Simple synthesis of multi-halogenated alkenes from 2-bromo-2-chloro-1,1,1-trifluoroethane (halothane)

• Yukiko Karuo,
• Atsushi Tarui,
• Kazuyuki Sato,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2022, 18, 1567–1574, doi:10.3762/bjoc.18.167

• detected (Table 2, entry 11). An aldehyde group was found to be incompatible with this method (Table 2, entry 12). Esters, which are susceptible to hydrolysis, can be used in the reaction under controlled conditions, i.e., with the temperature kept below 60 °C and THF as the solvent. However, the yield of

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

• unavailable building blocks 7 and 10 were chemically constructed from readily available starting materials. The synthesis of building block 10 commenced with the synthesis of compound 15 through Wittig reaction of Garner’s aldehyde (13) [16], which was readily obtained from tert-butyloxycarbonyl (Boc

Cyclometalated iridium complexes-catalyzed acceptorless dehydrogenative coupling reaction: construction of quinoline derivatives and evaluation of their antimicrobial activities

• Hongling Shui,
• Yuhong Zhong,
• Renshi Luo,
• Zhanyi Zhang,
• Jiuzhong Huang,
• Ping Yang and
• Nianhua Luo

Beilstein J. Org. Chem. 2022, 18, 1507–1517, doi:10.3762/bjoc.18.159

• released from the dehydrogenation of 2-aminobenzyl alcohol/1-phenylethanol according to the previous literature [28]. Lastly, the desired product 3aa was obtained by the condensation and cyclization of the aldehyde 5 with acetophenone (6) under base conditions. The potential antimicrobial activity of the

Oxa-Michael-initiated cascade reactions of levoglucosenone

• Julian Klepp,
• Thomas Bousfield,
• Hugh Cummins,
• Sarah V. A.-M. Legendre,
• Jason E. Camp and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2022, 18, 1457–1462, doi:10.3762/bjoc.18.151

• adducts similar to 3 would be possible, and so have investigated the reaction of 1 with aromatic aldehydes in the presence of base in alcohol. It was found that the reaction outcome was dependent on the type of aldehyde used, and the reactions gave unanticipated products. We now disclose a hitherto

• /benzaldehyde led to the bridged species 5a as the major product (Table 1, entries 1 and 2), however, excess aldehyde slowed the formation of 5a (Table 1, entry 3). The use of hydroxide in ethanol failed to yield any 5a indicating the sensitivity of the reaction to conditions (Table 1, entry 4). The most

• effective procedure was to combine the reagents in a 2:1 ratio of 1/aldehyde in a 1.0 M solution of NaOMe in MeOH and then heat the mixture (Table 1, entries 2, and 5–17). Once conditions for the synthesis of 5a had been identified, the scope of the reaction was explored with other aromatic aldehydes (Table

Synthesis of C6-modified mannose 1-phosphates and evaluation of derived sugar nucleotides against GDP-mannose dehydrogenase

• Sanaz Ahmadipour,
• Alice J. C. Wahart,
• Jonathan P. Dolan,
• Laura Beswick,
• Chris S. Hawes,
• Robert A. Field and
• Gavin J. Miller

Beilstein J. Org. Chem. 2022, 18, 1379–1384, doi:10.3762/bjoc.18.142

• aldehyde 2 followed by substrate attachment through Cys268 to form thiohemiacetal 3. A second oxidation reveals thioester 4 which, following hydrolysis, releases the product 5. As GMD does not exist in humans, strategies that could prevent its mechanism of action could open a pathway for new and selective

On drug discovery against infectious diseases and academic medicinal chemistry contributions

• Yves L. Janin

Beilstein J. Org. Chem. 2022, 18, 1355–1378, doi:10.3762/bjoc.18.141

• ][245] thought experiment and was quickly adopted by industrials [246][247], is also a noteworthy incentive for innovation in organic chemistry [248][249][250][251][252]. However, and still on COVID-19, the DNA-encoded chemical library approach which led to yet another aldehyde-bearing compound

Cyclodextrin-based Schiff base pro-fragrances: Synthesis and release studies

• Attila Palágyi,
• Jindřich Jindřich,
• Juraj Dian and
• Sophie Fourmentin

Beilstein J. Org. Chem. 2022, 18, 1346–1354, doi:10.3762/bjoc.18.140

• – cinnamaldehyde, cyclamen aldehyde, lilial, benzaldehyde, anisaldehyde, vanillin, hexanal, heptanal, citral, and 5-methylfurfural. Subsequently, the rate of release of the volatile compound from selected pro-fragrances, as a function of the environment (solvent, pH), was studied by 1H NMR spectroscopy (for

