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

• deprotection of the silyl group was accomplished in the presence of potassium carbonate (K2CO3) and methanol to provide the terminal alkyne 5 in 96% yield in two steps. The iodoarene 8 [12][16] was facilely synthesized from sesamol (6) via methylation and iodination in an overall yield of 67%. With the

Design, synthesis, and evaluation of chiral thiophosphorus acids as organocatalysts

• Karen R. Winters and
• Jean-Luc Montchamp

Beilstein J. Org. Chem. 2022, 18, 1471–1478, doi:10.3762/bjoc.18.154

• . The resolution of compound 1 was not conducted at this point because its synthesis was deemed problematic. While relatively short (5 steps), the overall yield was only 20% due to a low-yielding key step and a problematic thionation step immediately following. Unfortunately, thionation of 8 with an

• obtained in moderate yield. Crystallization gave a single diastereoisomer in 20% yield. Stec reaction [38][39][40] finally gave the desired CPA 4. Although the entire sequence proceeded in only 6% overall yield, it was conducted on a multigram-scale so that more than 0.4 g of 4 was obtained. Evaluation of

Mechanochemical synthesis of unsymmetrical salens for the preparation of Co–salen complexes and their evaluation as catalysts for the synthesis of α-aryloxy alcohols via asymmetric phenolic kinetic resolution of terminal epoxides

• Shengli Zuo,
• Shuxiang Zheng,
• Jianjun Liu and
• Ang Zuo

Beilstein J. Org. Chem. 2022, 18, 1416–1423, doi:10.3762/bjoc.18.147

• were summarized in Table 1. We were surprised that the overall yield from ball milling was lower than the overall yield from grinding, suggesting a higher revolution per minute (RPM) could be necessary to increase the reaction yield using ball milling. It is assumed that the forces are not equivalent

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

• we wondered whether it was possible to perform the whole synthetic sequence with this protecting group. Accordingly, the enol phosphate 13 was synthesized in five steps (26% overall yield) from 1,4-butanediol (Scheme 5). Since cycloaddition with the Wightman reagent 6 releases hydrogen chloride in

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

• -phosphate 17 as the sodium triethylamine salt. Overall, the synthesis of 17 was developed in 4 steps and 46% overall yield from 14. With the required C6-modified glycosyl 1-phosphates in hand, we next evaluated them as substrates for enzymatic sugar nucleotide synthesis. Enzymatic synthesis of C6-modified

Ionic multiresonant thermally activated delayed fluorescence emitters for light emitting electrochemical cells

• Merve Karaman,
• Abhishek Kumar Gupta,
• Subeesh Madayanad Suresh,
• Tomas Matulaitis,
• Lorenzo Mardegan,
• Daniel Tordera,
• Henk J. Bolink,
• Sen Wu,
• Stuart Warriner,
• Ifor D. Samuel and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2022, 18, 1311–1321, doi:10.3762/bjoc.18.136

• 23% overall yield. First, hydrolysis of 1, in situ conversion to the acyl chloride and subsequent Lewis acid-promoted Friedel–Crafts acylation reaction produced compound 2 (Scheme 1), where the AlCl3 was also responsible for the demethylation. Compound 2 was then subjected to monoalkylation with 1,4

• -dibromobutane in moderate yield, followed by a second alkylation step with 1-methylimidazole in very good yield. DiKTa-OBuIm was isolated as its hexafluorophosphate salt following anion metathesis with NH4PF6. DiKTa-DPA-OBuIm was obtained also in three steps at 35% overall yield from compound 4 using a similar

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

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

• with a medium pressure mercury lamp in Pyrex® glassware triggered a 1,6-HAT leading to biradical X which combined to the racemic pyrrolizidine 68 as a 1:1 mixture of diastereomers. Three more steps gave the target compound 69 in 31% overall yield. Corynoxine Hiemstra et al. used the α-ketoester moiety

• aniline 94 in three steps (Scheme 16). Subsequent deprotection and condensation with dimethyl mesoxalate (90b) gave imidazolidine 95. With compound 95 at hands, five further steps gave (−)-aplaminal (96) in a good overall yield of 19%. Cladoniamide G The unsymmetrical mesoxalic acid amide 102 was used by

