodine at the 7

Olefin metathesis catalysts embedded in β-barrel proteins: creating artificial metalloproteins for olefin metathesis

• Daniel F. Sauer,
• Johannes Schiffels,
• Takashi Hayashi,
• Ulrich Schwaneberg and
• Jun Okuda

Beilstein J. Org. Chem. 2018, 14, 2861–2871, doi:10.3762/bjoc.14.265

• nm indicated the presence of the GH-type catalyst. Finally, the peak for the biohybrid conjugate was observed in ESI–TOF–MS suggesting successful covalent anchoring. Beside ring-closing metathesis (RCM) of 2,2-diallylpropane-1,3-diol to yield the corresponding cyclopentane derivative, the synthesized

Synthesis of pyrrolidine-based hamamelitannin analogues as quorum sensing inhibitors in Staphylococcus aureus

• Jakob Bouton,
• Kristof Van Hecke,
• Reuven Rasooly and
• Serge Van Calenbergh

Beilstein J. Org. Chem. 2018, 14, 2822–2828, doi:10.3762/bjoc.14.260

• -closing metathesis of 24 now smoothly afforded 25 in high yield. Dihydroxylation selectively yielded the desired stereoisomer of diol 26, which was subsequently protected as isopropylidene acetal. In the next step, after removal of the TBS group and mesylation, attempted substitution with NaN3 resulted

Synthesis of α-D-GalpN₃-(1-3)-D-GalpN₃: α- and 3-O-selectivity using 3,4-diol acceptors

• Emil Glibstrup and
• Christian Marcus Pedersen

Beilstein J. Org. Chem. 2018, 14, 2805–2811, doi:10.3762/bjoc.14.258

• azido precursor has been studied and optimized in terms of steps, yields and selectivity. It has been found that glycosylation of the 3,4-diol acceptor is an advantage over the use of a 4-O-protected acceptor and that both regio- and anomeric selectivity is enhanced by bulky 6-O-protective groups. The

• synthesis, we realized that the synthesis of the α-D-GalpNAc-(1-3)-β-D-GalpNAc part worked more efficiently, when using the 3,4-diol acceptor instead of a fully protected 3-OH. As some protective group manipulations can be avoided and at the same time the yield and α-selectivity improved, we consider this

• nucleophilicity and accessibility of the axial 4-OH versus the equatorial 3-OH [40], we wondered, if this could be used to simplify the synthesis of the α-D-GalpN3-(1-3)-D-GalpN3 unit. When consulting the literature, surprisingly few reports were describing diol glycosylations targeting the galacto-configured

Unprecedented nucleophile-promoted 1,7-S or Se shift reactions under Pummerer reaction conditions of 4-alkenyl-3-sulfinylmethylpyrroles

• Takashi Go,
• Akane Morimatsu,
• Hiroaki Wasada,
• Genzoh Tanabe,
• Osamu Muraoka,
• Yoshiharu Sawada and
• Mitsuhiro Yoshimatsu

Beilstein J. Org. Chem. 2018, 14, 2722–2729, doi:10.3762/bjoc.14.250

• the sulfur atom. Bis(trifluoro)acetate 16 resulted from the opening of the ring is hydrolysed by TBAH to yield diol 17. Conversely, sterically hindered double bonds of 14 are not easily accessible to the sulfonium ion; therefore, the Pummerer intermediate α-thio carbenium ion 18 is generated through

• with p-methoxybenzenethiol/TBAH, which exclusively produced 9a (the diol 24a was not detected by ESI mass spectroscopy). A similar result was obtained from the reaction of 5a with p-chlorobenzenethiol/TBAH. These results support the hypothesis that the reaction proceeds via the initial formation of the

• key intermediate 15, of which the sulfanyl group would intramolecularly migrate to produce 16 stereoselectively (path c, not d). The hydrolysis of 16 using TBAH yields diol 17. We further confirmed the mechanism of the 1,7-S shift reaction by performing density functional theory (DFT)-based

Domino ring-opening–ring-closing enyne metathesis vs enyne metathesis of norbornene derivatives with alkynyl side chains. Construction of condensed polycarbocycles

• Ritabrata Datta and
• Subrata Ghosh

Beilstein J. Org. Chem. 2018, 14, 2708–2714, doi:10.3762/bjoc.14.248

• (G-II) was used. The norbornene derivative 7a was first chosen for investigating ROM–RCEYM. Compound 7a was prepared in the following way (Scheme 3). Reaction of the known lactol 5 [33] with propargyl magnesium bromide afforded the diol 6 in 88% yield (For detailed experimental procedures and

• characterization data see Supporting Information File 1). The stereochemical orientation of the secondary hydroxy group was determined through X-ray crystal structure of a compound derived from it in a subsequent step. The primary hydroxy group in the diol 6 was then selectively protected to provide the silyl

• retigeranic acids, the norbornene derivative 16 was chosen. Addition of lithium (trimethylsilyl)acetylide to the lactol 5 followed by desilylation by using methanolic K2CO3 afforded diol 15 (Scheme 4). The primary hydroxy group in compound 15 was selectively protected to produce the silyl ether 16 in 95

