Synthesis of a tyrosinase inhibitor by consecutive ethenolysis and cross-metathesis of crude cashew nutshell liquid

• Jacqueline Pollini,
• Valentina Bragoni and
• Lukas J. Gooßen

Beilstein J. Org. Chem. 2018, 14, 2737–2744, doi:10.3762/bjoc.14.252

• subsequent hydrogenation step. Overall, the target compound was obtained in an overall yield of 61% based on the unsaturated anacardic acid content and 34% based on the crude CNSL. Keywords: cashew nutshell liquid; cross-metathesis; renewable feedstock; sustainable chemistry; tyrosinase inhibitor

• -hexene followed by a hydrogenation and thus, selectively obtain the target product 2-hydroxy-6-tridecylbenzoic acid (3). Results and Discussion Ethenolysis of crude CNSL After thorough optimization, we found that natural CNSL, a highly viscous brown oil, obtained by ether extraction of cashew nutshells

• single run. One-pot cross-metathesis/hydrogenation We next sought for suitable conditions that would allow the cross-metathesis of 2 with 1-hexene to give 2-hydroxy-6-(tridec-8-enyl)benzoic acid (5). When performing the hexenolysis of 2 with 7 equivalents of 1-hexene using 1 mol % of Ru-1 in

The design and synthesis of an antibacterial phenothiazine–siderophore conjugate

• Abed Tarapdar,
• James K. S. Norris,
• Oliver Sampson,
• Galina Mukamolova and
• James T. Hodgkinson

Beilstein J. Org. Chem. 2018, 14, 2646–2650, doi:10.3762/bjoc.14.242

• azotochelin. Catechol-based siderophores can act as xenosiderophores and be recognised for uptake by Gram-negative bacteria and mycobacteria [14][15]. Most commonly benzyl protecting groups are used in the synthesis of catechol siderophores and cleaved in the final step by palladium catalysed hydrogenation

• . However, as our final conjugate contains an aromatic halide we wanted to avoid hydrogenation as the final step and we instead chose to use the para-methoxybenzyl (PMB) protecting group which can be removed under acidic conditions. PMB-protected benzoic acid building block 7 was prepared following a

Synthesis of dihydroquinazolines from 2-aminobenzylamine: N³-aryl derivatives with electron-withdrawing groups

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

Beilstein J. Org. Chem. 2018, 14, 2510–2519, doi:10.3762/bjoc.14.227

• , some ruthenium complexes bearing a 3,4-dihydroquinazoline ligand have been studied as hydrogenation-transfer catalysts, showing good to excellent activity for the reduction of ketones [17]. In the context of our research on heterocyclic amidine N-oxides [18][19][20][21][22], we recently prepared some

Synthesis of a leopolic acid-inspired tetramic acid with antimicrobial activity against multidrug-resistant bacteria

• Luce Mattio,
• Loana Musso,
• Leonardo Scaglioni,
• Andrea Pinto,
• Piera Anna Martino and
• Sabrina Dallavalle

Beilstein J. Org. Chem. 2018, 14, 2482–2487, doi:10.3762/bjoc.14.224

• protect the oxygen at C-4 [15]. We selected a benzyl protecting group, as it could be cleaved by catalytic hydrogenation together with the benzyl ester of L-phenylalanine in the ureidodipeptide fragment (see synthesis of compound 20) by a one-pot reaction. To increase the reaction rate toward O-alkylation

• hand, we finally accomplished the N-acylation reaction using n-BuLi in THF at −60 °C [15] in 60% yield. Removal of both protecting groups by catalytic hydrogenation, gave the desired compound 1 in 72% yield (Scheme 3). Compound 1 was subjected to a preliminary study to evaluate the antimicrobial

Synergistic approach to polycycles through Suzuki–Miyaura cross coupling and metathesis as key steps

• Sambasivarao Kotha,
• Milind Meshram and
• Chandravathi Chakkapalli

Beilstein J. Org. Chem. 2018, 14, 2468–2481, doi:10.3762/bjoc.14.223

• %). Next, exposure of the diallyl derivative 73a to G-II catalyst 2 yielded the cyclized product 74 (72%). Eventually, hydrogenation of the RCM product 74 was achieved with H2, Pd/C conditions to give the saturated 2,3,4,5-tetrahydro-1-benzazepine 75 in 81% yield (Scheme 11). Naphthoxepine derivatives play

