Progress and challenges in the synthesis of sequence controlled polysaccharides

• Giulio Fittolani,
• Theodore Tyrikos-Ergas,
• Denisa Vargová,
• Manishkumar A. Chaube and
• Martina Delbianco

Beilstein J. Org. Chem. 2021, 17, 1981–2025, doi:10.3762/bjoc.17.129

• could be converted into N-acetates upon reduction with tributyltin hydride and azobisisobutyronitrile (AIBN), and the N-Cbz groups were removed to liberate the free amino groups during hydrogenolysis over Pd/C [259]. A collection of well-defined COS with defined DP and PA was prepared by AGA [93][157

Chemical synthesis of C6-tetrazole ᴅ-mannose building blocks and access to a bioisostere of mannuronic acid 1-phosphate

• Eleni Dimitriou and
• Gavin J. Miller

Beilstein J. Org. Chem. 2021, 17, 1527–1532, doi:10.3762/bjoc.17.110

• % and exclusively β-selective [11]. Isomeric separation of this complex mixture was not completed at this stage and the material was next deprotected using hydrogenolysis to remove the benzyl groups. This furnished 20 in excellent yield (96%) as a 3:1 α/β mixture (δ 100.5 ppm [1JC1-H1 = 172 Hz, for the

• α-anomer]). Additionally, glycosylation of dibenzyl phosphate using the mixture 18/19 was successful and furnished the expected mixture of tetrazole N-regioisomers in 72% yield. These materials were not separated and instead exposed to hydrogenolysis conditions to deliver free ᴅ-manno C6-tetrazole 1

One-step synthesis of imidazoles from Asmic (anisylsulfanylmethyl isocyanide)

• Louis G. Mueller,
• Allen Chao,
• Embarek AlWedi and
• Fraser F. Fleming

Beilstein J. Org. Chem. 2021, 17, 1499–1502, doi:10.3762/bjoc.17.106

• to substituted imidazoles. Raney nickel hydrogenolysis was effective in interchanging the C4 anisylsulfanyl group for hydrogen (Scheme 3); attempted lithium–anisylsulfanyl exchange [19] or palladium- [22] or nickel- [23] anisylsulfanyl cross coupling was not successful. Raney nickel reduction of 7f

Double-headed nucleosides: Synthesis and applications

• Vineet Verma,
• Jyotirmoy Maity,
• Vipin K. Maikhuri,
• Ritika Sharma,
• Himal K. Ganguly and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2021, 17, 1392–1439, doi:10.3762/bjoc.17.98

• with either uracil or N6-benzoyladenine via Vorbrüggen’s method of nucleobase coupling to produce the double-headed nucleosides 85 and 86. Catalytic hydrogenolysis of the iodinated double-headed nucleoside 85 gave the nucleoside 87 (Scheme 19) [59]. Horton and Tsai [13] synthesized double-headed

Synthesis of multiply fluorinated N-acetyl-D-glucosamine and D-galactosamine analogs via the corresponding deoxyfluorinated glucosazide and galactosazide phenyl thioglycosides

• Vojtěch Hamala,
• Lucie Červenková Šťastná,
• Martin Kurfiřt,
• Petra Cuřínová,
• Martin Dračínský and
• Jindřich Karban

Beilstein J. Org. Chem. 2021, 17, 1086–1095, doi:10.3762/bjoc.17.85

• -catalyzed hydrogenolysis in ethanol/acetic anhydride appeared to be a logical deprotection step [26], the desired fluoro sugars were contaminated with varying quantities of unidentified byproducts. However, clean debenzylation was achieved by first converting the azide to an acetamide on reaction with

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

• -dimethylaminopyridine (DMAP) as the base. Then, the palladium-catalyzed hydrogenation of compounds B1–21 in THF or EtOAc led to the hydroxy derivatives C1–21. It has been observed that a catalytic amount of triethylamine (TEA) in EtOAc enhances the rate of the hydrogenolysis of benzyl ethers. Compounds C1–21 were then

Valorisation of plastic waste via metal-catalysed depolymerisation

• Francesca Liguori,
• Carmen Moreno-Marrodán and
• Pierluigi Barbaro

Beilstein J. Org. Chem. 2021, 17, 589–621, doi:10.3762/bjoc.17.53

• (a solvent is the reagent and solvolyses include hydrolysis, glycolysis, alcoholysis and aminolysis) and hydrogenolysis reactions (H2 as reagent). Hydrolysis (sometimes called hydrocracking) is in between thermochemical and chemolytic processing, basically consisting of depolymerisation by the

• conditions. For instance, for polyesters, alcoholysis may provide mixed monomers formally derived from transesterification reactions [89][90], while aminolysis provides amides and alcohols [91][92]. In the search of “greener” technologies for plastic recycling, catalytic hydrogenolysis processes have been

