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

• intermediate thioiminium salt, which was heated under the reflux of triethylamine and trimethyl phosphite, providing compound 28 in 69% yield. The catalytic hydrogenation of 28 occurred in platinum (H2, Pt/C) under a pressure of 60 psi of hydrogen (about 4 atm), resulting in amide 29 in 96% yield. This

• 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

All-carbon [3 + 2] cycloaddition in natural product synthesis

• Zhuo Wang and
• Junyang Liu

Beilstein J. Org. Chem. 2020, 16, 3015–3031, doi:10.3762/bjoc.16.251

• quaternary carbon stereocenters in 86% yield. Reduction of aldehyde 119 and subsequent transesterification produced a lactone (not shown). It was exposed to SeO2 to install the allylic hydroxy group to give 120 in 65% yield. Upon catalytic hydrogenation of 120, alcohol 121 was formed. This alcohol 120 was

• hydrodesulfurization with Raney nickel as catalyst and subsequent catalytic hydrogenation produced (±)-cuparene (13) in 90% yield. All-carbon [3 + 2] annulation in natural product synthesis The all-carbon [3 + 2] cycloaddition demonstrated the ability to assemble intricate polycyclic structures in the synthesis of

Syntheses of spliceostatins and thailanstatins: a review

• William A. Donaldson

Beilstein J. Org. Chem. 2020, 16, 1991–2006, doi:10.3762/bjoc.16.166

• Kitahara’s synthesis [8][9], the Wittig olefination of 24, followed by a catalytic hydrogenation, removal of the dimethylaminal protecting group, and lactonization gave 25 as a mixture of diastereomers (Scheme 2). The further transformation of 25 afforded the dihydropyran 26, which upon catalytic

• catalysts, this group found that the intramolecular oxa-Michael addition using 20 mol % of the diarylprolinol organocatalyst 37 in the presence of benzoic acid gave 38. The use of the enantiomer of 37 gave the dihydropyran with the opposite configuration at C-11. The catalytic hydrogenation of 38 proceeded

• hydrogenation over Pt2O and then low-temperature DIBAL reduction afforded the all-cis tetrasubstituted tetrahydropyran 27. In Koide et al.’s synthesis, the unsaturated lactone 29 was prepared via the Wittig methenylation of 24, followed by aminal hydrolysis, methallylation of the 2° alcohol 28, and ring-closing

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

• gave 11 in good yield. Likewise, 6-O-benzyl derivative 12 was prepared to reduce reaction steps and to ensure a clean progress of the benzyl protecting group removal by catalytic hydrogenation (Scheme 2). The direct thioglycosylation of 11 with ethanethiol in the presence of BF3∙OEt2 afforded 2-thio-ᴅ

• protecting group in derivative 14 led to alcohol 15 as the common intermediate for the synthesis of target structures 2a and 3a. The fully deprotected target compound 2a was obtained in good yield by acidic hydrolysis of the acetonide protecting group with 3 M HCl in THF followed by catalytic hydrogenation

• of 16. On the other hand, direct catalytic hydrogenation of 15 furnished target structure 3a with the hydroxy groups protected on C3 and C4 as an acetonide. Direct thioglycosylation of diacetonide 12 with corresponding thiols (PhSH, iPrSH) led to expected 2-thio-ᴅ-tagatofuranosides 17a and 17b in 44

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

• acetic anhydride to give the azalactone 56. The subsequent basic hydrolysis of 56 gave 57 that, on catalytic hydrogenation, afforded racemic difluorinated Phe 58. The isomers were separated by selective hydrolysis using a protease from Bacillius sp to generate the (S)-N-acetyl acid 59 with >99.5% ee and

• which was immediately hydrolyzed to provide the racemic carboxamide 172. The subsequent removal of the chiral auxiliary by catalytic hydrogenation then afforded the carboxamide 173. Finally, an acid-mediated hydrolysis of the carboxamide 173 to generate the free amino acids ʟ- or ᴅ-168a, was carried out

Synthesis of disparlure and monachalure enantiomers from 2,3-butanediacetals

• Adam Drop,
• Hubert Wojtasek and
• Bożena Frąckowiak-Wojtasek

Beilstein J. Org. Chem. 2020, 16, 616–620, doi:10.3762/bjoc.16.57

• the pheromone structures was attached giving compound 20 in 74% yield. Next, removal of the protecting group from the secondary alcohol followed by a Swern oxidation gave aldehyde 21 which was subjected to Wittig reactions with either of the two different alkyl derivatives and catalytic hydrogenation

Chemical tuning of photoswitchable azobenzenes: a photopharmacological case study using nicotinic transmission

• Lorenzo Sansalone,
• Jun Zhao,
• Matthew T. Richers and
• Graham C. R. Ellis-Davies

