Highly stereocontrolled total synthesis of racemic codonopsinol B through isoxazolidine-4,5-diol vinylation

• Lukáš Ďurina,
• Anna Ďurinová,
• František Trejtnar,
• Ľuboš Janotka,
• Lucia Messingerová,
• Jana Doháňošová,
• Ján Moncol and
• Róbert Fischer

Beilstein J. Org. Chem. 2021, 17, 2781–2786, doi:10.3762/bjoc.17.188

• hydrogenolysis conditions led only to the formation of several undesired byproducts. To our satisfaction when compound 12 was subjected to catalytic hydrogenation using Pd(OH)2/C in methanol [39], 2 was formed in 71% yield. Finally, (±)-codonopsinol B (1) was directly obtained from 12 in the yield of 58% (over

Recent advances in the tandem annulation of 1,3-enynes to functionalized pyridine and pyrrole derivatives

• Yi Liu,
• Puying Luo,
• Yang Fu,
• Tianxin Hao,
• Xuan Liu,
• Qiuping Ding and
• Yiyuan Peng

Beilstein J. Org. Chem. 2021, 17, 2462–2476, doi:10.3762/bjoc.17.163

• the hydrogenation of dihydropyridinones 32 and a following desulfonylation and aromatization to give pyridine derivatives 33 in moderate to good yield. Synthesis of pyrroles via tandem annulation of 1,3-enynes Recently, great achievements have been made in electrophilic iodocyclization of alkynes for

Synthesis of 5-arylacetylenyl-1,2,4-oxadiazoles and their transformations under superelectrophilic activation conditions

• Andrey I. Puzanov,
• Dmitry S. Ryabukhin,
• Anna S. Zalivatskaya,
• Dmitriy N. Zakusilo,
• Darya S. Mikson,
• Irina A. Boyarskaya and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2021, 17, 2417–2424, doi:10.3762/bjoc.17.158

• , as a hydride ion source, was conducted to achieve the ionic hydrogenation of intermediate cationic species. However, no products of ionic hydrogenation were obtained, only the product of the hydrophenylation of the acetylene bond 5a was quantitatively isolated (compare with data shown in Scheme 5

Strategies for the synthesis of brevipolides

• Yudhi D. Kurniawan and
• A'liyatur Rosyidah

Beilstein J. Org. Chem. 2021, 17, 2399–2416, doi:10.3762/bjoc.17.157

• -carbon precursor for the synthesis. The forward synthesis transformed 2-acetylfuran (20) to its corresponding alcohol 21 through an asymmetric transfer hydrogenation catalyzed by a ruthenium complex (0.5 mol %) in 98% yield with 95% ee (Scheme 2). The azeotropic mixture of HCO2H/Et3N 5:2 was employed as

• ) asymmetric dihydroxylation and epoxidation; 3) asymmetric hydrogenation; 4) Horner–Wadsworth–Emmons olefination; and 5) cyclopropanation, which are summarized in Table 4, including the overall yields and the number of steps required. This work is expected to provide useful information for researchers to

Recent advances in the syntheses of anthracene derivatives

• Giovanni S. Baviera and
• Paulo M. Donate

Beilstein J. Org. Chem. 2021, 17, 2028–2050, doi:10.3762/bjoc.17.131

• brominated naphthalene 153 with PhLi yielded compound 154, which collapsed to naphthotriyne 155 at elevated temperatures. Sequential addition of furan generated the trisadduct 156. Then, dibenz[a,c]anthracene 158 was obtained in good yield (86%) in two steps by hydrogenation of 156 and further dehydration of

Sustainable manganese catalysis for late-stage C–H functionalization of bioactive structural motifs

• Jongwoo Son

Beilstein J. Org. Chem. 2021, 17, 1733–1751, doi:10.3762/bjoc.17.122

• multipeptides of varying ring size were successfully obtained with excellent functional group tolerance. In addition, selective N-methylation of the 2-pyridine directing group and successive hydrogenation processes provided an efficient traceless removal of the directing group, affording free-NH tryptophan

Methodologies for the synthesis of quaternary carbon centers via hydroalkylation of unactivated olefins: twenty years of advances

• Thiago S. Silva and
• Fernando Coelho

Beilstein J. Org. Chem. 2021, 17, 1565–1590, doi:10.3762/bjoc.17.112

• products instead of reductive ones. Their formation also leads to the generation of Pd(0) species that require the presence of an external oxidant to regenerate the active Pd(II) complex, as well as an additional hydrogenation step, if the hydrofunctionalized product is desired [18]. This particularity

