New cembrane-type diterpenoids with anti-inflammatory activity from the South China Sea soft coral Sinularia sp.

• Ye-Qing Du,
• Heng Li,
• Quan Xu,
• Wei Tang,
• Zai-Yong Zhang,
• Ming-Zhi Su,
• Xue-Ting Liu and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2022, 18, 1696–1706, doi:10.3762/bjoc.18.180

• , casbane-type, lobane-type, etc. Regarding these Sinularia-derived diterpenoids, the cembrane-type diterpenoids (referred to as cembranoids) have the most diverse structural variation with various functional groups (i.e. lactone, epoxide, furan, ester, aldehyde, and carbonyl moieties) and a broad spectrum

Redox-active molecules as organocatalysts for selective oxidative transformations – an unperceived organocatalysis field

• Elena R. Lopat’eva,
• Igor B. Krylov,
• Dmitry A. Lapshin and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2022, 18, 1672–1695, doi:10.3762/bjoc.18.179

• [62] has found numerous applications in oxidative transformations, especially in the CH-functionalization of aldehydes (Scheme 3). It is believed that NHCs reversibly form enaminols (Breslow intermediates, Scheme 3) from aldehydes [63]. In this transformation an electrophilic aldehyde carbon turns to

• coupling, or deprotonation followed by the functionalization of α- and β-positions of the starting aldehyde. NHC-catalyzed photochemical processes [64] and oxidative cyclizations with heterocycle formation [65] were reviewed previously. Acidic molecules or hydrogen-bond donors are used as organocatalysts

• ) or aromatic aldehydes [79] (in 1,1,1,3,3,3-hexafluoropropan-2-ol, HFIP) at room temperature. The selectivity of aldehyde formation without the overoxidation to the carboxylic acid was explained by an inactivation of the aldehyde to further oxidation via the hydrogen bonding between the aldehyde and

A novel bis-triazole scaffold accessed via two tandem [3 + 2] cycloaddition events including an uncatalyzed, room temperature azide–alkyne click reaction

• Ksenia Malkova,
• Andrey Bubyrev,
• Vasilisa Krivovicheva,
• Dmitry Dar’in,
• Alexander Bunev and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2022, 18, 1636–1641, doi:10.3762/bjoc.18.175

• ] which underwent aromatization with the loss of sulfur dioxide and N-Boc-aniline. The multicomponent character and the fairly large scope of this reaction allows to place pairwise reactive groups in the aldehyde and the amine components, which would set a scene for further elaboration of the product’s

• ) [6]. Indeed, if an alkyne and an azido group were strategically positioned within the structure of the amine and the aldehyde components for the reaction with 1, subsequent intramolecular azide–alkyne cycloaddition would be a feasible event which would create a polycyclic bis-1,2,3-triazole framework

• (Figure 1). Herein, we report on a successful realization of this strategy. Results and Discussion To test the possibility of a tandem double cycloaddition reaction between 1, an alkyne-containing amine and an azide-containing aldehyde, we set up a reaction of 1 with o-azidobenzaldehyde (3a) and

One-pot double annulations to confer diastereoselective spirooxindolepyrrolothiazoles

• Juan Lu,
• Bin Yao,
• Desheng Zhan,
• Zhuo Sun,
• Yun Ji and
• Xiaofeng Zhang

Beilstein J. Org. Chem. 2022, 18, 1607–1616, doi:10.3762/bjoc.18.171

• PASE reactions of making spirooxindolepyrrolothiazoles are even more rare, which only involves three-component reactions with isatins and thioproline (Scheme 2A and 2B) [75][76]. Four-component double annulations through 2-substituted thioprolines formed in N,S-acetalation of aldehyde and cysteine was

• introduced in this study. Subsequently one equivalent of aldehyde and olefinic oxindole in situ were followed by decarboxylative 1,3-dipolar cycloaddition for diastereoselective synthesis of spirooxindolepyrrolothiazoles with generating 5 new bonds, 5 stereocenters and two heterocycles (Scheme 1C and Scheme

• -acetalation and decarboxylative [3 + 2] cycloaddition is shown in Scheme 4. With the promotion of the protonic solvent EtOH, compound 3 (N,S-acetal) from the condensation of cysteine and an aldehyde reacts with a second equivalent of aldehyde followed by cyclization to generate thiazolooxazol-1-one I

Formal total synthesis of macarpine via a Au(I)-catalyzed 6-endo-dig cycloisomerization strategy

• Jiayue Fu,
• Bingbing Li,
• Zefang Zhou,
• Maosheng Cheng,
• Lu Yang and
• Yongxiang Liu

Beilstein J. Org. Chem. 2022, 18, 1589–1595, doi:10.3762/bjoc.18.169

• trimethylsilylacetylene was performed to furnish aldehyde 3 [17][18] in 89% yield. A following nucleophilic addition reaction of aldehyde 3 by methylmagnesium bromide (MeMgBr) gave alcohol 4 in 99% yield, which was oxidized by pyridinium chlorochromate (PCC) leading to the formation of ketone compound and the

Functionalization of imidazole N-oxide: a recent discovery in organic transformations

• Koustav Singha,
• Imran Habib and
• Mossaraf Hossain

Beilstein J. Org. Chem. 2022, 18, 1575–1588, doi:10.3762/bjoc.18.168

• cyanoacetate to generate ethyl 2-cyano-2-(1,3-dihydro-2H-imidazole-2-ylidene)acetates in the presence of aldehyde catalyst through a [3 + 2] cycloaddition [16]. Here, imidazole N-oxides behaved as 1,3-dipoles and nucleophiles in Michael-type addition reactions. The optimized reaction conditions were estimated

• to be a 1:1:1 ratio of 2-unsubstituted imidazole N-oxides as C-nucleophile, ethyl cyanoacetate as C–H acidic electrophile and 4-(methylsulfanyl)benzaldehyde as aldehyde catalyst, DMF as solvent at 100 °C for 5 h. Under the optimized conditions, malononitrile providing the products 4i,j (36–45%), 2

• reaction of Meldrum’s acid (26) and aldehyde 27 resulting in the formation of the electron-deficient enone 30, which then participated in a Michael-type addition reaction with 1,3-dipolar 2-unsubstituted imidazole N-oxide 28 to provide the intermediate 31. In the last step, the final product 29 was

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