Selective preparation of tetrasubstituted fluoroalkenes by fluorine-directed oxetane ring-opening reactions

• Clément Q. Fontenelle,
• Thibault Thierry,
• Romain Laporte,
• Emmanuel Pfund and
• Thierry Lequeux

Beilstein J. Org. Chem. 2020, 16, 1936–1946, doi:10.3762/bjoc.16.160

• lactone product 15 (containing 10% of ester Z-13) and proved successful with phosphonolactone 21 being isolated in 77% yield after column chromatography (Scheme 7). To access tetrasubstituted alkenes, reduction of 21 to generate diol 22 was explored with lithium borohydride in Et2O. However, the reaction

• was slow at 20 °C and did not progress beyond 50% conversion even after the addition of excess LiBH4. After purification by flash chromatography starting lactone 21 was obtained in 49% yield and the desired diol 22 in 47% yield. When the reaction was carried out in refluxing THF, a complete conversion

• precursors of ACN (VII) bearing different functional groups (Scheme 9). A particular focus was applied to the preparation of the phosphonate 29, a precursor of VII that is not accessible from diol VIII. First, starting from pure alkene E-9, the introduction of a protected alcohol as a mimic of the naturally

Stereoselective Biginelli-like reaction catalyzed by a chiral phosphoric acid bearing two hydroxy groups

• Xiaoyun Hu,
• Jianxin Guo,
• Cui Wang,
• Rui Zhang and
• Victor Borovkov

Beilstein J. Org. Chem. 2020, 16, 1875–1880, doi:10.3762/bjoc.16.155

• BINOL, 2,2-dimethyltetraphenyl-1,3-dioxolane-4,5-dimethanol (TADDOL) was also widely used as a C2 chiral diol. However, TADDOL-derived phosphoric acids were not comprehensively investigated as catalysts in Biginelli and Biginelli-like reactions yet. The first example of their successful application was

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

• reaction with the metal complexes or catalysts, and the reaction of a diol with toxic phosgene are the most common processes [16][17][33][34][35][36]. CSI, a highly reactive and versatile isocyanate, reacts with epoxides to give five-membered cyclic carbonates and oxazolidinones [37][38][39]. In 1984

Synthesis of the tetrasaccharide repeating unit of the O-specific polysaccharide of Azospirillum doebereinerae type strain GSF71^T using linear and one-pot iterative glycosylations

• Arin Gucchait,
• Pradip Shit and
• Anup Kumar Misra

Beilstein J. Org. Chem. 2020, 16, 1700–1705, doi:10.3762/bjoc.16.141

• the product in CH3CN (10 mL) was added HClO4-SiO4 (50 mg) and the mixture was allowed to stir at room temperature for 15 min. Then, the reaction mixture was filtered and the filtrate was concentrated under reduced pressure. To a solution of the diol in CH2Cl2 (5 mL) were added pyridine (100 μL, 1.24

NHC-catalyzed enantioselective synthesis of β-trifluoromethyl-β-hydroxyamides

• Alyn T. Davies,
• Mark D. Greenhalgh,
• Alexandra M. Z. Slawin and
• Andrew D. Smith

Beilstein J. Org. Chem. 2020, 16, 1572–1578, doi:10.3762/bjoc.16.129

• as a nucleophile gave the corresponding ester, however, this product proved unstable to purification. Generation of the ester in situ, followed by subsequent reduction with LiAlH4, gave the diol 11 in 48% isolated yield as a single diastereoisomer in 96:4 er. Subsequent variation of the electronic

Recent synthesis of thietanes

• Jiaxi Xu

Beilstein J. Org. Chem. 2020, 16, 1357–1410, doi:10.3762/bjoc.16.116

• 1966 [32]. They treated 3,5-dichloropentan-2-ol (9) with K2S to produce 1-(thietan-2-yl)ethan-1-ol (10) in 65% yield (Scheme 1). In 2007, Nishizono and co-workers used 2,2-bis(bromomethyl)propane-1,3-diol (11) as starting material to prepare thietanose nucleosides 2 and 14. They first carried out a