• benzaldehyde) and static headspace-gas chromatography (for benzaldehyde, heptanal, and 5-methylfurfural). The aldehyde release rate from the imine was shown to depend substantially on the pH from the solution and the air humidity from the solid state. Keywords: aldehyde; controlled release; cyclodextrin

• example of flavor compounds. The imine bond was chosen for its relative stability; on the other hand, it can be readily hydrolyzed forming the starting non-volatile amine and releasing the aldehyde. The kinetics of the aldehyde release was studied by 1H NMR techniques in buffers with different pH values

Synthesis and electrochemical properties of 3,4,5-tris(chlorophenyl)-1,2-diphosphaferrocenes

• Almaz A. Zagidullin,
• Farida F. Akhmatkhanova,
• Mikhail N. Khrizanforov,
• Robert R. Fayzullin,
• Tatiana P. Gerasimova,
• Ilya A. Bezkishko and
• Vasili A. Miluykov

Beilstein J. Org. Chem. 2022, 18, 1338–1345, doi:10.3762/bjoc.18.139

• bromides from one starting aryl aldehyde. Diethyl phosphite was allowed to react with appropriately substituted benzaldehydes in THF for 48 hours at 25 °C to afford diethyl (hydroxy(aryl)methyl)phosphonates 1, which were detected by 31P NMR spectroscopy in THF (21.4 ppm for 1a, 21.0 ppm for 1b, and 21.5

Cytochrome P450 monooxygenase-mediated tailoring of triterpenoids and steroids in plants

• Karan Malhotra and
• Jakob Franke

Beilstein J. Org. Chem. 2022, 18, 1289–1310, doi:10.3762/bjoc.18.135

• celastrol, a potent anti-obesity metabolite [42][43]. In two independent studies, transcriptome mining and functional studies in Nicotiana benthamiana were used to identify the CYPs CYP712K1, CYP712K2, CYP712K3, and CYP712K4 capable of oxidising friedelin (8) into polpunonic acid via an aldehyde

• modification of monocyclic marnerol and tricyclic thalianol (12) in Arabidopsis [27][41]. Marneral synthase (MRN1) produces two oxidation products, one is marneral (aldehyde) and the other marnerol (alcohol). Arabidopsis CYP71A16 hydroxylates the allylic methyl side-chain of monocyclic marneral/marnerol to 23

Enantioselective total synthesis of putative dihydrorosefuran, a monoterpene with an unique 2,5-dihydrofuran structure

• Irene Torres-García,
• Josefa L. López-Martínez,
• Rocío López-Domene,
• Manuel Muñoz-Dorado,
• Ignacio Rodríguez-García and
• Miriam Álvarez-Corral

Beilstein J. Org. Chem. 2022, 18, 1264–1269, doi:10.3762/bjoc.18.132

• dihydrorosefuran, a compound allegedly identified in Artemisia pallens and Tagetes mendocina, has been developed. The key steps in the five-step 36% overall yield synthesis are a CpTiIIICl2 mediated Barbier-type allenylation of a linear aldehyde and the formation of a 2,5-dihydrofuran scaffold through a Ag(I

• of the hydroxy group to the terminal double bond of the allene in compound 3. Another key step is the Ti(III)-mediated straightforward synthesis of this α-hydroxyallene, which could be achieved through a regioselective Barbier-type coupling of a propargylic halide (1-bromo-2-butyne) with the aldehyde

• 4 mediated by the organometallic half-sandwich complex [CpTiIIICl2] [11][12]. Following this retrosynthetic proposal, our route starts from ethyl 4-oxobutanoate (4) [13] which was prepared by ozonolysis of commercially available ethyl pent-4-enoate (Scheme 2). Coupling of the aldehyde 4 with 1

Modular synthesis of 2-furyl carbinols from 3-benzyldimethylsilylfurfural platforms relying on oxygen-assisted C–Si bond functionalization

• Sebastien Curpanen,
• Per Reichert,
• Gabriele Lupidi,
• Giovanni Poli,
• Julie Oble and
• Alejandro Perez-Luna

Beilstein J. Org. Chem. 2022, 18, 1256–1263, doi:10.3762/bjoc.18.131

• activation [19]. Thereby, C3-triorganosilyl-substituted furfurals could be suitable platforms to develop a two-step modular approach to 3-substituted 2-furyl carbinols, entailing nucleophilic addition to the aldehyde function and oxygen-assisted electrophilic substitution of the C–Si bond (Scheme 1). Results

