A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

• authors screened several other 3D printed reactors evaluating materials (PTFE, PLA or Nylon), volumes (1 or 10 mL), and channel shape (circular, square, or rectangular). The process was then merged with a hydrogenation step using the H-Cube® apparatus (Pd/C, 30 °C, 15 bar) for the continuous preparation

Recent advances in palladium-catalysed asymmetric 1,4–additions of arylboronic acids to conjugated enones and chromones

• Jan Bartáček,
• Jan Svoboda,
• Martin Kocúrik,
• Jaroslav Pochobradský,
• Alexander Čegan,
• Miloš Sedlák and
• Jiří Váňa

Beilstein J. Org. Chem. 2021, 17, 1048–1085, doi:10.3762/bjoc.17.84

• Minnaard group reported a protocol for the addition of boronic acids to enones [37]. At first, they tested the combination of Pd(OAc)2 with triflic acid (TfOH) to obtain a Pd(II) complex with a weakly coordinating anion that is necessary for a fast Pd–C bond cleavage and thus avoiding the undesired β

Application of the Meerwein reaction of 1,4-benzoquinone to a metal-free synthesis of benzofuropyridine analogues

• Rashmi Singh,
• Tomas Horsten,
• Rashmi Prakash,
• Swapan Dey and
• Wim Dehaen

Beilstein J. Org. Chem. 2021, 17, 977–982, doi:10.3762/bjoc.17.79

• unknown compounds 14–16 opens many synthetic possibilities for the preparation of novel fused derivatives of 1-aza-9-oxafluorene. The nitro compounds 14 and 15 were reduced to the corresponding aniline derivatives using hydrogen and Pd/C as a catalyst. The resulting aminophenols 17 and 18 were further

β-Lactamase inhibition profile of new amidine-substituted diazabicyclooctanes

• Zafar Iqbal,
• Lijuan Zhai,
• Yuanyu Gao,
• Dong Tang,
• Xueqin Ma,
• Jinbo Ji,
• Jian Sun,
• Jingwen Ji,
• Yuanbai Liu,
• Rui Jiang,
• Yangxiu Mu,
• Lili He,
• Haikang Yang and
• Zhixiang Yang

Beilstein J. Org. Chem. 2021, 17, 711–718, doi:10.3762/bjoc.17.60

• h, 44%. Synthesis of intermediate 2. Reagents and conditions: (i) Pd/C (wet), EtOAc/CH2Cl2, H2, 45 psi, rt, 2 h, 95%; (ii) imidazole, CH2Cl2, rt, 16 h, 46%; (iii) Al(Me)3, NH4Cl, CH2Cl2, 0 °C-rt, 40 h, 23%. Synthesis of intermediates 3–5. Reagents and conditions: (i) (Ac)2O, CH2Cl2, rt, 24 h, 95–99

• %; (ii) aqueous NaOH, 0 °C, 2 h, 85–99%; (iii) (Ac)2O, H2O, rt, 3 h, 68%. Synthesis of compounds A1–21. Reagents and conditions: (i) acetyl chloride, TEA, CH2Cl2, rt, 16 h, 97% (for B1), HATU, DIPEA or DCC, DMAP, DMF or THF, rt, 16–24 h, 43–98%. (ii) Pd/C (wet), THF or EtOAc/TEA, H2, rt, 16 h, 22–96

Total synthesis of decarboxyaltenusin

• Lucas Warmuth,
• Aaron Weiß,
• Marco Reinhardt,
• Anna Meschkov,
• Ute Schepers and
• Joachim Podlech

Beilstein J. Org. Chem. 2021, 17, 224–228, doi:10.3762/bjoc.17.22

• , K2CO3, DMF/acetone 1:2, 80 °C, 43 h (98%). Final steps in the synthesis of biaryl 1. Conditions: h) Pd(OAc)2, SPhos, Cs2CO3, dioxane/H2O 7:1, 70 °C, 18 h, (R = TBS: 98%, containing non-separable impurities; R = Bn: 89%) ; i) R = Bn: Pd/C (10%), H2, THF, 8 bar, 24 h, 40 °C (88%). NMR data of natural and

