Redox-active molecules as organocatalysts for selective oxidative transformations – an unperceived organocatalysis field

• Elena R. Lopat’eva,
• Igor B. Krylov,
• Dmitry A. Lapshin and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2022, 18, 1672–1695, doi:10.3762/bjoc.18.179

• activation for hydrogenation of various organic substrates. More recently, SET reactivity of FLP was discovered [155]. The FLP-catalyzed dehydrogenation of N-protected indolines with H2 release [156] is depicted in Scheme 39. According to the proposed mechanism, the reaction starts with a hydride transfer

Synthetic study toward the diterpenoid aberrarone

• Liang Shi,
• Zhiyu Gao,
• Yiqing Li,
• Yuanhao Dai,
• Yu Liu,
• Lili Shi and
• Hong-Dong Hao

Beilstein J. Org. Chem. 2022, 18, 1625–1628, doi:10.3762/bjoc.18.173

• was further confirmed through X-ray crystallographic analysis. With the key intermediate 10 in hand, we were in a position to test the planned two-step transformation including the palladium-catalyzed reductive cross coupling with HCO2H followed by Pd/C-catalyzed hydrogenation. To our surprise, the

• hydrogenation turned out to be a difficult transformation due to the steric hindered environment of the trisubstituted double bond, mainly caused by the bulky OTBS group. However, direct subjection of compound 16 to hydrogenation [38] afforded reduction of both triflate and double bond. The plausible pathway

• for this facile transformation might proceed with first hydrogenation followed by the substitution of the labile triflate ester (for details, see Supporting Information File 1). Moving forward, compound 17 was further converted into alkynone 9 through DIBAL-H reduction, nucleophilic addition and Dess

A new route for the synthesis of 1-deazaguanine and 1-deazahypoxanthine

• Raphael Bereiter,
• Marco Oberlechner and
• Ronald Micura

Beilstein J. Org. Chem. 2022, 18, 1617–1624, doi:10.3762/bjoc.18.172

• under Pd/C-catalyzed hydrogenation to provide 1-deazaguanine (11) in six steps and 6% overall yield. A total of 120 mg of 11 were obtained in the course of this study. At this point, we note that N9-tert-butyloxycarbonyl-protected 6-iodo-1-deazapurine was successfully synthesized but not stable during

• tetrahydropyranyl protecting group. The final step was then accomplished by hydrogenation of benzyl ether 31 to obtain 1-deazahypoxanthine (30) in 44% overall yield. Conclusion We have developed convenient synthetic routes for 1-deazaguanine (11) and 1-deazahypoxanthine (30). Starting from readily accessible 6-iodo

Solid-phase total synthesis and structural confirmation of antimicrobial longicatenamide A

• Takumi Matsumoto,
• Takefumi Kuranaga,
• Yuto Taniguchi,
• Weicheng Wang and
• Hideaki Kakeya

Beilstein J. Org. Chem. 2022, 18, 1560–1566, doi:10.3762/bjoc.18.166

• synthesis, and then hydrogenation of the double bond in 17 provided intermediate 18. Oxidation of the alcohol 18 to acid 10 was realized with the combination of Dess–Martin oxidation [17][18] and Pinnick oxidation [19]. Another unusual amino acid 7 was also synthesized from ᴅ-serine (20, Scheme 3). The

Efficient synthesis of aziridinecyclooctanediol and 3-aminocyclooctanetriol

• Emine Salamci and
• Ayse Kilic Lafzi

Beilstein J. Org. Chem. 2022, 18, 1539–1543, doi:10.3762/bjoc.18.163

• relative to the proton H-2. For the synthesis of the aminocyclooctanetriol 13, hydrogenation of the azido alcohol 11 gave amine 12 in 95% yield (Scheme 2). Subsequent, benzyl deprotection with BCl3 of 12 resulted in the target compound 13 in 85% yield. The structures of compounds 12 and 13 are completely

Design, synthesis, and evaluation of chiral thiophosphorus acids as organocatalysts

• Karen R. Winters and
• Jean-Luc Montchamp

Beilstein J. Org. Chem. 2022, 18, 1471–1478, doi:10.3762/bjoc.18.154

• asymmetric organocatalysis. In order to eliminate the need for C2-symmetry in common CPAs, various scaffolds containing C1-symmetrical thiophosphorus acids were chosen. These new compounds were synthesized and evaluated in the asymmetric transfer hydrogenation of 2-phenylquinoline. Although the efficacy of

