Sulfate radical anion-induced benzylic oxidation of N-(arylsulfonyl)benzylamines to N-arylsulfonylimines

• Joydev K. Laha,
• Pankaj Gupta and
• Amitava Hazra

Beilstein J. Org. Chem. 2023, 19, 771–777, doi:10.3762/bjoc.19.57

• , however, in varying yields (Table 1, entries 8–11). While replacing the solvent MeCN with DCE delivered 2a in 89% yield, and a dramatic reduction in the yield of 2a was observed when H2O was used as the solvent (Table 1, entries 12 and 13). Therefore, the conditions listed in entry 5 of Table 1 were

Honeycomb reactor: a promising device for streamlining aerobic oxidation under continuous-flow conditions

• Masahiro Hosoya,
• Yusuke Saito and
• Yousuke Horiuchi

Beilstein J. Org. Chem. 2023, 19, 752–763, doi:10.3762/bjoc.19.55

• , which diminishes the atom economy [2]. To overcome this limitation, the use of molecular oxygen (O2) present in air as an oxidant is one of the ideal solutions [10][11]. The reduction of O2 generates only water as a byproduct, leading to high atom-economy processes. However, the use of O2 as an oxidant

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

• of o-nitrotoluene (22) Reduction to 2,2'-diaminobibenzyl (20) Ring-closing via amine condensation Catalytic dehydrogenation 1.1 Oxidative coupling of o-nitrotoluene (22) and reduction to 2,2'-diaminobibenzyl (20) The preparation of dinitrobibenzyl (21) can be achieved by the oxidative coupling of

• transition metal (Ni, Fe, V) porphyrin catalysts and oxygen. Catalytic reduction (H2, Pd/C) affords 2,2'-diaminobibenzyl (20) in the subsequent step [28]. 1.2 Ring-closing via amine condensation The initial synthesis of 10,11-dihydro-5H-dibenzo[b,f]azepine (2a) was reported in 1899 by Thiele and Holzinger

• relies on a double Sonogashira coupling [(i) and (iii)], reduction (iv), and bromination (v), followed by Buchwald–Hartwig amination (viii) (Scheme 14). While interesting, the reaction has limited substrate scope due to the reliance on a late-stage bromination. To achieve the correct ortho-bromo

Synthesis of medium and large phostams, phostones, and phostines

• Jiaxi Xu

Beilstein J. Org. Chem. 2023, 19, 687–699, doi:10.3762/bjoc.19.50

• . The RCM reaction was performed in the presence of Grubbs first generation catalyst in DCM, affording 2-(4-methylphenyl)benzothiophene-fused 2-(benzyloxy)-3,4,5,6,7,10-hexahydro-1,2-oxaphosphecine 2-oxide 31 in 70% yield. After hydrazine reduction and Pd-catalyzed hydrogenolysis, it was converted into

Synthesis, structure, and properties of switchable cross-conjugated 1,4-diaryl-1,3-butadiynes based on 1,8-bis(dimethylamino)naphthalene

• Semyon V. Tsybulin,
• Ekaterina A. Filatova,
• Alexander F. Pozharskii,
• Valery A. Ozeryanskii and
• Anna V. Gulevskaya

Beilstein J. Org. Chem. 2023, 19, 674–686, doi:10.3762/bjoc.19.49

• electrode, and reference electrode Ag/Ag+ 0.01 M AgNO3 (Figure 11, Table 4). Compounds 5a–d displayed two waves of irreversible oxidation in the potentials range of 0.0–1.1 V and one reduction wave (−1.5 to −1.6 V) with the little variation of the potentials induced by the substituent R. The CV curve of

• nitro derivative 5e demonstrated the minimum peak current. Considering that the current is a quantitative expression of how fast an electrochemical process is happening, compound 5e shows the lowest oxidation rate. In this case, two quasi-reversible reduction waves with lower E1/2ox compared to the

• shows the most positive oxidation potential and rate of the first oxidation as well as the lowest rate of reduction. However, the relatively small differences may simply be due to the different local solvation of the CF3 substituent. Conclusion Glaser–Hay homocoupling of 2-ethynyl-7-(arylethynyl)-1,8

Photocatalytic sequential C–H functionalization expediting acetoxymalonylation of imidazo heterocycles

• Deepak Singh,
• Shyamal Pramanik and
• Soumitra Maity

Beilstein J. Org. Chem. 2023, 19, 666–673, doi:10.3762/bjoc.19.48

• functionalization at the newly incorporated active methylene center. Cycle-1 is initiated with the reduction of bromomalonate 2a by the photoexcited catalyst PC* to malonyl radical I. This is followed by the Minisci-type addition of radical I to the imidazopyridine, preactivated by Lewis acidic Zn(OAc)2 [29]. PC

Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles

• Péter Kisszékelyi and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44

• enantiomeric purity. Further transformations of the products were demonstrated in several examples, including reduction, acidic deprotection and subsequent base-mediated cyclization, or Baeyer–Villiger oxidation. At about the same time, Huang and co-workers have developed similar asymmetric tandem sequences

C3-Alkylation of furfural derivatives by continuous flow homogeneous catalysis

• Grédy Kiala Kinkutu,
• Catherine Louis,
• Myriam Roy,
• Juliette Blanchard and
• Julie Oble

Beilstein J. Org. Chem. 2023, 19, 582–592, doi:10.3762/bjoc.19.43

• system was thus found to be compatible with the realization of this type of C‒H functionalization. This process led to a significant reduction of the reaction time compared to the batch, in particular by increasing the temperature to 200–250 °C, without significant losses of activity and selectivity

A new oxidatively stable ligand for the chiral functionalization of amino acids in Ni(II)–Schiff base complexes

• Alena V. Dmitrieva,
• Oleg A. Levitskiy,
• Yuri K. Grishin and
• Tatiana V. Magdesieva

Beilstein J. Org. Chem. 2023, 19, 566–574, doi:10.3762/bjoc.19.41

• and the reaction scope, making possible new types of transformations [32][33][34][35]. On the other hand, it puts additional requirements on the design of the chiral ligand. Another important structurally tunable parameter comprises the oxidation or reduction potential of the complex. Additionally, as

• . This result is important; it indicates the possibility for further oxidative functionalization of the amino acid fragment using the Ni–Schiff base templates derived from the new ligand L7. One-electron reduction of the complex (GlyNi)L7 is mainly metal centered (with some impact of the π* orbital of

• cyclic voltammetry time scale. The spin density in the radical anion is mainly localized on the Ni d-orbitals and on the N and O atoms of its coordination environment (see Supporting Information File 1). The reduction of the complex (ΔAlaNi)L7 is irreversible at scan rates lower 2000 mV/s. Full

Transition-metal-catalyzed domino reactions of strained bicyclic alkenes

• Austin Pounder,
• Eric Neufeld,
• Peter Myler and
• William Tam

Beilstein J. Org. Chem. 2023, 19, 487–540, doi:10.3762/bjoc.19.38

• initiates with the in situ reduction of Ni(II) to Ni(0) followed by the side-on coordination of the alkene and alkyne substrates to the metal center with subsequent oxidative cyclometallation to form a nickel metallacycle, similar to several reported Ni-catalyzed [2 + 2] cycloadditions [29][30]. Rather than

• arnottianum Maxim which possesses some antibiotic properties [34]. Mechanistically, the authors proposed the reaction begins with the in situ reduction of Ni(II) to Ni(0) by zinc to generate Ni(0) which undergoes oxidative addition with the organo iodide to yield Ni(II) intermediate 11. Coordination of 11 to

• catalytic cycle starts with a diaryl Fe(II)–(S,S)-chiraphos complex 80 being generated through the reduction of FeCl3 with excess diarylzinc in the presence of the phosphine ligand. Side-on coordination to the exo face of the azabicycle 77a generates 81 where subsequent migratory insertion affords the alkyl

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

• an ester reduction with H2 as terminal reducing agent utilizing bifunctional copper(I)/NHC complex 5 bearing a guanidine moiety as additional catalytic unit [48]. This catalyst acts by employing the copper(I)/NHC complex for H2 activation on the one hand and by using the guanidine subunit for

• for catalytic ester reduction with H2 [48], led to lower catalyst activity. Possible coordination of residual phosphate to the guanidine moiety was excluded as analysis by 31P NMR experiments. The copper(I)-catalyzed 1,2-reduction of functionalized ester 10 was also successfully achieved using the

Asymmetric synthesis of a stereopentade fragment toward latrunculins

• Benjamin Joyeux,
• Antoine Gamet,
• Nicolas Casaretto and
• Bastien Nay

Beilstein J. Org. Chem. 2023, 19, 428–433, doi:10.3762/bjoc.19.32

• analogue synthesis, starting from (+)-β-citronellene. Key stereoselective transformations involve an asymmetric Krische allylation, an aldol reaction under 1,5-anti stereocontrol, and a Tishchenko–Evans reduction accompanied by a peculiar ester transposition, allowing to install key stereogenic centers of

• ring, while latrunculin C (3) lacks this ring due to the reduction of C-15. The biological activities of latrunculins A and B have early been reported [3]. These compounds induce important but reversible morphological changes on mouse neuroblastoma and fibroblast cells at low concentrations such as 50

• PMB group in 72% yield (18), after deprotonation with NaH and reaction with PMBBr. The ester moiety of 18 was then chemoselectively reduced into alcohol 19 in 90% yield, in presence of LiBH4 to avoid the reduction of the thiazolidinone part. Finally, the aldehyde (8) was generated in 78% yield by