Recent progress in the synthesis of homotropane alkaloids adaline, euphococcinine and N-methyleuphococcinine

• Dimas J. P. Lima,
• Antonio E. G. Santana,
• Michael A. Birkett and
• Ricardo S. Porto

Beilstein J. Org. Chem. 2021, 17, 28–41, doi:10.3762/bjoc.17.4

• acetal, cat. (CH2OH)2, BF3·Et2O, 85%; x) 1. Luche reduction, 98%; 2. a) NaH; b) CS2, c) MeI, 88%; 3. Bu3SnH, AIBN, heat, 75%; xi) 1. cat. Pd(MeCN)2Cl2, wet acetone, 95%; 2. H2, Pd-C, 90%. Synthesis of (+)-euphococcinine (2). Reagents and conditions: i) 1. Cp2ZrCl2,AlMe3, CH2Cl2; 2. p-menthyl-3

Synthesis, crystal structures and properties of carbazole-based [6]helicenes fused with an azine ring

• Daria I. Tonkoglazova,
• Anna V. Gulevskaya,
• Konstantin A. Chistyakov and
• Olga I. Askalepova

Beilstein J. Org. Chem. 2021, 17, 11–21, doi:10.3762/bjoc.17.2

• -dibromopyridine it was the only way for us to synthesize the target [4]helicenes [70]. Unfortunately, the coupling of 2,3-dichloroquinoxaline (3a) with 9-ethyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-9H-carbazole in the 5% Pd-C/PPh3/K2CO3/toluene/H2O catalytic system at 100 °C for 24 h (method A) gave the

Chiral anion recognition using calix[4]arene-based ureido receptors in a 1,3-alternate conformation

• Tereza Horáčková,
• Jan Budka,
• Vaclav Eigner,
• Wen-Sheng Chung,
• Petra Cuřínová and
• Pavel Lhoták

Beilstein J. Org. Chem. 2020, 16, 2999–3007, doi:10.3762/bjoc.16.249

• the nitro groups or (ii) concomitant reduction of the nitro groups and the allyl moieties. Thus, the reaction of 4a with SnCl2∙2H2O in ethanol gave the corresponding amine 5 in 57% yield after column chromatography on alumina. On the other hand, the four-day stirring of 4a with Pd/C under a H2

Optical detection of di- and triphosphate anions with mixed monolayer-protected gold nanoparticles containing zinc(II)–dipicolylamine complexes

• Lena Reinke,
• Julia Bartl,
• Marcus Koch and
• Stefan Kubik

Beilstein J. Org. Chem. 2020, 16, 2687–2700, doi:10.3762/bjoc.16.219

• °C, 60 min → 25 °C, 80 min, 94%; ii) NaN3, acetone/water 5:1 (v/v), reflux 20 h, 95%; iii) H2, Pd/C (10%), 1 mol/L HCl (1 equiv), methanol, 25 °C, 8 d, 86%; iv) rac-lipoic acid (for rac-1) or (R)-lipoic acid (for (R)-1), TBTU, DIPEA, DMF, 25 °C, 6 d, rac-1: 51%, (R)-1: 44%. Synthesis of ligand 2

Synthetic approaches to bowl-shaped π-conjugated sumanene and its congeners

• Shakeel Alvi and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 2212–2259, doi:10.3762/bjoc.16.186

• -trimethyltriphenylene (6) in 46% yield. Later on, they first directly tried to convert compound 6 into the expected sumanene (2) by using a cyclodehydrogenation reaction in the presence of Pd/C at 400 °C, surprisingly they obtained only mono-bridged compound 7 in around 70% yield along with some of an unidentified

• reaction followed by the reduction of the nitro functionality into the amine group and subsequently performing a Sandmeyer reaction as shown in Scheme 20 [14]. Additionally, they have reported the hydrogenation of sumanene to generate compound 89 having one benzene ring intact in the framework using Pd/C

• -selective cation–π interaction (Scheme 27) [60]. In this study, they used already discussed formylsumanene 66 and aminosumanene 114 prepared from nitrosumanene through the reduction of 80 with Pd/C/H2. As can be seen from Scheme 27, these attractive building blocks 66 and 114 were then converted into the