Synthesis of eunicellane-type bicycles embedding a 1,3-cyclohexadiene moiety

• Alex Frichert,
• Peter G. Jones and
• Thomas Lindel

Beilstein J. Org. Chem. 2018, 14, 2461–2467, doi:10.3762/bjoc.14.222

• The first synthesis of diterpenoid eunicellane skeletons incorporating a 1,3-cyclohexadiene moiety is presented. Key step is a low-valent titanium-induced pinacol cyclization that proved to be perfectly diastereoselective. Determination of the relative configuration of the diol was aided by the

• coupling to 16 and deprotection to 17 worked satisfyingly. As in the case of a benzene partial structure (8), it was a diol that was formed from 17 under McMurry conditions (20 equiv TiCl4, 40 equiv Zn, THF, rt). No alkene was detected. McMurry-type pinacol cyclizations have shown varying degrees of

• 18 to the acyloin (IBX, MeCN) and subsequent reduction (LiAlH4, THF, Scheme 2). Diastereomers 18 and 19 show distinct sets of NMR signals. The largest chemical shift differences are observed for the secondary carbinol group (δ2-H 5.18, δC2 73.1 for 18 vs δ2-H 4.14, δC2 87.2 for 19). For diol 18, we

Microfluidic light-driven synthesis of tetracyclic molecular architectures

• Javier Mateos,
• Nicholas Meneghini,
• Marcella Bonchio,
• Nadia Marino,
• Tommaso Carofiglio,
• Xavier Companyó and
• Luca Dell’Amico

Beilstein J. Org. Chem. 2018, 14, 2418–2424, doi:10.3762/bjoc.14.219

• manipulation involved the treatment of 4a with PhMgBr, converting the lactone moiety into the corresponding aromatic ketone. Product 8a formed in 71% yield without diastereoisomeric loss. Finally, LiAlH4 reduction of 4a furnished the bicyclic 1,3-diol 9a in quantitative yield, again without the need of

Stereoselective total synthesis and structural revision of the diacetylenic diol natural products strongylodiols H and I

• Pamarthi Gangadhar,
• Sayini Ramakrishna,
• Ponneri Venkateswarlu and
• Pabbaraja Srihari

Beilstein J. Org. Chem. 2018, 14, 2313–2320, doi:10.3762/bjoc.14.206

• the first enantioselective total synthesis of the two diacetylenic diol natural products strongylodiol H and strongylodiol I and of an enantiomer of strongylodiol H. Our synthesis assisted us to revise the structure of both natural products strongylodiol H and I. The synthetic procedure involved the

Investigation of the electrophilic reactivity of the biologically active marine sesquiterpenoid onchidal and model compounds

• Melissa M. Cadelis and
• Brent R. Copp

Beilstein J. Org. Chem. 2018, 14, 2229–2235, doi:10.3762/bjoc.14.197

• Z diester 21 (10%, Scheme 3). The reduction of diesters 20 (E) and 21 (Z) with LiAlH4 afforded diols 22 and 23 in 63% and 67% yield, respectively. Subsequent oxidation of 22 with DMP afforded dialdehyde 11 in 31% yield. Correspondingly, the reaction of diol 23 with DMP afforded a mixture of

D-Fructose-based spiro-fused PHOX ligands: synthesis and application in enantioselective allylic alkylation

• Michael R. Imrich,
• Jochen Kraft,
• Cäcilia Maichle-Mössmer and
• Thomas Ziegler

Beilstein J. Org. Chem. 2018, 14, 2082–2089, doi:10.3762/bjoc.14.182

• -fructose derivatives with different protective groups at position 3, 4 and 5 the hydroxy group of 6a was first protected to afford 6b. After removing the isopropylidene group, positions 4 and 5 of the resulting diol 7c were protected to afford 7d. A convenient method for constructing anomeric 2-oxazolines

Design, synthesis and structure of novel G-2 melamine-based dendrimers incorporating 4-(n-octyloxy)aniline as a peripheral unit

• Cristina Morar,
• Pedro Lameiras,
• Attila Bende,
• Gabriel Katona,
• Emese Gál and
• Mircea Darabantu

Beilstein J. Org. Chem. 2018, 14, 1704–1722, doi:10.3762/bjoc.14.145

• hindrance, starburst effect [18][58][59], against authentic free rotation upon heating. This fact was not quite surprising because we previously reported a related situation in the case of some G-0 dendrons as N,N’-disubstituted 2-chloro-4,6-diamino-s-triazines with bulky azaspirodecane and propane-1,3-diol

Heterogeneous acidic catalysts for the tetrahydropyranylation of alcohols and phenols in green ethereal solvents

• Ugo Azzena,
• Massimo Carraro,
• Gloria Modugno,
• Luisa Pisano and
• Luigi Urtis

Beilstein J. Org. Chem. 2018, 14, 1655–1659, doi:10.3762/bjoc.14.141

• alcohol 4fa in 78% yield (Scheme 4). Under similar conditions, protection of 1f in CPME, followed by filtration and dropwise addition of the resulting solution to a suspension of LiAlH4 in the same solvent, afforded the monoprotected diol 4fb in almost quantitative yield (Scheme 5). Conclusion The above