Beilstein J. Org. Chem. 2019, 15, 2812–2821, doi:10.3762/bjoc.15.274

• catalytic hydrogenation to 4 followed by protection with TBDMS to give 5 in 63% yield for three steps. The synthesis of the other half of the photochrome started with bromination of difluorinated aniline to give 6 followed by copper-catalyzed cyanation to 7 in 62% overall yield. Diazonization of 7 with

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

• chiral auxiliary ([92]. The authors established that the Mannich addition occurred exclusively on the Si-face of the N-acyliminium ions, resulting in the threo-isomer as the major isomer (with moderate yields and good diastereomeric ratios). Upon catalytic hydrogenation followed by methanolysis, threo

N-(1-Phenylethyl)aziridine-2-carboxylate esters in the synthesis of biologically relevant compounds

• Iwona E. Głowacka,
• Aleksandra Trocha,
• Andrzej E. Wróblewski and
• Dorota G. Piotrowska

Beilstein J. Org. Chem. 2019, 15, 1722–1757, doi:10.3762/bjoc.15.168

• catalytic hydrogenation but metal-ammonia reduction (Birch reaction) and organic acid in anisole (vide infra) can be efficiently applied. We begin with a short presentation of syntheses of aziridine-2-carboxylates, the corresponding aldehydes and 2-methanols. Review Syntheses of starting materials Synthesis

• nucleophiles to provide 9 or even by catalytic hydrogenation to form 10. Thus, biologically important fragments like vicinal amino alcohols 11 or 2-amino-1,3-propanediols 12a [Nu = OH] can be obtained in highly enantioselective procedures preserving the absolute configuration at C2. The latter compounds are

• NaBH4/ZnCl2 mixture (chelation controlled) gave the aziridine alcohol 20 as a major product. Reductive opening of the aziridine ring produced the amino alcohol 21 which was transformed into the substituted oxazolidin-2-one 22. Its catalytic hydrogenation effected deoxygenation at the benzylic position

Heck- and Suzuki-coupling approaches to novel hydroquinone inhibitors of calcium ATPase

• Robert J. Kempton,
• Taylor A. Kidd-Kautz,
• Soizic Laurenceau and
• Stefan Paula

Beilstein J. Org. Chem. 2019, 15, 971–975, doi:10.3762/bjoc.15.94

• appended. Unfortunately, reactions of 6 and 8 utilizing catalytic hydrogenation, lithium aluminium hydride by itself as well as with added aluminium chloride or samarium iodide produced only trace amounts of an amine (e.g., 9). When samarium iodide was used as the reagent, the only discernible product (not

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

• 6. [3,3]-Sigmatropic rearrangement of tertiary cyclopropenylcarbinyl acetates 10a–c. [3,3]-Sigmatropic rearrangement of secondary cyclopropenylcarbinyl esters 10d–h. [3,3]-Sigmatropic rearrangement of trichoroacetimidates 12a–i. Reaction of trichloroacetamide 13f with pyrrolidine. Catalytic

• hydrogenation of (arylmethylene)cyclopropropane 13f. Instability of trichloroacetimidates 21a–c derived from cyclopropenylcarbinols 20a–c. [3,3]-Sigmatropic rearrangement of cyanate 27 generated from cyclopropenylcarbinyl carbamate 26. Synthesis of alkylidene(aminocyclopropane) derivatives 30–37 from carbamate

Unnatural α-amino ethyl esters from diethyl malonate or ethyl β-bromo-α-hydroxyiminocarboxylate

• Eloi P. Coutant,
• Vincent Hervin,
• Glwadys Gagnot,
• Candice Ford,
• Racha Baatallah and
• Yves L. Janin

Beilstein J. Org. Chem. 2018, 14, 2853–2860, doi:10.3762/bjoc.14.264

• 2ae. First of all, reduction of the alkylidenemalonate 6ae using a palladium-based catalytic hydrogenation also led to the concomitant hydrogenation of the furan ring to give compound 8. As depicted, this actually allowed us to prepare to the 2-tetrahydrofuranyl-bearing α-aminoester 10 in a 35

• the water formed in situ. The 1H NMR monitoring of crude samples pointed out a complete conversion, most often overnight at 60 °C, and the resulting solutions of alkylidenemalonates 6a–al were then directly reduced to give the malonates 3a–al. For this reduction step, palladium-based catalytic

• hydrogenation was preferably used although, when incompatible with the substrates, sodium borohydride was employed. In most cases, large proportion of the expected substituted malonates 3a–al were observed by 1H NMR. Thus, in order to simplify even further this procedure, these crude malonates were subjected to

Synthesis of unnatural α-amino esters using ethyl nitroacetate and condensation or cycloaddition reactions

• Glwadys Gagnot,
• Vincent Hervin,
• Eloi P. Coutant,
• Sarah Desmons,
• Racha Baatallah,
• Victor Monnot and
• Yves L. Janin