Regioselective cobalt(II)-catalyzed [2 + 3] cycloaddition reaction of fluoroalkylated alkynes with 2-formylphenylboronic acids: easy access to 2-fluoroalkylated indenols

• Tatsuya Kumon,
• Miroku Shimada,
• Jianyan Wu,
• Shigeyuki Yamada and
• Tsutomu Konno

Beilstein J. Org. Chem. 2020, 16, 2193–2200, doi:10.3762/bjoc.16.184

• -fluoroalkylated indenone 6 in 98% yield. Subsequently, a hydrogenolysis with 1 mol % of Pd/C under a hydrogen atmosphere in methanol at room temperature for 15 h produced the desired 2-fluoroalkylated indanone 7 as the trans-isomer in 69% yield [33][34][35]. The stereochemical assignment of 5aA and 7 was carried

Convenient access to pyrrolidin-3-ylphosphonic acids and tetrahydro-2H-pyran-3-ylphosphonates with multiple contiguous stereocenters from nonracemic adducts of a Ni(II)-catalyzed Michael reaction

• Alexander N. Reznikov,
• Dmitry S. Nikerov,
• Anastasiya E. Sibiryakova,
• Victor B. Rybakov,
• Evgeniy V. Golovin and
• Yuri N. Klimochkin

Beilstein J. Org. Chem. 2020, 16, 2073–2079, doi:10.3762/bjoc.16.174

• . Hydrogenation in the presence of Raney nickel or Pd/C in various solvents leads to a mixture of products, among which 8 and 9 are identified (Scheme 1). A satisfactory yield of the desired product 7 (78% by 31P NMR of reaction mixture) was achieved when the hydrogenation was carried out in acetic acid in the

• presence of Pd/C. However, phosphonate 7 was unstable: already during its isolation, it was partially transformed into compounds 8 and 9. It can be assumed that N-alkylation by the phosphoryl group occurs [47][48][49]. To avoid this undesirable process, the product 7 was formylated before its isolation

Synthesis of monophosphorylated lipid A precursors using 2-naphthylmethyl ether as a protecting group

• Jundi Xue,
• Ziyi Han,
• Gen Li,
• Khalisha A. Emmanuel,
• Cynthia L. McManus,
• Qiang Sui,
• Dongmian Ge,
• Qi Gao and
• Li Cai

Beilstein J. Org. Chem. 2020, 16, 1955–1962, doi:10.3762/bjoc.16.162

• catalytic hydrogenolysis over Pd/C under 15 kg/cm2 of H2 to give the target lipid X monosaccharide 1 (as triethylammonium salt) in good yield. Having the glycosyl donor 20 and acceptor 18 at hand (Scheme 2), in order to prepare the disaccharide precursor, the glycosylation reaction was performed first

• 7, EDC·HCl, DMAP, CH2Cl2, rt, 67.5% (2 steps); (c) HF/Py, THF, −40 °C to rt, 78%; (d) tetrabenzyl pyrophosphate, LHMDS, THF, −78 °C, 91%; (e) H2 (15 kg/cm2), Pd/C, THF/H2O, 38 °C, 86%. Synthesis of the disaccharide lipid A precursor 2. Conditions: (a) TfOH, 4 Å MS, dry CH2Cl2, 94%; (b) Zn, AcOH

Synthesis, docking study and biological evaluation of ᴅ-fructofuranosyl and ᴅ-tagatofuranosyl sulfones as potential inhibitors of the mycobacterial galactan synthesis targeting the galactofuranosyltransferase GlfT2

• Marek Baráth,
• Jana Jakubčinová,
• Zuzana Konyariková,
• Stanislav Kozmon,
• Katarína Mikušová and
• Maroš Bella