• from E, and thus affording the C3-lithiated furan derivative G upon 1,4-silyl migration as well as the electrophilic substitution product H in the presence of an appropriate electrophile (Scheme 3, bottom). However, treatment of aldehyde 1b with n-BuLi, followed by addition of benzaldehyde in THF/DMPU

• combination with CuI (20 mol %), cross-coupling between 4c and iodobenzene was achieved, giving 18 in reasonably good yield (70%). 4-Iodoanisole could also be coupled (giving 19 in 57% yield), but not electron-deficient 1-iodo-4-nitrobenzene. At this point, it should be mentioned that treatment of aldehyde 2c

Vicinal ketoesters – key intermediates in the total synthesis of natural products

• Marc Paul Beller and
• Ulrich Koert

Beilstein J. Org. Chem. 2022, 18, 1236–1248, doi:10.3762/bjoc.18.129

• species to the α-ketoester 15 (Scheme 3) [6]. The ketoester 15 was synthesized by a chiral pool approach starting from (+)-3-carene derived cycloheptenone 13 [7][8] and aldehyde 12 (accessible from (R)-Roche ester [9]) via the γ-lactone 14. The ketoester moiety was established by an enolate hydroxylation

• was synthesized by a Horner–Wadsworth–Emmons reaction of phosphonate 48 with aldehyde 47. Enantiopure aldehyde 47 was easily accessible from oxazolidinone 46 via Evans-aldol chemistry [23]. Heating of the α-ketoester 49 led to the highly substituted cyclopentanol 50 in a good dr of ≈5:1 (minor

• for different purposes in the syntheses of a range of oxindole alkaloids. The start of the synthesis of (rac)-corynoxine (76) was the conversion of tryptamine (70) to oxindole 71, which was used in a chemoselective Mannich reaction with aldehyde 72, introducing the α-ketoester moiety (Scheme 12) [27

Lewis acid-catalyzed Pudovik reaction–phospha-Brook rearrangement sequence to access phosphoric esters

• Jin Yang,
• Dang-Wei Qian and
• Shang-Dong Yang

Beilstein J. Org. Chem. 2022, 18, 1188–1194, doi:10.3762/bjoc.18.123

• recognized as challenging since there is no single report on such a sequence under Lewis acid catalysis. Herein, we report the synthesis of phosphoric esters by a Lewis acid Cu(OTf)2-catalyzed one-pot Pudovik reaction–phospha-Brook rearrangement sequence between pyridinyl-substituted aldehyde or pyridone

Experimental and theoretical studies on the synthesis of 1,4,5-trisubstituted pyrrolidine-2,3-diones

• Nguyen Tran Nguyen,
• Vo Viet Dai,
• Nguyen Ngoc Tri,
• Luc Van Meervelt,
• Nguyen Tien Trung and
• Wim Dehaen

Beilstein J. Org. Chem. 2022, 18, 1140–1153, doi:10.3762/bjoc.18.118

• 70%. However, an increase in the yield of product 4a to 77% could be observed with the ratio of 1:1:1.5 of reactants 1a, 2, and 3, respectively (Table 1). The product 4a was obtained in 80% yield when the concentration of the aromatic aldehyde 1a in solvent increased to 0.75 M while remaining the

• aromatic aldehyde, aniline, and ethyl 2,4-dioxovalerate, respectively, in acetic acid as solvent was used to synthesize other substituted 4-acetyl-3-hydroxy-3-pyrroline-2-ones. It may be surmised that the first step in the three-component reaction to synthesize substituted 4-acetyl-3-hydroxy-3-pyrroline-2

• -ones 4a–c occurs via the acid-catalyzed condensation of the aromatic aldehyde 1a–c and aniline (2) to produce imine intermediate 5 which is then protonated to the iminium species 6. In addition, ethyl 2,4-dioxovalerate (3) containing an activated methylene group is in fast equilibrium with enol

Synthesis of N-phenyl- and N-thiazolyl-1H-indazoles by copper-catalyzed intramolecular N-arylation of ortho-chlorinated arylhydrazones

• Yara Cristina Marchioro Barbosa,
• Guilherme Caneppele Paveglio,
• Claudio Martin Pereira de Pereira,
• Sidnei Moura,
• Cristiane Storck Schwalm,
• Gleison Antonio Casagrande and
• Lucas Pizzuti

Beilstein J. Org. Chem. 2022, 18, 1079–1087, doi:10.3762/bjoc.18.110

• -bottom flask, the o-chlorinated aromatic aldehyde (5 mmol) and phenylhydrazine (0.540 g, 5 mmol) were dissolved in methanol (25 mL). Glacial acetic acid (0.060 g, 20 mol %) and sodium acetate (0.082 g, 20 mol %) were added, and the solution was stirred for 4 h at room temperature. The resulting mixture