Synthesis of tryptophan-dehydrobutyrine diketopiperazine and biological activity of hangtaimycin and its co-metabolites

• Houchao Xu,
• Anne Wochele,
• Minghe Luo,
• Gregor Schnakenburg,
• Yuhui Sun,
• Heike Brötz-Oesterhelt and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2022, 18, 1159–1165, doi:10.3762/bjoc.18.120

• diminished yield for 15 (70%), lowering the overall yield of TDD to 33% over eight steps. The major enantiomer of 4 obtained from this second route was identical to natural TDD (Figure 1D) which is thus S-configured, i.e., derived from ʟ-tryptophan. Moreover, the olefinic double bond in 4 is Z-configured as

Synthesis and HDAC inhibitory activity of pyrimidine-based hydroxamic acids

• Virginija Jakubkiene,
• Gabrielius Ernis Valiulis,
• Markus Schweipert,
• Asta Zubriene,
• Daumantas Matulis,
• Franz-Josef Meyer-Almes and
• Sigitas Tumkevicius

Beilstein J. Org. Chem. 2022, 18, 837–844, doi:10.3762/bjoc.18.84

• increase in the overall yield (from 52 to 71%) and selectivity (from 1.4:1 to 2.5:1) in favor of the O-isomer 24a were observed (compare entries 5 and 6 in Table 1). The best alkylation results were obtained when the alkylation reaction was carried out at 50–60 °C. These reaction conditions proved to be

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

• . For compound 6, both individual steps were combined for a two-step aldol condensation/hydrogenation flow sequence providing raspberry ketone methyl ether (6) on a gram scale in 75% overall yield. Interestingly, also alternative flow protocols for the synthesis of 4-aryl-3-buten-2-ones 3 and 4 were

Complementarity of solution and solid state mechanochemical reaction conditions demonstrated by 1,2-debromination of tricyclic imides

• Petar Štrbac and
• Davor Margetić

Beilstein J. Org. Chem. 2022, 18, 746–753, doi:10.3762/bjoc.18.75

• in a 1:1.3 ratio (inseparable mixture, 32% overall yield). The minor isomer has a linear structure with carbomethoxy groups in the equatorial plane as depicted for 37, whereas in the major isomer 38 the carbomethoxy groups are positioned in axial plane of the molecule. The bent structure of 38 was

BINOL as a chiral element in mechanically interlocked molecules

• Matthias Krajnc and
• Jochen Niemeyer

Beilstein J. Org. Chem. 2022, 18, 508–523, doi:10.3762/bjoc.18.53

• -capping. The resulting compounds were treated with chloroacetic anhydride and then with thiazole. After anion exchange the chiral thiazolium salts (R)-35a/b, which differ in the chain length of the axle, were obtained in 9%/42% overall yield (see Figure 8a). For comparison, a rotaxane containing a BINOL

• , rotaxane (R)-38 was obtained in 35% overall yield (see Figure 8b). These rotaxanes where then used as catalysts for the asymmetric benzoin condensation of benzaldehyde (39). The best yield (90%) could be generated at 0 °C in methanol with 10 mol % of catalyst (R)-35a, albeit with a low stereoselectivity

• pyridine axle, followed by ion exchange, gave rise to the cationic rotaxanes 64a/b in 23/37% overall yield, both of which feature four iodotriazoles as XB donors. While rotaxane (S)-64a only possesses the BINOL unit as a stereogenic element, the system (S,S,S)-64b features two additional chiral centers on

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

• -naphthoquinone (18) were obtained in 80% yield with a 75:25 ratio, respectively (Scheme 2, method A). In the methylation reaction using methyl radicals generated by the redox decomposition of H2O2 in DMSO solution, compounds 10 and 18 were obtained in an overall yield of 80–90% with a 77:23 ratio, respectively

• 1,3-butadiene, followed by dehydrogenation gave menadione (10). This proved to be a good synthetic route, leading to menadione in approximately 80% overall yield (Scheme 6). Another interesting synthetic approach was reported by Mal and co-workers, who synthetized menadione (10) via a

