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

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

• of some of the products was investigated and selected synthetic transformations of the obtained tetrahydrofuro[3,2-c]pyridines were shown. Keywords: acid hydrolysis; 1,4-diketone; tetrahydrofuro[3,2-c]pyridines; Paal–Knorr reaction; Pictet–Spengler reaction; Introduction Hydrogenated furo[3,2-c

• hydrolysis of 4a was observed in most cases in trace amounts; an exception is entry 18 (Table 1), in which the 1,4-diketone 5a was isolated in 10% yield. With the optimized reaction conditions in hand, we investigated the scope of the developed tetrahydrofuro[3,2-c]pyridine synthesis. We found that a wide

• hydrolysis could be a convenient tool for the synthesis of substituted 3-(2-oxopropyl)piperidin-4-ones 5. Using tetrahydrofuro[3,2-c]pyridine 4a as the model compound, we studied the effect of various Brønsted acids, temperature, concentrations, and the nature of the solvent on the efficiency of the reaction

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

• hydrolysis, (−)-fumimycin (146) was obtained (Scheme 36) [66]. Conclusion The aza-Friedel–Crafts reaction is a powerful reaction that allows the incorporation of an aminoalkyl functionality in aromatic systems through C–C bond formation. This C–H bond functionalization methodology of aromatic systems also

Clauson–Kaas pyrrole synthesis using diverse catalysts: a transition from conventional to greener approach

• Dileep Kumar Singh and
• Rajesh Kumar

Beilstein J. Org. Chem. 2023, 19, 928–955, doi:10.3762/bjoc.19.71

• synthesis of various acid- or heat-sensitive N-substituted pyrrole derivatives 27. In this method, 2,5-dimethoxytetrahydrofuran undergoes mild hydrolysis in water to provide an activated species that reacts with various primary amines 26 in the presence of acetate buffer solution at ambient temperature to

• hydrolysis of 2,5-DMTHF (2), which provide intermediate C after the removal of methanol in the presence of CuCl2. In the next steps, nucleophilic addition reaction of amines 34 with intermediate C, dehydration, and intramolecular aromatization affords N-substituted pyrroles 35. In 2018, Patil and Kumar [70

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

• ]. Regioselective palladium-catalyzed prenylation of 2 with prenylboronic acid pinacol ester and subsequent hydrolysis with LiOH provided the linear prenylated acid 4 in good yield. Coupling acid 4 with N-hydroxyphthalimide using DCC and a catalytic amount of DMAP afforded the key intermediate 5 in 59% yield. With

• interconvertible to each other by hydration or dehydration, i.e., a plausible precursor of the allylic alcohol would be the diene, and vice versa [90]. Since both 8 and 10 are easily obtainable from 2 by Mozoroki–Heck coupling with commercially available 2-methyl-3-buten-2-ol, ester hydrolysis (LiOH in THF/H2O

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

• reactions (e.g., hydrolysis, esterification, oxidation) might be due to the isolation conditions or they could be attributed to unspecific enzymatic biotransformations. For compound 1, no spontaneous conversion to the ester 2 was observed, even after storage in methanol for two months. In contrast, the

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

• migratory insertion of the alkene into the metal–C bond of 23 gives the intermediate 24a on reaction with styrene 18 and intermediate 24b in the presence of alkene 20. The intermediates 24a and 24b then undergo further hydrolysis to give the desired linear products 19 and branched products 21, respectively

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

• ). Carbamoylation of 151 gives the intermediate oxcarbazepine 152, whereafter hydrolysis of the methyl enol ether affords oxcarbazepine (153) [32][56]. 6.2.2 Ring functionalisation: Weng et al. [80] reported the synthesis of dihydrodibenzo[b,f]azepine (2a)-based pincer ligands for Rh and Ir metal complexes. The

Cassane diterpenoids with α-glucosidase inhibitory activity from the fruits of Pterolobium macropterum

• Sarot Cheenpracha,
• Ratchanaporn Chokchaisiri,
• Lucksagoon Ganranoo,
• Sareeya Bureekaew,
• Thunwadee Limtharakul and
• Surat Laphookhieo

Beilstein J. Org. Chem. 2023, 19, 658–665, doi:10.3762/bjoc.19.47

• enzyme responsible for the hydrolysis of carbohydrates in the body, is widely used for the management of type 2 diabetes. The agents, such as acarbose, miglitol, and voglibose, can retard the digestion and absorption of dietary carbohydrates [3][4]. Some cassane-type diterpenoids such as pulcherrimin C

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

• , transformation to potassium trifluoroborate salt, hydrolysis, C–C cross-coupling, base-mediated elimination, radical C–B cleavage) [72]. Therefore, enantioenriched boronates are commonly applied intermediates in organometallic, medicinal, and other fields of chemistry. At the same time, some organoboronic acid

