Recent applications of chiral calixarenes in asymmetric catalysis

• Mustafa Durmaz,
• Erkan Halay and
• Selahattin Bozkurt

Beilstein J. Org. Chem. 2018, 14, 1389–1412, doi:10.3762/bjoc.14.117

• to the noncovalent interactions, aluminum complexes of calixarene diphosphites 118a–e were synthesized via lower-rim functionalization of the p-tert-butylcalix[4]arene core with axially chiral diol ligands 117 (Scheme 37). The asymmetric MPV reduction of various substituted acetophenones were

Synthesis of chiral 3-substituted 3-amino-2-oxindoles through enantioselective catalytic nucleophilic additions to isatin imines

• Hélène Pellissier

Beilstein J. Org. Chem. 2018, 14, 1349–1369, doi:10.3762/bjoc.14.114

• asymmetric formal [3 + 2] annulation reaction between N-Boc-isatin imines 3 and 1,4-dithiane-2,5-diol (53) as equal equivalent of 2-mercaptoacetaldehyde [78]. The domino reaction catalyzed by chiral tertiary amine-squaramide catalyst 54 began with the addition of 2-mercaptoacetaldehyde to isatin imine 3

• cinchona alkaloid-derived thiourea. Aza-Henry reaction of N-Boc-isatin imines with nitromethane catalyzed by a bifunctional guanidine. Domino addition/cyclization reaction of N-Boc-isatin imines with 1,4-dithiane-2,5-diol (53) catalyzed by a tertiary amine-squaramide. Nickel-catalyzed additions of methanol

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

• pseudo-high-dilution conditions to afford 20 and 21 as described previously [16]. Then the diol was transformed into the epoxide following a three-step one-pot reaction as extensively used in the synthesis of cryptophycin analogues [46]. Cryptophycin analogues 22 and 23 were obtained in good purity after

Rapid transformation of sulfinate salts into sulfonates promoted by a hypervalent iodine(III) reagent

• Elsa Deruer,
• Vincent Hamel,
• Samuel Blais and
• Sylvain Canesi

Beilstein J. Org. Chem. 2018, 14, 1203–1207, doi:10.3762/bjoc.14.101

• diol derivative containing a linear chain in only one step. One alcohol is available as a leaving group and the second is protected by conversion into a trichloroacetate moiety (Scheme 4). Conclusion A novel oxidative method for producing sulfonates from sulfinates using hypervalent iodine reagents has

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

• synthesis of 7-hydroxy-2,3-benzotropone (241) was successfully realized by Dastan’s group (Scheme 47) [149]. Thiourea reduction of the peroxide linkage of 213 to the diol 282 and then simultaneously dehydration in situ gave the corresponding benzotropolone 241 in nearly quantitative yield. Recently, Arican

• ) [174]. Catalytic hydrogenation of 241 over Adams's catalyst (PtO2.H2) gave the diol 295 (Scheme 49) [162][165][174]. Treatment of 241 with alkaline hydrogen peroxide caused degradative fission to give o-carboxycinnamic acid (296) [165], while nitration of 241 with nitric acid in an acetic acid solution

• were catalyzed by NaOH. 5.4.2. Reaction of 4-hydroxy-2,3-benzotropone (174): The structure of 174 was confirmed by the reduction of both benzotropolone 174 and diketone 300 into the diol 305 with catalytic hydrogenation (Scheme 51) [178]. 6. Halobenzotropones 6.1. Monohalobenzotropones 6.1.1. One-step

Phosphodiester models for cleavage of nucleic acids

• Satu Mikkola,
• Tuomas Lönnberg and
• Harri Lönnberg

Beilstein J. Org. Chem. 2018, 14, 803–837, doi:10.3762/bjoc.14.68

Enzyme-free genetic copying of DNA and RNA sequences

• Marilyne Sosson and
• Clemens Richert

Beilstein J. Org. Chem. 2018, 14, 603–617, doi:10.3762/bjoc.14.47

• constants had to be determined. Among the rate constants was that for the hydrolysis of activated monomers. Hydrolysis was expected to be fast for highly reactive monomers, and the reactivity toward water was expected to be similar to the reactivity toward the terminal diol of an RNA primer, so hydrolysis

