Recent total synthesis of natural products leveraging a strategy of enamide cyclization

• Chun-Yu Mi,
• Jia-Yuan Zhai and
• Xiao-Ming Zhang

Beilstein J. Org. Chem. 2025, 21, 999–1009, doi:10.3762/bjoc.21.81

• cyclopentane ring, dihydroxylation, and oxidation of the diol to a diketone, produced intermediate 25 in its enol form. From this common intermediate, regioselective etherification at the less hindered position formed an enol ether. Final reduction of both the amide and the ketone using alane completed the

The effect of neighbouring group participation and possible long range remote group participation in O-glycosylation

• Rituparna Das and
• Balaram Mukhopadhyay

Beilstein J. Org. Chem. 2025, 21, 369–406, doi:10.3762/bjoc.21.27

• first introduced the 2,2-dimethylpentenoate protecting group 32 (Figure 1) similar to the pivalate group which showed versatility in its cleavage principle [101]. Hydroboration oxidation of the olefinic bond helped in the removal of the protecting group. On the other hand, dihydroxylation with osmium

Non-covalent organocatalyzed enantioselective cyclization reactions of α,β-unsaturated imines

• Sergio Torres-Oya and
• Mercedes Zurro

Beilstein J. Org. Chem. 2024, 20, 3221–3255, doi:10.3762/bjoc.20.268

• catalysts are synthesized by joining together two fragments of cinchona alkaloids. In this manner, it is possible to obtain a symmetric catalyst, which can engage in hydrogen bonding interactions and deprotonation processes. Although they were originally used for Sharpless dihydroxylation, they have been

Access to optically active tetrafluoroethylenated amines based on [1,3]-proton shift reaction

• Yuta Kabumoto,
• Eiichiro Yoshimoto,
• Bing Xiaohuan,
• Masato Morita,
• Motohiro Yasui,
• Shigeyuki Yamada and
• Tsutomu Konno

Beilstein J. Org. Chem. 2024, 20, 2776–2783, doi:10.3762/bjoc.20.233

• by Linclau et al. They have reported that the asymmetric Sharpless dihydroxylation of readily available (E)-5-bromo-4,4,5,5-tetrafluoro-2-penten-1-ol derivative 6 led to the corresponding chiral diols 7 with an excellent enantiomeric excess, 96% ee (reaction 1 in Scheme 1) [20][21]. It has also been

Efficient modification of peroxydisulfate oxidation reactions of nitrogen-containing heterocycles 6-methyluracil and pyridine

• Alfiya R. Gimadieva,
• Yuliya Z. Khazimullina,
• Aigiza A. Gilimkhanova and
• Akhat G. Mustafin

Beilstein J. Org. Chem. 2024, 20, 2599–2607, doi:10.3762/bjoc.20.219

• dihydroxylation product – was only obtained after the oxidation of the previously synthesized HPy (9, Scheme 2). The overall yield of the 2,5-dihydroxy derivative 11 with PcCo, PcFe(II), and PcFe(III) ranged from 37–72%, with the highest yield (72%) obtained at 0.15 wt % PcCo. Increasing the catalyst quantity did

A review of recent advances in electrochemical and photoelectrochemical late-stage functionalization classified by anodic oxidation, cathodic reduction, and paired electrolysis

• Nian Li,
• Ruzal Sitdikov,
• Ajit Prabhakar Kale,
• Joost Steverlynck,
• Bo Li and
• Magnus Rueping

Beilstein J. Org. Chem. 2024, 20, 2500–2566, doi:10.3762/bjoc.20.214

• − is protonated to produce DDQH2. The anodic oxidation of DDQH2 regenerates DDQ, which re-enters the catalytic cycle (Scheme 29). Furthermore, Qiu and coworkers disclosed a metal-free electrochemical dihydroxylation of unactivated alkenes using water as the hydroxy source under air conditions [40

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

• furnished the α,β-unsaturated ester 69. The subsequent catalytic hydrogenation led to the desired phenol 70 (Scheme 13) [44][45]. An Ullmann coupling reaction using compounds 66 and 70 gave the corresponding diaryl ether 71, which was submitted to an asymmetric dihydroxylation reaction using (DHQD)2PHAL to

