Green and sustainable approaches for the Friedel–Crafts reaction between aldehydes and indoles

• Periklis X. Kolagkis,
• Eirini M. Galathri and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2024, 20, 379–426, doi:10.3762/bjoc.20.36

• various oxidation and hydrogenation reactions [105]. NanoAg-Pt doped silicate constitutes an efficient and recyclable catalyst that can be reused without a notable loss in catalytic activity (Scheme 17). Wanting to avoid the use of conventional heating, Karthikeyan and his co-workers turned to microwave

Optimizations of lipid II synthesis: an essential glycolipid precursor in bacterial cell wall synthesis and a validated antibiotic target

• Milandip Karak,
• Cian R. Cloonan,
• Brad R. Baker,
• Rachel V. K. Cochrane and
• Stephen A. Cochrane

Beilstein J. Org. Chem. 2024, 20, 220–227, doi:10.3762/bjoc.20.22

• , followed by in situ re-acetylation of the C2-amino group and C6-alcohol with acetic anhydride, resulting in the formation of disaccharide 4 in a one-pot fashion. The anomeric benzyl protecting group in disaccharide 4 was then removed via a Pd/C-catalyzed hydrogenation reaction, producing a mixture of α/β

Chiral phosphoric acid-catalyzed transfer hydrogenation of 3,3-difluoro-3H-indoles

• Yumei Wang,
• Guangzhu Wang,
• Yanping Zhu and
• Kaiwu Dong

Beilstein J. Org. Chem. 2024, 20, 205–211, doi:10.3762/bjoc.20.20

• synthesis of optically active difluoro-substituted indoline derivatives starting from the corresponding 3H-indoles by chiral phosphoric acid-catalyzed transfer hydrogenation was developed. Using Hantzsch ester as the hydrogen source under mild reaction conditions, the target products can be obtained with

• excellent yield and enantioselectivity. Keywords: asymmetric organocatalysis; chiral Brønsted acid; 3,3-difluoroindoline; Hantzsch ester; transfer hydrogenation; Introduction The introduction of fluoro atoms into organic molecules can alter their lipophilicity, solubility, metabolic stability, and

• great attention in organic synthesis. Various methods [9], including reductive hydrogenation [10][11], kinetic resolution [12][13][14], functionalization of indole [15], and de novo construction of chiral 2-substituted indolines, have been developed [16][17][18][19][20]. In recent years, the metal

N-Boc-α-diazo glutarimide as efficient reagent for assembling N-heterocycle-glutarimide diads via Rh(II)-catalyzed N–H insertion reaction

• Grigory Kantin,
• Pavel Golubev,
• Alexander Sapegin,
• Alexander Bunev and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2023, 19, 1841–1848, doi:10.3762/bjoc.19.136

• , resulting in glutarimides with a heterocyclic fragment at the α-position 1a–e – structures in demand for the design of CRBN ligands and immunomodulatory drugs. In compound 6n, catalytic hydrogenation was used to reduce the nitro group, resulting in the production of a benzotriazole analog of pomalidomide

Synthetic approach to 2-alkyl-4-quinolones and 2-alkyl-4-quinolone-3-carboxamides based on common β-keto amide precursors

• Yordanka Mollova-Sapundzhieva,
• Plamen Angelov,
• Danail Georgiev and
• Pavel Yanev

Beilstein J. Org. Chem. 2023, 19, 1804–1810, doi:10.3762/bjoc.19.132

• the nitro group with subsequent cyclization of the reduced intermediate (Scheme 2, conditions iv). We tried to carry out these reactions either with Zn in acetic acid/dichloromethane or by transfer hydrogenation with ammonium formate in the presence of Pd on charcoal. Both types of reductive

• get reduced to quinolones 5/8, which were isolated in good yields (Table 3 and Table 4). In the case of the Pd-catalyzed transfer hydrogenation of intermediates 3 the yields of products 5 in most cases were lower than those obtained with Zn/AcOH, regardless of the reaction duration. On the other hand

• , limiting the reaction time to 60–90 min under these conditions allowed some of the N-hydroxy derivatives 4 to be isolated in good yield (Table 5), even though it did not entirely prevent the formation of products 5. Palladium catalysis was not appropriate for the hydrogenation of compounds 3f and 3g

Recent advancements in iodide/phosphine-mediated photoredox radical reactions

• Tinglan Liu,
• Yu Zhou,
• Junhong Tang and
• Chengming Wang

Beilstein J. Org. Chem. 2023, 19, 1785–1803, doi:10.3762/bjoc.19.131

• hydrogenation or hydrogen transfer [40], electrocatalysis coupled with water oxidation [41], and sustained visible-light-induced photocatalysis [42]. Among the different strategies available, the use of a mild photocatalytic process involving hole-driven hydrogen transfer with hydrogen donors or hole scavengers