• not outcompete the monomer over time, and the reaction will largely proceed as expected for a second-order reaction with a competing reaction that just drains active monomer (hydrolysis). In the third case the primer is fairly unreactive, being equipped with just the terminal diol of natural RNA

• extension occurs as expected, most probably via addition/elimination, including a pentavalent intermediate and possibly by a pseudorotation to place the ethylimidazole leaving group in an apical position. Since either of the two alcohols of the terminal diol of the primer can attack, a mixture of 3',5'- and

Electrochemical Corey–Winter reaction. Reduction of thiocarbonates in aqueous methanol media and application to the synthesis of a naturally occurring α-pyrone

• Ernesto Emmanuel López-López,
• José Alvano Pérez-Bautista,
• Fernando Sartillo-Piscil and
• Bernardo A. Frontana-Uribe

Beilstein J. Org. Chem. 2018, 14, 547–552, doi:10.3762/bjoc.14.41

• 6 was prepared in two steps from pyrone dioxolane 7 [7]. Acid hydrolysis of 7 to 1,2-diol 8 followed by the reaction with 1,1’-thiocarbonyldiimidazole afforded thiocarbonate precursor 6 in high overall yield (Scheme 3). Compounds 6 and 8 were prepared in a similar manner as described in reference [7

Synthetic and semi-synthetic approaches to unprotected N-glycan oxazolines

• Antony J. Fairbanks

Beilstein J. Org. Chem. 2018, 14, 416–429, doi:10.3762/bjoc.14.30

• key Manβ(1–4)GlcNAc disaccharide both the 3- and 6-hydroxy groups of the mannose residue were deprotected, and the resulting diol underwent a double glycosylation with a selectively protected trichloroacetimidate donor. An added advantaged of approaches that use total synthesis is the possibility of

5-Aminopyrazole as precursor in design and synthesis of fused pyrazoloazines

• Ranjana Aggarwal and
• Suresh Kumar

Beilstein J. Org. Chem. 2018, 14, 203–242, doi:10.3762/bjoc.14.15

• equimolar amount of trifluoromethyl-β-diketones 17. To gain an insight of the reaction mechanism, the intermediate, 5-methyl-3-phenyl-7-trifluoromethyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-5,7-diol 125 was isolated by performing the reaction in DCM at −15 °C for 6 h which was later converted to 7

Gram-scale preparation of negative-type liquid crystals with a CF₂CF₂-carbocycle unit via an improved short-step synthetic protocol

• Tatsuya Kumon,
• Shohei Hashishita,
• Takumi Kida,
• Shigeyuki Yamada,
• Takashi Ishihara and
• Tsutomu Konno

Beilstein J. Org. Chem. 2018, 14, 148–154, doi:10.3762/bjoc.14.10

• the multicyclic mesogens 1 and 2 containing a CF2CF2 carbocycle which is shown in Scheme 1. The desired multicyclic molecules 1 with a tetrafluorocyclohexadiene or 2 with a tetrafluorocyclohexane moiety could be prepared starting from the same precursor, e.g., tetrafluorocyclohexane-1,4-diol 3

• : through dehydration in the case of 1 or radical reduction through the corresponding bisxanthate derivative in the case of 2. The required diol 3 could be obtained through a simultaneous hydrogenation of both, the cyclohexene and vinyl moieties of 1-aryl-4-vinyl-5,5,6,6-tetrafluorocyclohex-2-ene-1,4-diol 4

• compound 4a in hand, the successive hydrogenation in the presence of 20 mol % of Pd/C in methanol was performed for 1 d and generated the corresponding tetrafluorinated cyclohexane-1,4-diol 3a in quantitative yield. Compound 3a could be converted to the cyclohexadiene 1a in 82% isolated yield under the

Aminosugar-based immunomodulator lipid A: synthetic approaches

• Alla Zamyatina

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

• reductive opening of benzylidene acetal using the borane−THF complex in the presence of Bu2BOTf. Regioselective TMSOTf-catalysed glycosylation of the diol 4 by the imidate donor 3 resulted in the formation of a single product, the β(1→6)-linked disaccharide 5. After the 2’-N-Fmoc group in 5 was removed with