Borylated norbornadiene derivatives: Synthesis and application in Pd-catalyzed Suzuki–Miyaura coupling reactions

• Robin Schulte and
• Heiko Ihmels

Beilstein J. Org. Chem. 2022, 18, 368–373, doi:10.3762/bjoc.18.41

• with t-BuLi and the following reaction with bis(pinacolato)diborone in 15% overall yield (Scheme 1) [27]. The low yield of this reaction as compared with the ones of resembling reactions of the substrate 1b [27] may be caused by the unfavorable clash of the sterically demanding borylating reagent and

New efficient synthesis of polysubstituted 3,4-dihydroquinazolines and 4H-3,1-benzothiazines through a Passerini/Staudinger/aza-Wittig/addition/nucleophilic substitution sequence

• Long Zhao,
• Mao-Lin Yang,
• Min Liu and
• Ming-Wu Ding

Beilstein J. Org. Chem. 2022, 18, 286–292, doi:10.3762/bjoc.18.32

• intermediate 7a. In the presence of K2CO3 in CH3CN at refluxing temperature, the 3,4-dihydroquinazoline 8a was finally obtained in 84% yield (Table 1, entry 1, the overall yield is 73%) by intramolecular nucleophilic substitution. The reaction conditions for the transformation of guanidine intermediate 7a into

• obtained in the presence of K2CO3/CH3CN probably due to the lower reactivity of the -OAc leaving group. In case when R was a 4-NO2C6H4 group, 86% yield of the product 8a was obtained, however, in this case the Passerini product 4a (R = 4-NO2C6H4) was obtained only in 62% yield and the overall yield of

Iridium-catalyzed hydroacylation reactions of C1-substituted oxabenzonorbornadienes with salicylaldehyde: an experimental and computational study

• Angel Ho,
• Austin Pounder,
• Krish Valluru,
• Leanne D. Chen and
• William Tam

Beilstein J. Org. Chem. 2022, 18, 251–261, doi:10.3762/bjoc.18.30

• revolutionized the modern chemist’s synthetic toolbox, prior installation of these functional groups requires a number of steps, leading to undesired side-products and reduced overall yield. An attractive alternative is the catalytic activation and subsequent functionalization of otherwise inert carbon–hydrogen

Anomeric 1,2,3-triazole-linked sialic acid derivatives show selective inhibition towards a bacterial neuraminidase over a trypanosome trans-sialidase

• Peterson de Andrade,
• Sanaz Ahmadipour and
• Robert A. Field

Beilstein J. Org. Chem. 2022, 18, 208–216, doi:10.3762/bjoc.18.24

• acid derivatives was synthesised as outlined in Figure 2B. Emulating our previous work with anomeric azide CuAAC click chemistry [17][22][23][24], the well-known α-azidosialic acid 1 [25] was synthesised from N-acetylneuraminic acid in four steps [26] in good overall yield (55%). The assignment of the

Ready access to 7,8-dihydroindolo[2,3-d][1]benzazepine-6(5H)-one scaffold and analogues via early-stage Fischer ring-closure reaction

• Irina Kuznetcova,
• Felix Bacher,
• Daniel Vegh,
• Hsiang-Yu Chuang and
• Vladimir B. Arion

Beilstein J. Org. Chem. 2022, 18, 143–151, doi:10.3762/bjoc.18.15

• closely related analogues, one containing a bromo substituent and the other one incorporating an 8-membered instead of a 7-membered ring. The key transformation in this four-step synthesis, with an overall yield of 29%, is the Fischer indole reaction of 2-nitrophenylacetyl acetoacetate with 1-benzyl-1

Chemical and chemoenzymatic routes to bridged homoarabinofuranosylpyrimidines: Bicyclic AZT analogues

• Sandeep Kumar,
• Jyotirmoy Maity,
• Banty Kumar,
• Sumit Kumar and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2022, 18, 95–101, doi:10.3762/bjoc.18.10

• chemoenzymatic method was found to be superior over the chemical method in respect of the number of synthetic steps and overall yield of the final product. Keywords: bicyclic AZT analogues; bridged homoarabinofuranosylpyrimidine nucleosides; chemical pathway; Lipozyme® TL IM; regioselective enzymatic