Beilstein J. Org. Chem. 2020, 16, 1853–1862, doi:10.3762/bjoc.16.152

• by GlfT2. Reagents and conditions: a) 1. (BnO)2P-NMe2, 1H-tetrazole, 0 °C→rt, 1 h, 2. m-CPBA, 0 °C→rt, 1.5‒2 h; b) H2, 10% Pd/C, MeOH, rt, 3‒4 h. Reagents and conditions: a) PivCl, pyridine, CH2Cl2, rt, overnight; b) BnBr, NaOH, TBAB, THF, reflux, 3 h. Reagents and conditions: a) EtSH, BF3∙OEt2

• , CH2Cl2, 0 °C, 2 h; b) 1. (BnO)2P-NMe2, 1H-tetrazole, 0 °C→rt, 1 h, 2. m-CPBA, 0 °C→rt, 1.5‒2 h; c) MeONa, MeOH, rt, 1.5 h; d) H2, 10% Pd/C, MeOH, rt, 3‒4 h; e) 3 M HCl, THF, 40 °C, 8 h. Reagents and conditions: a) PhSH, or iPrSH, BF3·OEt2, CH2Cl2, −5 °C, 1 h; b) BF3·OEt2, Ac2O, 0 °C, 1.5 h; c) PhSH, BF3

• ·OEt2, CHCl3, −20 °C, 1.5 h. Reagents and conditions: a) 1. (BnO)2P-NMe2, 1H-tetrazole, 0 °C→rt, 1 h, 2. m-CPBA, 0 °C→rt, 1.5‒2 h; b) H2, 10% Pd/C, MeOH, rt, 3‒4 h; c) 3 M HCl, THF, 40 °C, 8 h. Observed docking score and predicted Ki values of the docked compounds 1‒3. Evaluation of the effects of

One-pot synthesis of isosorbide from cellulose or lignocellulosic biomass: a challenge?

• Isaline Bonnin,
• Raphaël Mereau,
• Thierry Tassaing and
• Karine De Oliveira Vigier

Beilstein J. Org. Chem. 2020, 16, 1713–1721, doi:10.3762/bjoc.16.143

• Teflon inserts for a reaction time between 1 h to 5 h. Another study was performed using sulfuric or hydrochloric acid in the presence of Pt/C, Pd/C or Ru/C catalysts [21]. In the presence of Pt/C and Pd/C associated to HCl or H2SO4 the isosorbide yield was very low (below 4%) for a total conversion of

• yield (50% under optimized conditions, 220 °C under 40 bar of H2 for 2 h and 0.5 M H2SO4 (aq) 30 mL, 40 mg of Ru/C (5 wt % of Ru) in a glass insert in an autoclave) than Pt/C, Pd/C and Rh/C catalysts for the one-pot one step conversion of BP to isosorbide. The nature of the acids to catalyze the

Synthesis of Streptococcus pneumoniae serotype 9V oligosaccharide antigens

• Sharavathi G. Parameswarappa,
• Claney L. Pereira and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2020, 16, 1693–1699, doi:10.3762/bjoc.16.140

• removal of all methyl and benzoate esters under basic conditions to obtain the partially protected pentasaccharide 32 that was hydrogenated using Pd/C and hydrogen to afford pentasaccharide 4 without the acetate group at the C-6 position of the mannosamine. Pentasaccharide 5, containing a C-6 O-acetate on

• mannosamine was obtained from 33, that in turn was a product of the benzylation of 32. Cleavage of the benzylidene group in 33 yielded 34 that was selectively acetylated at the primary alcohol at low temperature to obtain 35 [30]. The subsequent removal of the benzyl groups using hydrogenation with Pd/C in an

In silico rationalisation of selectivity and reactivity in Pd-catalysed C–H activation reactions

• Liwei Cao,
• Mikhail Kabeshov,
• Steven V. Ley and
• Alexei A. Lapkin

Beilstein J. Org. Chem. 2020, 16, 1465–1475, doi:10.3762/bjoc.16.122

• initial guess due to particularly bad initial geometry – discard the conformer/intermediate, (iv) decomposed intermediate (no Pd–C bond determined by interatomic distance analysis) – discard intermediate. Literature validation In order to test the developed algorithm, a representative literature data