Application of N-heterocyclic carbene–Cu(I) complexes as catalysts in organic synthesis: a review

• Nosheen Beig,
• Varsha Goyal and
• Raj K. Bansal

Beilstein J. Org. Chem. 2023, 19, 1408–1442, doi:10.3762/bjoc.19.102

• multifunctional catalytic system 142 incorporating ruthenium nanoparticles (RuNPS) and an NHC–Cu–Cl complex supported on silica (Scheme 56). The catalyst, Ru@SiO2–[Cu(NHC)] was successfully applied to a one-pot tandem A3 reaction of an aldehyde, alkyne, and secondary amine followed by hydrogenation of the

• resulting propargylamines to give allylamines 144 and alkylamines 145 in quantitative yields (Scheme 57). This system is made up of a silica support that has been modified with a covalently linked NHC–Cu complex for the A3 coupling, as well as RuNPs for hydrogenation. Detailed investigations revealed that

• the A3 reaction is catalyzed by the NHC–Cu complex while the selective hydrogenation is catalyzed by Ru(0) nanoparticles. The versatility of this tandem catalytic approach was established by using a wide range of substrates. Furthermore, the catalytic activity and selectivity remained fairly constant

Synthesis of ether lipids: natural compounds and analogues

• Marco Antônio G. B. Gomes,
• Alicia Bauduin,
• Chloé Le Roux,
• Romain Fouinneteau,
• Wilfried Berthe,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2023, 19, 1299–1369, doi:10.3762/bjoc.19.96

• protection was not regioselective (a mixture of primary and secondary protected alcohols was formed). The acylation of the secondary alcohol was then achieved with acetic anhydride in the presence of pyridine. Then, the deprotection of the trityl moiety of compound 12.4 by catalytic hydrogenation failed

• trimethylamine to yield the phosphate 17.10 as an intermediate. Then, its reaction with trimethylamine produced the phosphocholine moiety and compound N3-PAF (17.11). Then, the amine (NH2-PAF) 17.12 was formed by catalytic hydrogenation and subsequently the (acetamido-PAF) 17.13 was formed by acetylation of the

• produced the PAF-analogue 19.3. The analogue 19.5 was prepared from 19.2 by debenzylation using catalytic hydrogenation to produce 19.4 that was then acetylated to produce 19.5. 19.3 or 19.5 were not able to induce either platelet aggregation or bronco-constrictive activities. A third modification of the

Enabling artificial photosynthesis systems with molecular recycling: A review of photo- and electrochemical methods for regenerating organic sacrificial electron donors

• Grace A. Lowe

Beilstein J. Org. Chem. 2023, 19, 1198–1215, doi:10.3762/bjoc.19.88

• another experiment, the team chemically oxidized the sacrificial donor and regenerated it by hydrogenation. Carpenter and co-workers briefly discussed phase separation to enable sacrificial donor recycling by improving the recovery of the oxidized donor [32]. This idea was central to the works published

• reactor [39]. Itoh and co-workers were studying electrochemical hydrogenation for LOHCs rather than the regeneration of sacrificial donors. A lot of small organic compounds have been considered for electrochemical hydrogenation for LOHCs but many do not have the required oxidation potentials to be

• sacrificial donors [40]. More recently, other groups have published the electrochemical hydrogenation of carbonyl compounds using more earth-abundant electrocatalysts. For instance, Siewert and co-worker used a manganese complex as an electrocatalyst for the chemoselective carbonyl hydrogenation [41

Photoredox catalysis harvesting multiple photon or electrochemical energies

• Mattia Lepori,
• Simon Schmid and
• Joshua P. Barham

Beilstein J. Org. Chem. 2023, 19, 1055–1145, doi:10.3762/bjoc.19.81

Strategies in the synthesis of dibenzo[b,f]heteropines

• David I. H. Maier,
• Barend C. B. Bezuidenhoudt and
• Charlene Marais

Beilstein J. Org. Chem. 2023, 19, 700–718, doi:10.3762/bjoc.19.51

• ]oxepine derivatives 101 (Scheme 21). Lin et al. [62] used copper-catalysed coupling in their total synthesis of bulbophylol-B (105), a substituted dihydrobenzo[b,f]oxepine. The authors synthesised an intermediate stilbene via Wittig reaction, followed by hydrogenation to give dihydrostilbene 104, which