• % overall yield starting from compound 11, respectively (Scheme 2). The use of lipase as biocatalyst was employed for the selective acetylation of the primary hydroxy group present in trihydroxy nucleosides 14a,b. This led to the screening of two different lipases, viz Candida antarctica lipase-B (CAL-B

First total synthesis of hoshinoamide A

• Haipin Zhou,
• Zihan Rui,
• Yiming Yang,
• Shengtao Xu,
• Yutian Shao and
• Long Liu

Beilstein J. Org. Chem. 2021, 17, 2924–2931, doi:10.3762/bjoc.17.201

• tripeptide 7 was obtained in 36% yield. Similar conditions were selected by Iwasaki’s group during the total synthesis of hoshinoamide C. To our delight, when HATU was used, the overall yield of tripeptide 7 was rised to more than 70% (Table 1, entries 2 and 3). Tripeptide 7 was produced in 78% isolated

Total synthesis of the O-antigen repeating unit of Providencia stuartii O49 serotype through linear and one-pot assemblies

• Tanmoy Halder and
• Somnath Yadav

Beilstein J. Org. Chem. 2021, 17, 2915–2921, doi:10.3762/bjoc.17.199

• monosaccharide acceptor 7 was added, followed by the addition of NIS and TMSOTf. After 15 min of reaction, TLC monitoring showed complete consumption of the donor. Work-up of the reaction mixture followed by chromatographic purification afforded the pure trisaccharide 2 as a single isomer in an overall yield of

• target protected trisaccharide was also synthesized through a [1 + 1 + 1] one-pot strategy involving sequential glycosylations from the reducing end to the non-reducing end. The one-pot synthesis provided the final trisaccharide in an overall yield of 73% compared to the overall yield of 66% from the two

Synthetic strategies toward 1,3-oxathiolane nucleoside analogues

• Umesh P. Aher,
• Dhananjai Srivastava,
• Girij P. Singh and
• Jayashree B. S

Beilstein J. Org. Chem. 2021, 17, 2680–2715, doi:10.3762/bjoc.17.182

• in the presence of levamisole, which gave an improved overall yield of 52 of up to 67%. In this approach, the required stereochemistry of the thioacetal compound was created, so that the coupling with a nucleobase in a further step determines the stereochemistry of the attaching nucleobase at the

Synthesis of highly substituted fluorenones via metal-free TBHP-promoted oxidative cyclization of 2-(aminomethyl)biphenyls. Application to the total synthesis of nobilone

• Ilya A. P. Jourjine,
• Lukas Zeisel,
• Jürgen Krauß and
• Franz Bracher

Beilstein J. Org. Chem. 2021, 17, 2668–2679, doi:10.3762/bjoc.17.181

• obtained via TBHP-mediated cyclization of 23 and subsequent TBS-deprotection of intermediate 24 with pyridine and HF·pyridine complex [66] in a total yield of 26% over the two steps. The longest linear sequence was 7 steps, with an overall yield of 5%. Finally, the reaction mechanism of the oxidative

• nobilone (25) in 8 steps in an overall yield of 2%. This protocol allows the synthesis of variously substituted fluorenones, since the required 2-(aminomethyl)biphenyls are readily available from commercially available building blocks (substituted benzonitriles or benzaldehydes, areneboronic acids) via

• varying degree on the overall yield. This new protocol was utilized for the first total synthesis of the natural fluorenone nobilone (1d). Selected fluorenone-type natural products. Overview of published cyclization methodologies for the synthesis of fluorenones starting from functionalized biaryls

N-Sulfinylpyrrolidine-containing ureas and thioureas as bifunctional organocatalysts

• Viera Poláčková,
• Dominika Krištofíková,
• Boglárka Némethová,
• Renata Górová,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2021, 17, 2629–2641, doi:10.3762/bjoc.17.176

• which the key intermediate, pyrrolidine derivative 2, can be obtained in three steps according to the literature procedure [32]. Using this method, we obtained the product 2 in a yield comparable (56% overall yield) to that described in the literature. However, the difficult chromatographic separation