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

• benzyl fluorides and the proposed mechanism. Borane-catalysed S‒H borylation of thiols and the proposed mechanism. Borane-catalysed hydroalumination of alkenes and allenes. a) Aluminium-catalysed hydroboration of alkynes and example catalysts. b) Deprotonation mechanistic proposal. c) Hydroalumination

Synthesis and reactivity of azole-based iodazinium salts

• Thomas J. Kuczmera,
• Annalena Dietz,
• Andreas Boelke and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2023, 19, 317–324, doi:10.3762/bjoc.19.27

• indazole salt 5be was isolated in 30% yield and the benzyl-bridged, seven-membered salt 5bf could not be obtained under our optimized reaction conditions. Single crystal structures of selected salts were obtained to gain a better understanding of the bonding situation and the coordination states in these

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

• endocyclic nitrogen with a benzyl or alkyl unit functionalized either with non-polar hydrocarbons or a polar amine, amidine and guanidine group. The ensuing assay with the model GMIIb enzyme (fruit fly Golgi α-mannosidase II) revealed that N-substitution improved both potency and selectivity, achieving

• –7 times less active toward AMAN-2 than GMIIb and had poorer selectivities (SI below 35). In contrast, imino-ᴅ-lyxitols bearing a non-polar N-arylalkyl chain (benzyl, p-iodobenzyl, 2-naphthylmethyl) showed slightly higher inhibitory activities toward AMAN-2 and good to excellent selectivities [22

• substituted at the endocyclic nitrogen by the most successful arylalkyl chains (benzyl, p-iodobenzyl, 2-naphthylmethyl) found in our previous studies [22][30][33]. The biological activity of the novel synthesized compounds was evaluated toward the GH38 family enzymes (AMAN-2, GMIIb, fruit fly lysosomal α

Strategies to access the [5-8] bicyclic core encountered in the sesquiterpene, diterpene and sesterterpene series

• Cécile Alleman,
• Charlène Gadais,
• Laurent Legentil and
• François-Hugues Porée

Beilstein J. Org. Chem. 2023, 19, 245–281, doi:10.3762/bjoc.19.23

• a TBDPS substituent in compound 40 was assumed unfavorable, since this bulky residue generates a steric hindrance precluding the cyclization (Scheme 6, path A) [27]. Its replacement by a sterically less demanding benzyl protecting group (compound 44) allowed the reaction to occur (Scheme 6, path B

• -dimethyl and benzyl protecting group, did not undergo the tandem process and furnished the monocyclized product 105. To circumvent this monocyclization reaction, Gao and co-workers decided to simplify the gem-dimethyl group by a methyl residue and prepared the analogous compounds of 102 and 103, namely 106

Investigation of cationic ring-opening polymerization of 2-oxazolines in the “green” solvent dihydrolevoglucosenone

• Solomiia Borova and
• Robert Luxenhofer

Beilstein J. Org. Chem. 2023, 19, 217–230, doi:10.3762/bjoc.19.21

• NMR spectra (Figure S6), indicating no interaction between the solvent and the monomer. Polymerization of 2-ethyl-2-oxazoline Six different electrophiles, acetyl chloride (AcCl), propionyl chloride (PrCl), benzyl bromide (BnBr), MeOTf, MeOTs, and EtOxMeOTf, were examined as initiators for the EtOx

• benzyl-initiated PEtOx with Br-termini carrying Na+ (α) ion doping. Interestingly, no signals attributed to the initiator were observed in the resulting 1H NMR spectra. Signals that could be attributed to PEtOx terminated by water, carrying sodium (β) or terminated by DLG derivatives with K+ (γ) or Na

• polymerization initiated with methyl triflate (black), methyl tosylate (red), 2-ethyl-3-methyl-2-oxazolinium triflate (blue), benzyl bromide (green) after 3 h of incubation and acyl chloride (dark red), propionyl chloride (purple) after 24 h of incubation in DLG. Peaks marked with asterisks originate from

1,4-Dithianes: attractive C2-building blocks for the synthesis of complex molecular architectures

• Bram Ryckaert,
• Ellen Demeyere,
• Frederick Degroote,
• Hilde Janssens and
• Johan M. Winne

Beilstein J. Org. Chem. 2023, 19, 115–132, doi:10.3762/bjoc.19.12

• dependence [95]. On the other hand, simple benzyl cations can undergo more controlled (3 + 2) annulations, as is illustrated by the long-known Friedel–Crafts-type acid-catalyzed cascade reaction of styrene leading to the cyclic styrene dimer 86 (Scheme 13c) [96][97]. This (3 + 2) cycloaddition reactivity of