• ), bis(2-hydroxyethyl)terephthalate (BHET), terephthalamides (TPM [171]) and EG (Figure 3). Catalytic hydrogenolysis, hydrolysis, methanolysis and glycolysis reactions of (postconsumer) PET have been reviewed, each showing their own advantages and disadvantages [172][173]. For instance, glycolysis

Synthetic strategies of phosphonodepsipeptides

• Jiaxi Xu

Beilstein J. Org. Chem. 2021, 17, 461–484, doi:10.3762/bjoc.17.41

• 17 was synthesized via the coupling of methyl N-Cbz-1-aminoethylphosphonochloridate (13b) generated from phosphonic monomethyl ester 12b and methyl (S)-2-hydroxy-3-phenylpropanoate (18) followed by hydrogenolysis. It was further coupled to cyclen to afford various cyclen-containing

• methyl N-Cbz-protected 1-aminoethylphosphonochloridate 13b with methyl ᴅ-lactate (22a) and methyl mercaptoacetate (22b), respectively, followed by a basic hydrolysis and hydrogenolysis. The bioassay results indicated that the phosphonothiodepsidipeptide 20b did not inhibit VanX (Scheme 3) [21]. It was

• -aminoethylphosphonochloridate (13b) with different benzyl 1-hydroxyalkanoates 26 followed by hydrogenolysis and hydrolysis. The bioassay results indicated that six out of the seven synthetic phosphonodepsipeptides 25 inhibited VanX with IC50 values ranging from 0.48 to 8.21 mM (Scheme 4) [7]. Two optically active

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

• hydrogenolysis of benzyl ethers (H2, Pd) [72], DIBAL-H reduction of esters to form alcohols [73], oxidative cleavage of vinyl groups to form carboxylic acids (KMnO4) [74], and the conversion of the acids into amines using the Curtius rearrangement (SOCl2, followed by Me3SiN3, thermolysis, and acid hydrolysis of

• -difluorocyclopropanes in the synthesis of fluoroalkenyl-substituted compounds (monofluoroalkenes) have been actively studied. Great opportunities exist for the use of transition metal catalysis. The catalytic hydrogenolysis of 1,1-difluoro-3-methyl-2-phenylcyclopropane (151) led to the regioselective C2–C3 distal bond

Progress in the total synthesis of inthomycins

• Bidyut Kumar Senapati

Beilstein J. Org. Chem. 2021, 17, 58–82, doi:10.3762/bjoc.17.7

• , it was transformed into (E)-vinylboronate (+)-145b in perfect stereoselectivity by using the recently developed boron-Wittig reaction with bis[(pinacolato)boryl]methane (144) [79]. By applying the Corey–Fuchs dibromoolefination and followed by Pd-catalyzed hydrogenolysis under Uenishi's conditions

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

• subjected to simultaneous catalytic hydrogenation and hydrogenolysis of the protecting group Cbz to give (−)-adaline (1) in 90% yield. The asymmetric synthesis achieved by Liebeskind et al. presented a high enantiomeric excess and good yields. Also, the proposed route differed from the previously mentioned

Vicinal difluorination as a C=C surrogate: an analog of piperine with enhanced solubility, photostability, and acetylcholinesterase inhibitory activity

• Yuvixza Lizarme-Salas,
• Alexandra Daryl Ariawan,
• Ranjala Ratnayake,
• Hendrik Luesch,
• Angela Finch and
• Luke Hunter

Beilstein J. Org. Chem. 2020, 16, 2663–2670, doi:10.3762/bjoc.16.216

• formation of this side-product but did not lead to an overall increase in the yield of 11. Despite the modest optimised yield of the difluoroalkane 11, a sufficient quantity of this material was secured to continue with the synthesis. The hydrogenolysis of the benzyl ether of 11 provided the primary alcohol

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

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

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

• conversion of cellulose and even spruce in a one-step hydrogenolysis reactions to form C4 to C6 sugar alcohols [20]. For the C6 sugar alcohols including the isosorbide formation, the yield was below 6% whatever catalyst was used at 160 °C, under 50 bar of H2 in a 36 mL stainless steel autoclave equipped with

• experiments were made in a batch reactor containing 500 mg of α-cellulose, 100 mg of 5 wt % Ru/C catalyst and 10 mL of water with an acid concentration from 3.47 to 55.1 mmol·L−1 at 160 °C under 50 bar of H2 (25 °C). It was reported that the rate of cellulose hydrogenolysis reaction depends on the acid