• %). Subsequently, hydrogenation of compounds 126 and 125 was accomplished with H2 under Pd/C catalysis conditions to afford the respective saturated macrocyclic products 127 (80%) and 128 (90%). Since the small ring cyclophane is highly strained, compound 125 was formed as a minor product (Scheme 19). Recently, Li

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

• ketoaldehyde precursor [11]. However, compound 8 proved to be very resistant towards any attempt of partial hydrogenation of the benzene moiety. Systems embedding a cyclohexadiene ring should be more versatile, e.g., by allowing regio- and stereoselective hydrogenation and oxygenation towards partial

Non-metal-templated approaches to bis(borane) derivatives of macrocyclic dibridgehead diphosphines via alkene metathesis

• Tobias Fiedler,
• Michał Barbasiewicz,
• Michael Stollenz and
• John A. Gladysz

Beilstein J. Org. Chem. 2018, 14, 2354–2365, doi:10.3762/bjoc.14.211

• -BuLi (4.4 equiv) and Br(CH2)6CH=CH2 (4.0 equiv) to afford the tetraalkenyl precursor (H2C=CH(CH2)6)2(H3B)P((CH2)14)P(BH3)((CH2)6CH=CH2)2 (11·2BH3; 18%). Alternative approaches to 11·2BH3 (e.g., via 11) were unsuccessful. An analogous metathesis/hydrogenation/chromatography sequence with 11·2BH3 (0.0010

• ; crystal structures; homeomorphic isomerization; hydrogenation; in/out isomers; metathesis; phosphine boranes; Introduction We have found that a variety of metal complexes with trans-phosphine ligands of the formula P((CH2)mCH=CH2)3 (1; m = 4–14) undergo threefold interligand ring closing alkene

• , reactions of 12 and H3B·SMe2 (2.1 equiv) afforded only insoluble material. Thus, despite the low yield of the final step in Scheme 3, reasonable quantities of the diphosphine diborane 11·2BH3 could be stockpiled. As shown in Scheme 5, 11·2BH3 was subjected to a metathesis/hydrogenation/column chromatography

A novel and practical asymmetric synthesis of eptazocine hydrobromide

• Ruipeng Li,
• Zhenren Liu,
• Liang Chen,
• Jing Pan,
• Kuaile Lin and
• Weicheng Zhou

Beilstein J. Org. Chem. 2018, 14, 2340–2347, doi:10.3762/bjoc.14.209

• purity. With purified 4 in hand, the next step was the reduction. When compound 4 was reduced by catalytic hydrogenation at 0.4 MPa in the presence of Raney-Ni as catalyst in NH3/CH3OH, compounds 9 and 10 were formed as the main products instead of the expected compound 5. When the solvent NH3/CH3OH was

• ) using the conditions in entry 9 and a similar yield was obtained (Table 2, entry 11). When cyano compound 12 was reduced by hydrogenation in the presence of Raney-Ni as catalyst in NH3/CH3OH, the proposed primary amine 13 was obtained in 73% yield. Then, for the Mannich cyclization, when 13 was reacted

• improved the reaction yield (Table 3, entries 4 and 5). The reductive methylation of 14 under Eschweiler–Clarke conditions (HCOOH/formalin/reflux) furnished 15 in quantitative yield. The latter was reduced by NaBH4 in methanol at room temperature, and then dehydration and hydrogenation with H2/Pd/C in

Cobalt bis(acetylacetonate)–tert-butyl hydroperoxide–triethylsilane: a general reagent combination for the Markovnikov-selective hydrofunctionalization of alkenes by hydrogen atom transfer

• Xiaoshen Ma and
• Seth B. Herzon

Beilstein J. Org. Chem. 2018, 14, 2259–2265, doi:10.3762/bjoc.14.201

• reagent combination suggests it as a useful starting point to develop HAT reactions in complex settings. Keywords: HAT; hydrogen atom transfer; hydrofunctionalization; Introduction Many powerful methods to effect alkene hydrogenation [1][2][3][4] and Markovnikov-selective hydroheterofunctionalization (H

A general and atom-efficient continuous-flow approach to prepare amines, amides and imines via reactive N-chloramines

• Katherine E. Jolley,
• Michael R. Chapman and
• A. John Blacker

Beilstein J. Org. Chem. 2018, 14, 2220–2228, doi:10.3762/bjoc.14.196

• use of heated CSTRs would be useful to explore. The formation of both imines 20 and 21 are of interest as an asymmetric reduction would give an optically pure amine. To demonstrate this, imine 20, formed in situ, underwent asymmetric-transfer hydrogenation in both batch and flow modes, using [IrCp*Cl2

