Regioselectivity of the S_EAr-based cyclizations and S_EAr-terminated annulations of 3,5-unsubstituted, 4-substituted indoles

• Jonali Das and
• Sajal Kumar Das

Beilstein J. Org. Chem. 2022, 18, 293–302, doi:10.3762/bjoc.18.33

• regioselective cyclization of an indole-tethered donor–acceptor cyclopropane. Indole C5 regioselective epoxide–arene cyclization. Funding We acknowledge the financial supports received from DST-SERB, New Delhi (Grant No. CRG/2018/003021) and Council of Scientific and Industrial Research (CSIR), New Delhi (Grant

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

• postulated a mechanistic pathway for this cyclization process, where two consecutive inversions of configuration at the C5′ centre enabled the retention of stereochemistry. Thus, formation of 5,6-epoxide moieties was common in case of hexose carbohydrates, where the C6-OH group attacked the C5 centre and

• substituted the mesyl group present at C5 to form 5,6-epoxide moieties [32][33][34]. Herein, we elucidated the mechanistic pathway for conversion of 16a,b into 9a,b through the formation of an intermediate epoxide II, which has (S) stereochemistry at the C5′ due to first inversion of configuration by attack

• from the C6′-OH group (Scheme 6). The second inversion at the C5′ centre occurred when the C2′-OH attacked the same chiral centre and opened the epoxide ring by SN2 reaction and inverted the configuration of the centre into (R). In the chemical route for synthesis of bridged nucleosides 9a,b, an

Efficient and regioselective synthesis of dihydroxy-substituted 2-aminocyclooctane-1-carboxylic acid and its bicyclic derivatives

• İlknur Polat,
• Selçuk Eşsiz,
• Uğur Bozkaya and
• Emine Salamci

Beilstein J. Org. Chem. 2022, 18, 77–85, doi:10.3762/bjoc.18.7

• -functional theory (DFT) computations were used to explain the reaction mechanism for the ring opening of the epoxide and the formation of five-membered lactones. The stereochemistry of the synthesized compounds was determined by 1D and 2D NMR spectroscopy. The configuration of methyl 6-hydroxy-9-oxo-8

• formation of the target β-amino acid 6, which was characterized based on its NMR spectra (Scheme 1). The N-Boc-amino ester 4 was reacted with m-CPBA to give epoxide 7 as the sole product in 94% yield (Scheme 2). The structure of 7 was assigned based on its NMR spectra. Epoxide 7 was used as the precursor

• the neighbouring carboxyl group, which was formed by hydrolysis of the corresponding methyl ester. For the synthesis of other isomeric β-amino acid derivatives, epoxide 7 was treated with two equivalent amounts of NaHSO4 [27] in methylene chloride/MeOH at room temperature (Scheme 3). The formation of

Highly stereocontrolled total synthesis of racemic codonopsinol B through isoxazolidine-4,5-diol vinylation

• Lukáš Ďurina,
• Anna Ďurinová,
• František Trejtnar,
• Ľuboš Janotka,
• Lucia Messingerová,
• Jana Doháňošová,
• Ján Moncol and
• Róbert Fischer

Beilstein J. Org. Chem. 2021, 17, 2781–2786, doi:10.3762/bjoc.17.188

• methodology based on the trans-stereoselective epoxidation reaction of 2,3-dihydroisoxazoles followed by the regioselective hydrolysis of the corresponding isoxazolidinyl epoxide [15][16]. Very recently, we have reported the synthesis of γ-(hydroxyamino)-α,β-diols by the addition of Grignard reagents to

• the expected high syn diol diastereoselectivity (Scheme 1). The obtained anti,syn-(hydroxyamino)alkenol 4 will be then subjected to reductive cleavage of the N–O bond. Next, a key intermediate epoxide 5 with the desired syn (threo) configuration between the hydroxy group and the epoxide oxygen could

• be prepared by substrate-directed epoxidation. A subsequent SN2 intramolecular epoxide ring-opening cyclization could provide an N-Cbz-protected pyrrolidine derivative with a hydroxymethyl group at C-5 and with trans configuration relative to the hydroxy group at C-4. Finally, (±)-codonopsinol B (1

α-Ketol and α-iminol rearrangements in synthetic organic and biosynthetic reactions

