Selective and scalable oxygenation of heteroatoms using the elements of nature: air, water, and light

• Damiano Diprima,
• Hannes Gemoets,
• Stefano Bonciolini and
• Koen Van Aken

Beilstein J. Org. Chem. 2023, 19, 1146–1154, doi:10.3762/bjoc.19.82

• resulted in a significant reduction in kinetics and selectivity (Table 1, entry 3). Other more green and biobased solvent alternatives, such as ethanol [36], can effectively replace the acetonitrile (for the complete scope of solvents, please consult Supporting Information File 1, Table S2), but reaction

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

• generation of super-reductants [15] and by Wagenknecht in 2018 for the generation of super-oxidants [16]. Herein, initial excitation of the photocatalyst by a single photon is followed by reduction or oxidation by a sacrificial SET donor (e.g., Et3N [15]) or acceptor (e.g., SF6 [16]) to yield the catalyst

• doublet states which are photoexcited to yield super-oxidants or super-reductants while recycling e-PRC involves the turnover of a ‘standard’ (typically closed-shell) photoredox catalyst (PC) by means of anodic oxidation or cathodic reduction [28][29]. Furthermore, a series of new protocols using

• , commercially available aryl halides are chlorides [37][38], with potentials for reduction that almost exclusively lie beyond the threshold of monophotonically-excited photoredox catalysts (i.e., more deeply negative than E1/2 = −2.0 V vs SCE). Considering this, state-of-the-art developments have focused on the

The effect of dark states on the intersystem crossing and thermally activated delayed fluorescence of naphthalimide-phenothiazine dyads

• Liyuan Cao,
• Xi Liu,
• Xue Zhang,
• Jianzhang Zhao,
• Fabiao Yu and
• Yan Wan

Beilstein J. Org. Chem. 2023, 19, 1028–1046, doi:10.3762/bjoc.19.79

• reduction wave was observed at −1.78 V (vs Fc/Fc+) due to the reduction of the NI unit. For all the dyads containing a native PTZ unit, the oxidation potentials are virtually the same. However, the reduction potential changes to some extent, which is consistent with our molecular design to keep the donor

• after oxidation, and there was still a reversible reduction potential at −1.53 V (vs Fc/Fc+). Slightly cathodically shifted reduction waves were observed for other dyads containing an oxidized PTZ unit, i.e., NI-PTZ-Ph-O and NI-PTZ-C5-O. The redox potentials of the compounds are collected in Table 3

Five new sesquiterpenoids from agarwood of Aquilaria sinensis

• Hong Zhou,
• Xu-Yang Li,
• Hong-Bin Fang,
• He-Zhong Jiang and
• Yong-Xian Cheng

Beilstein J. Org. Chem. 2023, 19, 998–1007, doi:10.3762/bjoc.19.75

• (Table 3). The difference is that the carboxylic acid at C-4 in 3 undergoes reduction to form a hydroxymethyl group at C-4 in 5. This alteration is supported by the analysis of the HMBC correlations (Figure 2) of H-3/C-4 (δC 128.6), C-14 (δC 63.5) and H-14/C-4, C-5 (δC 141.9). Thus, the planar structure

Synthesis of tetrahydrofuro[3,2-c]pyridines via Pictet–Spengler reaction

• Elena Y. Mendogralo and
• Maxim G. Uchuskin

Beilstein J. Org. Chem. 2023, 19, 991–997, doi:10.3762/bjoc.19.74

• construction of tetrahydrofuro[3,2-c]pyridines is based on a Bischler–Napieralski cyclocondensation followed by the C=N bond reduction (Scheme 1d) [36][37][38][39]. Despite the simplicity of the latter approach and availability of 2-(furan-2-yl)ethanamine, the instability of intermediate dihydrofuro[3,2-c

Aromatic C–H bond functionalization through organocatalyzed asymmetric intermolecular aza-Friedel–Crafts reaction: a recent update