• 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

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

• ideal diversification point to access (−)-curvulamine (171) by CBS reduction, bipolamines D (173) and E (172) by additional BH3·DMS hydroboration, and bipolamine G (174) initially by dihydroxylation of the alkene moiety with osmium tetroxide, followed by acidic etherification and reduction. Finally

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

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

• catalyse the initial C22,16 dihydroxylation of cholesterol (3) [35]; in contrast, the related CYP DzCYP90B71 was found to catalyse only the first hydroxylation at C22 [66]. This step is followed by a rate-limiting cyclisation step through unstable furostanol intermediate 14 that involves CYP-catalysed

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

• acid (17) (Scheme 4). The β-hydroxy moiety in 44 can be installed via Sharpless dihydroxylation of the silyl enol ether derived from ketone 45. The 5,6-dihydro-α-pyrone group in ketone 45 is envisaged from protected diol 46 by the sequence of Mitsunobu esterification, ring-closing metathesis, and base

• followed by addition of TBSOTf at low temperature successfully formed the (Z)-silyl enol ether 54. Application of the Sharpless asymmetric dihydroxylation, promoted by AD-mix-β, gave the expected β-(R)-hydroxy cyclopropyl product 55 in 84% yield with moderate diastereoselectivity (dr = 2). The formation of

• Jin’s one step dihydroxylation–oxidation protocol using a NaIO4/(cat.) OsO4 system. Allylation of the resulting aldehyde 74 was best performed under Brown’s protocol at low temperature utilizing a chiral allyl reagent prepared from allylmagnesium bromide and (+)-B-chloro-diisopinocampheylborane. By this

Synthetic strategies of phosphonodepsipeptides

• Jiaxi Xu

Beilstein J. Org. Chem. 2021, 17, 461–484, doi:10.3762/bjoc.17.41

• shown in Scheme 11. First, dibenzyl allylphosphonate (65) was converted to benzyl allylphosphonochloridate (66), which was then coupled with benzyl 2-azido-3-hydroxy-2-methylpropanoate (67) producing benzyl [allyl(benzyloxy)phosphoryl)oxy]propanoate (68). After the dihydroxylation with osmium tetroxide

Regioselective chemoenzymatic syntheses of ferulate conjugates as chromogenic substrates for feruloyl esterases

• Olga Gherbovet,
• Fernando Ferreira,
• Apolline Clément,
• Mélanie Ragon,
• Julien Durand,
• Sophie Bozonnet,
• Michael J. O'Donohue and
• Régis Fauré

Beilstein J. Org. Chem. 2021, 17, 325–333, doi:10.3762/bjoc.17.30

• tetroxide-mediated dihydroxylation in the presence of N-methylmorpholine N-oxide (NMMO) afforded 11 in 90% yield. Finally, the regioselective transferuloylation of the primary hydroxy group of the triol derivative 11 with Lipozyme® TL IM was performed, and the expected chromogenic substrate 12 was isolated

Diels–Alder reaction of β-fluoro-β-nitrostyrenes with cyclic dienes

• Savva A. Ponomarev,
• Roman V. Larkovich,
• Alexander S. Aldoshin,
• Andrey A. Tabolin,
• Sema L. Ioffe,
• Jonathan Groß,
• Till Opatz and
• Valentine G. Nenajdenko

Beilstein J. Org. Chem. 2021, 17, 283–292, doi:10.3762/bjoc.17.27

• straightforward way to numerous fluorine-containing bicyclic compounds not previously available. The syn-dihydroxylation of compound 2f with the N-methylmorpholine-N-oxide (NMO)–OsO4 system resulted in a mixture of the corresponding diols 5 in a 36:64 ratio in 65% yield. Again, exo-dihydroxylation is to be