• manually examined to ensure they represent the intermediates according to the particular mechanism. In particular, the bond length between the palladium atom and the corresponding carbon atom was given a maximum value of 2.4 Å to filter out inappropriate intermediates where there is no stable Pd–C bond [40

Highly selective Diels–Alder and Heck arylation reactions in a divergent synthesis of isoindolo- and pyrrolo-fused polycyclic indoles from 2-formylpyrrole

• Carlos H. Escalante,
• Eder I. Martínez-Mora,
• Carlos Espinoza-Hicks,
• Alejandro A. Camacho-Dávila,
• Fernando R. Ramos-Morales,
• Francisco Delgado and
• Joaquín Tamariz

Beilstein J. Org. Chem. 2020, 16, 1320–1334, doi:10.3762/bjoc.16.113

• using manganese oxide or DDQ as the oxidizing reagents, or even including Pd/C at high temperatures (250 °C) [45], failed to obtain the series of indoles 23. It is likely that the electron withdrawing effect of the formyl group at the C-7 position counterbalance the delocalization direction of the

Synthesis of esters of diaminotruxillic bis-amino acids by Pd-mediated photocycloaddition of analogs of the Kaede protein chromophore

• Esteban P. Urriolabeitia,
• Pablo Sánchez,
• Alexandra Pop,
• Cristian Silvestru,
• Eduardo Laga,
• Ana I. Jiménez and
• Carlos Cativiela

Beilstein J. Org. Chem. 2020, 16, 1111–1123, doi:10.3762/bjoc.16.98

• Figure 5, provides additional information. Complex 4a has a dinuclear structure in which each Pd atom is surrounded by one C,N-ortho-metallated oxazolone and two oxygen atoms of the trifluoroacetate ligands, which act as bridging ligands between the two Pd(C^N) fragments. In turn, the two Pd(C^N

• necessary in order to obtain a clean release of the truxillic esters. In addition to the methoxycarbonylation of the Pd–C, the reaction also involves ring opening of the oxazolone moiety to afford the corresponding ester and amido groups. This ring opening was also observed in the case of the hydrogenation

• -diaminotruxillic bis-amino acids. The reaction of the cyclobutanes 4 with CO (1 atm) in MeOH/NCMe results in the ring opening of the oxazolone group, methoxycarbonylation of the Pd–C bonds, reductive elimination, and finally release of the 1,3-diaminotruxillic bis-amino esters 5 as single isomers (ε-isomer). The

Palladium-catalyzed regio- and stereoselective synthesis of aryl and 3-indolyl-substituted 4-methylene-3,4-dihydroisoquinolin-1(2H)-ones

• Valeria Nori,
• Antonio Arcadi,
• Armando Carlone,
• Fabio Marinelli and
• Marco Chiarini

Beilstein J. Org. Chem. 2020, 16, 1084–1091, doi:10.3762/bjoc.16.95

• catalytic system showed that the ligand-free PdCl2 was the most effective catalyst (Table 1, entry 14). Other catalysts such as Pd(PPh3)4, Pd/C or Pd(OAc)2 provided inferior results (Table 1, entries 11–13). We then examined the reaction of 2a with 1.5 equiv of a variety of arylboronic acids. Using the

Efficient synthesis of dipeptide analogues of α-fluorinated β-aminophosphonates

• Marcin Kaźmierczak and
• Henryk Koroniak

Beilstein J. Org. Chem. 2020, 16, 756–762, doi:10.3762/bjoc.16.69

• into the salts 14 was applied. The salts 14 could be then crystallized and subjected to X-ray studies. A standard N−debenzylation protocol was employed to remove the benzyl protecting group. The hydrogenolysis reaction was catalyzed by palladium on carbon (Pd/C), and was carried out in trifluoroethanol

• acetate 60:40, v/v). The NMR spectroscopic data for fluorides 11 were in good agreement with our previous research [31]. Procedure for the synthesis of amines 13 The amines 13 were prepared in a similar manner as described in [35]. Fluoride 11 (1 equiv) was dissolved in 5 mL of TFE and then 10% Pd/C (20