• isopropylidene group furnished diol 13. Regioselective boron trifluoride diethyl etherate-promoted glycosylation of the 6-OH group in 13 with Kdo-fluoride donor 14 afforded an inseparable mixture of α- and β-anomeric products (α/β = 9:1) [78]. Phosphitylation of the remaining OH group in position 4’ and facile

Quinone-catalyzed oxidative deformylation: synthesis of imines from amino alcohols

• Xinyun Liu,
• Johnny H. Phan,
• Benjamin J. Haugeberg,
• Shrikant S. Londhe and
• Michael D. Clift

Beilstein J. Org. Chem. 2017, 13, 2895–2901, doi:10.3762/bjoc.13.282

• with para-anisidine, to deliver imine 7a. Vicinal diamine 8 was also a compatible substrate, delivering imine 7a in 63% yield. Finally, we subjected diol 9 to the optimal reaction conditions; no product was observed, indicating that condensation between the substrate and catalyst to form an

Acid-catalyzed ring-opening reactions of a cyclopropanated 3-aza-2-oxabicyclo[2.2.1]hept-5-ene with alcohols

• Katrina Tait,
• Alysia Horvath,
• Nicolas Blanchard and
• William Tam

Beilstein J. Org. Chem. 2017, 13, 2888–2894, doi:10.3762/bjoc.13.281

• includes the reduction to form alkane 8 [3], oxidative cleavage of the C=C bond to form 9 [4], ring-opening metathesis to form functionalized alkenes 10 and 11 [4], dihydroxylation to form diol 12 [5], ruthenium-catalyzed [2 + 2] cycloaddition with unsymmetrical alkynes to form regioisomers 13 and 14 [6

The synthesis of the 2,3-difluorobutan-1,4-diol diastereomers

• Robert Szpera,
• Nadia Kovalenko,
• Kalaiselvi Natarajan,
• Nina Paillard and
• Bruno Linclau

Beilstein J. Org. Chem. 2017, 13, 2883–2887, doi:10.3762/bjoc.13.280

• substituents is of interest. Here we describe optimisation efforts in the synthesis of anti-2,3-difluorobutane-1,4-diol, as well as the synthesis of the corresponding syn-diastereomer. Both targets were synthesised using an epoxide opening strategy. Keywords: acetal isomerization; deoxyfluorination; epoxide

• -difluorobutane-1,4-diol (anti-5) starting from commercially available cis-but-2-ene-1,4-diol (Scheme 1) [17]. The vicinal-difluoride group was introduced by a two-step sequence, with initial nucleophilic epoxide [18] opening by a fluoride source [19], followed by nucleophilic deoxyfluorination [9][10][11]. In

• -step process was only moderate (30%). Synthesis of (±)-syn-5 The synthesis of (±)-syn-5 (Scheme 5) was achieved starting from the trans-configured but-2-ene-1,4-diol (1), which is not commercially available in geometrically pure form. Hence, according to literature procedures, reduction of 1,4

Fluorination of some highly functionalized cycloalkanes: chemoselectivity and substrate dependence

• Attila Márió Remete,
• Melinda Nonn,
• Santos Fustero,
• Matti Haukka,
• Ferenc Fülöp and
• Loránd Kiss

Beilstein J. Org. Chem. 2017, 13, 2364–2371, doi:10.3762/bjoc.13.233

• -amino ester stereo- and regioisomers, derived from unsaturated cyclic β-amino acids is described. The nucleophilic fluorinations involving hydroxy–fluorine exchange of some highly functionalized alicyclic diol derivatives have been carried out in view of selective fluorination, investigating substrate

• . Results and Discussion Our aim in this study was to explore the chemical behavior of some alicyclic, highly functionalized vicinal diol derivatives (accordingly possessing two fluorine precursor moieties in their structures) under fluorination protocols. During the past two decades multifunctionalized

