Aromatic C–H bond functionalization through organocatalyzed asymmetric intermolecular aza-Friedel–Crafts reaction: a recent update

• Anup Biswas

Beilstein J. Org. Chem. 2023, 19, 956–981, doi:10.3762/bjoc.19.72

• ’-diol (SPINOL)-derived phosphoric acids with different substituents in the 2,2’-positions of the aromatic framework have been extensively explored as axially chiral catalysts in the field of asymmetric transformations including aza-Friedel–Crafts reactions. In 2018, Nakamura and co-workers designed an

Asymmetric synthesis of a stereopentade fragment toward latrunculins

• Benjamin Joyeux,
• Antoine Gamet,
• Nicolas Casaretto and
• Bastien Nay

Beilstein J. Org. Chem. 2023, 19, 428–433, doi:10.3762/bjoc.19.32

• a 1,5-anti induction of the aldol reaction [18][19][20] based on chiral alkoxy partner 9. Furthermore, it could be envisaged to reduce the resulting β-hydroxyketone 7 in a diastereoselective manner to obtain a 1,3-diol. This synthetic strategy could thus bring new stereochemical opportunities to

• %). This compound results from the transposition of the para-nitrobenzoyl (PNBz) group onto the 13-OH, which could be favoured by the steric hindrance of C-15 and a possible π–π stacking with the OPMB group. These PNBz esters were readily hydrolyzed to furnished diol 24 in 97% yield. The oxydation of the

Combretastatins D series and analogues: from isolation, synthetic challenges and biological activities

• Jorge de Lima Neto and
• Paulo Henrique Menezes

Beilstein J. Org. Chem. 2023, 19, 399–427, doi:10.3762/bjoc.19.31

• yield diol 72. The 3R,4S configuration of compound 72 was expected based on Pettit’s work [16][17] and the optical purity of the obtained product was more than 95% by 1H NMR using [Eu(hfc)3] as a chiral shift reagent. Subsequent silylation followed by ester hydrolysis and removal of the pivaloyl group

• alcohol 143 with pivaloyl chloride [64] and subsequent dihydroxylation of the double bond in 144 according to the Sharpless protocol using AD-mix-β [65], furnished the required syn-diol 145 in 59% yield and >99% ee. The hydroxy groups were protected [66] as TIPS ethers 146 and treatment with DIBAL-H led

• to both, cleavage of the Piv group and reduction of the aldehyde yielding the diol 147. Selective oxidation [67] of the benzyl alcohol with MnO2 gave the compound 148, which was esterified with S-acetylthioacetic acid (129) and reduced to the benzyl alcohol 150. Deacetylation followed by

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

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

• most intense peak (m/z = 991) (α), can be attributed to PEtOx chains that are terminated by a molecule of DLG diol with a potassium ion doping (Figure 3). However, α-distribution can also be attributed to DLG-initiated PEtOx. The presence of signals attributed to a polymer with a solvent fragment

• which interfere with the cationic ring-opening polymerization of 2-oxazolines (Figure 5). It has been reported that DLG can undergo keto–enol tautomerism and form enols or can participate in nucleophilic addition reactions [49]. Furthermore, it can react with water to its hydrated form, a geminal diol

• -diol terminating group carrying potassium and sodium ion doping, respectively. Signals at m/z = 3325 and m/z = 3341 could be attributed to methyl-initiated PEtOx with OH moieties carrying Na+ (δ) and K+ (γ), respectively. We also cannot exclude the possibility that these signals resulted from PEtOx

Nostochopcerol, a new antibacterial monoacylglycerol from the edible cyanobacterium Nostochopsis lobatus

• Naoya Oku,
• Saki Hayashi,
• Yuji Yamaguchi,
• Hiroyuki Takenaka and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2023, 19, 133–138, doi:10.3762/bjoc.19.13

• , interconnection of the acyl and glyceryl units via an ester linkage was verified by three HMBC correlations from the terminal protons (H1, H2, and H1') of both units to the carboxy carbon (C1), leaving two protons to occupy C2' and C3' diol. Thus, compound 1 was determined to be a new monoacylglycerol and named

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

• the commercially available 1,4-dithiane-2,5-diol (4) [26]. The diol 4 is commercially available in large quantities and is formally also a 1,4-dithiane derivative, but except for its dehydration to 1,4-dithiin, it is almost exclusively used as a source of mercapto acetaldehyde (of which it is a direct