• underwent intramolecular Ullmann-type coupling catalysed by CuBr·DMS to form the fused dihydro[b,f]oxepine ring system in 89% yield, whereafter hydrogenation afforded 105 in almost quantitative yield (Scheme 22). The method is a sequence of 12 steps, the majority of which are to prepare Wittig reagent

Mechanochemical solid state synthesis of copper(I)/NHC complexes with K₃PO₄

• Ina Remy-Speckmann,
• Birte M. Zimmermann,
• Mahadeb Gorai,
• Martin Lerch and
• Johannes F. Teichert

Beilstein J. Org. Chem. 2023, 19, 440–447, doi:10.3762/bjoc.19.34

• been shown to be active in a variety of reduction/hydrogenation transformations employing dihydrogen as terminal reducing agent. Keywords: ball mill; bifunctional catalysis; catalytic hydrogenations; copper; mechanochemical synthesis; N-heterocyclic carbenes; Introduction Prominent goals of green

• inactive complexes (see Supporting Information File 1 for details). This also supports the notion that during catalytic ester hydrogenation, the guanidinium moiety acts as a hydrogen bond donor to the esters [48]. The formation of a CO2 adduct hinders the ability to form hydrogen bonds. Furthermore

• the standard reactions for catalytic hydrogenations with copper(I)/NHC complexes [4]. In this vein, we tested complex 5 from solid and liquid phase synthesis in the catalytic hydrogenation of esters, carbonyl compounds and in the semihydrogenation of alkynes. In the catalytic hydrogenation of ethyl

Combretastatins D series and analogues: from isolation, synthetic challenges and biological activities

• Jorge de Lima Neto and
• Paulo Henrique Menezes

Beilstein J. Org. Chem. 2023, 19, 399–427, doi:10.3762/bjoc.19.31

• reaction [33]. Thus, Knoevenagel condensation using the diaryl ether 29 and malonic acid gave the corresponding α,β-unsaturated compound 30, which was submitted to a concomitant hydrogenation of the double bond and the nitro group to give compound 31. Sequential diazotization/halogenation and

• esterification reactions gave the ester 33 which was submitted to a Sonogashira coupling reaction with propargyl alcohol to give the advanced intermediate 34 [34]. Partial hydrogenation of the triple bond in 34 using Lindlar’s catalyst led to the cis-allylic alcohol 35 and subsequent ester hydrolysis led to the

• -unsaturated ester 42. Conversion of the installed alkene to the corresponding thioether followed by the reduction of the ester moiety using DIBAL gave the compound 43, which was subjected to a Stille coupling reaction [38] to yield compound 45. Hydrogenation reaction in the presence of metallic Mg [39

Continuous flow synthesis of 6-monoamino-6-monodeoxy-β-cyclodextrin

• János Máté Orosz,
• Dóra Ujj,
• Petr Kasal,
• Gábor Benkovics and
• Erika Bálint

Beilstein J. Org. Chem. 2023, 19, 294–302, doi:10.3762/bjoc.19.25

• hydrogenation of N3-β-CD (3) in the presence of Pd/C under a H2 atmosphere. In CD chemistry, this method was first described by Petter et al. [8] in the early 1990s. This method is very popular with small-scale syntheses because only gaseous N2 is formed as a byproduct and no purification is required when pure

• ), evaporate the water/THF solvent, and introduce the Ts-β-CD (2) dissolved in DMF to the second part of the flow system. In order to simplify the azidation and subsequent reduction, Ts-β-CD (2) prepared from batch and properly purified was utilized. The azidation and the hydrogenation were compatible with

• each other, however, after the azidation took place, water needed to be introduced to the system before the hydrogenation to ensure full conversion during the reduction. According to our previous results, the reduction of N3-β-CD (3) went to completion in a DMF/H2O 1:4 mixture, so this solvent was

Strategies to access the [5-8] bicyclic core encountered in the sesquiterpene, diterpene and sesterterpene series

• Cécile Alleman,
• Charlène Gadais,
• Laurent Legentil and
• François-Hugues Porée

Beilstein J. Org. Chem. 2023, 19, 245–281, doi:10.3762/bjoc.19.23

• unit. The final steps of this synthesis involved alcohol deprotection, double bond hydrogenation and oxidation, and allowed the total synthesis of (−)-nitidasin (93) in 27 steps. Naupliolide (97) was first isolated from the aerial parts of Nauplius graveolens in 2006. This tetracyclic natural product

Investigation of cationic ring-opening polymerization of 2-oxazolines in the “green” solvent dihydrolevoglucosenone