Total synthesis of ent-pavettamine

• Memory Zimuwandeyi,
• Manuel A. Fernandes,
• Amanda L. Rousseau and
• Moira L. Bode

Beilstein J. Org. Chem. 2021, 17, 1440–1446, doi:10.3762/bjoc.17.99

• on these results, it was evident that the selective removal of the trityl group in the presence of the benzyl group is substrate specific. Eventually, hydrogenation under neutral conditions at atmospheric pressure for 24 h allowed for the selective removal of the benzyl group, affording amine 20 in a

• tosylate under basic conditions affording 24 in a yield of 83%. The displacement of the tosyl group with an azide whilst heating the reaction at 80 °C allowed for the isolation of azide 25 in a good yield of 75%. Heating at higher temperatures resulted in product decomposition. Hydrogenation of the azide

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

• protection of 16 followed by introduction of an azide group in the C-2′ position of the molecule to afford nucleoside 22. The treatment of azide 22 with pyrrolidine in acetonitrile followed by hydrogenation afforded aminonucleoside 23, which was used as a key intermediate for the synthesis of the double

• . Global deprotection of 32 using palladium-catalyzed hydrogenation conditions resulted in the formation of the targeted double-headed nucleoside 33 (Scheme 8) [33]. The double-headed nucleoside 33 was dimethoxytritylated, phosphitylated, and incorporated into duplex and its ability to recognize

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

• also proved the possibility to perform an in situ hydrogenation of 86 by mixing the resin with a Pd catalyst (50% Amberlyst® 15/2% Pd on silica/alumina). The desired material was indeed obtained with high yields (up to 80%) and selectivity (up to 95%) [124]. In 2013, a continuous-flow multistep

• 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

N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

• been also an advanced intermediate in the synthesis of alkaloids. For instance, hydrogenation of 117 yielded (+)-coniine (118), the major alkaloid extracted from poison hemlock and responsible for its toxicity, as its hydrochloride, and N-Boc protected derivative of 117 submitted to Wacker oxidation

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

• of S:R isomers = 6:1). The synthesis of intermediate 2 started from the hydrogenation of 7 by following a previously described method using N,N-dimethylformamide (DMF)/CH2Cl2 [23] as solvent led to a low yield in our hands. Therefore, we planned to switch the solvent from DMF to EtOAc whereupon the

• -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

Stereoselective syntheses of 3-aminocyclooctanetriols and halocyclooctanetriols

• Emine Salamci and
• Yunus Zozik

Beilstein J. Org. Chem. 2021, 17, 705–710, doi:10.3762/bjoc.17.59

• should have a cis configuration relative to the protons H-3 and H-4. Next, the reduction of azidotriol 10 by hydrogenation afforded the target aminotriol 12 in 95% yield. For the synthesis of the other aminocyclooctanetriol 18, the diol 6a [33] was reacted with m-CPBA to give trans-epoxide isomer 13 [33

• the small coupling constant (J = 2.2 Hz) the cis relation of the protons H-3 and H-2. Finally, the desired aminocyclooctanetriol 18 was obtained by hydrogenation of the azide functionality in compound 16 in 97% yield. In the second part of this work, we turned our attention to the stereospecific

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

• transfer hydrogenation (CTH) methods from safer reagents have thus been developed and successfully applied to lignocellulose polymers [104][105]. 2.2 Catalysts Catalysts of various types, including homogeneous and heterogeneous, have been reported for the above-mentioned depolymerisation processes of

• reactions of PET were developed mostly using Ru metal-based catalysts, due to their higher affinity for C=O bond (ester) hydrogenation compared to other metals (Scheme 2) [181][182]. Thus, a 73% BDM yield was obtained using a soluble Ru(II)–PNN complex at 110 °C in THF/anisole solvent, 50 bar of hydrogen

•  4, bottom). No details of byproducts were provided. Ethanol and butanol were much less reactive under identical reaction conditions. The as-prepared DMT could be used for the production of hydrocarbon jet fuels by catalytic hydrogenation. Metal-catalysed methanolysis of PET was described in previous

Metal-free visible-light-enabled vicinal trifluoromethyl dithiolation of unactivated alkenes

• Xiaojuan Li,
• Qiang Zhang,
• Weigang Zhang,
• Jinzhu Ma,
• Yi Wang and
• Yi Pan