• as inhibitor of kinases, insecticides, and acaricides, its sulfur analogue, 6-amino-2-thiaspiro[3,3]heptane (28) was prepared from the cheap starting material 2,2-bis(bromomethyl)propane-1,3-diol (11). Compound 11 was converted into 3-(tert-butoxycarbonyl)-1,1-bis(hydroxymethyl)aminocyclobutane (25

• converted to the final thietane-containing spironucleoside 46 [41] (Scheme 10). In 2011, Nishizono and co-worker synthesized two anomeric thietanose nucleosides with (Z)-but-2-ene-1,4-diol (47) as the starting material. They first converted the diol 47 into dimethanesulfonates 48 of 1,5-dibenzyloxypentane

The charge-assisted hydrogen-bonded organic framework (CAHOF) self-assembled from the conjugated acid of tetrakis(4-aminophenyl)methane and 2,6-naphthalenedisulfonate as a new class of recyclable Brønsted acid catalysts

• Svetlana A. Kuznetsova,
• Alexander S. Gak,
• Yulia V. Nelyubina,
• Vladimir A. Larionov,
• Han Li,
• Michael North,
• Vladimir P. Zhereb,
• Alexander F. Smol'yakov,
• Artem O. Dmitrienko,
• Michael G. Medvedev,
• Igor S. Gerasimov,
• Ashot S. Saghyan and
• Yuri N. Belokon

Beilstein J. Org. Chem. 2020, 16, 1124–1134, doi:10.3762/bjoc.16.99

• contracted and expanded their pores in the presence of guest gases [42]. In the limiting case, the framework may even become partially dissolved in a polar solvent. The CAHOF F-1 was also catalytically active for the conversion of styrene oxide (2) into the diol 4 (Table 1, runs 8–14). This reaction was a

• reaction was stirred. After 3 (or 24) hours, the solid catalyst was filtered, the layers were separated, evaporated, and analyzed. The aqueous layer contained only the diol 4 and some dissolved F-1. The organic mixture contained a mixture of the epoxide 2 and the diol 4. Therein, the catalyst was a

• recovered by evaporating the aqueous layer, adding dichloromethane to the residue and filtering the insoluble catalyst. The efficiency of the multiphase reactions should depend on the rate of stirring the reaction. The runs 8–12 in Table 1 illustrated the dependence of the yield of the diol 4 on the

Fluorinated phenylalanines: synthesis and pharmaceutical applications

• Laila F. Awad and
• Mohammed Salah Ayoup

Beilstein J. Org. Chem. 2020, 16, 1022–1050, doi:10.3762/bjoc.16.91

• of type III 2.1. Fluorination of protected (1R,2R)-2-amino-ʟ-phenylpropane-1,3-diol Recently, Okuda et al. reported the synthesis of (3R)-3-fluoro-ʟ-phenylalanine (121) from (1R,2R)-2-amino-ʟ-phenylpropane-1,3-diol (116). Thus, Boc-protection of the amine group in 116 followed by the protection of

• -difluorophenylalanine 115. Synthesis of β-fluorophenylalanine via 2-amino-1,3-diol derivatives. Synthesis of β-fluorophenylalanine derivatives via the oxazolidinone chiral auxiliary 122. Synthesis of β-fluorophenylalanine from pyruvate hemiketal 130. Synthesis of β-fluorophenylalanine (136) via fluorination of β

Aldehydes as powerful initiators for photochemical transformations

• Maria A. Theodoropoulou,
• Nikolaos F. Nikitas and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2020, 16, 833–857, doi:10.3762/bjoc.16.76

• α-hydroxybenzyl radical 90, which then coupled, forming the 1,2-diol 92 (Scheme 23). In 2014, Melchiorre and co-workers found that 4-anisaldehyde (52) could efficiently catalyze the intermolecular atom transfer radical addition (ATRA) of the haloalkanes 93 to the olefins 94 under irradiation with a

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

• of cyclopentene-1,4-diol that was obtained by the enzymatic desymmetrization of the corresponding diacetate, an enyne metathesis precursor was accessed by a Mitsunobu-type coupling reaction with propargylic amide. The ring-rearrangement metathesis (RRM) of this enyne precursor was carried out using