• Solomiia Borova and
• Robert Luxenhofer

Beilstein J. Org. Chem. 2023, 19, 217–230, doi:10.3762/bjoc.19.21

• Dihydrolevoglucosenone (DLG) is prepared by hydrogenation of levoglucosenone in the presence of palladium as a catalyst. Recently, Debsharma et al. reported the CROP of levoglucosenyl alkyl ether in CH2Cl2 at 0 °C and at room temperature using triflic acid or boron trifluoride etherate as initiators [46][47][48]. The 1H

Germacrene B – a central intermediate in sesquiterpene biosynthesis

• Houchao Xu and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2023, 19, 186–203, doi:10.3762/bjoc.19.18

• Humulus lupulus, and the structures of both compounds were elucidated by 1H NMR spectroscopy and catalytic hydrogenation, yielding the same compound selinane in both cases [54]. Both compounds were later also isolated from Cannabis sativa [55]. Unfortunately, no optical rotations were given in these

• catalytic hydrogenation to 27, dehydration to a mixture of alkenes (28) and hydrogenation to selinane (29) it was concluded that 11 was a selinane sesquiterpene alcohol (Scheme 9B) [75]. Four years later, based on NMR data Bhattacharyya and co-workers suggested a cis-ring junction for 11 [76], but a

• through Wagner–Meerwein rearrangement to I2c and deprotonation, but also this compound is not known as a natural product. This hydrocarbon has been obtained by partial hydrogenation of (+)-α-vetispirene (49) in a small scale reaction using PtO2 hydrate in CHCl3 as a catalyst (Scheme 12F). The amounts of

1,4-Dithianes: attractive C2-building blocks for the synthesis of complex molecular architectures

• Bram Ryckaert,
• Ellen Demeyere,
• Frederick Degroote,
• Hilde Janssens and
• Johan M. Winne

Beilstein J. Org. Chem. 2023, 19, 115–132, doi:10.3762/bjoc.19.12

• alkylations. Herein, the lithiated sulfur-heterocycles act as a cis-vinyl anion equivalent, a strategy that was developed by Palumbo and co-workers. The method shows some complementarity to the more classical acetylene alkylations, followed by partial hydrogenation to the cis-olefin (see Scheme 10 and Scheme

• some experimentation, the desired chemoselective transformation can be achieved in almost all cases, including for sensitive substrates such as yohimbine-derived compound 102 [30]. A common problem is the concomitant hydrogenation of alkenes, which can be hard to avoid, as seen in the

• . This was required to avoid undesired hydrogenation of both the vinyl and the cyclopropane moieties, which both proved sensitive to the action of Raney nickel. A particularly troublesome episode that demonstrates the problems one can encounter in dithiane desulfurizations, was encountered in our labs

Organophosphorus chemistry: from model to application

• György Keglevich

Beilstein J. Org. Chem. 2023, 19, 89–90, doi:10.3762/bjoc.19.8

• newly prepared thiophosphorus acids were not efficient in the asymmetric transfer hydrogenation of 2-phenylquinoline. However, they may find application in other model reactions. These days, stereoselective syntheses incorporating “green" chemical considerations are of utmost importance in medicinal

Inline purification in continuous flow synthesis – opportunities and challenges

• Jorge García-Lacuna and
• Marcus Baumann

Beilstein J. Org. Chem. 2022, 18, 1720–1740, doi:10.3762/bjoc.18.182

• reported by Pitts and collaborators. This study achieves full removal of metal species after common homogenous catalytic reactions such as a Suzuki–Miyaura reaction, Sonogashira reaction or hydrogenation mediated by Wilkinson’s catalyst [84]. Other interesting examples to remove transition metals in

Total synthesis of grayanane natural products

• Nicolas Fay,
• Rémi Blieck,
• Cyrille Kouklovsky and
• Aurélien de la Torre

Beilstein J. Org. Chem. 2022, 18, 1707–1719, doi:10.3762/bjoc.18.181

• alcohol on the A ring in 75% yield. The C3 epimer was also obtained in 4% yield and confirmed by X-ray diffraction. Hydrogenation of the sterically hindered C1–C2 alkene was accomplished using a combination of Mn(dpm)3 and Ph(iPrO)SiH2, providing grayanotoxin III in 51% yield. The authors also achieved

• presented some difficulties, and the authors decided to investigate the use of a free ketone. The partial hydrogenation of alkyne 72 proved to be inefficient, due to a lack of chemoselectivity involving competitive olefin reduction on the bicylo[3.2.1]octane. To overcome the over-oxidation, 72 was treated

• with m-CPBA, providing epoxide 73 as the main product in 71% yield (dr = 6:1). Lindlar hydrogenation of the alkyne and cyclization proceeded smoothly, and the tetracyclic skeleton 74 was obtained in moderate yield. However, the synthesis of pierisformaside C was never completed. The missing

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