• benzyl cations can also be extended to ‘mixed’ cycloadditions [98], as is illustrated by the commercially exploited synthesis of the common pentamethylindane-derived perfumes (Scheme 13d) [99][100]. The popular perfume building block 87 is readily obtained from α-methylstyrene and an excess of amylene to

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

• °C and with the use of 1.3 equivalents of AgOTf. Finally, we sought to check the reactivity of other substituents on the amine component of acyclic imine substrates. With the use of benzyl-substituted aldimine, the aza-Nazarov product 19l was obtained in 49% yield and with 10:1 dr. Similarly, the aza

NaI/PPh₃-catalyzed visible-light-mediated decarboxylative radical cascade cyclization of N-arylacrylamides for the efficient synthesis of quaternary oxindoles

• Dan Liu,
• Yue Zhao and
• Frederic W. Patureau

Beilstein J. Org. Chem. 2023, 19, 57–65, doi:10.3762/bjoc.19.5

• %). Interestingly, a cyclic N-arylamide derivative was also well tolerated, furnishing polycyclic structure 3la in 67% yield. In addition, substrates with different N-substituents, such as ethyl, benzyl, and phenyl, could be converted into the expected products 3ma–oa in good yields. It should be noted that

Two-step continuous-flow synthesis of 6-membered cyclic iodonium salts via anodic oxidation

• Julian Spils,
• Thomas Wirth and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2023, 19, 27–32, doi:10.3762/bjoc.19.2

• continuous-flow procedure for the generation of six-membered diaryliodonium salts. The accompanying scalability and atom economy are significant improvements to existing batch methods. Benzyl acetates are submitted to this two-step procedure as highly available and cheap starting materials. An acid-catalyzed

• , we improved the formation of iodoarenes through a Brønsted acid-mediated Friedel–Crafts reaction followed by an oxidative cyclization to form the desired CDIS 1 (Scheme 1A). This one-pot approach is based on ortho-iodinated benzyl alcohols as starting materials. It allows access to a variety of

• further by increasing the charge (Table 2, entry 5). For a final combination of the two reaction steps, benzyl acetate 3a was chosen as a model substrate due to its high solubility and good reactivity as was previously demonstrated by us (Table 3) [28]. We determined an optimal reaction time of 20 min for

Combining the best of both worlds: radical-based divergent total synthesis

• Kyriaki Gennaiou,
• Antonios Kelesidis,
• Maria Kourgiantaki and
• Alexandros L. Zografos

Beilstein J. Org. Chem. 2023, 19, 1–26, doi:10.3762/bjoc.19.1

• thermodynamic position of a Wieland−Miescher ketone derivative 68 with benzyl bromide 69. Despite the challenging O- and C7-alkylations that required suppression, the desired C9-alkylation was achieved in 72% yield under thermodynamically controlled conditions (t-BuOK in THF at −40 °C). This coupled the terpene

• , requiring only two purification steps [77]. FGI of 146 led to (−)-enantiomer 147, which serves as the radical point od divergence of this plan. HAT-initiated transannular free-radical cyclization of (−)-enantiomer 147 according to Baran’s protocols [78] provided the benzyl-protected (−)-pseudocopsinine 148

• -step sequence. The cyclization of the formed radical is 6-exo-trig and leads to the formation of a benzyl radical that is further oxidized to 188. From this common scaffold, the group managed to access several natural products of the class, majorly by utilizing the ability of conjugated alkenes to be

Inline purification in continuous flow synthesis – opportunities and challenges

• Jorge García-Lacuna and
• Marcus Baumann

Beilstein J. Org. Chem. 2022, 18, 1720–1740, doi:10.3762/bjoc.18.182

• group where an immobilized lipase (e.g., CALB) facilitated the derivatization of high-boiling benzyl alcohol in scaled Curtius rearrangement reactions. Ultimately, this approach negated the use of column chromatography in favor of a simple trituration process to isolate pure carbamate products [106

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

• , protection of the secondary alcohol as a benzyl ether, oxidation of the sulfur and Pummerer rearrangement (Scheme 3). A Wittig reaction gave compounds 8, as a 10:1 separable diastereomeric mixture. A diastereoselective Diels–Alder cycloaddition followed by oxidation of the resulting epimeric mixture gave

• substituted cyclohexanone 9, corresponding to the future C ring [24]. After deprotonation, the C3 position was stereoselectively alkylated using propargyl bromide, and the benzyl protecting group was cleaved with FeCl3, leading to spontaneous lactone closure. A Luche reduction stereoselectively converted

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

• benzyl iodides was observed. Besides classical NHPI/PINO-catalyzed CH-functionalization processes, there is a significant number of works in which PINO plays the role of both the catalyst for C–H bond cleavage and the reagent intercepting the resultant C-centered radical [90]. As a rule, stoichiometric