Recent advances in Cu-catalyzed C(sp³)–Si and C(sp³)–B bond formation

• Balaram S. Takale,
• Ruchita R. Thakore,
• Elham Etemadi-Davan and
• Bruce H. Lipshutz

Beilstein J. Org. Chem. 2020, 16, 691–737, doi:10.3762/bjoc.16.67

• 327. In addition, the formation of an anti-1,2-diol with high enantioselectivity is also another outcome resulting from this protocol (Scheme 52) [95]. Catalytic Cu-mediated conversions of (Z)-3-arylallylic phosphates 332 to nonracemic trans-2-aryl and -heteroaryl-substituted cyclopropylboronates 333

Towards the total synthesis of chondrochloren A: synthesis of the (Z)-enamide fragment

• Jan Geldsetzer and
• Markus Kalesse

Beilstein J. Org. Chem. 2020, 16, 670–673, doi:10.3762/bjoc.16.64

• ). A subsequent transesterification under mild conditions with Bu2SnO provided dihydroxy ester 7 in 72% yield. The 1,3-diol in 7 was methylated with an excess of the Meerwein reagent and TIPDS-removal afforded ester 9 in good yields. A double TBS-protection and liberation of the primary alcohol

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

• 19 instead. This compound was obtained from both aldehyde 15 and its precursor ethyl thioester methyl ester 14, respectively (Scheme 3). Both substrates 14 and 15 were reduced to the corresponding diol 17 with lithium aluminum hydride with 73% or 83% yield, respectively. Next, the selective

• ), and (−)-monachalure (4) from diols 5–8. Isomerization of trans-2,3-butanediacetals 9–11 to cis-2,3-butanediacetals 12–14. Synthesis of diol 17 and its subsequent modifications. Synthesis of (+)-disparlure (1) and (+)-monachalure (2). Synthesis of (−)-disparlure (3) and (−)-monachalure (4). Conditions

Efficient synthesis of 3,6,13,16-tetrasubstituted-tetrabenzo[a,d,j,m]coronenes by selective C–H/C–O arylations of anthraquinone derivatives

• Seiya Terai,
• Yuki Sato,
• Takuya Kochi and
• Fumitoshi Kakiuchi

Beilstein J. Org. Chem. 2020, 16, 544–550, doi:10.3762/bjoc.16.51

• examining various carbonyl methylenation methods, we found that the dimethylenation products 6 can be obtained in high yields through methylation of the carbonyl groups, followed by dehydration. Thus, the reaction of 4aa with methyllithium and subsequent treatment of the crude diol with NaH2PO2·H2O and NaI

Regioselectivity of glycosylation reactions of galactose acceptors: an experimental and theoretical study

• Enrique A. Del Vigo,
• Carlos A. Stortz and
• Carla Marino

Beilstein J. Org. Chem. 2019, 15, 2982–2989, doi:10.3762/bjoc.15.294

• coefficients (Table 2). Nevertheless, the change in selectivity predicted for the benzylated diol analogs of 1α/1β did not match the experimental trend. Similar results were observed with the M06-2X functional (Table 2). The calculations gave a good prediction of the higher OH-3 group’s reactivity, but an

• acceptors and donors. Model Galp 3,4-diol acceptors and data obtained with B3LYP. Synthesis of glycosyl acceptors 1α/β and 2α/β. a) BzCl, pyridine, 0 °C, 2 h; b) BF3·OEt2, MeOH, CH2Cl2, 4 h; c) SnCl4, MeOH, CH2Cl2, 20 h; d) NaOMe/MeOH, CH2Cl2, 0 ºC, 2 h; e) (CH3)2C(OCH3)2, p-TsOH, acetone, rt, 16 h; f) 50

A green, economical synthesis of β-ketonitriles and trifunctionalized building blocks from esters and lactones

• Daniel P. Pienaar,
• Kamogelo R. Butsi,
• Amanda L. Rousseau and
• Dean Brady

Beilstein J. Org. Chem. 2019, 15, 2930–2935, doi:10.3762/bjoc.15.287

• diols 1 and 8, thereby indicating that the hemiketals are still fully reducible under standard ketone reduction conditions. Purification of 6 afforded only a 10% overall yield of the diol 8, but the direct conversion of crude intermediate product 6 resulted in a doubling of the overall yield of the diol