• Scott Benz and
• Andrew S. Murkin

Beilstein J. Org. Chem. 2021, 17, 2570–2584, doi:10.3762/bjoc.17.172

• (Figure 15). Next, ring-expanding rearrangement is proposed to form 75. Finally, the C7 ketone is reduced, the C8–C9 bond is oxidized back to an alkene, the C5–C6 double bond is oxidized to an epoxide, and C15 is oxidized to a tertiary alcohol to yield 72. The authors not only structurally characterized

• similarity in reaction, 1-deoxy-ᴅ-xylulose-5-phosphate reductoisomerase (DXR) instead uses a retro-aldol/aldol sequence to accomplish its rearrangement of 68 to 69. c) The secondary metabolite aurachin C (71) is oxidized by the FAD-dependent monooxygenase AuaG to epoxide 72, which upon deprotonation by an

Strategies for the synthesis of brevipolides

• Yudhi D. Kurniawan and
• A'liyatur Rosyidah

Beilstein J. Org. Chem. 2021, 17, 2399–2416, doi:10.3762/bjoc.17.157

• desired epoxide 30 after one hour in 85% yield (dr 10:1). This species was next converted to the terminal carbonate derivative 31 to transform the epoxy functionality to a vicinal diol through a two-step manipulation involving protection of the terminal alcohol as Boc derivative followed by BF3·Et2O

• -promoted intramolecular oxacyclization. After TBS protection, intermediate 32 was collected in 86% yield from epoxide 30. Basic methanolysis of the cyclic carbonate followed by treatment with NaH and N-tosylimidazole then afforded terminal epoxide 34 in 97% yield. Unfortunately, attempts to open the

• epoxide using vinyl Grignard reagent followed by esterification with acrylic acid (35) proved to be inefficient due to low reproducibility and poor isolation of product 36. The strategy was altered by changing the terminal epoxide 34 to an allylic alcohol (95%) utilizing dimethyl sulfonium methylide

Allylic alcohols and amines by carbenoid eliminative cross-coupling using epoxides or aziridines

• Matthew J. Fleming and
• David M. Hodgson

Beilstein J. Org. Chem. 2021, 17, 2385–2389, doi:10.3762/bjoc.17.155

• heteroatom (hydroxy, amino) functionality (Scheme 2). Results and Discussion Our studies began (Scheme 3) by reaction of BuLi (4 equiv) with a mixture of stannane 4 [6] (2 equiv) and tetramethylpiperidine (TMP, 2 equiv), to generate methoxymethyllithium and LTMP, followed by addition of terminal epoxide 5

• %), which arises from hydrolysis during work-up of the enamine that is formed from trapping of the lithiated epoxide by LTMP [9][10]. Omitting LTMP gave a significantly improved yield of the allylic alcohol 6 (79%, using BuLi and stannane 4 (3 equiv each)). This latter result suggests that

• methoxymethyllithium is capable of deprotonating terminal epoxide 5, and this occurs in preference to direct attack at the (unlithiated) epoxide 5. In contrast, no reaction was observed with a 2,2-disubstituted epoxide: 1-oxaspiro[2.11]tetradecane (9) [11] being recovered (90%) under the reaction conditions. The one

Advances in mercury(II)-salt-mediated cyclization reactions of unsaturated bonds

• Sumana Mandal,
• Raju D. Chaudhari and
• Goutam Biswas

Beilstein J. Org. Chem. 2021, 17, 2348–2376, doi:10.3762/bjoc.17.153

• (II)-salt-catalyzed rearrangement to produce 2,3-disubstituted-2,3-dihydropyranone derivatives 136. The stereochemistry of substituents at 2,3-positions of 2,3-dihydropyranone 136 was controlled by cis- and trans-configuration of the epoxide of starting materials (Scheme 40) [96]. Several unsaturated

Natural products in the predatory defence of the filamentous fungal pathogen Aspergillus fumigatus

• Jana M. Boysen,
• Nauman Saeed and
• Falk Hillmann

Beilstein J. Org. Chem. 2021, 17, 1814–1827, doi:10.3762/bjoc.17.124

• decatetraenedioic acid connected via an ester bond. There is also a methoxy group, an epoxide and a terpene derived aliphatic chain that contains another epoxide, linked to cyclohexane. These unstable di-epoxides are responsible for the biological activity of fumagillin, which targets the active site of the

