1,4,6,10-Tetraazaadamantanes (TAADs) with N-amino groups: synthesis and formation of boron chelates and host–guest complexes

• Artem N. Semakin,
• Ivan S. Golovanov,
• Yulia V. Nelyubina and
• Alexey Yu. Sukhorukov

Beilstein J. Org. Chem. 2022, 18, 1424–1434, doi:10.3762/bjoc.18.148

• ). Such symmetrization can be explained by a pre-organization of N-amido groups through the coordination of water/alcohol leading to the host–guest complex observed in the X-ray. The formation of the inclusion complexes H2O@TAADs 4a and MeOH@4c·H+ was additionally explored by DFT calculations at the

Sinensiols H–J, three new lignan derivatives from Selaginella sinensis (Desv.) Spring

• Qinfeng Zhu,
• Beibei Gao,
• Qian Chen,
• Tiantian Luo,
• Guobo Xu and
• Shanggao Liao

Beilstein J. Org. Chem. 2022, 18, 1410–1415, doi:10.3762/bjoc.18.146

• the elucidation of its absolute configuration. The remaining known compounds were identified as (+)-pinoresinol di-O-β-ᴅ-glucopyranoside (4) [21], dehydrodiconiferyl alcohol-4-O-β-ᴅ-glucopyranoside (5) [22], and lariciresinol-4-O-β-ᴅ-glucopyranoside (6) [23] (Figure 1) by comparing their

Preparation of an advanced intermediate for the synthesis of leustroducsins and phoslactomycins by heterocycloaddition

• Anaïs Rousseau,
• Guillaume Vincent and
• Cyrille Kouklovsky

Beilstein J. Org. Chem. 2022, 18, 1385–1395, doi:10.3762/bjoc.18.143

• studies for the conversion of enol phosphate to the corresponding ketone were accomplished using an unprotected primary alcohol. However, it appeared that hydroxy group protection was necessary: control experiments made on the racemic cycloadduct 8 showed that basic hydrolysis of the enol phosphate led to

• ], together with a small amount of the over reduced alcohol 12b, which could be reoxidized to 11b (Scheme 4). Other substrates failed to deliver appreciable yields of the ketone under the same conditions. These studies validate the role of TIPS ether as protecting group for the primary alcohol. At this stage

• alcohol. Studies in fragment coupling We have previously reported the synthesis of the lactone fragment by catalytic asymmetric [2 + 2] cycloaddition followed by ring extension [18]. The initial product was the TMS-acetylene 18 which could be easily desilylated to give 21. However, model studies for

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

• Cannizaro’s reaction. At pH 12.80, the benzaldehyde was fully converted to benzyl alcohol and benzoic acid after 5 days. Static headspace analysis We first determined the Henry law constants and the formation constants with β-CD of three selected aldehydes (Table 1). As can be seen from Table 1, the studied

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

• 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

• alcohol 6 with amberlyst-15® leading to the monoterpene 1. Other systems tested for the elimination of the hydroxy group in 6 were pyridinium p-toluenesulfonate (PPTS) and camphorsulfonic acid (CSA), that gave poorer results, failing to afford a single product. On the other hand, lactone 5 could also be

• transformed into alcohol 6 through a simple change in the order of the reactions: addition of methylmagnesium bromide to 5 afforded 7, which was then transformed into 6 by the Ag(I)-mediated cyclization (Scheme 2). Once we had synthesized racemic compound 1, we designed a chiral version using a

• . Analysis of the NMR data of the Mosher's derivatives of 8 suggested (S) configuration for the alcohol (−)-3 [16]. On the other hand, enantiopure acetate (+)-(R)-9 was transformed into diol (+)-(R)-7 by the addition of an excess of MeMgBr. Finally, these enantiopure compounds, α-hydroxyallene (−)-(S)-3 and