• Anup Biswas

Beilstein J. Org. Chem. 2023, 19, 956–981, doi:10.3762/bjoc.19.72

• after recrystallization. Subsequent ozonolysis of the terminal alkene functionality with a follow-up reduction furnished primary alcohol 134 which was transformed into the azide 135. Reduction of the azide 135 was accompanied by debenzylation, was followed by tosylation of the primary amine and exchange

• of the Boc-protecting group with the Teoc group then gave phenol 136. Compound 136 was then subjected to a highly diastereoselective oxidative phenolic coupling giving fused tetracyclic architecture 137. Follow-up acid-mediated intramolecular aza-Michael addition and subsequent alkene reduction

Photoredox catalysis enabling decarboxylative radical cyclization of γ,γ-dimethylallyltryptophan (DMAT) derivatives: formal synthesis of 6,7-secoagroclavine

• Alessio Regni,
• Francesca Bartoccini and
• Giovanni Piersanti

Beilstein J. Org. Chem. 2023, 19, 918–927, doi:10.3762/bjoc.19.70

• manner due to their intrinsic mildness and broad substrate compatibility [16][17][18][19][20]. This transformative synthetic tool often utilizes direct single-electron transfer (SET) between an electronically excited photoredox catalyst and an organic substrate, resulting in oxidation or reduction, to

• carboxylate anion and/or reduction of the corresponding N-hydroxyphthalimide- (NHPI)-derived redox-active ester, although it destroys their stereochemical information [46][47][48][49][50][51]. In addition, the side-chains of aromatic amino acids (mainly electron-rich tryptophan and tyrosine) can be

• intramolecularly with the C4-pendant prenyl side-chain previously oxidized [76]. Closure of the photoredox catalytic cycle would then involve SET reduction, and protonation would deliver the desired carbocyclic ring (Figure 1c). If this cyclization reaction could be realized in either way, it would shorten the

Intermediates and shunt products of massiliachelin biosynthesis in Massilia sp. NR 4-1

• Till Steinmetz,
• Blaise Kimbadi Lombe and
• Markus Nett

Beilstein J. Org. Chem. 2023, 19, 909–917, doi:10.3762/bjoc.19.69

• aligns well with the observed increase in the degree of unsaturation and the reduction in mass by 2 Da. Compound 4 (0.5 mg) was obtained as a brown oil. It possesses a molecular ion at m/z 276.0985 [M + H]+, which suggests a molecular formula of C15H17NO2S (calcd. for C15H18NO3S, 276.1002) and is in

Synthesis of aliphatic nitriles from cyclobutanone oxime mediated by sulfuryl fluoride (SO₂F₂)

• Xian-Lin Chen and
• Hua-Li Qin

Beilstein J. Org. Chem. 2023, 19, 901–908, doi:10.3762/bjoc.19.68

• nitriles 3ba–da in excellent yields. Interestingly, when the loading of CH3COOK was reduced to 2 equivalents, we obtained a mixture of unsaturated nitrile 3aa and saturated nitrile 4 after column chromatography (Scheme 4). We speculated that the reduction of the base equivalent may induce the ionization of

• oxime derivatives with alkenes was proposed (Scheme 6). Initially, cyclobutanone oxime reacts with SO2F2, generating an oxime sulfonyl ester intermediate (fluorosulfonate) I promoted by the base. Subsequently, the intermediate fluorosulfonate I undergoes single-electron reduction by [Cun] in situ to

• ) was stirred at 100 °C under an SO2F2 atmosphere (balloon) for 12 h; yields refer to isolated compounds. Competition between two reactions caused by the reduction of base equivalent. Mechanistic investigations. A proposed plausible mechanism. Screening the optimized reaction conditions.a Supporting

Asymmetric tandem conjugate addition and reaction with carbocations on acylimidazole Michael acceptors

• Brigita Mudráková,
• Renata Marcia de Figueiredo,
• Jean-Marc Campagne and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 881–888, doi:10.3762/bjoc.19.65

• ]. These non-traditional electrophiles allow access to structurally highly interesting motifs. In addition, they are amenable to valuable synthetic transformations such as oxidative ring contraction of the cycloheptatrienyl ring or reduction of the benzodithiolyl group. In this context, we decided to study

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