• thioacid hybrid-CPAs (Scheme 5) [31]. The transfer hydrogenation of 2-phenylquinoline with a Hantzsch ester 19 is a test reaction commonly used in asymmetric synthesis. The best performing of Guinchard's thiophostones 18 was the pivalate ester (R1 = t-BuC(O)) with an 86% yield of 20 and a 52% ee (19 R2

• thiophosphorus acid 2. Synthesis of N-biphenyl-DOPO CPA 4. Transfer hydrogenation of 2-phenylquinoline and transition-state proposed by Guinchard and coworkers [28]. P-stereogenic CPAs in the transfer hydrogenation of quinolines. Supporting Information Supporting Information File 332: Experimental procedures

1,4,6,10-Tetraazaadamantanes (TAADs) with N-amino groups: synthesis and formation of boron chelates and host–guest complexes

• Artem N. Semakin,
• Ivan S. Golovanov,
• Yulia V. Nelyubina and
• Alexey Yu. Sukhorukov

Beilstein J. Org. Chem. 2022, 18, 1424–1434, doi:10.3762/bjoc.18.148

• . Hydrazinium dihydrochloride was isolated in some cases (confirmed by X-ray, mp, and FT-IR data) demonstrating the degradation of the heteroadamantane cage. Deprotection of Cbz derivatives by hydrogenation over Pd–C was more productive. Thus, hydrogenolysis of product 8b delivered the 1N,2O-TAAD derivative 15

B–N/B–H Transborylation: borane-catalysed nitrile hydroboration

• Filip Meger,
• Alexander C. W. Kwok,
• Franziska Gilch,
• Dominic R. Willcox,
• Alex J. Hendy,
• Kieran Nicholson,
• Andrew D. Bage,
• Thomas Langer,
• Thomas A. Hunt and
• Stephen P. Thomas

Beilstein J. Org. Chem. 2022, 18, 1332–1337, doi:10.3762/bjoc.18.138

• ]. Traditionally, the reduction of nitriles to primary amines relied on stoichiometric hydride reagents [4]. Current catalytic methods for nitrile reduction, hydrogenation [5][6] or hydroboration [7][8], generally rely on metal catalysts, designer ligands, forcing reaction conditions (such as elevated temperatures

• and pressures) or lack extensive functional group tolerance. In particular, catalysed nitrile hydroboration strategies are still underdeveloped compared with hydrogenation, but offer a nascent alternative to this established field. The pursuit of sustainable chemical transformations has driven

Vicinal ketoesters – key intermediates in the total synthesis of natural products

• Marc Paul Beller and
• Ulrich Koert

Beilstein J. Org. Chem. 2022, 18, 1236–1248, doi:10.3762/bjoc.18.129

• -substitution. Subsequent transesterification gave the α-ketoester 75, which was used in a Wittig reaction. The undesired Z-configured double bond was isomerized to the E-alkene and final hydrogenation delivered corynoxine (76). (+)-Gracilamine The Mannich reaction was also used by Nagasawa et al. as a key step

Derivatives of benzo-1,4-thiazine-3-carboxylic acid and the corresponding amino acid conjugates

• Péter Kisszékelyi,
• Tibor Peňaška,
• Klára Stankovianska,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2022, 18, 1195–1202, doi:10.3762/bjoc.18.124

• hydrogenation; Introduction Heterocyclic compounds with a benzothiazine moiety are attractive building blocks in medicinal chemistry. Benzo-1,4-thiazine derivatives possess a wide range of biological and pharmacological properties, such as anticancer and antitumor, antioxidant, antimicrobial, antibacterial

• isocyanoacetate (13). The palladium-catalyzed hydrogenation of intermediate 14 gave the racemic N-formyl-protected amino acid methyl ester 15 in good yield. Using either concentrated HCl (aq) or in situ-formed HCl from the reaction of MeOH and acetyl chloride, compound 15 could easily be deprotected to gain

• either the salt 16a·HCl or the free amine 16a in good to excellent yield (Scheme 3). We also explored the asymmetric catalytic hydrogenation of adduct 14. Our first attempt at the reduction using organocatalyzed transfer hydrogenation was unsuccessful (see Supporting Information File 1). The (R)-Ru(OAc)2

Synthesis of tryptophan-dehydrobutyrine diketopiperazine and biological activity of hangtaimycin and its co-metabolites