• benzyl radical on the O or N atom of the PINO radical, respectively. It should be noted that this method works well even without the excess of CH-reagent [94]. The formation of the mixture of C–O and C–N coupling products may be the main factor limiting the application of this method. The selective C–O

• different chemoselectivity: secondary and benzyl alcohols are more easily oxidized. The great diversity of catalytic systems based on amine-N-oxyl radicals for alcohol oxidation was proposed [74][76][77][95]. Amine-N-oxyl organocatalysts with enhanced catalytic activity were developed by the modification of

A novel spirocyclic scaffold accessed via tandem Claisen rearrangement/intramolecular oxa-Michael addition

• Anastasia Vepreva,
• Alexander Yanovich,
• Dmitry Dar’in,
• Grigory Kantin,
• Alexander Bunev and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2022, 18, 1649–1655, doi:10.3762/bjoc.18.177

• crystallography. In all other cases, only the pure syn diastereomer was isolated and characterized. The yields of spirocyclic products were generally modest to good over two steps. An electron-accepting group in the benzylidene portion (5j) or an N-benzyl substitution in the starting material (5g) lowered the

Rhodium-catalyzed intramolecular reductive aldol-type cyclization: Application for the synthesis of a chiral necic acid lactone

• Motoyuki Isoda,
• Kazuyuki Sato,
• Kenta Kameda,
• Kana Wakabayashi,
• Ryota Sato,
• Hideki Minami,
• Yukiko Karuo,
• Atsushi Tarui,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2022, 18, 1642–1648, doi:10.3762/bjoc.18.176

• to the literature, a Sharpless dihydroxylation of benzyl tiglate (8) to form a chiral diol 9 was followed by a Parikh–Doering oxidation to give the corresponding product 10 in 62% yield (Scheme 4) [58][59]. Subsequent acryloylation in the presence of DMAP and hydroquinone gave the intramolecular

A new route for the synthesis of 1-deazaguanine and 1-deazahypoxanthine

• Raphael Bereiter,
• Marco Oberlechner and
• Ronald Micura

Beilstein J. Org. Chem. 2022, 18, 1617–1624, doi:10.3762/bjoc.18.172

• intermediates. Here, we present a new tactic for the syntheses of 1-deazaguanine and 1-deazahypoxanthine stimulated by a recently published route of our research group for the corresponding nucleosides [16][17], employing the same key reaction, namely the copper-catalyzed coupling of an aryl iodide with benzyl

• was carried out to obtain the desired 4-hydroxy-2,3,6-triaminopyridine (15) in unspecified yield (Scheme 3). This approach was optimized in 1975 by Schelling and Salemink using benzyl ether protection of the O4 during the imidazopyridine formation to increase the overall yield up to 37% [20]. The last

• be easily prepared from its commercially available 6-chloro derivative [16]. To enable C–O coupling with benzyl alcohol, protection of the N9 with a tetrahydropyranyl group was necessary due to limited solubility of the aryl iodide. Therefore, 6-iodo-1-deazapurine was treated with tosylic acid and

Preparation of β-cyclodextrin-based dimers with selectively methylated rims and their use for solubilization of tetracene

• Konstantin Lebedinskiy,
• Volodymyr Lobaz and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2022, 18, 1596–1606, doi:10.3762/bjoc.18.170

• selectively permethylated on the primary side is shown in Scheme 3. The method described by Varga [25] was not suitable for the preparation of 11 because of the strong reductive conditions required for the cleavage of benzyl protective groups. Other described procedures [23][24] also have disadvantages, such

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

• , the breaking of the C–C bond of intermediate 7 led to the generation of the expected final product 4a through retro-one reaction. It was also shown that the side product, 1-benzyl-4,5-dimethyl-1,3-dihydro-2H-imidazol-2-one (8) was formed from 1a through simply thermal rearrangement. Nucleophilic

• using aldehydes and Meldrum’s acid under metal-free and mild reaction conditions [20]. The optimization conditions were estimated to be 1.0 mmol of 1-benzyl-4,5-dimethylimidazole N-oxide as substrate, 1.0 mmol of aldehydes and 1.0 mmol of Meldrum’s acid (26) in 6.0 mL of acetonitrile as solvent at

• reflux for 5 h. In this operationally simple procedure, the imidazole N-oxide plays the role of a ‘C’-nucleophile when there is no involvement of acid or base catalyst. 1-Benzyl-4,5-dimethylimidazole N-oxide (28) was chosen as the N-oxide substrate to react with Meldrum’s acid (26) and several aldehydes

A study of the DIBAL-promoted selective debenzylation of α-cyclodextrin protected with two different benzyl groups