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

• . An o-phenolic coupling between two units of tyrosine furnishes the intermediate Int-1, which by deamination, selective reduction of one of the carboxylate groups, macrolactonization, and subsequent structural modifications would lead to the aforementioned combretastatins D (Scheme 1). The second

• carboxylic acid 20, which underwent protection with Troc-Cl and selective reduction in the presence of sodium borohydride to form the alcohol 21. After ester hydrolysis the desired seco-acid 22 was obtained in 82% yield. However, several attempts to achieve the macrolactonization of 22 using PPh3 and DEAD

• coupling reaction. Thus, the olefination reaction of aldehyde 15 with phosphonate 23, followed by the reduction of the obtained ester 24 using DIBAL led to the alcohol 25. The latter was submitted to the reaction with carboxylic acid 26 under Mitsunobu conditions [30], giving the corresponding ester 27 in

CuAAC-inspired synthesis of 1,2,3-triazole-bridged porphyrin conjugates: an overview

• Dileep Kumar Singh

Beilstein J. Org. Chem. 2023, 19, 349–379, doi:10.3762/bjoc.19.29

• -induced applications. Similar to porphyrins, fullerene C60 also possesses superior acceptor properties, low reduction potential and low reorganization energy [48][49]. Thus, keeping the diverse properties of fullerene in mind, de Miguel et al. [50] successfully prepared and characterized the triazole

Group 13 exchange and transborylation in catalysis

• Dominic R. Willcox and
• Stephen P. Thomas

Beilstein J. Org. Chem. 2023, 19, 325–348, doi:10.3762/bjoc.19.28

• reduction with Me2S·BH3 was investigated by Fontaine, and applied to a catalytic variant using HBpin as the turnover reagent (Scheme 7) [70]. Computational analysis showed two plausible, cooperative catalytic cycles: 1) hydroboration of indole 25 with BH3 to give a H2B-N-indoline 26, which then underwent B

• a B‒O/B‒H transborylation in catalysis was the catalytic Midland reduction of propargylic ketones developed by Thomas to give enantioenriched propargylic alcohols (Scheme 10) [74]. The reaction was proposed to occur by enantioselective reduction of the propargylic ketone 42 by myrtanyl borane 43 to

• . Alongside this, H-B-9-BBN underwent reduction of the ester or lactone 57, to give a hemiacetal intermediate 58, which underwent B‒O/B‒H transborylation with HBpin to give an O-Bpin hemiacetal 59. Borane-mediated collapse of the O-Bpin hemiacetal gave an aldehyde 60 which reacted with the O-Bpin enolate 52

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

• and reduction. All reaction steps were studied separately and optimized under continuous flow conditions. After the optimization, the reaction steps were coupled in a semi-continuous flow system, since a solvent exchange had to be performed after the tosylation. However, the azidation and the

• reduction steps were compatible to be coupled in one flow system obtaining 6-monoamino-6-monodeoxy-β-cyclodextrin in a high yield. Our flow method developed is safer and faster than the batch approaches. Keywords: azidation; continuous flow; β-cyclodextrin; H-cube; 6-monoamino-6-monodeoxy-β-cyclodextrin

• ; monosubstitution; reduction; Introduction Cyclodextrins (CDs), as cyclic oligosaccharides, consist of a macrocyclic ring of glucose subunits linked by α-1,4-glycosidic bonds [1]. They are widely used in pharmaceutical, food and chemical industries, as well as in agriculture. It has been known for decades, that CD

Synthesis, α-mannosidase inhibition studies and molecular modeling of 1,4-imino-ᴅ-lyxitols and their C-5-altered N-arylalkyl derivatives

• Martin Kalník,
• Sergej Šesták,
• Juraj Kóňa,
• Maroš Bella and
• Monika Poláková

Beilstein J. Org. Chem. 2023, 19, 282–293, doi:10.3762/bjoc.19.24

• in two steps from known ʟ-ribitol 1 [34] in good overall yield. Next, it was converted to the C-5 deoxygenated N-benzylpyrrolidine 6 via trityl ether cleavage, tosylation of the deprotected OH group, and reduction of the tosylate 5. Hydrogenolysis of the N-benzyl group in 6 followed by a removal of

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

• 183 in 56%, even at large scale (2 g). Having this tricyclic structure in hands, several more steps were needed to access advanced intermediate 184 for the synthesis of both natural products. Thus, they first selectively hydrogenated the double bond on the eight-membered ring, and ketone reduction

An efficient metal-free and catalyst-free C–S/C–O bond-formation strategy: synthesis of pyrazole-conjugated thioamides and amides

