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

• facilitated the in-situ redox mediator recycling and separation. The authors actually employed this strategy using 3 different reactor configurations (Figure 2). The first and simplest ex-situ photorecycling method involved adding and extracting 2 aqueous phases containing the catalysts and reactant to

• of enzymes [47]. The enzymes reduce carbon dioxide to methanol and consumed NADH which was then recycled at the photoelectrode functionalized with the rhodium complex. The overall electron donor in this work was water which makes it an excellent example of in-situ recycling. Kuk et al. also noted

• -sensitized solar cells [50][51]. As discussed, if a sacrificial donor is recycled in-situ it becomes a redox mediator. In artificial photosynthesis redox mediators are most commonly employed in Z-schemes. A Z-scheme describes the combination of two photocatalytic systems, one for photooxidation and one for

Retraction: One-pot odourless synthesis of thioesters via in situ generation of thiobenzoic acids using benzoic anhydrides and thiourea

• Mohammad Abbasi and
• Reza Khalifeh

Beilstein J. Org. Chem. 2023, 19, 1170–1170, doi:10.3762/bjoc.19.85

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

• conditions. In 2020, the Polyzos group also demonstrated the carbonylative amidation of aryl halides in continuous flow with the in situ-generated [Ir2]0 (Figure 19A) [79]. This multi-photon tandem photocatalysis protocol provides an elegant alternative to established classical procedures for condensing

• radical. This is strongly supported by a single turnover experiment, where exclusive excitation of [FeII(btz)3]2+ with 700 nm LEDs after in situ generation and substrate addition in the dark generated 5% of product even with only 0.5 mol % of catalyst present. In its ground state, [FeII(btz)3]2+ is not

Copper-catalyzed N-arylation of amines with aryliodonium ylides in water

• Kasturi U. Nabar,
• Bhalchandra M. Bhanage and
• Sudam G. Dawande

Beilstein J. Org. Chem. 2023, 19, 1008–1014, doi:10.3762/bjoc.19.76

• ]. Further, a few reports are also available for the copper and palladium-catalyzed N-arylation of primary and secondary aliphatic as well as aromatic amines using diaryliodonium salts as aryl sources [33][34][35] (Scheme 1a). Similarly, iodonium ylides undergo a wide range of reactions through in situ

The unique reactivity of 5,6-unsubstituted 1,4-dihydropyridine in the Huisgen 1,4-diploar cycloaddition and formal [2 + 2] cycloaddition

• Xiu-Yu Chen,
• Hui Zheng,
• Ying Han,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2023, 19, 982–990, doi:10.3762/bjoc.19.73

• as one of the most valuable synthons to construct diverse carbocyclic and heterocyclic systems as well as many open-chain compounds [9][10][11][12][13][14][15]. In recent years, in situ generated Huisgen 1,4-dipoles were also widely employed to design highly efficient multicomponent and domino

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

• reaction proceeding through aza-Friedel–Crafts reaction and lactonization steps. Main focus of this article was to demonstrate a racemic process between α-naphthol or phenol derivatives and in situ-generated N-acetyl ketimine from methyl 2-acetamidoacrylate (18) in the course of preparing 3-NHAc

• dehydration to generate isoxazolium cation 80 paired with a phosphate anion. This chiral phosphate is engaged in H-bonding with the free NH of the heteroarene ring to ease the stereoselective 1,2-addition to in situ generate the cationic heterocyclic scaffold 81. The reaction proceeded faster with pyrroles

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

• works, we contemplated that the N–O bond of cyclobutanone oxime derivatives could be activated by SO2F2 in situ to enable cleavage of the C–C bond, which could achieve this transformation without going through inefficient pre-introduction of electrophores. Herein, we describe how this concept has been

• 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

• the [Cun] catalyst and intermediate V. The critical β-H elimination step occurs smoothly in the presence of excessive base to generate the final nitrile product. Due to the high reactivity of the intermediate fluorosulfonate I, the attempt of isolation or detecting the in situ generated intermediate I