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

• [25], afforded only the addition product 3b without any detectable formation of product 9, expected from 1,4-silyl migration/electrophilic substitution of 8 (Scheme 4, top). Conversely, treatment of alcohol 3a with t-BuOCu in the presence of allyl chloride, according to conditions developed by Takeda

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

• cycloisomerization of the α-ketoester 22, which can be described as a Friedel–Crafts-type reaction or an aldol reaction of an S,O-ketene acetal (Scheme 4). The required ketoester 22 was synthesized from sulfonylchromenone 20, accessible from dihydroxyacetophenone 19 and thiol 18 derived from known alcohol 17 [11][12

• natural product preussochromone D (30) reported by Koert et al. [13]. The synthesis commenced with the efficient production of alcohol 26 from 5-hydroxy-4H-chromen-4-one (25, Scheme 5) [14]. The ketoester moiety was build up via oxidation and nucleophilic addition of methyl diazoacetate, yielding alcohol

• 27. Subsequent oxidation gave α-ketoester 28 which was used in an intramolecular, Lewis acid-mediated aldol reaction, presumably via tridentate complex transition state III, to give diol 29 as a single diastereomer. Inversion of the secondary alcohol and deprotection gave preussochromone D (30

Electro-conversion of cumene into acetophenone using boron-doped diamond electrodes

• Mana Kitano,
• Tsuyoshi Saitoh,
• Shigeru Nishiyama,
• Yasuaki Einaga and
• Takashi Yamamoto

Beilstein J. Org. Chem. 2022, 18, 1154–1158, doi:10.3762/bjoc.18.119

• conversion is found to proceed electrochemically. Results and Discussion First, we carried out the electrolysis of cumene (1) in 0.1 M Bu4NBF4/MeCN under constant current conditions in an undivided beaker-type cell (Table 1, entry 1). The main product was acetophenone (3) and α-cumyl alcohol (4) was also

Enzymes in biosynthesis

• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2022, 18, 1131–1132, doi:10.3762/bjoc.18.116

• proceed through multistep cationic cascade reactions and usually produce a polycyclic terpene hydrocarbon or alcohol with multiple stereogenic centers. While these transformations require only a single enzyme, polyketide and nonribosomal peptide biosyntheses are catalyzed by megasynthases that follow an

Electrochemical formal homocoupling of sec-alcohols

• Kosuke Yamamoto,
• Kazuhisa Arita,
• Masashi Shiota,
• Masami Kuriyama and
• Osamu Onomura

Beilstein J. Org. Chem. 2022, 18, 1062–1069, doi:10.3762/bjoc.18.108

• anode-free electrochemical protocol for the synthesis of pinacol-type vic-1,2-diols from sec-alcohols, namely benzyl alcohol derivatives and ethyl lactate. The corresponding vic-1,2-diols are obtained in moderate to good yields, and good to high levels of stereoselectivity are observed for sec-benzyl

• alcohol derivatives. The present transformations smoothly proceed in a simple undivided cell under constant current conditions without the use of external chemical oxidants/reductants, and transition-metal catalysts. Keywords: alcohols; dimerization; electrooxidation; electroreduction; paired

• ]. Kim et al. reported the formation of vic-1,2-diols in the sacrificial anode-free electrocarboxylation of 1-phenylethanol and benzyl alcohol which involves tetramethylpiperidine-1-oxyl-mediated alcohol oxidation as an anodic event [46]. However, vic-1,2-diols were obtained only as minor products and

Electrochemical hydrogenation of enones using a proton-exchange membrane reactor: selectivity and utility

• Koichi Mitsudo,
• Haruka Inoue,
• Yuta Niki,
• Eisuke Sato and
• Seiji Suga

Beilstein J. Org. Chem. 2022, 18, 1055–1061, doi:10.3762/bjoc.18.107

• of 1a under the indicated conditions gave 3a in 79% yield with 98% selectivity. In contrast, electroreduction of cyclopent-2-en-1-one (1b) gave cyclopentanol 3b in 29% yield (46% selectivity), but the reason has not been elaborated yet. With 3-methyl-2-cyclohexen-1-one (1c), alcohol 3c was obtained