• Houchao Xu,
• Anne Wochele,
• Minghe Luo,
• Gregor Schnakenburg,
• Yuhui Sun,
• Heike Brötz-Oesterhelt and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2022, 18, 1159–1165, doi:10.3762/bjoc.18.120

• -tryptophan (5) that was converted through a standard transformation into the methyl ester 6 and then through sequential reductive aminations with benzaldehyde and paraformaldehyde into 7 (Scheme 2) [13]. Cleavage of the benzyl group by catalytic hydrogenation afforded 8 that was coupled with tert

• step using milder conditions (Scheme 3). The newly developed synthesis started from 7 that was Boc-protected at the indole to yield 11. Removal of the benzyl group by catalytic hydrogenation to 12 was followed by coupling with benzyloxycarbonyl (Cbz) and methoxymethyl (MOM)-protected threonine to give

• 13. Removal of the Cbz group by catalytic hydrogenation proceeded with spontaneous cyclisation to 14. With this material, the elimination of the MOM group smoothly proceeded by treatment with KH and 18-crown-6 in THF at 25 °C to 15, that upon removal of the Boc group with TFA and 1,3-dimethoxybenzene

Electrochemical hydrogenation of enones using a proton-exchange membrane reactor: selectivity and utility

• Koichi Mitsudo,
• Haruka Inoue,
• Yuta Niki,
• Eisuke Sato and
• Seiji Suga

Beilstein J. Org. Chem. 2022, 18, 1055–1061, doi:10.3762/bjoc.18.107

• Koichi Mitsudo Haruka Inoue Yuta Niki Eisuke Sato Seiji Suga Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University, 3-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530, Japan 10.3762/bjoc.18.107 Abstract Electrochemical hydrogenation of enones using a

• proton-exchange membrane reactor is described. The reduction of enones proceeded smoothly under mild conditions to afford ketones or alcohols. The reaction occurred chemoselectively with the use of different cathode catalysts (Pd/C or Ir/C). Keywords: enone; hydrogenation; iridium; palladium; PEM

• reactor; Introduction Catalytic hydrogenation of α,β-enones is a significant transformation in organic synthesis [1]. Hydrogenation of enones can give ketones, allyl alcohols, and saturated alcohols, and the control of the chemoselectivity is important. Therefore, there have been numerous studies on the

Synthesis of odorants in flow and their applications in perfumery

• Merlin Kleoff,
• Paul Kiler and
• Philipp Heretsch

Beilstein J. Org. Chem. 2022, 18, 754–768, doi:10.3762/bjoc.18.76

• . For compound 6, both individual steps were combined for a two-step aldol condensation/hydrogenation flow sequence providing raspberry ketone methyl ether (6) on a gram scale in 75% overall yield. Interestingly, also alternative flow protocols for the synthesis of 4-aryl-3-buten-2-ones 3 and 4 were

• of hydrogen with a pressure of 1 bar, a good selectivity for the hydrogenation of the external alkene is achieved providing enone 27. The reaction mixture containing enone 27 is then mixed with tosylhydrazone and passed through a column with sulfonic acidic resin Amberlyst-15 to catalyze the

• -nonadien-1-al are nearly ubiquitous in modern perfumery for both women and men, even appearing in dark or woody fragrances such as Hugo Boss: Soul. In 2012, Barbaro and co-workers developed a synthesis for alkene 32 by selective hydrogenation of the corresponding alkyne (Scheme 7) [37]. Instead of using a

Inductive heating and flow chemistry – a perfect synergy of emerging enabling technologies

• Conrad Kuhwald,
• Sibel Türkhan and
• Andreas Kirschning

Beilstein J. Org. Chem. 2022, 18, 688–706, doi:10.3762/bjoc.18.70

• hydrogenation. 2.3 Dry and steam methane reforming The commencement of the energy transformation is associated with the search for alternative and more environmentally friendly energy sources [27]. The dry reforming of methane is a particularly interesting process in this context (Scheme 2, reaction 1). A

• pressure, much higher temperatures around 950 °C are actually required. At these high temperatures, the selectivity of the process is a challenge. Possible side reactions such as hydrogenation of CO and CO2, decomposition of CH4, and the Boudouard reaction lead to the formation of elemental carbon [31

• performance is characterized by the specific absorption rate (SAR) of the material. The tested materials showed high SAR values when brought into an electromagnetic field of 50 mT at a frequency of 54 kHz. Under these conditions the particles were able to catalyze the hydrogenation of CO. The presence of