• imines reported within our study. Of these examples, the latter was further explored by immediate asymmetric-transfer hydrogenation of an in situ formed imine under continuous-flow conditions, as a potentially productive route to chiral amines. Continuous-flow process to produce and react N-chloramines

• . Left: Laboratory scale CSTR developed by our group [8]. Right: 5-stage CSTR configuration using co-feeds of amine in toluene and aqueous NaOCl. Continuous-flow amide 18 formation using 1-stage CSTR. Blue squares: FeCl3 included; red circles: FeCl3 not included. Continuous-flow transfer hydrogenation 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

• efficient catalysts in various asymmetric reactions, for instance allylic substitution and enantioselective hydrogenation [9]. They were also applied in the stereoselective synthesis of complex natural products [10][11][12]. PHOX ligands are nonsymmetrical ligands which can coordinate to a metal center

Diazirine-functionalized mannosides for photoaffinity labeling: trouble with FimH

• Femke Beiroth,
• Tomas Koudelka,
• Thorsten Overath,
• Stefan D. Knight,
• Andreas Tholey and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2018, 14, 1890–1900, doi:10.3762/bjoc.14.163

• from p-nitrophenyl α-D-mannopyranoside (1), which was first reduced to the corresponding amine 6 [26][27] by catalytic hydrogenation (Scheme 1). HATU-mediated peptide coupling with Boc-protected glycine under basic conditions led to 7. After removal of the Boc protecting group using trifluoroacetic

An amine protecting group deprotectable under nearly neutral oxidative conditions

• Shahien Shahsavari,
• Chase McNamara,
• Mark Sylvester,
• Emily Bromley,
• Savannah Joslin,
• Bao-Yuan Lu and
• Shiyue Fang

Beilstein J. Org. Chem. 2018, 14, 1750–1757, doi:10.3762/bjoc.14.149

• groups for the purpose mainly include those deprotectable by acid (e.g., tert-butyloxycarbonyl (Boc) group) [2][3][4], base (e.g., 9-fluorenylmethyloxycarbonyl (Fmoc) group and trifluoroacetyl group) [5][6][7], catalytic hydrogenation (e.g., benzyl group) [8], photoirradiation (e.g., 2-nitrophenylethyl

• arylamines. This group could be removed under nearly neutral oxidative conditions, which are orthogonal to the commonly used conditions for deprotection of protected amines including acid, base, and catalytic hydrogenation. Compared to Dmoc, dM-Dmoc has the advantage of being stable under a wide range of

Mild and selective reduction of aldehydes utilising sodium dithionite under flow conditions

• Nicole C. Neyt and
• Darren L. Riley

Beilstein J. Org. Chem. 2018, 14, 1529–1536, doi:10.3762/bjoc.14.129

• reduction utilizing solid mixes of sodium borohydride, lithium chloride and celite [12], and the Ley group were able to demonstrate a green transfer hydrogenation of ketones under flow using catalytic lithium tert-butoxide in isopropanol [13]. We recently published a batch–flow hybrid synthesis of the

Spectroelectrochemical studies on the effect of cations in the alkaline glycerol oxidation reaction over carbon nanotube-supported Pd nanoparticles

• Dennis Hiltrop,
• Steffen Cychy,
• Karina Elumeeva,
• Wolfgang Schuhmann and
• Martin Muhler

Beilstein J. Org. Chem. 2018, 14, 1428–1435, doi:10.3762/bjoc.14.120

• activity relation is in good agreement with studies applying these catalysts in ethanol electrooxidation and olefin hydrogenation [34][35]. Analogous CV experiments were also carried out in NaOH and the obtained CVs are shown in Figure 2. The current densities recorded for Pd/OCNT are significantly lower

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

• reaction in the following order: phase-transfer catalysis, Henry reaction, Suzuki–Miyaura cross-coupling and Tsuji–Trost allylic substitution, hydrogenation, Michael addition, aldol and multicomponent Biginelli reactions, epoxidation, Meerwein−Ponndorf−Verley reduction, aza-Diels−Alder and epoxide ring