• the synthesis of glycomimetic products from sugar lactones, and for the synthesis of various pyrimidines. Proposed retrosynthesis of the free diol 1. Preparation of O-unprotected, trifunctionalized synthons from lactones. Preparation of a variety of β-ketonitriles. Supporting Information Supporting

Current understanding and biotechnological application of the bacterial diterpene synthase CotB2

• Ronja Driller,
• Daniel Garbe,
• Norbert Mehlmer,
• Monika Fuchs,
• Keren Raz,
• Dan Thomas Major,
• Thomas Brück and
• Bernhard Loll

Beilstein J. Org. Chem. 2019, 15, 2355–2368, doi:10.3762/bjoc.15.228

• release of TNF-α by BALB/3T3 cells [75]. This cancer prevention activity can be initiated at an IC50 of only 2.5 µM. Other bioactive target molecules structurally accessible from compound 7 could be both epimers of (6R)-2,7,11-cembratriene-4,6-diol either 4S: α-CBT 16 or 4R: β-CBT 17 (Scheme 3). Both were

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

• later stage the optical purity could be improved (see below). Diol protection gave dioxolane 14, which underwent Saegusa oxidation to afford enone 15. Subsequent α-iodination gave access to α-iodoenone 16, which could be stereoselectively reduced under Corey–Itsuno conditions to yield allylic alcohol 17

• . The use of a chiral oxazaborolidine catalyst led to kinetic resolution and increased the optical purity of 17 to 95% ee. Deprotection of the diol moiety followed by Stille cross coupling with vinyl stannane 18 finally gave 5 in excellent yield (Scheme 2). Since acremine F (5) can be expected to be the

Azologization and repurposing of a hetero-stilbene-based kinase inhibitor: towards the design of photoswitchable sirtuin inhibitors

• Christoph W. Grathwol,
• Nathalie Wössner,
• Sören Swyter,
• Adam C. Smith,
• Enrico Tapavicza,
• Robert K. Hofstetter,
• Anja Bodtke,
• Manfred Jung and
• Andreas Link

Beilstein J. Org. Chem. 2019, 15, 2170–2183, doi:10.3762/bjoc.15.214

• with a Torus DIOL (Waters) or Phenomenex CSP (Lux Amylose-2, i-Amylose-3, i-Cellulose-5), a degasser (DGU-20A5R), a communications module (CBM-20A), and two back pressure regulators BPR A and B (SFC-30A). UV and MS spectra were recorded via photodiode array detection (SPD-M20A) and electrospray

α-Photooxygenation of chiral aldehydes with singlet oxygen

• Dominika J. Walaszek,
• Magdalena Jawiczuk,
• Jakub Durka,
• Olga Drapała and
• Dorota Gryko

Beilstein J. Org. Chem. 2019, 15, 2076–2084, doi:10.3762/bjoc.15.205

• byproducts (Scheme 2) [14]. Photooxygenation of 3,4-diphenylbutanal (1) affording the desired diol 6 accompanied by alcohol 9 as the only byproduct was chosen as a model reaction for optimization studies. From a practical point of view it was important that diastereoisomers syn-6 and anti-6 could be

• mixture and oxygen was purged. After the reduction diol 6 was obtained in 12% yield, as a nearly equimolar mixture of syn-(2R,3R)- and syn’-(2S,3S)-6 enantiomers (Table 2, entry 1). So, in the one-pot procedure a decrease in both yield and stereoselectivity was observed as compared to the two-step

• its rather simple structure diol 6 was not previously reported in the literature. The ratio of stereoisomers 6 was determined by HPLC analysis while the absolute configuration of the newly created stereocenter was established using a chiroptical spectroscopic method. Samples of stereoisomers syn-6 and

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

• ], helminthosporol (7) [15], bipolenin A (8) [3], secolongifolene diol (9) [15], dihydroprehelminthosporol (10) [1] and sorokinianin (11) [2], and the cytotoxic sesterterpenoid, terpestacin (12) [16][17] (Figure 1). Bipolenin K (1) was isolated as a colourless oil. Its molecular formula was determined as C15H22O3

• ), secolongifolene diol (9), dihydroprehelminthosporol (10) and sorokinianin (11), together with a sesterterpenoid, terpestacin (12). We demonstrated that 6 and 10 have weak necrotic activity against wheat leaves, while 7 inhibited wheat seed germination at 100 ppm. These compounds served as markers for identifying

Isolation and characterisation of irinans, androstane-type withanolides from Physalis peruviana L.