New synthesis of a late-stage tetracyclic key intermediate of lumateperone

• Mátyás Milen,
• Bálint Nyulasi,
• Tamás Nagy,
• Gyula Simig and
• Balázs Volk

Beilstein J. Org. Chem. 2022, 18, 653–659, doi:10.3762/bjoc.18.66

• carbonyl (21b→22b) preceded the reduction of the C–C double bond of 22b. Both the hydrolytic desethoxycarbonylation of (±)-9a as well as the removal of the benzyloxycarbonyl group of (±)-9b by catalytic hydrogenation afforded (±)-10 which was N-alkylated with 4-chloro-1-(4-fluorophenyl)butan-1-one (11) to

• . Reduction of the quaternary ammonium salt 28 with sodium borohydride gave tetrahydroquinoxaline 29. Its reaction with trifluoroacetic anhydride (TFAA) to give 30 and removal of the benzyl group by catalytic hydrogenation afforded N-trifluoroacetyl-1,2,3,4-tetrahydroquinoxaline (31). Compound 31 was then

BINOL as a chiral element in mechanically interlocked molecules

• Matthias Krajnc and
• Jochen Niemeyer

Beilstein J. Org. Chem. 2022, 18, 508–523, doi:10.3762/bjoc.18.53

• ) [59]. The catenane catalyst allows for the asymmetric transfer hydrogenation of 2-substituted quinolines by Hantzsch esters in a highly stereoselective fashion [60]. It was found that the catenated catalyst gives superior stereoselectivities in comparison to the macrocyclic and the acyclic reference

• desymmetrization reaction of meso-1,2-diols with rotaxane (R)-42. Synthesis of Niemeyer´s axially chiral [2]catenane (S,S)-47. Results for the enantioselective transfer hydrogenation of 2-phenylquinoline with catalysts (S,S)-47, (S)-48, and (S)-49. Synthesis of Niemeyer´s chiral [2]rotaxanes (S)-56/57. Results for

Tosylhydrazine-promoted self-conjugate reduction–Michael/aldol reaction of 3-phenacylideneoxindoles towards dispirocyclopentanebisoxindole derivatives

• Sayan Pramanik and
• Chhanda Mukhopadhyay

Beilstein J. Org. Chem. 2022, 18, 469–478, doi:10.3762/bjoc.18.49

• generation of new cascade reactions to construct carbo- and heterocyclic moieties [27][28], we aimed to synthesize dispirocyclopentanebisoxindoles in one pot operation using a new protocol. Chemical hydrogenation of double bonded compounds like α,β-unsaturated ketones, approaching to saturated ketones, is an

The asymmetric Henry reaction as synthetic tool for the preparation of the drugs linezolid and rivaroxaban

• Martin Vrbický,
• Karel Macek,
• Jaroslav Pochobradský,
• Jan Svoboda,
• Miloš Sedlák and
• Pavel Drabina

Beilstein J. Org. Chem. 2022, 18, 438–445, doi:10.3762/bjoc.18.46

• 26 were chosen. The reduction of the nitro groups in 24 and 26 via the hydrogenation procedure proceeded smoothly with almost quantitative yields; the amine intermediates were immediately used in the next step. Hence, the N-acylation reactions were performed by the action of the corresponding

Menadione: a platform and a target to valuable compounds synthesis

• Acácio S. de Souza,
• Ruan Carlos B. Ribeiro,
• Dora C. S. Costa,
• Fernanda P. Pauli,
• David R. Pinho,
• Matheus G. de Moraes,
• Fernando de C. da Silva,
• Luana da S. M. Forezi and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 381–419, doi:10.3762/bjoc.18.43

• deposition of gold on metallic fluorides allowed the one-pot hydroacetylation of menadione (10) to diacetylated menadiol 72, while the deposition of gold on silica allowed only the hydrogenation of 10 to 14 (Scheme 22B). The authors also observed that catalysis by hydroxylated fluorides led to a higher

Site-selective reactions mediated by molecular containers

• Rui Wang and
• Yang Yu

Beilstein J. Org. Chem. 2022, 18, 309–324, doi:10.3762/bjoc.18.35

• hydrogenation reaction mediated by a supramolecular catalyst was reported by Raymond, Bergman and Toste in 2019 (Figure 7) [64]. In this example, the supramolecular catalyst was prepared in situ by mixing a rhodium complex with the Ga4L612− cage host G, which had a relatively larger size with pyrene-walled