Progress in the total synthesis of inthomycins

• Bidyut Kumar Senapati

Beilstein J. Org. Chem. 2021, 17, 58–82, doi:10.3762/bjoc.17.7

• transformed into (−)-101 using a three-step sequence. Upon iodination of (−)-101 produced iodide (+)-102 in excellent yield. Deiodination of (+)-102 followed by regioselective dihydroxylation with Sharpless’ AD mix-β reagent [64][65] provided diol (−)-103 as a mixture of stereoisomers. Significantly, the diol

Recent progress in the synthesis of homotropane alkaloids adaline, euphococcinine and N-methyleuphococcinine

• Dimas J. P. Lima,
• Antonio E. G. Santana,
• Michael A. Birkett and
• Ricardo S. Porto

Beilstein J. Org. Chem. 2021, 17, 28–41, doi:10.3762/bjoc.17.4

• second generation Grubbs catalyst 57 in 99% yield. The azabicyclic system (+)-51 underwent dihydroxylation with the OsO4-NMO system to form diol (+)-52 as the only product in 97% yield. Diol (+)-52 was regioselectively protected in the presence of tert-butyldimethylsilane triflate, and triethylamine

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

• tetracyclic compound 56. Dihydroxylation of freshly prepared 56 with OsO4 and then selective tosylation afforded 57 in 39% yield over two steps. Exposure of 57 to DBU upon heating gave the elimination product 58, which was subjected to an oxidative rearrangement with PDC to give enone 59 in 68% yield. Copper

• produce 135 and 136 in 85% yield in the ratio of 1:1.16. A six-step synthesis from the major product 136 gave lactone 137. This compond was subjected to successive desilylation, OsO4-mediated dihydroxylation and subsequent oxidative cleavage of the C=C double bond with Pb(OAc)4 to give ketoaldehyde 138 in

Vicinal difluorination as a C=C surrogate: an analog of piperine with enhanced solubility, photostability, and acetylcholinesterase inhibitory activity

• Yuvixza Lizarme-Salas,
• Alexandra Daryl Ariawan,
• Ranjala Ratnayake,
• Hendrik Luesch,
• Angela Finch and
• Luke Hunter

Beilstein J. Org. Chem. 2020, 16, 2663–2670, doi:10.3762/bjoc.16.216

• ] was protected as the benzyl ether then subjected to a Sharpless asymmetric dihydroxylation reaction to furnish the diol 8 in modest yield. The diol 8 was then converted into the cyclic sulfate 9, which was ring-opened using TBAF to furnish the fluorohydrin 10. A Mosher ester analysis of the

• fluorohydrin 10 suggested that the earlier dihydroxylation reaction had proceeded with 90% ee. The deoxyfluorination of 10 was then attempted using several reagents including DeoxoFluor, DeoxoFluor in combination with TMS-morpholine [29], and PyFluor [30]. The optimal yield of the threo-difluoroalkane 11 was

• moiety throughout (Scheme 3). Thus, the α,β-unsaturated ester 15 [25] was carried through a similar sequence to that previously described, i.e., dihydroxylation, cyclic sulfate formation, ring-opening with TBAF (although note the regioselectivity [31]), deoxyfluorination, and deprotection to deliver the

Synthesis of 3-substituted isoxazolidin-4-ols using hydroboration–oxidation reactions of 4,5-unsubstituted 2,3-dihydroisoxazoles

• Lívia Dikošová,
• Júlia Laceková,
• Ondrej Záborský and
• Róbert Fischer

Beilstein J. Org. Chem. 2020, 16, 1313–1319, doi:10.3762/bjoc.16.112

• isoxazolidines by means of dihydroxylation [9][10] and epoxidation [11][12] reactions. Regarding the stereochemistry, almost all of the realized additions proceed with an excellent trans stereoselectivity relative to the substituent at C-3, giving isoxazolidine-4,5-diols and isoxazolidinyl epoxides with a C-3/4

• , respectively, according to our procedure [7][10]. The compounds 5a and 5b were first converted into the isoxazolidine-4,5-diols by the treatment with potassium osmate/N-methylmorpholine N-oxide (NMO). The dihydroxylation reactions proceeded with an excellent trans selectivity with respect to the substituent at