Synthetic study toward tridachiapyrone B

• Morgan Cormier,
• Florian Hernvann and
• Michaël De Paolis

Beilstein J. Org. Chem. 2022, 18, 1741–1748, doi:10.3762/bjoc.18.183

• was carried out through a two-step sequence including dihydroxylation (K2OsO4·H2O, 90% yield) of 8 and oxidative cleavage (NaIO4, 91% yield) of the diol intermediate. Note that both ozonolysis and the one-pot Lemieux–Johnson oxidative cleavage process of 8 led instead to methyl ketone 11 in a

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

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

• SnCl2-catalyzed coupling reaction [20] between 21 and 22 afforded β-keto ester 23, which was then reduced to the corresponding β-hydroxy ester 24 by K-Selectride (dr > 20:1), and subsequent acidic removal of the acetonide furnished diol 25. The stereochemistry of the newly generated hydroxy group was

• determined using the modified Mosher’s method [21]. Protection of diol 25 by tert-butyl(dimethyl)silyl (TBS) group followed by selective deprotection of the primary alcohol led to 27. Finally, acid 7 was obtained from alcohol 27 through the same two-step oxidation used to obtain compound 10. Having

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

• gives access to 6A-mono- and 6A,D diol (3) in high yields and purity, and by extension of this method further deprotection on the primary [10][11][12] and secondary rim can be made [13][14][15]. The reaction of 2 with DIBAL leads quite rapidly to diol 3 and then much slower to triol 4 and tetrol 5

• and 13C NMR (800/201 MHz), COSY, HSQC, TOCSY, and ROESY (Supporting Information File 1) which gave the NMR assignments shown in Table 2 and identification of 8 as the 6A,D diol. The most significant observations in this assignment were 1) the compound is symmetric with only 3 different sugar residues

• C134H137Cl8O30+, 2511.6706 (71.9%); found, 2511.69097. Structure of α-cyclodextrins 1–10. The reaction of perbenzylated α-cyclodextrin with iBu2AlH. Reaction conditions for the partial debenzylation of 7. The solvent was always toluene. 1H and 13C NMR (800/201 MHz, CDCl3) chemical shifts of diol 8. 1H and 13C

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

• )cyclooctene 6 in 70% yield (Scheme 1). Oxidation of the dibenzylated compound 6 with OsO4/NMO provided the corresponding diol 7 in 90% yield. The exact configuration of 7 was confirmed by 1H and 2D NMR spectroscopic data. Next, mesylation of the hydroxy groups in 7 with MsCl in pyridine yielded dimesylate 8

• in 90% yield. Thus, the dimesylate 8, which is one of the most relevant precursors for the synthesis of aminocyclitols, was synthesized from the diol 7. The structure of compound 8 was assigned on the basis of NMR spectroscopy. In the 1H NMR spectrum, we observed that methyl signals of the mesylate

Supramolecular approaches to mediate chemical reactivity

• Pablo Ballester,
• Qi-Qiang Wang and
• Carmine Gaeta

Beilstein J. Org. Chem. 2022, 18, 1463–1465, doi:10.3762/bjoc.18.152

• rotaxanes. MIMs show interesting structural and topological features and offer conceptually new possibilities as catalysts. In their minireview, Krajnc and Niemeyer [21] highlighted the use of the axially chiral 1,1'-binaphthyl-2,2'-diol (BINOL) unit as a stereogenic element in MIMs. The authors comment on

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

• intimate affinity of unsymmetrical salens chelating with metals. The HKR of epichlorohydrin with water catalyzed by Co–salens 2 was studied and chiral 2f showed an outstanding catalytic ability to afford the diol product in high ee (98%). A library of α-aryloxy alcohols was thereafter synthesized through

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

• quite similar to that of (E)-5,5′-(but-2-ene-1,4-diyl)bis(3-methoxybenzene-1,2-diol) [15]. The main difference was that the hydroxy group at C-4 and C-4′ in (E)-5,5′-(but-2-ene-1,4-diyl)bis(3-methoxybenzene-1,2-diol) was substituted by a methoxy group in 2, which was confirmed by the HMBC correlation

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

• . 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

• diol (+)-(R)-7, can be used to prepare both enantiomers of compound 1 following the procedures shown in Scheme 2. Unfortunately, once the racemic synthesis was successfully completed and the chiral design was fulfilled, it was found that the spectroscopic data of compound 1 did not match neither with

• signals of the oxygenated carbons (C2 and C5). The same behavior pattern can be observed in the 1H NMR data. This made us think that the natural product of T. mendocina could have an acyclic skeleton instead of a dihydrofuran one. For this reason, we propose this compound should be the diol called