• achieved with just the rhodium catalyst, by which in contrast, the fully hydrogenated product was obtained. Other series of intermolecular comparative experiments also showed the selectivity of the hydrogenation for the sterically accessible alkene over other sites and even in the presence of inherently

• more reactive alkynes and allylic alcohols. Both the microenvironment of the supramolecular catalyst and the steric profile of the substrate were responsible for the site-selectivity of hydrogenation. This beautiful work of a supramolecular-mediated catalytic site-selective reaction exhibited the

Synthesis and late stage modifications of Cyl derivatives

• Phil Servatius and
• Uli Kazmaier

Beilstein J. Org. Chem. 2022, 18, 174–181, doi:10.3762/bjoc.18.19

• as impurity, which could not be separated from the product. Subsequent hydrogenation proceeded readily and afforded the saturated cyclopeptide 13. However, the impurity could also not be removed on this stage. Apparently, the Cyl derivatives with a short side chain are not good candidates for further

Ready access to 7,8-dihydroindolo[2,3-d][1]benzazepine-6(5H)-one scaffold and analogues via early-stage Fischer ring-closure reaction

• Irina Kuznetcova,
• Felix Bacher,
• Daniel Vegh,
• Hsiang-Yu Chuang and
• Vladimir B. Arion

Beilstein J. Org. Chem. 2022, 18, 143–151, doi:10.3762/bjoc.18.15

• led exclusively to the desired isomer 5 with the nitrophenyl group in position 3, most likely due to the steric effect. Then, the nitro group in 5 was reduced by hydrogenation under 4 bar using Pd/C as catalyst to yield the desired amine 6 in 78% yield. Subsequently, the desired chloroacetyl

• previous observations [38]. Reduction of the nitro group by palladium-catalyzed hydrogenation in dry methanol gave 2a in 92% yield. Interestingly compound 2a undergoes ring-closure reaction spontaneously at room temperature to give trace amounts of 3a (59 mg, 2%) after column chromatography, when a 3.1 g

• [2,3-d][1]benzazepin-6(5H)-one (3a). This procedure delivered analytically pure 3a in 80% yield as also confirmed by SC-XRD (Figure 3). The final step to structure C required removal of the benzyl group. Debenzylation of amines is commonly performed by palladium-catalyzed hydrogenation [40]. However

Recent advances and perspectives in ruthenium-catalyzed cyanation reactions

• Thaipparambil Aneeja,
• Cheriya Mukkolakkal Abdulla Afsina,
• Padinjare Veetil Saranya and
• Gopinathan Anilkumar

Beilstein J. Org. Chem. 2022, 18, 37–52, doi:10.3762/bjoc.18.4

• 2008, Bhanage et al. developed a novel methodology for the synthesis of alkyl iodides/nitriles using ruthenium tris(2,2,6,6-tetramethyl-3,5-heptanedionate) (Ru(TMHD)3) as the catalyst (Scheme 24) [47]. This catalyst was found highly efficient in the hydrogenation, iodination, and cyanation reaction of

The enzyme mechanism of patchoulol synthase

• Houchao Xu,
• Bernd Goldfuss,
• Gregor Schnakenburg and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2022, 18, 13–24, doi:10.3762/bjoc.18.2

• proceeded with full retainment of the labelling in both cases (Scheme 1B). Subsequent chemical degradation through acid catalysed conversion into 5, oxidative cleavage to the diketone 13, BF3∙OEt2 mediated ring closure by aldol reaction and catalytic hydrogenation gave 14. For both experiments a full

• experiment with [12,13-14C,1-3H]FPP was expected for the aldol reaction of 13, but is more difficult to understand in the experiment with [12,13-14C,6-3H]FPP. In this case the loss of 3H was explained by an exchange against 1H during catalytic hydrogenation [9]. One year later, Akhila et al. proposed an

First total synthesis of hoshinoamide A

• Haipin Zhou,
• Zihan Rui,
• Yiming Yang,
• Shengtao Xu,
• Yutian Shao and
• Long Liu

Beilstein J. Org. Chem. 2021, 17, 2924–2931, doi:10.3762/bjoc.17.201

• , ensuring the smooth progress of the total synthesis of hoshinoamide A. With the tripeptide 7 in hand, we went on to construct the peptide scaffold (Scheme 3). When tripeptide 7 was subjected to Pd-catalyzed hydrogenation conditions [16], the benzyl group was selectively cleaved to generate 8. Treatment of