• various solvents (e.g., PhMe, THF, and CH2Cl2) at different temperatures. Hereby Deoxofluor in CH2Cl2 with or without adding DBU was found to be the most suitable reagent. The diol derivatives, obviously, are expected to deliver the corresponding difluorinated products. In spite of this anticipation, the

Synthesis of ergostane-type brassinosteroids with modifications in ring A

• Vladimir N. Zhabinskii,
• Darya A. Osiyuk,
• Yuri V. Ermolovich,
• Natalia M. Chaschina,
• Tatsiana S. Dalidovich,
• Miroslav Strnad and
• Vladimir A. Khripach

Beilstein J. Org. Chem. 2017, 13, 2326–2331, doi:10.3762/bjoc.13.229

• biosynthetic precursors/metabolites differing by the ring A fragment. The protocol is based on the use of readily available phytohormones of this class bearing a 2α,3α-diol moiety (epibrassinolide or epicastasterone) as starting materials. The required functionalities (Δ2-, 2α,3α- and 2β,3β-epoxy-, 2α,3β-, 2β

• ; metabolites; Introduction The group of steroid plant hormones called brassinosteroids (BS) currently comprises about 70 compounds [1]. It is generally accepted that only few of them (such as brassinolide, castasterone, epibrassinolide, etc.), possessing 2α,3α-, (22R,23R)-diol groups, B-lactone, and 6-ketone

• preparation of a set of minor ergostane-type BS bearing A-ring structural units 3–12 (Scheme 1). The required functionalities were thought to be realized via a relatively short synthetic route starting from 2α,3α-diol fragment 13 of epicastasterone (1) or epibrassinolide (2). Results and Discussion Δ2

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

• in diol 2 is not possible. Thus we decided to differentiate the terminal positions in the stage of higher sugar 1. The replacement of the hydroxy group at the C12-position with an azide, accomplished successfully under Mistunobu conditions, afforded azide 4 in 95% yield (Scheme 1). The crucial step

Preactivation-based chemoselective glycosylations: A powerful strategy for oligosaccharide assembly

• Weizhun Yang,
• Bo Yang,
• Sherif Ramadan and
• Xuefei Huang

Beilstein J. Org. Chem. 2017, 13, 2094–2114, doi:10.3762/bjoc.13.207

• + 110 + 110 + 110 + 113) successfully produced protected Galf30 30-mer 114 in 68% yield (Scheme 19b). Following similar reaction protocols, Araf31 was prepared, which upon glycosylation of a Galf30 diol acceptor and deprotection, led to arabinogalactan 92-mer 116 (Figure 4) [62]. This is the largest

Enzymatic separation of epimeric 4-C-hydroxymethylated furanosugars: Synthesis of bicyclic nucleosides

• Neha Rana,
• Manish Kumar,
• Vinod Khatri,
• Jyotirmoy Maity and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2017, 13, 2078–2086, doi:10.3762/bjoc.13.205

• -isopropylidene-α-D-ribofuranose (3a) can be obtained from D-glucose via diacetonylation followed by selective deprotection of 5,6-isopropylidene protection, sodium periodate oxidation of the vicinal diol and mixed aldol–Cannizaro reaction on the resulted aldehyde 2. However, this methodology always leads to the

Intramolecular glycosylation

• Xiao G. Jia and
• Alexei V. Demchenko

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

• succinoyl group at C-2 was coupled to the diol galactosyl acceptor 6 in the presence of DCC and DMAP. The resulting tether compound 7 was obtained in 63% yield. The intramolecular glycosylation of the latter gave cyclic compound 8 in 76% yield, which was sequentially deacylated and per-benzoylated to afford

• intermediate, thereby circumventing the formation of the cyclized product [91]. This was achieved by protecting the 3,4-trans-diol with a cyclic bis-ketal. Primary aliphatic alcohols underwent glycosylation very readily with donor 65 affording glycosides in excellent yields with high β-selectivity (>1:32

• ]. Arylboronic esters have recently been probed by Toshima and co-workers as a successful linkage for the IAD method [109]. The arylboronic sugar derivatives, such as 79, can be easily obtained from the corresponding 4,6-diol 78 and a arylboronic acid in toluene at reflux (Scheme 19). Boronic ester 79 was then