• selectivity was the chiral oxazoline unit and not the inherent chirality of calixarene skeleton. Asymmetric hydrogenation Starting with distally O-dialkylated calixarene precursors, a series of BINOL-derived calix[4]arene-diphosphite ligands 40a–g were synthesized by Liu and Sandoval through phosphorylation

• efficient ligands in asymmetric catalytic reactions, the Rh-catalyzed asymmetric hydrogenation of methyl acetamidoacrylate (41a) and the corresponding cinnamate (41b) was evaluated in the presence of ligands 40a–g (Scheme 11). The active catalyst was readily prepared in situ by mixing Rh(COD)2BF4 and

Oligonucleotide analogues with cationic backbone linkages

• Melissa Meng and
• Christian Ducho

Beilstein J. Org. Chem. 2018, 14, 1293–1308, doi:10.3762/bjoc.14.111

• route using Wittig–Horner olefination and catalytic asymmetric hydrogenation as key steps (reactions not shown) [86][87][90][91][92]. Using 'dimeric' building blocks (S)-49, (R)-49, (S)-50, and (R)-50 (Scheme 5), automated DNA synthesis under standard conditions enabled the preparation of partially

• peptide synthesis using the monomeric 3'-amino-nucleosyl amino acids (S)-56 and (R)-56, respectively, as building blocks. The synthesis of thymidinyl amino acids 56 was again started from a corresponding 5'-aldehyde 57 using Wittig–Horner olefination and catalytic asymmetric hydrogenation as key steps

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

• -bromo-6-hydroxylamino-2,3-benzotropone oximes 262 were obtained. Hydrolysis of these oximes 262 with sulfuric acid gave 5-bromo-6-hydroxy-2,3-benzotropone and the 4-bromo isomer 263, which were debrominated with catalytic hydrogenation to give 239 (Scheme 41). Although 239 is capable of existing as two

• of azo, nitro, and amino derivatives of 6-hydroxy-2,3-benzotropone (239) (Scheme 42) [164]. While 7-amino derivative 264 was prepared via diazo coupling of 239 with diazotized p-toluidine in a pyridine solution followed by hydrogenation, the nitration of 239 in acetic acid solution afforded nitro

• ) [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

Synthetic avenues towards a tetrasaccharide related to Streptococcus pneumonia of serotype 6A

• Aritra Chaudhury,
• Mana Mohan Mukherjee and
• Rina Ghosh

Beilstein J. Org. Chem. 2018, 14, 1095–1102, doi:10.3762/bjoc.14.95

• conditions [41], followed by hydrogenation with H2/Pd-C in EtOH/EtOAc/AcOH solvent to give the deprotected tetrasaccharide 23 in 85% yield over two steps. 1H NMR in D2O of the target tetrasaccharide 23 showed the anomeric protons of the galactose, glucose, and rhamnose residues from the non-reducing end

The first Pd-catalyzed Buchwald–Hartwig aminations at C-2 or C-4 in the estrone series

• Ildikó Bacsa,
• Dávid Szemerédi,
• János Wölfling,
• Gyula Schneider,
• Lilla Fekete and
• Erzsébet Mernyák

Beilstein J. Org. Chem. 2018, 14, 998–1003, doi:10.3762/bjoc.14.85

• several aminated steroids in the literature, but the efficient generation of a C(sp2)–N bond on the aromatic ring A of estrone derivatives still remains a challenge. Aminoestrones substituted at C-2 or C-4 are mainly produced by the reduction or hydrogenation of the corresponding nitro derivatives [5

Recent advances in synthetic approaches for medicinal chemistry of C-nucleosides

• Kartik Temburnikar and
• Katherine L. Seley-Radtke

Beilstein J. Org. Chem. 2018, 14, 772–785, doi:10.3762/bjoc.14.65

• (compound 23) is shown in Figure 9, which involves installing an allyl group at C1' (20) and converting the C2'–CN to an aldehyde (21) followed by a Wittig reaction to install a second allyl group at C2' (22). Second generation Grubb’s catalyst was used for the ring formation, followed by hydrogenation to

• reaction gave the unsaturated compounds (47 and 48), which, upon hydrogenation in presence of Crabtree’s catalyst, gave the saturated compounds with the desired diasteroselectivity (49 and 50). In the case of nitrogen containing heterocycles, Pd(OH)2 was found to be a suitable catalyst that gave a

• hydrogenation afforded the optically pure carbocyclic tubercidine analogue (−)-53. This compound has shown potent activity against breast cancer cell lines and human foreskin fibroblasts [53]. Conclusion With increasing reports of emerging and reemerging infectious diseases globally, there is a need to develop