Beilstein J. Org. Chem. 2018, 14, 2846–2852, doi:10.3762/bjoc.14.263

• acid in ethanol overnight gave a sufficient amount of the (pure) target phenyl-bearing α-amino ester 10 which had been previously obtained by catalytic hydrogenation using palladium [20]. The same transformation sequences were used starting with compound 6n and provided the furan-bearing α-amino ester

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

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

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

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

• ) [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

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

• conditions for their cleavage. Secondly some glycosyl oxazolines are also prone to reductive cleavage by catalytic hydrogenation [41], presenting a significant further limitation as to which OH-protecting groups may be employed. Most of the reports in the literature have therefore used a protecting group

• removed. Treatment with UDP-Gal and a β(1–4)-galactosyl transferase led to the addition of galactose residues to all of the 4-hydroxy groups of the GlcNAcs. Deprotection of the remaining benzyl protecting groups and removal of the SPh at the reducing terminus by catalytic hydrogenation gave the completely

Aminomethylation/hydrogenolysis as an alternative to direct methylation of metalated isoquinolines – a novel total synthesis of the alkaloid 7-hydroxy-6-methoxy-1-methylisoquinoline

• Benedikt C. Melzer,
• Jan G. Felber and
• Franz Bracher

Beilstein J. Org. Chem. 2018, 14, 130–134, doi:10.3762/bjoc.14.8

• material 3. Due to the very similar polarities of 3 and 4, chromatographic separation was very tedious, and only 34% of methyl compound 4 was isolated, accompanied by about 30% of starting material 3 and mixed fractions. Debenzylation of 4 by catalytic hydrogenation in methanol solution under palladium

• highly reactive benzylammonium residue still takes place, but O-debenzylation is predominantly suppressed by this catalyst poison. Finally, poisoning of the catalyst was prevented by simply passing a solution of the methoiodide 7 through a chloride-loaded ion exchanger prior to catalytic hydrogenation

Aminosugar-based immunomodulator lipid A: synthetic approaches

• Alla Zamyatina

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

• deprotection by catalytic hydrogenation furnished lipid A 31. Alternatively, the lactol 30 was phosphitylated by application of the phosphoramidite procedure with (benzyloxy)[(N-Cbz-3-aminopropyl)oxy](N,N-diisopropylamino)phosphine in the presence of 1H-tetrazole and subsequent oxidation with dimethyldioxirane

The use of 4,4,4-trifluorothreonine to stabilize extended peptide structures and mimic β-strands

• Yaochun Xu,
• Isabelle Correia,
• Tap Ha-Duong,
• Nadjib Kihal,
• Jean-Louis Soulier,
• Julia Kaffy,
• Benoît Crousse,
• Olivier Lequin and
• Sandrine Ongeri

Beilstein J. Org. Chem. 2017, 13, 2842–2853, doi:10.3762/bjoc.13.276

• with TFA and then performing the coupling reaction with Boc-L-Ala-OH in the presence of HBTU/HOBt/DIPEA or DMTMM(Cl−)/NMM. Catalytic hydrogenation, using 10% Pd/C or Pd(OH)2, under H2 atmosphere, gave pentapeptides 1a–3a in moderate to quantitative yield. After acidic removal of the Boc group, the

Synthesis of oligonucleotides on a soluble support

• Harri Lönnberg

Beilstein J. Org. Chem. 2017, 13, 1368–1387, doi:10.3762/bjoc.13.134

• linker was replaced with the 4-carboxymethylbenzoic acid linker 9, the fully protected oligomer could be released by catalytic hydrogenation. This allowed the preparation of appropriately protected dimeric and trimeric building blocks having only the 3´-terminal hydroxy function unprotected and, hence

Phosphorus pentasulfide mediated conversion of organic thiocyanates to thiols

• Chandra Kant Maurya,
• Avik Mazumder and
• Pradeep Kumar Gupta

Beilstein J. Org. Chem. 2017, 13, 1184–1188, doi:10.3762/bjoc.13.117

• , Zn–HCl, catalytic hydrogenation (H2–molybdenum disulfide) and metal hydrides like LAH [12][13][14][15][16][17]. These methods, however, suffer from disadvantages like slow reaction rates, poor product yields, involvement of expensive and harsh reagents [16] and predominant side reactions leading to

Continuous-flow processes for the catalytic partial hydrogenation reaction of alkynes

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

Beilstein J. Org. Chem. 2017, 13, 734–754, doi:10.3762/bjoc.13.73

• greener manufacturing methods [24][25]. Nonetheless, in order to be competitive on the large-scale, continuous-flow systems for the catalytic hydrogenation of alkynes should not only provide their intrinsic benefits over conventional batch processes, but also be advantageous, or at least equal, either in

• Lindlar-based batch process [155][156]. Several systems have been reported on the lab scale for the catalytic hydrogenation of 11 under continuous-flow conditions. An accurate study was carried out using the Pd@MonoBor monolithic catalyst [136], showing how the subtle effect of fine adjustments of