Remarkable functions of sn-3 hydroxy and phosphocholine groups in 1,2-diacyl-sn-glycerolipids to induce clockwise (+)-helicity around the 1,2-diacyl moiety: Evidence from conformation analysis by ¹H NMR spectroscopy

• Yoshihiro Nishida,
• Mengfei Yuan,
• Kazuo Fukuda,
• Kaito Fujisawa,
• Hirofumi Dohi and
• Hirotaka Uzawa

Beilstein J. Org. Chem. 2017, 13, 1999–2009, doi:10.3762/bjoc.13.196

• conformational properties of a series of 1,2-dibenzoyl-sn-glycerols bearing different sn-3 substituting groups were examined. As shown in Figure 1, gt(+) is one of the gauche conformers with a right-handed (+)-helicity around 1,2-diol, while gg(−) is another gauche conformer with an antipodal left-handed

The chemistry and biology of mycolactones

• Matthias Gehringer and
• Karl-Heinz Altmann

Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159

• family known to date. A structure was proposed by the Small group based on mass fragmentation and 1H/2D NMR spectroscopic data. This structure, which features a tetraenoate (lower) side chain with a terminal 1,3-diol motif was once again confirmed by total synthesis in the Kishi laboratory; the relative

• and absolute stereochemistry of the compound was assigned by NMR in conjunction with HPLC on a chiral stationary phase [59]. Of note, the stereochemistry of the 1,3-diol motif of the polyunsaturated side chain of mycolactone F (8) is antipodal to the same motif in all other natural mycolactones with

• known configuration. Intriguingly, salt water fish-infesting M. marinum produces a remote diastereomer [60] of mycolactone F (dia-mycolactone F, 9) that exhibits the regular configuration of the 1,3-diol motif at the end of the lower side chain [61]. Most recently, the Kishi laboratory isolated two new

Effect of uridine protecting groups on the diastereoselectivity of uridine-derived aldehyde 5’-alkynylation

• Raja Ben Othman,
• Mickaël J. Fer,
• Laurent Le Corre,
• Sandrine Calvet-Vitale and
• Christine Gravier-Pelletier

Beilstein J. Org. Chem. 2017, 13, 1533–1541, doi:10.3762/bjoc.13.153

• of the uracile. Our results show that while the N-3 protection has little influence on the alkynylation diastereoselectivity, the nature of the diol protecting group strongly impact the diastereoselective outcome of the reaction. Indeed, whatever the ketal group used, the major 5’R-isomer is obtained

• with a 2:1 ratio whereas the protection as silyl ethers leads to an inverse diastereoselectivity in favor of the 5’S-isomer. We propose stereochemical models to rationalize the observed diastereoselectivity. Furthermore by increasing the bulkiness of the silyl group both on the diol and the Grignard

Total synthesis of elansolids B1 and B2

• Liang-Liang Wang and
• Andreas Kirschning

Beilstein J. Org. Chem. 2017, 13, 1280–1287, doi:10.3762/bjoc.13.124

• this temperature and the reaction was terminated by addition of a saturated bicarbonate solution. The aqueous solution was extracted with Et2O for three times. The combined organic phases were dried over Na2SO4, filtered and concentrated under reduced pressure to afford the corresponding diol suitably

• pure for directly being employed in the next step. An aqueous solution of LiOH (1 M, 0.3 mL, 107 equiv) was added to crude diol in iPrOH (0.3 mL) and THF (0.3 mL) at room temperature. After stirring for 5 h, the reaction was terminated by slowly adding HCl (1 N, 0.24 mL), phosphate buffer (pH 7, 0.1 mL

• (1 M, 0.3 mL, 107 equiv) was added to the crude diol (3.1 µmol) described for the synthesis of elansolid B1 (2) in MeOH (0.3 mL) and THF (0.3 mL) at room temperature. After stirring for 5 h, the reaction was terminated by slowly adding HCl (1 N, 0.24 mL), phosphate buffer (pH 7, 0.1 mL) and MeOH (0.3