Beilstein J. Org. Chem. 2021, 17, 551–557, doi:10.3762/bjoc.17.49

• approaches for the trifluoromethylthio (SCF3) difunctionalization of alkenes, such as cyanation [23], etherification [24][25][26][27], amination [28][29][30], chlorination [31][32], hydrogenation [33], trifluoromethylation [34], phosphonization [35], arylation [36][37][38], trifluoromethylthiolation [39

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

• hydrogenation of difluorocyclopropenes [73][79]. Enzymatic hydrolysis or esterification: The first example of the enzymatic resolution of gem-difluorocyclopropanes was reported by Itoh et al. [80]. The prochiral diacetate of cis-1,2-bis-(hydroxymethyl)-3,3-difluorocyclopropane was converted into the

• biotransformation of gem-difluorocyclopropanecarboxamide (±)-83 (Scheme 34) occurred rapidly and under mild conditions to give (1R,3R)-amide 83 (46% yield, >99% ee) and (1S,3S)-acid 82 (51% yield, 87 % ee). Enantioselective hydrogenation of difluorocyclopropenes: Recently, Mikami and co-workers reported the

• enantioselective hydrocupration of difluorocyclopropenes in the presence of chiral diphosphine ligands using stoichiometric hydride sources that included polymethylhydrosiloxane (PMHS) and organoboranes (Scheme 35) [79]. Cossy and co-workers have achieved the catalytic asymmetric transfer hydrogenation with

Novel library synthesis of 3,4-disubstituted pyridin-2(1H)-ones via cleavage of pyridine-2-oxy-7-azabenzotriazole ethers under ionic hydrogenation conditions at room temperature

• Romain Pierre,
• Anne Brethon,
• Sylvain A. Jacques,
• Aurélie Blond,
• Sandrine Chambon,
• Sandrine Talano,
• Catherine Raffin,
• Branislav Musicki,
• Claire Bouix-Peter,
• Loic Tomas,
• Gilles Ouvry,
• Rémy Morgentin,
• Laurent F. Hennequin and
• Craig S. Harris

Beilstein J. Org. Chem. 2021, 17, 156–165, doi:10.3762/bjoc.17.16

• -azabenzotriazole; hinge-binder; ionic hydrogenation; library; pyridine-2(1H)-one; Introduction During a recent medicinal chemistry program targeting a kinase to treat skin disorders, we identified the 4-amino-3-carboxamide disubstituted pyridine-2(1H)-one motif (1) as an interesting starting point. Recently, both

• our attention to ionic hydrogenation conditions [12]. Although ionic hydrogenation conditions have never been cited for this type of transformation, we anticipated that, if successful, sample preparation would be further simplified for the final preparative LC–MS purification step owing to the high

• hydrogenation [15], through addition of the hydride from triethylsilane to afford 1 after in situ hydrolysis of the triethylsilyloxy bond. HOAt alone does not degrade under these conditions and intermediate 21 has been identified and characterized from the reaction medium although we did not identify 2

Direct synthesis of anomeric tetrazolyl iminosugars from sugar-derived lactams

• Michał M. Więcław and
• Bartłomiej Furman

Beilstein J. Org. Chem. 2021, 17, 115–123, doi:10.3762/bjoc.17.12

• as the aldol reaction [30], Michael addition [31], Mannich reaction [32], and hydrogenation [33]. Results and Discussion Quite recently Xie and Dixon showed that it is possible to synthesize α-tetrazolylamines from simple and linear tertiary amides using an iridium-based catalytic protocol [19]. They

• widely used as organocatalysts. Such moieties are employed in a number of important synthetic transformations, including the aldol reaction [30], Michael addition [31], Mannich reaction [32], and hydrogenation [33]. We plan to test these possibilities in the near future. Stereochemistry and configuration

Progress in the total synthesis of inthomycins

• Bidyut Kumar Senapati

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

• enyne 127 in the presence of Pd(PPh3)4, CuI, and triethylamine to give (+)-135 in 62% yield. The double desilylation of compound (+)-135 using HF·pyridine in acetonitrile afforded (–)-136 in 91% yield. The semi-hydrogenation of (–)-136 to produce the desired (Z,Z,E)- triene (+)-87 was challenging under

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

• hydrogenation occurred with high stereoselectivity producing a single diastereoisomer of 29. Then, the amide was treated with methyllithium at −78 °C to provide ketone 30 in 85% yield. Subsequently, the intramolecular Mannich reaction was carried out, leading to the desired alkaloid, via precursor 32. Ketone 30