• 60 using the following eluent: hexane/AcOEt 98:2 for 2a,b,d,e, petroleum ether/AcOEt 98:2 for 2f, hexane/AcOEt 90:10 for 2g,i,i’, and hexane/AcOEt 80:20 for 2h. General experimental procedure for the synthesis of hydrazones 3a–i The o-chlorinated aromatic aldehyde (1.5 mmol), thiosemicarbazide (0.136

New azodyrecins identified by a genome mining-directed reactivity-based screening

• Atina Rizkiya Choirunnisa,
• Kuga Arima,
• Yo Abe,
• Noritaka Kagaya,
• Kei Kudo,
• Hikaru Suenaga,
• Junko Hashimoto,
• Manabu Fujie,
• Noriyuki Satoh,
• Kazuo Shin-ya,
• Kenichi Matsuda and
• Toshiyuki Wakimoto

Beilstein J. Org. Chem. 2022, 18, 1017–1025, doi:10.3762/bjoc.18.102

• azodyrecins (Scheme 2). The pathway is likely initiated by Ady2, a putative dehydrogenase that recruits fatty acids from primary metabolism to generate an aldehyde, which would be converted to an aliphatic amine by the pyridoxal phosphate (PLP)-dependent transaminase Ady4. The amine would be N-hydroxylated by

First example of organocatalysis by cathodic N-heterocyclic carbene generation and accumulation using a divided electrochemical flow cell

• Daniele Rocco,
• Ana A. Folgueiras-Amador,
• Richard C. D. Brown and
• Marta Feroci

Beilstein J. Org. Chem. 2022, 18, 979–990, doi:10.3762/bjoc.18.98

• , under galvanostatic conditions (I = 134 mA, telectrolysis = 12 min) with a flow rate of 36 mL/min, anode solution as in Table 3, and with 1.0 Faraday per mole of aldehyde. At the end of the electrolysis, 1 mmol of cinnamaldehyde was added to the catholyte and the mixture was left under stirring for five

• electrochemically generated NHC into the corresponding thione by its reaction with elemental sulfur. Umpolung of the aldehyde carbonyl carbon atom. Formation of the Breslow intermediate using NHCs. Electrogenerated NHC-catalyzed self-annulation of cinnamaldehyde. Byproduct obtained from the reaction between

On Reuben G. Jones synthesis of 2-hydroxypyrazines

• Pierre Legrand and
• Yves L. Janin

Beilstein J. Org. Chem. 2022, 18, 935–943, doi:10.3762/bjoc.18.93

• amine) on the most electrophilic component of the α-ketoaldehyde (its aldehyde) to give intermediate 5. However, the ensuing cyclization (via a hydration of its imine bond to allow for a rotation) would then lead to compound 4 which is rarely the major reaction product. Since compound 3 is the main

Copper-catalyzed multicomponent reactions for the efficient synthesis of diverse spirotetrahydrocarbazoles

• Shao-Cong Zhan,
• Ren-Jie Fang,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2022, 18, 796–808, doi:10.3762/bjoc.18.80

• 3-substituted indole, which undergoes dehydration to form the key intermediate indole-based ortho-quinodimethanes (o-QDMs, A). In the meantime, the cyclic 1,3-diones and aromatic aldehyde undergo Knoevenagel condensation to afford the different kinds of dienophiles. Subsequently, the Diels–Alder

• . On the other hand, the tetrahydrospiro[carbazole-3,5'-pyrimidine] 4 can be converted to aromatized spiro[carbazole-3,5'-pyrimidine] 3 through the oxidation of DDQ. In the absence of the effective dienophile, the normal Friedel–Crafts alkylation of 2-methylindole with aromatic aldehyde gives the well

• provide great potential for applications in organic synthesis, pharmaceutical chemistry and materials science. Experimental 1. General procedure for the preparation of the spiro[carbazole-3,3'-inolines] 1a–j and 1a’–j’: A mixture of 2-methyl-1H-indole (0.5 mmol, 1.0 equiv), aldehyde (0.6 mmol, 1.2 equiv

Inductive heating and flow chemistry – a perfect synergy of emerging enabling technologies

• Conrad Kuhwald,
• Sibel Türkhan and
• Andreas Kirschning

Beilstein J. Org. Chem. 2022, 18, 688–706, doi:10.3762/bjoc.18.70

• an aldehyde 5, a secondary amine 6, and a terminal alkyne 7, afforded arylpropargylamines 8 in up to 84% yield under flow conditions (Scheme 7, reaction 2). Microwave irradiation interacted with a thin foil of Cu or Au that served as catalyst inside the glass capillary. The work must be highlighted