• g of 4 wt % Ru/C, 3 g of Amberlyst 70, isosorbide yield of 56% at 180 °C under 50 bar of H2 after 16 h of reaction. A comparison between these results and sequential reactions leading in the first step (hydrogenolysis of cellulose) to 51% of sorbitol and in the second step (dehydration of sorbitol

Synthesis of 3-substituted isoxazolidin-4-ols using hydroboration–oxidation reactions of 4,5-unsubstituted 2,3-dihydroisoxazoles

• Lívia Dikošová,
• Júlia Laceková,
• Ondrej Záborský and
• Róbert Fischer

Beilstein J. Org. Chem. 2020, 16, 1313–1319, doi:10.3762/bjoc.16.112

• (Scheme 4). According to the literature, the N-debenzylation by a Pd-catalyzed hydrogenolysis in methanol with formic acid as the hydrogen source [37][38] should allow the access to N-deprotected isoxazolidines. Unfortunately, all attempts to remove the benzyl group directly from the model isoxazolidine

Fluorinated phenylalanines: synthesis and pharmaceutical applications

• Laila F. Awad and
• Mohammed Salah Ayoup

Beilstein J. Org. Chem. 2020, 16, 1022–1050, doi:10.3762/bjoc.16.91

• high diastereoisomeric purity (Scheme 36). The subsequent deprotection of 151 had to be achieved with BrO3−, because hydrogenolysis resulted in defluorination [74]. Alternatively, a series of substituted anti-β-fluorophenylalanine derivatives 154a–d was obtained from the corresponding enantiopure α

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

Rhodium-catalyzed reductive carbonylation of aryl iodides to arylaldehydes with syngas

• Zhenghui Liu,
• Peng Wang,
• Zhenzhong Yan,
• Suqing Chen,
• Dongkun Yu,
• Xinhui Zhao and
• Tiancheng Mu

Beilstein J. Org. Chem. 2020, 16, 645–656, doi:10.3762/bjoc.16.61

• reacts with PPh3 to form RhCl(PPh3)3, which is able to activate C–I bonds in aryl iodides realizing the insertion of CO and hydrogenolysis with H2. The final trapping of HI by the base Et3N regenerates the catalyst to complete the reaction cycle. As far as we know, this is the first time that

Convenient synthesis of the pentasaccharide repeating unit corresponding to the cell wall O-antigen of Escherichia albertii O4

• Tapasi Manna,
• Arin Gucchait and
• Anup Kumar Misra

Beilstein J. Org. Chem. 2020, 16, 106–110, doi:10.3762/bjoc.16.12

• ) hydrogenolysis of benzyl ethers and benzylidene acetals over Pearlman’s catalyst [36] to furnish the desired pentasaccharide 1 in 49% overall yield (Scheme 4). The structure of compound 1 was unambiguously characterized by its NMR spectral analysis [signals at δ 5.37 (d, J = 2.0 Hz, H-1A), 5.29 (d, J = 3.5 Hz, H

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

• lactone with the lithium salt of dimethyl methylphosphonate followed by an elimination step of the resulting hemiketal, leading to the corresponding exo- and endo-glycal derivatives. The ensuing selective monodemethylation and hydrogenolysis of the benzyl groups and reduction of the 4-azido group gave the

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

• during hydrogenation, giving a complex mixture of deletion sequences lacking one to six arabinose moieties. To overcome this challenge, hydrogenolysis with Pd(OH)2 was performed to access the fully deprotected arabinomannosides 13–15 (Figure 2). Conclusion A collection of AM oligosaccharides containing α

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

• alkylation, reduction and catalytic hydrogenolysis, (+)-199 was converted to desired product (−)-200 with 80% ee (Scheme 62). An electrochemical method for the asymmetric oxidative dimerization of cinnamic acid derivatives was developed by Watanabe in 2016 [109]. The substrates for the electrochemical

Chemical synthesis of the pentasaccharide repeating unit of the O-specific polysaccharide from Escherichia coli O132 in the form of its 2-aminoethyl glycoside

• Debasish Pal and
• Balaram Mukhopadhyay

Beilstein J. Org. Chem. 2019, 15, 2563–2568, doi:10.3762/bjoc.15.249

• -acetylation using NaOMe in MeOH followed by hydrogenolysis in a ThalesNano continuous flow hydrogenation assembly using a 10% Pd-C cartridge [29]. After three cycles of hydrogenation, formation of the target pentasaccharide 1 was evident from the mass spectrum (Scheme 4). Conclusion In conclusion, the

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

• corresponding carboxylic acid followed by hydrogenolysis with H2/Pd-C led in spontaneous lactonization to give the key butenolide 66. Oxidation of 66 with CrO3/AcOH–H2O, followed by saponification and reduction afforded known benzyl alcohol 46 (19% from 66). Then, phenol 46 was converted to the corresponding