• -workers explored the copper-catalyzed asymmetric conjugate borylation of β-substituted cyclic enones using chiral bisphosphine ligand L21 [77]. Other than the oxidation and hydrolysis of the produced enantiomerically enriched tertiary boronates, in one example, they have demonstrated the utilization of

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

• product was recovered for analysis and purification. The NMR yields were calculated on the alkylated imine before purification (based on a starting concentration of furfural of 0.35 M), and the isolated yields corresponded to the C3-alkylated aldehydes after the hydrolysis step that took place during

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

• occurs producing 144. Subsequently, coordination of the Rh(I) to the electrophilic cyano group leads to an intramolecular addition producing 145. The imine undergoes a hydrolysis releasing the final carboannulated product 141 as well as regeneration of the active Rh(I) catalyst. A similar mechanism can

Transition-metal-catalyzed C–H bond activation as a sustainable strategy for the synthesis of fluorinated molecules: an overview

• Louis Monsigny,
• Floriane Doche and
• Tatiana Besset

Beilstein J. Org. Chem. 2023, 19, 448–473, doi:10.3762/bjoc.19.35

• to the formation of the species S. The latter complex S undergoes a reductive elimination leading to the compound 48’ along with the regeneration of the palladium catalyst. Finally, after hydrolysis of 48’, the expected product 48 is afforded together with the organocatalyst. Then, the group of Sun

Dipeptide analogues of fluorinated aminophosphonic acid sodium salts as moderate competitive inhibitors of cathepsin C

• Karolina Wątroba,
• Małgorzata Pawełczak and
• Marcin Kaźmierczak

Beilstein J. Org. Chem. 2023, 19, 434–439, doi:10.3762/bjoc.19.33

• of more effective fluorinated inhibitors of cathepsin C in our laboratory. Dixon plot for the hydrolysis of Gly-Phe-pNA substrate catalyzed by bovine cathepsin C in the presence of 9b (T = 37 °C, pH 5.0). Synthetic strategy towards 5 and 7. Synthesis of 9 and 11. (a) R = -CH3; (b) R = -CH(CH3)2; (c

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

• , the authors employed an Ullmann-type condensation [28] between ester 14 and 4-iodobenzaldehyde (15) to give the corresponding diaryl ether 16 in 78% yield. The subsequent demethylation reaction using boron triiodide also promoted the hydrolysis of the ester, and thus a re-esterification step was

• 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

• 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

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

• presence of CuSO4 and sodium ascorbate in THF/H2O furnished the bis-triazole-bridged porphyrin-cyclodextrin conjugate 125 in 65% yield. Finally, porphyrin 126 was obtained from porphyrin 125 after ester hydrolysis with KOH and demetallation with concentrated HCl. After the successful synthesis of porphyrin

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

• biochemical reaction and the many chemical reactions that accompany it is the hydrolysis reaction of ATP (adenosine 5’-triphosphate) to {ADP (adenosine 5’-diphosphate) + phosphate}: The apparent reaction quotient for this reaction is And the apparent equilibrium constant is Here, (aq) denotes that the

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 non-toxicity. However, partial hydrolysis of the p-toluenesulfonyl group takes place, so the final product is always contaminated with native β-CD (1). Despite this, the product mixture after precipitation from acetone was used in the next reaction step and a proper purification of the targeted

• 60–80% can be achieved. Partial hydrolysis can be avoided by using anhydrous DMF and purifying the starting Ts-β-CD (2) by crystallization. In this case, a lower amount of NaN3 (1–2 equiv) is required and only purification by precipitation from acetone is necessary. In order to prepare N3-β-CD (3) in

• change the solvent. According to the literature, DMF proved to be a suitable solvent to conduct this reaction under homogenous conditions. By prolonging the residence time, the conversion greatly increased (Table 2, entries 5–7). However, with longer residence times, increasing hydrolysis of Ts-β-CD (2

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

• the acetonide and subsequent alkylation of the liberated amine with the corresponding arylalkyl bromides under basic conditions provided the desired N-arylalkyl iminosugars 8 and 9 in moderate yields. In addition, acidic hydrolysis of the acetonide group in 6 afforded the target derivative 7 which

• -benzyl group with the Cbz group, trityl ether hydrolysis, oxidation of the liberated OH group, and stereoselective addition of MeMgBr to the resulting aldehyde functionality. Hydrogenolysis of the Cbz protecting group in 13 followed by N-alkylation afforded pyrrolidines 14–16 which after acidic

• hydrolysis of the isopropylidene moiety provided the desired derivatives 17–19. The hydrochloride salt of the free iminosugar 20 was obtained from N-benzyl derivative 17 under the same reaction conditions as described for the hydrochloride 10. Next, the configuration at the C-5 stereocenter in 13 was

Nostochopcerol, a new antibacterial monoacylglycerol from the edible cyanobacterium Nostochopsis lobatus