• was carried out with the use of H2O as a proton source by the PEM reactor with a Pd/C cathode catalyst (Scheme 5). Similar to the reaction with H2, the electroreduction proceeded with high chemoselectivity, and the desired ketone 2a was obtained in 70% yield, whereas alcohol 3a was not observed

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

• minutes and then the corresponding alcohol was added and the reaction was stirred for two hours at room temperature. Workup and column chromatography yielded esters 3a–c and unsaturated esters 4a,b as byproducts. Good yields were obtained using benzyl and methyl alcohols (73% and 68%, respectively), while

• with the isopropyl alcohol the formation of the ester was only 37%, probably due to steric hindrance. In two cases (Table 3, entries 1 and 2) oxidation byproducts (esters 4a and 4b) were obtained, where the olefinic double bond is preserved. In contrast to the internal redox reactions of cinnamaldehyde

• catholyte. The mixture was left under stirring for 5 minutes and then the corresponding alcohol (2.0 mmol) was added and the reaction was stirred for 2 hours at room temperature. The solvent was removed under reduced pressure and the residue was extracted with of Et2O (15 mL × 3) and purified by column

Electroreductive coupling of 2-acylbenzoates with α,β-unsaturated carbonyl compounds: density functional theory study on product selectivity

• Naoki Kise and
• Toshihiko Sakurai

Beilstein J. Org. Chem. 2022, 18, 956–962, doi:10.3762/bjoc.18.95

• 6a could not be purified, it was treated with 1 M HCl/dioxane 1:1 at 25 °C for 1 h to give desilylated alcohol 7a in 78% yield (2 steps) as a mixture of two diastereomers (78:22 dr). Dehydration of compound 7a in refluxing toluene in the presence of cat. PPTS produced 2-cyanonaphthalene-1-ol (3a) in

Morita–Baylis–Hillman reaction of 3-formyl-9H-pyrido[3,4-b]indoles and fluorescence studies of the products

• Nisha Devi and
• Virender Singh

Beilstein J. Org. Chem. 2022, 18, 926–934, doi:10.3762/bjoc.18.92

• leading to the formation of allylic alcohol; a highly functionalized product [41][42][43][44]. The chemistry of the MBH reaction is decorated with several unique features viz. atom economy, complexity generation and generation of a chiral center from a pro-chiral electrophile. The chemistry of the MBH

• ester 4a–e in high yield (83–87%) and ester functionality reduction with LiAlH4 in dry THF yielded the alcohols 5a–e in excellent yield (90–98%). The required 3-formyl-9H-β-carbolines 6a–e were obtained in 73–88% yield by oxidizing the alcohol derivatives 5a–e with MnO2 in dry DCM. The present

Efficient production of clerodane and ent-kaurane diterpenes through truncated artificial pathways in Escherichia coli

• Fang-Ru Li,
• Xiaoxu Lin,
• Qian Yang,
• Ning-Hua Tan and
• Liao-Bin Dong

Beilstein J. Org. Chem. 2022, 18, 881–888, doi:10.3762/bjoc.18.89

• alternative to bypass synthetic challenges. In this study, we constructed two truncated artificial pathways to efficiently produce terpentetriene and ent-kaurene, two representative clerodane and ent-kaurane diterpenes, in Escherichia coli. Both pathways depend on the exogenous addition of isoprenoid alcohol

• DMAPP from isopentenol (ISO) and dimethylallyl alcohol (DMAA) [15][19]. In this strategy, two independent kinases were used. ISO and DMAA were phosphorylated to form isopentenyl monophosphate (IP) and dimethylallyl monophosphate (DMAP), respectively, which were then phosphorylated by another kinase to