Double-headed nucleosides: Synthesis and applications

• Vineet Verma,
• Jyotirmoy Maity,
• Vipin K. Maikhuri,
• Ritika Sharma,
• Himal K. Ganguly and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2021, 17, 1392–1439, doi:10.3762/bjoc.17.98

• ′-ketonucloside 1 with trimethylsulfoxonium iodide in DMSO afforded the spironucleoside 2, which in turn was converted to the TIPDS-protected 2′-(pyrimidin-1-yl)methyl-/2′-(purin-9-yl)methylarabinofuranosyluracil derivatives 3a–f by nucleophilic epoxide ring opening with thymine, N-benzoyladenine, 6-O-allyl-N

• ]. Nielsen and co-workers [42] additionally synthesized 2′-(N-benzoylcytosin-1-yl)methylarabinofuranosyl-N-benzoylcytosine (7) from uridine using a similar methodology. Thus, the nucleophilic epoxide ring opening in spironucleoside 2 with uracil in DMF in a N1-regioselective manner afforded the TIPDS

• nucleosides where an aromatic moiety or a nucleobase is attached at the C-5′ position of the nucleoside. The synthetic methodology started with the 5′-epoxide 97, which was synthesized from 3′-O-(tert-butyldimethylsilyl)thymidine in three steps, where the oxidation of the C-5′-hydroxy group followed by a

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

• trimethylsilyl cyanide (TMSCN) in THF at −10 °C. The reaction product 142 was obtained in quantitative yield and good diastereomeric ratio. Further hydrolysis of the cyclic acetal, and subsequent epoxidation of the resulting diol under typical Mitsunobu conditions led to epoxide derivative 143. The piperidine

• ring was formed through a 6-endo-tet cyclization by treatment of the epoxide 143 with sodium carbonate in toluene at 80 °C. Hydrolysis of the cyano group under acidic conditions of compound 144 led to expected ʟ-hydroxypipecolic acid hydrochloride 145 in high yield (Scheme 39) [129]. In 2018, Wei and

Beyond ribose and phosphate: Selected nucleic acid modifications for structure–function investigations and therapeutic applications

• Christopher Liczner,
• Kieran Duke,
• Gabrielle Juneau,
• Martin Egli and
• Christopher J. Wilds

Beilstein J. Org. Chem. 2021, 17, 908–931, doi:10.3762/bjoc.17.76

• product is then reacted with unprotected thymine which, in the presence of stoichiometric amounts of sodium hydride, results in the epoxide ring opening and the formation of the glycol backbone. The pre-amidite is then phosphitylated yielding the desired GNA-T amidite (Scheme 3). Recently, this simple

Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects

• Shivani Gulati,
• Stephy Elza John and
• Nagula Shankaraiah

Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71

Stereoselective syntheses of 3-aminocyclooctanetriols and halocyclooctanetriols

• Emine Salamci and
• Yunus Zozik

Beilstein J. Org. Chem. 2021, 17, 705–710, doi:10.3762/bjoc.17.59

• should have a cis configuration relative to the protons H-3 and H-4. Next, the reduction of azidotriol 10 by hydrogenation afforded the target aminotriol 12 in 95% yield. For the synthesis of the other aminocyclooctanetriol 18, the diol 6a [33] was reacted with m-CPBA to give trans-epoxide isomer 13 [33

• ] (79% yield) as the sole product (Scheme 3). Ring opening of trans-epoxide 13 by HBr(g)–MeOH gave bromotriol 14, which is an ideal substrate for the synthesis of the aminocyclooctanetriol 18. For structural proof, bromotriol 14 was converted into the corresponding acetate 15 using Ac2O in pyridine and

• synthesis of chlorocyclooctanetriol 19 starting from the trans-epoxide 13 (Scheme 4). The hydroxy groups in 19 were acetylated to give 20 for further characterization of the structure. The position of the chlorine atom in 20 was confirmed with the help of the COSY spectra. The resonance signal of H-3

α,γ-Dioxygenated amides via tandem Brook rearrangement/radical oxygenation reactions and their application to syntheses of γ-lactams