• Annika Stein,
• Dave Compera,
• Bianka Karge,
• Mark Brönstrup and
• Jakob Franke

Beilstein J. Org. Chem. 2019, 15, 2003–2012, doi:10.3762/bjoc.15.196

• -oxidative Grob fragmentation could make use of a push–pull mechanism between C-17 and C-22, building on acid–base catalysis. Alternatively, an enzyme could cleave the C17–C20 diol oxidatively. Several P450 enzymes have been reported to be capable of cleaving diols, presumably via a ferric peroxo

Synthesis and anion binding properties of phthalimide-containing corona[6]arenes

• Meng-Di Gu,
• Yao Lu and
• Mei-Xiang Wang

Beilstein J. Org. Chem. 2019, 15, 1976–1983, doi:10.3762/bjoc.15.193

• and electron-neutral organic guests [22][23][24][25][26][27][28][29][30][31]. In our previous study we have developed an efficient protocol to synthesize oxygen and sulfur-linked corona[m]arene[n]tetrazines from aromatic diol and dithiol derivatives and 3,6-dichlorotetrazine, respectively, in a simply

Application of chiral 2-isoxazoline for the synthesis of syn-1,3-diol analogs

• Juanjuan Feng,
• Tianyu Li,
• Jiaxin Zhang and
• Peng Jiao

Beilstein J. Org. Chem. 2019, 15, 1840–1847, doi:10.3762/bjoc.15.179

• product in 95% yield, which was converted into tert-butyl (3S,5R)-6-hydroxy-3,5-O-isopropylidene-3,5-dihydroxyhexanoate in 14 steps through a β-hydroxy ketone. Keywords: β-hydroxy ketone; cycloaddition; 1,3-diol; isoxazoline; silyl nitronate; Introduction The chiral 1,3-diol structure is widespread in a

• broad spectrum of natural products [1][2]. (3R)-β-Hydroxy-δ-lactone or its open-ring equivalent (3R)-syn-3,5-dihydroxypentanoic acid, is a common structure in naturally occurring mevastatin (or compactin), lovastatin or closely related statins, and synthetic statins. Either the syn or anti-1,3-diol

• chiral β-hydroxy-δ-lactone moiety or its equivalents, pioneered by Wong [42], is equally competitive. Here, we report the preparations of tert-butyl (3S,5R)-6-hydroxy-3,5-O-isopropylidene-3,5-dihydroxyhexanoate and related syn-1,3-diol analogs from a chiral 2-isoxazoline (Scheme 1b). This work is part of

N-(1-Phenylethyl)aziridine-2-carboxylate esters in the synthesis of biologically relevant compounds

• Iwona E. Głowacka,
• Aleksandra Trocha,
• Andrzej E. Wróblewski and
• Dorota G. Piotrowska

Beilstein J. Org. Chem. 2019, 15, 1722–1757, doi:10.3762/bjoc.15.168

• diversified compounds. In this review we wish to focus attention on applications of 5–8 in syntheses of biologically important compounds having a 2-amino-1,3-disubstituted propane unit implanted into their structures because vicinal amino alcohol and 2-aminopropane-1,3-diol scaffolds are present in many

• secured in the starting aldehyde introduction of the two others required cis-dihydroxylation of the Z-alkene 111. The highest diastereoselectivity (99:1) was observed at −10 °C providing the aziridine diol (2S,1'S,2'R,1''R)-112 as a major diastereoisomer. The regioselective aziridine ring opening combined

• (Scheme 37) [32]. The major product (2S,1'R)-69b was subjected to Sharpless asymmetric dihydroxylation in the presence of AD-mix-α to give the diol 145a as a major (10:1) diastereoisomer. The ester moiety in 145a was reduced and hydroxy groups were protected to give the tribenzyloxy aziridine (2R,1'S,2'S