• diastereoisomeric mixture, converted to ketone (±)-37 via methylene derivative (±)-36, in 63% over two steps (Scheme 5). Ketone (±)-37 was converted to alkenyl triflate (±)-38 after treatment with LDA at −78 °C, followed by the Comins reagent [47]. (±)-38 was subjected to palladium-catalyzed hydrogenation

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

• -ketophosphonate 89 in 86% yield (Scheme 6A) [41]. Hydrogenation of 89 followed by an intramolecular Horner–Wadsworth–Emmons olefination produced hexacyclic enone 90 in 91% yield over two steps. The conversion of enone 90 to longeracinphyllin A (10) was achieved in three steps. The syntheses of daphenylline (11

• 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

3-Acetoxy-fatty acid isoprenyl esters from androconia of the ithomiine butterfly Ithomia salapia

• Florian Mann,
• Daiane Szczerbowski,
• Lisa de Silva,
• Melanie McClure,
• Marianne Elias and
• Stefan Schulz

Beilstein J. Org. Chem. 2020, 16, 2776–2787, doi:10.3762/bjoc.16.228

• of the fatty acid elongation cycle. The following elimination by a dehydratase (dh) leads to (2E,11Z)-2,11-octadecadienoic acid and after hydrogenation (hy) to (Z)-11-octadecenoic acid, completing the C2-elongation. A second elongation furnishes (Z)-3-hydroxy-13-eicosenoic acid. Similarly, a Δ11

Synthesis of purines and adenines containing the hexafluoroisopropyl group

• Viacheslav Petrov,
• Rebecca J. Dooley,
• Alexander A. Marchione,
• Elizabeth L. Diaz,
• Brittany S. Clem and
• William Marshall

Beilstein J. Org. Chem. 2020, 16, 2739–2748, doi:10.3762/bjoc.16.224

• relatively short list: the reduction of the OH group of the C(CF3)2OH moiety (this protocol was employed in the synthesis of enantiomerically pure (S)-5,5,5,5',5',5'-hexafluoroleucine [1]); the Wittig reaction of Ph3P=C(O)C(O)OR with hexafluoroacetone, followed by the hydrogenation of the CH=C(CF3)2 unit

Asymmetric Mannich reactions of (S)-N-tert-butylsulfinyl-3,3,3-trifluoroacetaldimines with yne nucleophiles

• Ziyi Li,
• Li Wang,
• Yunqi Huang,
• Haibo Mei,
• Hiroyuki Konno,
• Hiroki Moriwaki,
• Vadim A. Soloshonok and
• Jianlin Han

Beilstein J. Org. Chem. 2020, 16, 2671–2678, doi:10.3762/bjoc.16.217

• trifluoromethylpropargylamine is of general research interest [28][29][30][31][32]. The asymmetric Ru/(R)-CPA-catalyzed chemoselectivie biomimetic reduction [33] and the organocatalytic transfer hydrogenation [34] of fluorinated alkynylketimines have been developed for the synthesis of fluorinated propargylamines in good

A new method for the synthesis of diamantane by hydroisomerization of binor-S on treatment with sulfuric acid

• Rishat I. Aminov and
• Ravil I. Khusnutdinov

Beilstein J. Org. Chem. 2020, 16, 2534–2539, doi:10.3762/bjoc.16.205

• reaction stops after the hydrogenation step giving endo-endo-pentacyclo[7.3.1.12,5.18,10.03,7]tetradecane in 68% yield with excellent selectivity (100%). Keywords: binor-S; diamantane; hydroisomerization; sulfuric acid; tetrahydrobinor-S; Introduction Among the highly diverse polycyclic and cage

• compounds for the preparation of diamantane are three isomeric polycyclic hydrocarbons C14H20 3а–с, which are obtained by hydrogenation of the norbornadiene dimer, heptacyclo[8.4.0.02,12.03,8.04,6.05,9.011,13]tetradecane (binor-S, 2). Binor-S is hydrogenated in the presence of a platinum catalyst (Н2PtCl6

• diamantane in up to 99% yield (Scheme 1). As can be seen from Scheme 1, the synthesis of diamantane (1) from binor-S (2) is a two-step process, in which the hydrogenation performed in the first step is most complex and has always been an obstacle to the generation of large amounts of diamantane. In view of