Cathodic generation of reactive (phenylthio)difluoromethyl species and its reactions: mechanistic aspects and synthetic applications

• Sadanobu Iwase,
• Shinsuke Inagi and
• Toshio Fuchigami

Beilstein J. Org. Chem. 2022, 18, 872–880, doi:10.3762/bjoc.18.88

• both radical and anionic intermediates. In order to further clarify the reaction mechanism, the indirect cathodic reduction of compound 1 was performed in the presence of α-methylstyrene in MeCN containing cumene (iPrC6H5) and isopropyl alcohol (iPrOH). The former works as a hydrogen radical source

• -phthalonitrile as mediator in the presence of α-methylstyrene. Reaction of compound 1 with SmI2 in the presence and absence of α-methylstyrene. Indirect cathodic reduction of compound 1 with o-phthalonitrile in the presence of α-methylstyrene in MeCN containing cumene or isopropyl alcohol. Supporting

First series of N-alkylamino peptoid homooligomers: solution phase synthesis and conformational investigation

• Maxime Pypec,
• Laurent Jouffret,
• Claude Taillefumier and
• Olivier Roy

Beilstein J. Org. Chem. 2022, 18, 845–854, doi:10.3762/bjoc.18.85

• observed for Xaa–Pro amide bonds and polyproline chains can adopt either the all-trans type II (PPII) or the all-cis type I (PPI) helical conformations, the latter being only observed in alcohol-type solvents [14]. In contrast to the prolyl-amide bond in acyclic peptides (≈5% of cis-Pro) [15], the cis

Synthesis of odorants in flow and their applications in perfumery

• Merlin Kleoff,
• Paul Kiler and
• Philipp Heretsch

Beilstein J. Org. Chem. 2022, 18, 754–768, doi:10.3762/bjoc.18.76

• a method for the acetylation of isoamyl alcohol (9) catalyzed by Candida antarctica lipase B (Scheme 3) [26]. A biphasic system consisting of n-heptane and an aqueous buffer solution is used and efficiently mixed in a Corning AFRTM Low Flow reactor providing a fine dispersion of the reaction mixture

• min isoamyl acetate (10) is obtained in 59% yield according to GC analysis [26]. Related methods for the enzyme-catalyzed acetylation of isoamyl alcohol (9) have been developed utilizing biphasic systems, supercritical carbon dioxide as a solvent, or packed-bed reactors with immobilized enzymes [27

• mixture is combined with an aqueous solution of sodium thiosulfate before it is collected. Among the prepared alcohols, a few compounds were found to have interesting olfactory properties. Alcohol 22 has a citrus and menthol note, while its homolog 23 shows a turpentine-like, woody scent. In contrast

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

• up in an oscillating electromagnetic field because it does not exhibit conductive properties, so it had to be mixed with MagSilicaTM. Several oxidations were performed, including those of anthracene (33), propargyl alcohol 55 and testosterone (57), which proceeded smoothly with 80%, 93%, and 95

• included a carboxylation and a Parham cyclization and hence a Grignard alkylation of ketone 82 using reagent 81. The resulting alcohol 83 was subjected to thermolysis that led to water elimination. This step proceeded in just 30 s by employing the inductive heating technique. The crude elimination product

Chemistry of polyhalogenated nitrobutadienes, 17: Efficient synthesis of persubstituted chloroquinolinyl-1H-pyrazoles and evaluation of their antimalarial, anti-SARS-CoV-2, antibacterial, and cytotoxic activities

• Viktor A. Zapol’skii,
• Isabell Berneburg,
• Ursula Bilitewski,
• Melissa Dillenberger,
• Katja Becker,
• Stefan Jungwirth,
• Aditya Shekhar,
• Bastian Krueger and
• Dieter E. Kaufmann