• Naser-Abdul Yousefi,
• Morten L. Zimmermann and
• Mikael Bols

Beilstein J. Org. Chem. 2022, 18, 1553–1559, doi:10.3762/bjoc.18.165

• Naser-Abdul Yousefi Morten L. Zimmermann Mikael Bols Department of chemistry, University of Copenhagen, Universitetsparken 5, 2100, Copenhagen, Denmark 10.3762/bjoc.18.165 Abstract An α-cyclodextrin protected with 2,4-dichlorobenzyl groups on the primary alcohols and ordinary benzyl groups on the

• secondary alcohols was prepared and subjected to DIBAL (diisobutylaluminum hydride)-promoted selective debenzylation. Debenzylation proceeded by first removing two dichlorobenzyl groups from the 6A,D positions and then removing one or two benzyl groups from the 3A,D positions. Keywords: aluminum hydrides

• . These methods are so useful because virtually any chemical modification at the deprotected sites can be made followed by global deprotection of the O-benzyl groups with hydrogenolysis. Recently, we observed a strong substituent effect when substituted benzyl groups were used in these reactions with

Efficient synthesis of aziridinecyclooctanediol and 3-aminocyclooctanetriol

• Emine Salamci and
• Ayse Kilic Lafzi

Beilstein J. Org. Chem. 2022, 18, 1539–1543, doi:10.3762/bjoc.18.163

• cis,cis-1,3-cyclooctadiene. Results and Discussion The synthesis of the diol 5, which was prepared by reduction of the endoperoxide 4 with zinc was carried out as described in the literature [18]. Treatment of the diol 5 with benzyl bromide and NaH in DMF gave the corresponding (dibenzyloxy

• relative to the proton H-2. For the synthesis of the aminocyclooctanetriol 13, hydrogenation of the azido alcohol 11 gave amine 12 in 95% yield (Scheme 2). Subsequent, benzyl deprotection with BCl3 of 12 resulted in the target compound 13 in 85% yield. The structures of compounds 12 and 13 are completely

• a positive NOE clearly indicates that the protons H-2/H-7 should have a cis configuration relative to the protons H-1/H-8. Finally, benzyl deprotection with BCl3 of 14 afforded the product 16 in 84% yield. The structure of 16 was assigned on the basis of NMR spectroscopy. Conclusion In summary, we

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

• treatment of secondary amine 11 with ene-nitrosoacetal 12 [36] (Scheme 2b). The synthesis of products 7a,b containing two oxime groups was accomplished via double oximinoalkylation of benzylamine to give dioxime 13 [36], cleavage of the N-benzyl group, and reaction of the secondary amine 14 with α

• tetraazaadamantane cage, quaternization of the tertiary bridge-head nitrogen in Boc-protected TAADs 4c, 4e, 6a, and 8a was performed by benzylation [21][40] (Scheme 5). The obtained N-benzyl salts were quantitatively converted into corresponding deprotected TAADs 19–21 by reflux in water (Scheme 5, blue

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

• the cyclic hemiacetal 9 in modest yield (Scheme 2). Therefore, compound 8 was protected as silyl or benzyl ether using standard techniques. Unfortunately, no hydrolysis under several basic conditions provides the target ketone, no conversion and/or decomposition being observed (Scheme 3). Enol

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

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

• of benzaldehyde led to the formation of adduct 14 (in 75% yield), which arose from the addition of a benzyl carbanion 17 to benzaldehyde. The generation of such a nucleophile strongly suggests the formation of pentavalent silicon intermediate 15 [27], which then produced a (stabilized) benzylic

• -catalyzed arylation reactions (Scheme 7). Fluoride-promoted arylation reactions of benzyldimethyl(alkenyl)silanes have been reported, and it is established that they proceed through the cleavage of the benzyl moiety from the benzyldimethylsilyl groups, leading to either dimethylsilanols or cyclic siloxanes

A one-pot electrochemical synthesis of 2-aminothiazoles from active methylene ketones and thioureas mediated by NH₄I

• Shang-Feng Yang,
• Pei Li,
• Zi-Lin Fang,
• Sen Liang,
• Hong-Yu Tian,
• Bao-Guo Sun,
• Kun Xu and
• Cheng-Chu Zeng

Beilstein J. Org. Chem. 2022, 18, 1249–1255, doi:10.3762/bjoc.18.130

• reacted smoothly with thiourea 2a under the optimized conditions, giving the corresponding products in 30–80% yields (3a–d). In addition, allyl and benzyl acetoacetate were also suitable substrates to give the desired 2-aminothiazoles 3e and 3f in 78% and 52% yields, respectively. β-ketoesters containing