• Naoya Oku,
• Saki Hayashi,
• Yuji Yamaguchi,
• Hiroyuki Takenaka and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2023, 19, 133–138, doi:10.3762/bjoc.19.13

• , phylum Pteridophyta) [29]. Monoacylglycerols are non-ionic surfactants derivable by hydrolysis of fat, and exhibit antibacterial [30], antifungal [30], antiviral [31], and antiprotozoal [32] activities. Due to these useful properties, they have found a wide range of industrial applications as emulsifiers

Practical synthesis of isocoumarins via Rh(III)-catalyzed C–H activation/annulation cascade

• Qian-Ci Gao,
• Yi-Fei Li,
• Jun Xuan and
• Xiao-Qiang Hu

Beilstein J. Org. Chem. 2023, 19, 100–106, doi:10.3762/bjoc.19.10

• , which undergoes an intramolecular annulation to give 1-F. The final isocoumarin product 3ba can be generated from 1-F by elimination of imine 1-G [39]. Finally, the rapid hydrolysis of the resulting 1-G gives rise to acetaldehyde and dimethylamine as byproducts. Conclusion In summary, an efficient Rh

Catalytic aza-Nazarov cyclization reactions to access α-methylene-γ-lactam heterocycles

• Bilge Banu Yagci,
• Selin Ezgi Donmez,
• Onur Şahin and
• Yunus Emre Türkmen

Beilstein J. Org. Chem. 2023, 19, 66–77, doi:10.3762/bjoc.19.6

• formation of ester 16 in 90% yield (4.8 g, dr (diastereomeric ratio) = 2.6:1). Hydrolysis of the α,β-unsaturated ester 16 under basic conditions followed by acidification gave carboxylic acid 17 in 60% yield. Finally, the α,β-unsaturated acyl chloride 6b was obtained via the treatment of acid 17 with oxalyl

• cyclization of an in situ-formed iminium intermediate is not efficient under certain reaction conditions, then its hydrolysis with adventitious water, which might be present in the reaction medium, would lead to the formation of an aldehyde side product. Unfortunately, our attempts to isolate such a side

• product in pure form from a crude reaction mixture failed. However, when a mixture of imine 5a and methacryloyl chloride (31) was stirred in a biphasic mixture of CH2Cl2 and aqueous NaHCO3 solution, we were able to isolate and fully characterize aldehyde 32 which would form via the hydrolysis of iminium

Digyalipopeptide A, an antiparasitic cyclic peptide from the Ghanaian Bacillus sp. strain DE2B

• Adwoa P. Nartey,
• Aboagye K. Dofuor,
• Kofi B. A. Owusu,
• Anil S. Camas,
• Hai Deng,
• Marcel Jaspars and
• Kwaku Kyeremeh

Beilstein J. Org. Chem. 2022, 18, 1763–1771, doi:10.3762/bjoc.18.185

• advanced Marfey’s method [16][17][18] involving the complete hydrolysis of compound 1 followed by derivatization of the resultant amino acid residues with N-α-(2,4-dinitro-5-fluorophenyl)-ʟ-alanine amide (ʟ-FDAA). Similar derivatization reactions between ʟ-FDAA and authentic amino acid standards, followed

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

• hydrolysis, esterification, and Jones oxidation, affording intermediate 14 with a good 79% yield over 4 steps. Next, the methyl ketone was converted to an enol triflate, and then coupled with Li2CuCN(CH2SPh)2. A reduction of the ester with DIBAL, followed by Dess–Martin oxidation and Wittig reaction lead to

• protecting groups followed by hydrolysis of the acetyl protecting groups, affording the desired product with spectral data identical to reported natural samples. Shirahama’s synthesis was an illustrative example that rings A, B and the bicycle CD of grayananes could all be obtained by SmI2-promoted steps

Synthesis of (−)-halichonic acid and (−)-halichonic acid B

• Keith P. Reber and
• Emma L. Niner

Beilstein J. Org. Chem. 2022, 18, 1629–1635, doi:10.3762/bjoc.18.174

• anticipated that the amide 5 could be hydrolyzed to give a single enantiomer of amine 4. However, we found that amide 5 was remarkably resistant to hydrolysis, even under forcing conditions. For example, no amide hydrolysis was observed in concentrated aqueous NaOH solution at reflux (with or without an

• hydrolysis of compounds 8 and 9 to form the corresponding amino acids. Thus, treating bicycle 8 with aqueous lithium hydroxide resulted in hydrolysis of the ethyl ester, and subsequent neutralization with pH 7 phosphate buffer afforded halichonic acid ((−)-1) in 88% yield after purification by column

• chromatography. Similarly, hydrolysis of lactone 9 under analogous conditions afforded halichonic acid B ((−)-2) in 76% yield. 1H and 13C NMR data for the synthetic compounds (−)-1 and (−)-2 were identical to those reported for the halichonic acids, confirming the proposed structures of these natural products