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

• acylimidazole 3a (Table 1, entry 5) as monitored by TLC analysis. The reaction was completed after 3 hours, meaning that the in situ-formed enolate needed 3.3 equiv of tropylium NTf2 (2a) to complete the reaction. By this route, the tandem product 3a was isolated in a high yield of 93% but without any

• the reaction temperature led to improved reaction outcomes (Supporting Information File 1, Table S1, entries 2 and 11). We have continued the evaluation of reaction conditions for improving the diastereoselectivity of the reaction. We have tested transmetallation of the in situ-generated zinc enolate

Pyridine C(sp²)–H bond functionalization under transition-metal and rare earth metal catalysis

• Haritha Sindhe,
• Malladi Mounika Reddy,
• Karthikeyan Rajkumar,
• Akshay Kamble,
• Amardeep Singh,
• Anand Kumar and
• Satyasheel Sharma

Beilstein J. Org. Chem. 2023, 19, 820–863, doi:10.3762/bjoc.19.62

• N-oxide 119b was formed during benzylation of 2-ethylpyridine N-oxide. A possible mechanism has also been reported (Scheme 23b). Electrophilic palladation at the C2-position of pyridine N-oxide 9 provides intermediate 120. The radical intermediate 121 is generated in situ by H-atom abstraction from

• , facilitating the C–H arylation of pyridine. Dimethyl sulfate was used as a good N-methylating agent, which acts as transient activator. The group performed HRMS and KIE studies and proposed a catalytic cycle (Scheme 25b). The oxidative addition of ArBr 130 to the in situ-formed Pd(0) species gives species 132

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

• synthesis of synthetically useful N-arylsulfonylimines from N-(arylsulfonyl)benzylamines using K2S2O8 in the presence of pyridine as a base is reported herein. In addition, a “one-pot” tandem synthesis of pharmaceutically relevant N-heterocycles by the reaction of N-arylsulfonylimines, generated in situ

• approach, a gram-scale synthesis and a “one-pot” tandem synthesis of pharmaceutically relevant N-heterocycles by the reaction of in situ-generated N-arylsulfonylimines with various ortho-substituted anilines were also developed. The mechanism of the oxidation is believed to occur via hydrogen atom

• nucleophilic addition and as a result the corresponding cyclized product is not formed. The synthesis of these nitrogen heterocycles signifies the innate ability of in situ-generated N-arylsulfonylimines in a variety of reactions with various ortho-substituted anilines without the need for pre-isolation or

Palladium-catalyzed enantioselective three-component synthesis of α-arylglycine derivatives from glyoxylic acid, sulfonamides and aryltrifluoroborates

• Bastian Jakob,
• Nico Schneider,
• Luca Gengenbach and
• Georg Manolikakes

Beilstein J. Org. Chem. 2023, 19, 719–726, doi:10.3762/bjoc.19.52

• , e.g., the antiplatelet drug clopidogrel [7] or the β-lactam antibiotic amoxicillin [8] (Figure 1). Therefore, the chemical synthesis of α-aryglycines has received considerable attention. Among the different methods introduced over time, multicomponent reactions utilizing an in situ generated reactive

• electrophilic iminium carbon, leading to the amine product as racemic mixture. Consequently, examples for asymmetric Petasis borono-Mannich reactions are rare [13] and usually rely on the utilization of chiral amine components in stoichiometric amounts [10][11]. As part of our research program utilizing the in

• situ generation of reactive imine species, we have disclosed iron- and bismuth-catalyzed three-component reactions for the synthesis of α-arylglycines [14][15][16], in which the arylboronic acid could be replaced with an electron-rich (hetero)arene as nucleophile. In parallel, we have developed

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

• . through a multicomponent reaction system [57]. The authors provided a series of substituted derivatives through Pd/Rh-catalysed domino coupling. The reaction proceeded via a Suzuki coupling, followed by an in situ Buchwald–Hartwig amination. The authors reported moderate to good yields in a series with

• , whereafter Buchwald–Hartwig amination afford the various diarylazepines. A three-component one-pot process allowed for a second in situ Buchwald–Hartwig amination of the diarylazepine with aryl or benzyl halides to give the respective N-aryl and N-benzylazepine derivatives 83 and 84 (Scheme 16). 3.2 Mizoroki