• Shubham Sharma,
• Dharmender Singh,
• Sunit Kumar,
• Vaishali,
• Rahul Jamra,
• Naveen Banyal,
• Deepika,
• Chandi C. Malakar and
• Virender Singh

Beilstein J. Org. Chem. 2023, 19, 231–244, doi:10.3762/bjoc.19.22

• reaction under heating conditions at 70 °C, afforded the desired product 1C in 82% yield with a drastic reduction in the reaction time to 1 hour (entry 16, Table 1). Moreover, an increase in the amount of base had a negligible effect on the yield of the thioamide conjugate 1C (entries 17 and 18, Table 1

• ). Interestingly, a significant reduction in the reaction time was detected with 25 equiv as well as 10 equiv of H2O2. Next, we screened DMF, CH3CN, THF, and MeOH (2.0 equiv) with 10.0 equiv of H2O2 to increase the yield of the designed prototype 1F. An acceptable enhancement was observed in the yield of the

An accelerated Rauhut–Currier dimerization enabled the synthesis of (±)-incarvilleatone and anticancer studies

• Tharun K. Kotammagari,
• Sweta Misra,
• Sayantan Paul,
• Sunita Kunte,
• Rajesh G. Gonnade,
• Manas K. Santra and
• Asish K. Bhattacharya

Beilstein J. Org. Chem. 2023, 19, 204–211, doi:10.3762/bjoc.19.19

• (NADPH) dependent manner. Thus, reduction of MTT is closely related to the viability of the cells. Therefore, we have examined the growth-suppressive effect of all the synthesised compounds using the MTT assay [18][19][20]. The results revealed that the investigated compounds have a very minimal effect

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

• -workers [19], through a sequence of reduction to the alcohol, acetylation and reduction with lithium in ammonia (Scheme 3A) [20], and its structure was unambiguously assigned by X-ray crystallography of a silver nitrate adduct [21]. From natural sources, the compound was first obtained from Humulus

Identification and determination of the absolute configuration of amorph-4-en-10β-ol, a cadinol-type sesquiterpene from the scent glands of the African reed frog Hyperolius cinnamomeoventris

• Angelique Ladwig,
• Markus Kroll and
• Stefan Schulz

Beilstein J. Org. Chem. 2023, 19, 167–175, doi:10.3762/bjoc.19.16

• cleanly obtained in 75% yield from triethyl phosphite and 3-chloro-2-methylpropene by addition of NaI [14]. Subsequent reduction of the ester with LiAlH4 and oxidation with IBX gave aldehyde 7 in 95% yield. Grignard addition of vinylmagnesium bromide afforded the alcohol 8, which comprised the desired

Total synthesis of insect sex pheromones: recent improvements based on iron-mediated cross-coupling chemistry

• Eric Gayon,
• Guillaume Lefèvre,
• Olivier Guerret,
• Adrien Tintar and
• Pablo Chourreu

Beilstein J. Org. Chem. 2023, 19, 158–166, doi:10.3762/bjoc.19.15

• ]) are linear syntheses involving a great number of steps and purifications as well as cryogenic temperatures. Moreover, the introduction of the C=C unsaturation is achieved via a Wittig reaction or a Pd-catalyzed Sonogashira cross-coupling followed by a reduction by a borane reagent, methods which lead

Insight into oral amphiphilic cyclodextrin nanoparticles for colorectal cancer: comprehensive mathematical model of drug release kinetic studies and antitumoral efficacy in 3D spheroid colon tumors

• Sedat Ünal,
• Gamze Varan,
• Juan M. Benito,
• Yeşim Aktaş and
• Erem Bilensoy

Beilstein J. Org. Chem. 2023, 19, 139–157, doi:10.3762/bjoc.19.14

• -loaded nanoparticle formulations had better anticancer activity than the drug solution (Figure 5b). Moreover, the group treated with blank CS-(6-O-capro-β-CD) nanoparticles + CPT solution showed a substantial reduction in cell viability. Cell viability in HT29 cells cultured with CPT solution alone was

• solution in 3D HT29 spheroids. Again, it was observed that blank nanoparticles caused a significant decrease in cell viability in 3D cell studies compared to the control group [55][64]. The reduction in cell viability for the blank poly-β-CD-C6 derivative was even higher than for the group that was treated

Synthesis and characterisation of new antimalarial fluorinated triazolopyrazine compounds

• Kah Yean Lum,
• Jonathan M. White,
• Daniel J. G. Johnson,
• Vicky M. Avery and
• Rohan A. Davis

Beilstein J. Org. Chem. 2023, 19, 107–114, doi:10.3762/bjoc.19.11

• with fluoroalkyl moieties led to a reduction or loss of activity at the tested concentrations. These data indicate that additional medicinal chemistry efforts involving H-8 replacement with fluoroalkyl groups for this OSM series is not warranted. Experimental General procedure for Diversinate