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

• 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

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

• sacrificial anode would be a promising approach toward synthetically valuable vic-1,2-diol scaffolds without using low-valent metal reductants. However, sacrificial anodes produce an equimolar amount of metal waste, which may be a major issue in terms of sustainable chemistry. Herein, we report a sacrificial

• electrolysis; Introduction Carbon–carbon bond formation is one of the most fundamental and important reactions in synthetic organic chemistry. Reductive coupling of carbonyl compounds known as pinacol coupling would be a powerful method to construct vic-1,2-diol scaffolds through C–C bond formation [1][2

• substrate 1k gave 2k in a less satisfactory yield but with good diastereoselectivity. 1-Phenyl-1-propanol (1l) was successfully transformed into the desired product 2l in a moderate yield. In addition, ethyl lactate (1m) provided the corresponding vic-1,2-diol 2m in 60% yield but with low

Heteroleptic metallosupramolecular aggregates/complexation for supramolecular catalysis

• Prodip Howlader and
• Michael Schmittel

Beilstein J. Org. Chem. 2022, 18, 597–630, doi:10.3762/bjoc.18.62

• enantioselectivity (94% ee). Using similar reaction conditions, the non-assembled BINOL derivative (S)-3,3'-dibromo-[1,1'-binaphthyl]-2,2'-diol acted as a superior catalyst (99% yield) but achieved a lower enantioselectivity (84% ee). Therefore, this result indicates that the incorporation of multiple catalytic

A study of the photochemical behavior of terarylenes containing allomaltol and pyrazole fragments

• Constantine V. Milyutin,
• Andrey N. Komogortsev,
• Boris V. Lichitsky and
• Valeriya G. Melekhina

Beilstein J. Org. Chem. 2022, 18, 588–596, doi:10.3762/bjoc.18.61

• diastereospecificity of the studied process, which leads to the formation of a trans-diastereomer (mixture of S/S- and R/R-enantiomers). The structure of vicinal diol 18 was unambiguously established by single-crystal X-ray diffraction (Figure 4). Conclusion In summary, we have studied the photochemical behavior of

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

• '-binaphthyl-2,2'-diol (BINOL) unit as a stereogenic element in mechanically interlocked molecules (MIMs). We describe the synthesis and properties of such BINOL-based chiral MIMs, together with their use in further diastereoselective modifications, their application in asymmetric catalysis, and their use in

• planar chirality into at least one of the subcomponents. One of the most important chiral molecular frameworks in general is the 1,1'-binaphthyl-2,2'-diol unit (BINOL, see Figure 1). BINOL is an axially chiral molecule with a high configurational stability and a well-established synthetic chemistry

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

• -1,2-diol, etc.) [11]. Beside this, approaches in which asymmetric synthesis is included are also applicable. Recently, the utilization of an asymmetric Henry reaction for the preparation of two oxazolidine-type drugs, namely linezolid (1) and rivaroxaban (2), has been described [12][13]. These

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

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

• its extraction in the organic phase during work up procedure. So, the classical chemical route to synthesize nucleosides 9a,b started with the conversion of diacetone ᴅ-glucofuranose 10 to 3′-azido-3′-deoxy-β-ᴅ-allofuranoside 11, which on acidification with 80% acetic acid gave furanoside diol 17. The

• regioselective protection of the primary hydroxy group of diol 17 using TBDPS-Cl in pyridine at room temperature afforded TBDPS-protected furanoside 18, which on acetolysis using AcOH/Ac2O/H2SO4 (100:10:0.1) afforded the anomeric mixture of coupling sugar 19a,b in 80% yield. The Vorbrüggen coupling [29] of

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

• diol 5 as a single isomer in 91% yield. We assume that the trans selectivity of hydroxylation in ester 4 is due to the steric effect of the presence of the bulky Boc group. The structure of 5 was determined with the help of 1D (1H and 13C) and 2D (COSY and HMQC) NMR spectra. The diagonal peak at 4.10

• expected product 9 failed. The product 8 was obtained as the major product in 80% yield, and the expected product 9 was formed as the minor product in 4% yield. We propose that diol isomer mixture 9 can be formed by solvolysis. The presence of the lactone ring in 8 was determined by 2D NMR spectroscopic

• a mixture of products 10 and 11 in a 7:3 ratio was determined by NMR spectroscopy. The reaction mixture was purified using preparative silica gel TLC on a chromatotron with ethyl acetate/hexane (50:50) as the eluent to give carbamate 10 and diol isomer mixture 11 in 65% and 25% yields, respectively