• bromides and electron-withdrawing groups. The authors found that the addition of potassium iodide, and thus in situ palladium-catalysed halogen exchange, improved the yield of dibenzo[b,f]azepine 110. Unsymmetrical derivatives of 110 containing -CO2Me, -CF3, -NO2 and -CN substituents were synthesised in

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

• conversion into ZnBr2 (confirmed by HRMS). These in situ-generated free acetate ions function as a base, deprotonating carbocation III to produce the intermediate IV and AcOH. The first step of cycle-2 involves the oxidation of the excited photocatalyst by aerial oxygen to generate superoxide anion and PC

Nucleophile-induced ring contraction in pyrrolo[2,1-c][1,4]benzothiazines: access to pyrrolo[2,1-b][1,3]benzothiazoles

• Ekaterina A. Lystsova,
• Maksim V. Dmitriev,
• Andrey N. Maslivets and
• Ekaterina E. Khramtsova

Beilstein J. Org. Chem. 2023, 19, 646–657, doi:10.3762/bjoc.19.46

• to the plausible pathway shown in Scheme 6. As we expected, the nucleophile 2a attacked on the position C4 of the substrate 1a, which resulted in the cleavage of the S5–C4 bond and the formation of a thiol intermediate A (1-(2-thiophenyl)pyrrole derivative generated in situ as a precursor analog for

• the cleavage of the S–C bond of the 1,4-benzothiazine moiety under the action of the nucleophile to form in situ a 1-(2-thiophenyl)pyrrole derivative that undergoes an intramolecular cyclization to give the target pyrrolobenzothiazoles 3, 7, and 12. The developed approach works well with alkanols 2

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

• developed a copper/Rev-Josiphos-catalyzed asymmetric conjugate addition of Grignard reagents to 2-methylcyclopentenone (78), which provided 2,3-disubstituted cyclopentanones in high yields and enantiomeric purities [53]. The one-pot alkylation reaction of the in situ formed magnesium enolate with alkylating

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

• steps, and thus to consider the direct functionalization of furfural via the in-situ formation of furfurylimine. Furthermore, as the [Ru3(CO)11(PPh3)] comp4 catalyst showed an activity and a solubility in batch similar to comp1, we continued the optimization with the latter, triphenylphosphine being

• imine in situ. Furthermore, the optimized conditions with the pulsed-flow device proved to be effective, as an NMR yield of 62% of the C3-alkylated imine I2a was obtained by preheating at 130 °C for 5 min in reactor 1 (after introduction of mixture B), followed by heating at 180 °C for 45 min in reactor

• reaction conditions while providing products in shorter reaction times. In addition, the ability to couple multiple reactors with a flow apparatus could also enable us to perform these functionalizations directly from furfural by forming the imine in a first reactor. It should be noted that, in batch, in

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

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

• ) (Scheme 1d). In some cases, this transmetallation step is carried out in situ [14][15][29][30][31][32]. Notably, these generally successful synthetic routes produce a considerable amount of transition metal waste (next to the inherent use of solvents) and are therefore in misalignment with the principles

• of green chemistry. Syntheses via mechanochemical methods offer elegant and atom-economic alternatives to liquid state synthesis approaches [33][34][35][36][37][38][39][40][41][42][43]. In accordance with the in situ transmetallation route in liquid state synthesis, a one-pot two-step procedure in a

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

• oxidation in presence of DMP. The assembly of aldehyde 8 and methyl ketone 15 was envisaged through a stereoselective aldol reaction. After unsuccessful attempts of Mukaiyama aldol reactions with silyl enol ethers [28], we found that dicyclohexylboron enolate 20, made in situ from ketone 15 and Cy2BCl in

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

• hydroxybenzaldehyde 80 into the corresponding acetal followed by Ullmann-type coupling with 52, led to the formation of diaryl ether 83. Subsequent Corey–Fuchs reaction [49] and in situ alkylation led to formation of the propargylic alcohol 85. Deprotection of the aldehyde followed by chain elongation through the