• Petasis boron-Mannich (PBM) reaction of glyoxalic acid (30a) or salicylic aldehyde (30b), with morpholine (29) and p-methoxyphenylboronic acid (31) furnished α-aminocarboxylic acid 32a and phenol 32b in excellent yield (98% and 93%), again much higher than the yields found for the batch protocol (77% and

Rapid gas–liquid reaction in flow. Continuous synthesis and production of cyclohexene oxide

• Kyoko Mandai,
• Tetsuya Yamamoto,
• Hiroki Mandai and
• Aiichiro Nagaki

Beilstein J. Org. Chem. 2022, 18, 660–668, doi:10.3762/bjoc.18.67

• achieved by using a flow technique (Scheme 1). Cyclohexene oxide was selectively produced with high yield in our flow oxidation system using air and within only 1.4 min. The fast epoxidation of cyclohexene without added catalyst in the solution was achieved since the solution of cyclohexene and aldehyde in

• oxidation and decomposition of oxidants generated from air and aldehyde. Furthermore, the fast epoxidation is applicable for the continuous production process of cyclohexene oxide for 1 hour maintaining stable operation. Results and Discussion Batch experiment of epoxidation of cyclohexene with air As an

• from the lowered solubility of air in a solvent at a high temperature to produce peracid from the reaction of aldehyde and oxygen insufficiently, and the epoxidation was deaccelerated. The experimental results revealed that aerobic epoxidation of cyclohexene in a batch reactor required a longer

DDQ in mechanochemical C–N coupling reactions

• Shyamal Kanti Bera,
• Rosalin Bhanja and
• Prasenjit Mal

Beilstein J. Org. Chem. 2022, 18, 639–646, doi:10.3762/bjoc.18.64

• were well tolerated and gave the desired products 5h–k with high yields. In this context, biphenyl aldehyde with a chloro group was efficiently converted to 5l with 93% yield. Furthermore, aromatic aldehydes having a strong electron-withdrawing group (such as NO2) were smoothly converted to the

• containing fluoro, bromo, ethyl, and anthryl groups led to the corresponding products 6j, 6k, 6l, and 6p in good to excellent yield. Aliphatic aldehydes such as butyraldehyde gave the cyclized product 6m with an 86% yield. In this regard, an -OMe and -COMe group-containing biphenyl aldehyde resulted in the

The asymmetric Henry reaction as synthetic tool for the preparation of the drugs linezolid and rivaroxaban

• Martin Vrbický,
• Karel Macek,
• Jaroslav Pochobradský,
• Jan Svoboda,
• Miloš Sedlák and
• Pavel Drabina

Beilstein J. Org. Chem. 2022, 18, 438–445, doi:10.3762/bjoc.18.46

• highly efficient catalysts based on copper complexes of different types of chiral ligands, 2-(pyridin-2-yl)imidazolidine-4-ones (I–III), bis-oxazolines (IV–VII), or diamine (VIII) were chosen for the study (Figure 2). Furthermore, the modification of the structure of the prochiral aldehyde intermediates

• 15 and 19 was also performed with the aim to increase the enantiomeric purity of the corresponding nitroaldol products 21–26. The structural modification consisted in the introduction of different alkyl moieties to the carbamate functional group of the aldehyde intermediates 15–20. As bulky and/or

• modified synthetic procedure [14]. Here, it was included the chromatographic purification of the final chloroformates, which led to removing of corresponding alkyl chlorides formed as byproducts. The aldehyde 17 was prepared by a different way, because the acid-catalyzed hydrolysis of its acetal

Menadione: a platform and a target to valuable compounds synthesis

• Acácio S. de Souza,
• Ruan Carlos B. Ribeiro,
• Dora C. S. Costa,
• Fernanda P. Pauli,
• David R. Pinho,
• Matheus G. de Moraes,
• Fernando de C. da Silva,
• Luana da S. M. Forezi and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 381–419, doi:10.3762/bjoc.18.43

Amamistatins isolated from Nocardia altamirensis

• Till Steinmetz,
• Wolf Hiller and
• Markus Nett

Beilstein J. Org. Chem. 2022, 18, 360–367, doi:10.3762/bjoc.18.40

• C35H53N5O7 by the [M + H]+ ion at m/z 656.4019 (calcd for C35H54N5O7, 656.4023). Analysis of 1D and 2D NMR spectra confirmed that the aldehyde group in position 25 is missing. Therefore, compound 3 represents the N-desformyl analogue of 1. Compound 4 (1.9 mg) was obtained as a reddish oil. Its molecular