Beilstein J. Org. Chem. 2022, 18, 524–532, doi:10.3762/bjoc.18.54

• compared to chlorine [28]. The reaction of oxazolidine 6 with 2.3 equivalents of 7-chloro-4-hydrazinylquinoline in toluene at 90–95 °C for 30 h led to the formation of pyrazole 7 (yield 23%) together with considerable amounts of a resin (Scheme 5). We suggest that the lower yield of alcohol 7 is due to 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

• performed on sub-millimolar scales in isopropyl alcohol (IPA). The obtained products 21–26 were separated from the starting aldehydes 15–20 by column chromatography. The reaction conditions (i.e., temperature, reaction time, amount of catalyst, and solvent) were adopted from the pilot study [12] for

Cs₂CO₃-Promoted reaction of tertiary bromopropargylic alcohols and phenols in DMF: a novel approach to α-phenoxyketones

• Ol'ga G. Volostnykh,
• Olesya A. Shemyakina,
• Anton V. Stepanov and
• Igor' A. Ushakov

Beilstein J. Org. Chem. 2022, 18, 420–428, doi:10.3762/bjoc.18.44

• bromopropargylic alcohols and Cs2CO3. Keywords: acetylenic alcohol; bromoacetylene; 1,3-dioxolan-2-one; phenols; phenoxyketone; Introduction Due to the relative stability, ease of handling and the presence of reactive sites, bromoacetylenes are widely applied in synthetic organic chemistry. They are known to be

• highly selective hydration/acylation of tertiary bromopropargylic alcohols with carboxylic acids promoted by alkali metal carbonates [24]. The reaction proceeds via the ring-opening of 1,3-dioxolan-2-one intermediates formed with hydroxy and alkynyl groups of bromopropargylic alcohol and alkali metal

• carbonate. In the light of the above, it was unclear, in which direction would proceed the reaction of bromopropargylic alcohols and phenols. In the present paper, we report on the results of these studies. Results and Discussion Initially, bromopropargylic alcohol 1a and phenol (2a) were chosen as the

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

• three component catalyst system consisting of iron(III) chloride, pyridine-2,6-dicarboxylic acid (H2Pydic), and benzylamine (1:1:2.2) for the oxidation of 16 with H2O2, in tert-amyl alcohol (TAA), allowed to obtain 10 in 44% yield (Table 1, entry 9) [55]. Subsequently, Kulkarni’s group evaluated the

• different benzylamines (1:1:2.2) (Table 2, entry 7). The reaction was carried out in tert-amyl alcohol (TAA), which led to product 10 in 55% yield and 99% conversion of 17 [55]. In addition to hydrogen peroxide, other oxidizing agents can be used in the synthesis of menadione (10) from 17 and include

• method proved to be effective at recovering approximately 95% of the enantiopure alcohol 47. This allowed the alcohol’s effective reconversion to hydroperoxide 46 and proved to be a useful method for the enantioselective epoxidation of menadione (10) (Scheme 13). Pericyclic reactions The Diels–Alder

A resorcin[4]arene hexameric capsule as a supramolecular catalyst in elimination and isomerization reactions

• Tommaso Lorenzetto,
• Fabrizio Fabris and
• Alessandro Scarso

Beilstein J. Org. Chem. 2022, 18, 337–349, doi:10.3762/bjoc.18.38

• reactions involving the formation of cationic intermediate species [41] like water elimination from an alcohol to provide the corresponding alkene, the isomerization of β-pinene and α-pinene and the cyclization of (S)-citronellal to secondary alcohols. The key point to interpret the action of the capsule in

• evidence of the importance of an accessible cavity for the activation of the reaction after alcohol protonation. It is known that 16 behaves as a weakly acidic assembly with pKa of about 5.5 [42], while the resorcinol moiety presents a pKa of 9.15. This enhanced acidity is likely to promote the protonation

• carbocation species. It has also to be considered that water elimination during the progress of the reaction changes the ratio between capsules A and B thus accelerating product formation. The intrinsic stability of the carbocation formed by water elimination from the corresponding alcohol is crucial to