Starazo triple switches – synthesis of unsymmetrical 1,3,5-tris(arylazo)benzenes

• Andreas H. Heindl and
• Hermann A. Wegner

Beilstein J. Org. Chem. 2020, 16, 22–31, doi:10.3762/bjoc.16.4

• (E)-N-(3-nitro-5-(phenyldiazenyl)phenyl)acetamide (8), the reduction of the nitro group was attempted. However, the literature-known procedure of using sodium hydrosulfide did not yield the desired (E)-N-(3-amino-5-(phenyldiazenyl)phenyl)acetamide (9). Alternative reduction attempts, such as using Pd

• /C-catalyzed reduction by H2 in different solvents, SnCl2, or iron under acidic conditions were not successful either. In all cases, the reactions produced complicated mixtures, and the target compound could neither be identified nor isolated. At this stage, the second strategy via Pd-catalyzed

Automated glycan assembly of arabinomannan oligosaccharides from Mycobacterium tuberculosis

• Alonso Pardo-Vargas,
• Priya Bharate,
• Martina Delbianco and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2019, 15, 2936–2940, doi:10.3762/bjoc.15.288

• methanolysis, followed by Pd/C-catalyzed hydrogenolysis of the carboxybenzyl group and the benzyl ethers. Mannosides 4–6 were deprotected and purified using reversed-phase HPLC to obtain fully deprotected mannosides 10–12 (Figure 2). For the arabinomannosides 7–9, the acid-labile arabinose chain was cleaved

Chemical synthesis of tripeptide thioesters for the biotechnological incorporation into the myxobacterial secondary metabolite argyrin via mutasynthesis

• David C. B. Siebert,
• Roman Sommer,
• Domen Pogorevc,
• Michael Hoffmann,
• Silke C. Wenzel,
• Rolf Müller and
• Alexander Titz

Beilstein J. Org. Chem. 2019, 15, 2922–2929, doi:10.3762/bjoc.15.286

• , THF, −20 °C (for 20a, 20b, 30a); (c) PyBOP, DIPEA, CH2Cl2, 0 °C (for 20c, 20d, 30b); (d) 4 M HCl/dioxane, rt; (e) NaOH, dioxane, 0 °C; (f) KOH, H2O, 0 °C to rt; (g) (for 26a) HSCH2CH2NHAc (HSNAc), IBCF, NMM, THF, −20 °C; (for 26b–d, 35a,b) HSNAc, TFFH, DIPEA, CH2Cl2, 0 °C; (h) Pd/C, H2, MeOH, rt; (i

• ) EDC, CuCl, CH2Cl2, rt; (j) 0.5 M LiOH, THF/MeOH/H2O (4:1:2), 0 °C to rt. Improved synthesis of the tripeptide thioester 14. Reagents and conditions: (a) SOCl2, EtOH, 78 °C; (b) IBCF, NMM, THF, −20 °C; (c) Pd/C, H2, MeOH, rt; (d) EDC, CuCl, CH2Cl2, rt; (e) 0.5 M LiOH, THF/H2O (4:1:2), 0 °C to rt; (f

Photoreversible stretching of a BAPTA chelator marshalling Ca²⁺-binding in aqueous media

• Aurélien Ducrot,
• Arnaud Tron,
• Robin Bofinger,
• Ingrid Sanz Beguer,
• Jean-Luc Pozzo and
• Nathan D. McClenaghan

Beilstein J. Org. Chem. 2019, 15, 2801–2811, doi:10.3762/bjoc.15.273

• (5-hydroxy-2,1- phenylene)nitrilo]tetraacetate (1c). A solution of 1b (4.13 g, 5.16 mmol) in methanol (150 mL) and 10% Pd/C (0.5 g) was stirred vigorously under a H2 atmosphere for 24 h at room temperature. The reaction mixture was subsequently filtered over celite and the celite pad was washed with

• mmol), 10% Pd/C (0.02 g) and a few drops of triethylamine in 100 mL DCM/EtOH 1:1 (v/v) was stirred vigorously under a hydrogen atmosphere for 48 h. The reaction mixture was filtered over celite and the celite pad washed with hot EtOAc. Column chromatography (SiO2, EtOAc) yielded the title compound