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

• catalyse the hydroboration of alkynes with HBcat [50]. Hoshi later reported that Cy2BH [51] and in situ generated bis(pentafluorophenyl)borane, Piers’ borane [52], catalysed the hydroboration of alkynes with HBpin, to give alkenyl pinacol boronic esters. Tris(2,4,6-trifluorophenyl)borane [53], tris(3,4,5

• ‒H borylation, with an initial B‒Y/B‒H transborylation activating the precatalyst [62][63][64][65]. Zhang showed that benzoic acid decomposed HBpin to BH3 in situ to catalyse the C2‒H borylation of indoles (Scheme 4b) [66][67]. Gellrich reported the bis(pentafluorophenyl)borane-catalysed dimerisation

• transborylation in catalysis (Scheme 6) [69]. Reactive intermediates were characterised and BH3 was observed to be generated in situ by the decomposition of HBpin. The proposed catalytic cycle involved nucleophile-promoted decomposition of HBpin to various borohydride species 19, which reacted with the BH3

Recommendations for performing measurements of apparent equilibrium constants of enzyme-catalyzed reactions and for reporting the results of these measurements

• Robert N. Goldberg,
• Robert T. Giessmann,
• Peter J. Halling,
• Carsten Kettner and
• Hans V. Westerhoff

Beilstein J. Org. Chem. 2023, 19, 303–316, doi:10.3762/bjoc.19.26

• opposite directions of reaction. If the necessary substances are not readily available, it is necessary to prepare them in order to perform a rigorous measurement of the equilibrium constant. Labile or difficult to obtain substances may be prepared in situ [29]. For reactions that proceed without the need

• demonstrate the approach to equilibrium from different directions of reaction. Thus, as mentioned in section 3.9, some investigators have used very small quantities of a substrate that required substantial synthetic efforts [25] or have prepared the needed substrate in situ [27]. 3.14. Importance of careful

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

• , these two drawbacks are not a problem for large-scale flow synthesis when using an H-Cube system with an incorporated electrolytic cell producing H2 in situ from ultrapure water [47]. The Pd/C catalyst is placed in a stainless steel cartridge, so it is not necessary to separate it from the solution

• prepared in situ in the flow tube reactor, as the aqueous solution containing β-CD (1) and NaOH (1.5 equiv) was introduced into the reactor at twice the flow rate as the solution of TsCl in THF (Scheme 1). In this way, twice as many equivalents of TsCl were required compared to the general 1.3 equivalents

Sequential hydrozirconation/Pd-catalyzed cross coupling of acyl chlorides towards conjugated (2E,4E)-dienones

• Benedikt Kolb,
• Daniela Silva dos Santos,
• Sanja Krause,
• Anna Zens and
• Sabine Laschat

Beilstein J. Org. Chem. 2023, 19, 176–185, doi:10.3762/bjoc.19.17

• of 20 h at 50 °C led only to 8% yield (Table 2, entry 8). Trapping experiments of the in situ-formed (E)-alkenylzirconocene 24 revealed quantitative conversion of the starting material 25a and only traces of chain walking (less than 4%) (for details see Supporting Information File 1, chapter 2.1). To

• (dba) were catalytically inactive (Table 3, entries 6 and 7). Furthermore, in situ-formed Schwartz reagent was found to be less effective as compared to the use of isolated Cp2Zr(H)Cl and thus further experiments in this direction were abandoned. In order to explore the substrate scope of the

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

• , phosphate leaving groups, etc.) is still an unclear question, even if the latter species proved to have an unambiguous beneficial effect on the cross-coupling yields and selectivities. Several recent literature results which enlighten the role of those additives, either brought by external reagents or by in

• situ-formed intermediates, are gathered in Table 2. The beneficial role of the NMP co-solvent on the alkyl–alkenyl cross-coupling yield reported by Cahiez (Scheme 2b) and considerably used ever since was explained at a molecular level by Neidig in 2018. It was demonstrated that NMP did not act as a