• stereochemical results are consistent with our previous findings on the direct dihydroxylation and epoxidation reactions of 4,5-unsubstituted 2,3-dihydroisoxazoles [9][10][11][12]. To invert the relative C-3/4-trans stereochemistry, the isoxazolidin-4-ols 5a–c were first oxidized to the corresponding ketones

Combining enyne metathesis with long-established organic transformations: a powerful strategy for the sustainable synthesis of bioactive molecules

• Valerian Dragutan,
• Ileana Dragutan,
• Albert Demonceau and
• Lionel Delaude

Beilstein J. Org. Chem. 2020, 16, 738–755, doi:10.3762/bjoc.16.68

• , an intramolecular Ru-catalyzed alkene-alkyne (Ru-AA) coupling and a late-stage epoxidation were readily accomplished, while the installation of the α,α′-dihydroxy ketone through a dihydroxylation proved difficult. Noteworthy, the structural elucidation of the THP ring of des-epoxy-amphidinolide N

Synthesis of disparlure and monachalure enantiomers from 2,3-butanediacetals

• Adam Drop,
• Hubert Wojtasek and
• Bożena Frąckowiak-Wojtasek

Beilstein J. Org. Chem. 2020, 16, 616–620, doi:10.3762/bjoc.16.57

• enantioselective reactions, such as the Sharpless epoxidation [19][20][21][22][23][24], asymmetric dihydroxylation [25][26], chloroallyloboronation [27], or iodolactonization [28]. Most recently a method using the asymmetric chlorination of dodecanal by LiCl in the presence of a chiral imidazolidinone catalyst has

A review of asymmetric synthetic organic electrochemistry and electrocatalysis: concepts, applications, recent developments and future directions

• Munmun Ghosh,
• Valmik S. Shinde and
• Magnus Rueping

Beilstein J. Org. Chem. 2019, 15, 2710–2746, doi:10.3762/bjoc.15.264

• improvements of these methods have recently been achieved by Moeller et al. who designed a photovoltaic apparatus for the efficient Sharpless dihydroxylation of styrene in up to 94% enantiomeric excess [65]. Tanaka and co-workers explored the catalytic applicability of optically active Mn-salen complex 72

Synthesis of acremines A, B and F and studies on the bisacremines

• Nils Winter and
• Dirk Trauner

Beilstein J. Org. Chem. 2019, 15, 2271–2276, doi:10.3762/bjoc.15.219

• isolated from fungi of the genus Acremonium. Here, we present the asymmetric total synthesis of acremine F which hinges on a modestly enantioselective dihydroxylation and a subsequent kinetic resolution via a highly selective asymmetric reduction. Chemoselective oxidation of acremine F gave access to

• traced back to silyl enol ether 10. Ent-10 was first reported by Herzon and co-workers [9] and is derived from phenol silyl ether 11 via Birch reduction and dihydroxylation. Results and Discussion Our synthesis started with meta-cresol (12) which was protected as a TIPS ether and then subjected to Birch

• reduction conditions to afford cyclohexa-1,4-diene 13 [9]. Enantioselective Sharpless dihydroxylation proceeded in good chemoselectivity but with modest yield and optical purity (25% ee). Unfortunately, all attempts to improve the enantioselectivity of this reaction failed. We discovered, however, that at a

Bipolenins K–N: New sesquiterpenoids from the fungal plant pathogen Bipolaris sorokiniana

• Chin-Soon Phan,
• Hang Li,
• Simon Kessler,
• Peter S. Solomon,
• Andrew M. Piggott and
• Yit-Heng Chooi

Beilstein J. Org. Chem. 2019, 15, 2020–2028, doi:10.3762/bjoc.15.198

• with reduction of the lactone ring to the dialcohol and dihydroxylation of the Δ2,12 double bond. Detailed analysis of the 2D NMR data for 4 (Figure 2) confirmed the seco-sativene-type scaffold. The relative configurations at C-1, C-3, C-6, C-7 and C-13 were determined to be the same as those of 1–3