Nanoreactors for green catalysis

• M. Teresa De Martino,
• Loai K. E. A. Abdelmohsen,
• Floris P. J. T. Rutjes and
• Jan C. M. van Hest

Beilstein J. Org. Chem. 2018, 14, 716–733, doi:10.3762/bjoc.14.61

• reactions [95][97]. The first successful attempt was reported by Chung and Rhee, in which they showed the encapsulation of a bimetallic Pt–Pd catalyst in a highly branched PMAM-OH dendrimer corona [93]. These catalytic dendrimers were employed in partial hydrogenation of 1,3-cyclooctadiene into cyclooctene

• . The utility of these dendrimers in hydrogenation reactions resulted in efficient reactions that proceeded with unprecedented selectivity of 99%. Moreover, this system is one of the first of bimetallic catalytic systems to be used for hydrogenation reactions in water. Water soluble dendrimer-stabilized

• nanoparticles (DSN) have been shown to be highly efficient in the catalysis of olefin hydrogenation and in Suzuki coupling reactions [98][99]. Ornelas et al. entrapped a palladium catalyst with dendrimers containing triazole groups (DSN) (Figure 6) [100]. The aim here was to provide a platform to perform

Heterogeneous Pd catalysts as emulsifiers in Pickering emulsions for integrated multistep synthesis in flow chemistry

• Katharina Hiebler,
• Georg J. Lichtenegger,
• Manuel C. Maier,
• Eun Sung Park,
• Renie Gonzales-Groom,
• Bernard P. Binks and
• Heidrun Gruber-Woelfler

Beilstein J. Org. Chem. 2018, 14, 648–658, doi:10.3762/bjoc.14.52

• interface populated by catalyst particles. They deposited metallic Pd onto carbon nanotube–inorganic oxide hybrid nanoparticles and used them in emulsions for the hydrodeoxygenation of a phenolic compound and the hydrogenation and etherification of an aldehyde. The advantages of such a system include a high

High-yielding continuous-flow synthesis of antimalarial drug hydroxychloroquine

• Eric Yu,
• Hari P. R. Mangunuru,
• Nakul S. Telang,
• Caleb J. Kong,
• Jenson Verghese,
• Stanley E. Gilliland III,
• Saeed Ahmad,
• Raymond N. Dominey and
• B. Frank Gupton

Beilstein J. Org. Chem. 2018, 14, 583–592, doi:10.3762/bjoc.14.45

• chemistry; hydrogenation; hydroiodic acid; hydroxychloroquine; Introduction Our research group has been focused on the development of new synthetic methods for the preparation of a variety of active pharmaceutical ingredients for global health applications by employing the principles of process

• ). Continuous flow hydrogenation was performed using a FlowCAT instrument. Synthesis of 5-iodopentan-2-one (10) Two solutions, 2-acetylbutyrolactone (8, 1.176 mL, 10.35 mmol, 1.0 equiv) and hydroiodic acid (55% aqueous solution) were pumped at 1.0 mL min−1 using peristaltic pumps through a 10 mL coil

An alternative to hydrogenation processes. Electrocatalytic hydrogenation of benzophenone

• Cristina Mozo Mulero,
• Alfonso Sáez,
• Jesús Iniesta and
• Vicente Montiel

Beilstein J. Org. Chem. 2018, 14, 537–546, doi:10.3762/bjoc.14.40

• Cristina Mozo Mulero Alfonso Saez Jesus Iniesta Vicente Montiel Instituto de Electroquímica, Universidad de Alicante, Apartado 99, 03080 Alicante, Spain 10.3762/bjoc.14.40 Abstract The electrocatalytic hydrogenation of benzophenone was performed at room temperature and atmospheric pressure using

• electrochemically hydrogenated in EtOH/water (90/10 v/v) plus 0.1 M H2SO4. Current densities of 10, 15 and 20 mA cm−2 were analysed for the preparative electrochemical hydrogenation of benzophenone and such results led to the highest fractional conversion (XR) of around 30% and a selectivity over 90% for the

• synthesis of diphenylmethanol upon the lowest current density. With regards to an increase by ten times the Pd electrocatalytic loading the electrocatalytic hydrogenation led neither to an increase in fractional conversion nor to a change in selectivity. Keywords: benzophenone; diphenylmethanol