• Mikhail K. Klychnikov,
• Radek Pohl,
• Ivana Císařová and
• Ullrich Jahn

Beilstein J. Org. Chem. 2021, 17, 688–704, doi:10.3762/bjoc.17.58

• cyclizations to lactams of type 10 based on the persistent radical effect (PRE) are unknown and may provide a simple access to 3,4-disubstituted γ-lactams. We report here that tandem nucleophilic epoxide ring-opening/Brook rearrangement/radical oxygenation reactions are indeed very effective for the synthesis

• enantiomerically pure epoxides (S)-7b, (R)-7b, or (S)-7e (Table 2, entries 8–12) at 0 °C. The epoxide opening/Brook rearrangement steps were typically complete after an hour, except for cyclohexene oxide 7f for which the nucleophilic opening and Brook rearrangement steps took 24 h (Table 2, entry 13). Ferrocenium

• hexafluorophosphate (4) and TEMPO (3) were subsequently added to trigger the single electron oxidation of the formed amide enolates and radical oxygenation affording α-(aminoxy)amides 9a–n in good 51–77% isolated yields. Cyclic units in the allylic N-substituent (Table 2, entries 14 and 15) and the epoxide (Table 2

A new and efficient methodology for olefin epoxidation catalyzed by supported cobalt nanoparticles

• Lucía Rossi-Fernández,
• Viviana Dorn and
• Gabriel Radivoy

Beilstein J. Org. Chem. 2021, 17, 519–526, doi:10.3762/bjoc.17.46

• a variety of alkenes as an interesting heterogeneous system. This cobalt oxide mesoporous nanomaterial showed good activity and selectivity to the epoxide product and could be recovered and reused, but the multistep (not straightforward) synthesis of the catalyst and the use of DMF as the solvent

• (Table 1, entries 1–4), only the CoNPs/MgO catalyst gave a modest 28% conversion to the desired epoxide 2a (Table 1, entry 2) together with undesired formamide byproducts, probably coming from DMF decomposition under the reaction conditions. Then, we decided to use acetontrile (MeCN) as the solvent with

• poorer conversions and selectivities (Table 1, entries 11 and 12). Next, we worked on the optimization of the catalyst loading. Thus, when the amount of catalyst was decreased from 50 mg to 20 mg, a higher conversion was observed along with a slight drop in the selectivity towards the epoxide product 2a

Synthesis of legonmycins A and B, C(7a)-hydroxylated bacterial pyrrolizidines

• Wilfred J. M. Lewis,
• David M. Shaw and
• Jeremy Robertson

Beilstein J. Org. Chem. 2021, 17, 334–342, doi:10.3762/bjoc.17.31

• , was also reported in 1980 [10]. Following a 23-year hiatus, two papers submitted within two weeks of each other reported, respectively: (1) the isolation from Streptomyces sp. UMA-044 and characterization of NP25302, that differs from bohemamine in lacking the 6,7-epoxide functionality [11] and (2

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

All-carbon [3 + 2] cycloaddition in natural product synthesis

• Zhuo Wang and
• Junyang Liu

Beilstein J. Org. Chem. 2020, 16, 3015–3031, doi:10.3762/bjoc.16.251

• -workers in 2014 [49] (Scheme 9A). The synthesis began with the conversion of ketone 112 into alcohol 113 in four steps, which involved a hypervalent iodine-mediated ring expansion [60]. A two-step synthesis from 113 gave epoxide 114. Epoxide 114 was converted to the corresponding β-ketoester and

Easy access to a carbohydrate-based template for stimuli-responsive surfactants

• Thomas Holmstrøm,
• Daniel Raydan and
• Christian Marcus Pedersen

Beilstein J. Org. Chem. 2020, 16, 2788–2794, doi:10.3762/bjoc.16.229

• with high regioselectivity via the Černý epoxide [20]. Results and Discussion Synthesis The synthesis was initiated by a regioselective esterification of levoglucosan (1) with tosyl chloride in pyridine, first presented by Černý and co-workers, in order to afford the 1,6-anhydro-2,4-di-O-tosyl-β-ᴅ

• -glucopyranose as an intermediate. The latter could be used in the next step upon concentration of the reaction mixture under reduced pressure (Scheme 1) [20]. The intermediate was then treated with sodium methoxide in the presence of pyridine in order to generate the Černý epoxide 2 in a 73% yield over two

• steps [20]. Subjecting the Černý epoxide to sodium azide at an elevated temperature in a mixture of DMF and water afforded the diazide 3 in a 76% yield [21][22]. The presence of the azido groups was supported by a band at ≈2100 cm−1 in the FTIR spectrum of the diazide 3. The 1,6-anydro functionality

3-Acetoxy-fatty acid isoprenyl esters from androconia of the ithomiine butterfly Ithomia salapia

• Florian Mann,
• Daiane Szczerbowski,
• Lisa de Silva,
• Melanie McClure,
• Marianne Elias and
• Stefan Schulz

Beilstein J. Org. Chem. 2020, 16, 2776–2787, doi:10.3762/bjoc.16.228

• -enoate (12) was performed to verify the structural proposal and to determine the absolute configuration of the natural product (Scheme 4). The commercially available epoxide (S)-22 served as chiral starting material. 1,9-Nonanediol (19) was monobrominated and oxidized with IBX to yield 9-bromononanal (20

• ). A Wittig reaction with pentylphosphonium bromide resulted in bromoalkene 21 in a 9:1 Z/E-mixture. In the following step, the Grignard reagent of 21 was converted into the respective Gilman cuprate with Cu(I)I for the selective reaction with the epoxide function of (S)-22 [34]. The hydroxyester 23

Syntheses of spliceostatins and thailanstatins: a review

• William A. Donaldson

Beilstein J. Org. Chem. 2020, 16, 1991–2006, doi:10.3762/bjoc.16.166

• oxidation stereoselectively generated the spirocyclic epoxide 76. A second-protecting group shuffle afforded the primary alcohol 77. A Mitsunobu substitution of 77 with 2-mercaptobenzothiazole, followed by an oxidation with a large excess of mCPBA afforded the sulfone 78. While not producing the identical

• removal of the dithiane protecting group and the cyclic-ketal formation gave 84. The oxidative hydrolysis of the PMB ether and the reaction with mCPBA afforded the epoxide 85. While relatively short (9 steps), the nonstereoselective formation of 81a/b led to a lower overall yield. Syntheses of the C-1–C-6

• exocyclic epoxide prior to the formation of the C-6–C-9 conjugated diene was necessary in order to avoid the unwanted epoxidation of the C-6–C-7 olefin. Koide employed a unique strategy in which the exocyclic epoxide was generated as the initial stereocenter (Scheme 15) [12][13]. The Sharpless asymmetric

One-pot synthesis of oxazolidinones and five-membered cyclic carbonates from epoxides and chlorosulfonyl isocyanate: theoretical evidence for an asynchronous concerted pathway

• Esra Demir,
• Ozlem Sari,
• Yasin Çetinkaya,
• Ufuk Atmaca,
• Safiye Sağ Erdem and
• Murat Çelik

Beilstein J. Org. Chem. 2020, 16, 1805–1819, doi:10.3762/bjoc.16.148

• natural products ranging from small molecules, such as sugars, lipids and amino acids to huge molecules [56]. Computational results A detailed mechanistic investigation of the synthesis of oxazolidinone and five-membered cyclic carbonate derivatives by the reaction between epoxide 7f and CSI has been

• performed. Formation of oxazolidinone 9f There are two possible channels for the cyclization reaction of epoxide 7f with CSI to form oxazolidinone intermediates 10 and 11 as shown in Figure 1. In both transition states it is found that the ring-opening reaction of the epoxide, a nucleophilic attack of N4

• N4 onto the less sterically encumbered C1 atom of the epoxide 7f forming intermediate 11. Optimized geometries of transition structures are depicted in Figure 1. Our calculated results for the reaction indicate 17.4 kcal/mol (gas phase) and 26.7 kcal/mol (in DCM) preference for the TS1 over the TS1

An overview on disulfide-catalyzed and -cocatalyzed photoreactions

• Yeersen Patehebieke

Beilstein J. Org. Chem. 2020, 16, 1418–1435, doi:10.3762/bjoc.16.118

• , cyclopentanone, and three carbon ring-expanded 1,3-diones from vinyl spiro epoxides [14]. The reaction is initiated by the addition of a thiyl radical to the vinyl epoxide 24, followed by the epoxide fragmentation to the alkoxy radical 25. Then, the β-cleavage to form the carbon-centered radical 26, the final