A review of the total syntheses of triptolide

• Xiang Zhang,
• Zaozao Xiao and
• Hongtao Xu

Beilstein J. Org. Chem. 2019, 15, 1984–1995, doi:10.3762/bjoc.15.194

• include the regioselective dihydroxylation and etherification to introduce the C-14 hydroxy group and the construction of the butenolide moiety. Particularly, the characteristics of Li’s route are low cost, high yield (9 steps, 44% yield) and easy handling (all intermediates could be scaled up to 100

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

• 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

• phosphatase 1 and 2A inhibitors [93]. An interesting structural feature of calyculins is a C33–C37 fragment γ-amino acid (2S,3S,4S)-159. Its stereocontrolled synthesis involved cis-dihydroxylation of the aziridine cis-acrylate (2R,1'R)-156a which led to the formation of a 91:9 mixture of diastereoisomeric

The LANCA three-component reaction to highly substituted β-ketoenamides – versatile intermediates for the synthesis of functionalized pyridine, pyrimidine, oxazole and quinoxaline derivatives

• Tilman Lechel,
• Roopender Kumar,
• Mrinal K. Bera,
• Reinhold Zimmer and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2019, 15, 655–678, doi:10.3762/bjoc.15.61

• . The easily introduced C-2 alkenyl groups may also be oxidized. Thus, dihydroxylation of the vinyl group in PM7 followed by oxidative cleavage afforded pyrimidine derivative PM50 having a formyl group at C-2 (Scheme 12) [31]. Next, the conversion of the 5-alkoxy groups of the pyrimidine derivatives PM

A chemoenzymatic synthesis of ceramide trafficking inhibitor HPA-12

• Seema V. Kanojia,
• Sucheta Chatterjee,
• Subrata Chattopadhyay and
• Dibakar Goswami

Beilstein J. Org. Chem. 2019, 15, 490–496, doi:10.3762/bjoc.15.42

• synthesis of the title compound has been developed using an efficient and highly enantioselective lipase-catalyzed acylation in a hydrophobic ionic liquid, [bmim][PF6], followed by a diastereoselective asymmetric dihydroxylation as the key steps for incorporating the stereogenic centers. The further

• (S)-4 with benzyl bromide (BnBr) and Bu4NI in the presence of NaH produced compound 6 (Scheme 2). This was subjected to asymmetric dihydroxylation (ADH) using AD mix-β [K2OsO2(OH)4 and (DHQD)2-PHAL]. The reaction proceeded predominantly from the α-face, resulting in the formation of the 1,3-anti diol

Synthesis of nonracemic hydroxyglutamic acids

• Dorota G. Piotrowska,
• Iwona E. Głowacka,
• Andrzej E. Wróblewski and
• Liwia Lubowiecka

Beilstein J. Org. Chem. 2019, 15, 236–255, doi:10.3762/bjoc.15.22

• acid [(2S,3S,4R)-4] was obtained as the hydrochloride. To avoid racemization at Cα in sensitive amino acids the carboxy group was frequently masked as an orthoester. To illustrate this strategy dihydroxylation of the orthoester 92 (derived from L-pyroglutamic acid [97]) was performed to afford a single

• ). Dihydroxylation of the C=C bond gave a 10:1 mixture with (2S,3S,4R)-121 as a major product which was transformed into the isopropylidene derivative (2S,3S,4R)-122 to facilitate purification. Hydrogenolysis allowed to remove the N- and O-protecting groups and was followed by the spontaneous cyclization to a

• pyrrolidine-2-one (3S,4S,5R)-123 [111]. Oxidation of the hydroxymethyl group and acid hydrolysis gave (2S,3S,4S)-4 [112]. By enantioselective conjugate addition and asymmetric dihydroxylation An orthogonally protected 3,4-dihydroxy-L-glutamic acid was envisioned as an intermediate in the projected synthesis

Systematic synthetic study of four diastereomerically distinct limonene-1,2-diols and their corresponding cyclic carbonates

• Hiroshi Morikawa,
• Jun-ichi Yamaguchi,
• Shun-ichi Sugimura,
• Masato Minamoto,
• Yuuta Gorou,
• Hisatoyo Morinaga and
• Suguru Motokucho

Beilstein J. Org. Chem. 2019, 15, 130–136, doi:10.3762/bjoc.15.13

• . Dihydroxylation of (a) (R)-limonene and (b) (R)-dihydrolimonene. Reduction of LM5CC (1a) and carbonation of LMdiol (2a). Overall synthetic routes to LM5CCs and LMdiols. The 93% value (standing for *) from 1d to 2d was cited from ref [27]. Reagents and conditions: (a) 5 MPa CO2, 10 mol % TBAC, 100 °C, 72 h; (b

Synthesis of pyrrolidine-based hamamelitannin analogues as quorum sensing inhibitors in Staphylococcus aureus

• Jakob Bouton,
• Kristof Van Hecke,
• Reuven Rasooly and
• Serge Van Calenbergh

Beilstein J. Org. Chem. 2018, 14, 2822–2828, doi:10.3762/bjoc.14.260

• ’-homoazanucleosides. This possible precursor was synthesized convergently in 12 steps [20]. The pyrrolidine ring was constructed via alkylation of 6 and 7, followed by ring-closing metathesis. Stereoselective dihydroxylation of the resulting alkene then furnished the protected iminosugar 5. However, using

• -closing metathesis of 24 now smoothly afforded 25 in high yield. Dihydroxylation selectively yielded the desired stereoisomer of diol 26, which was subsequently protected as isopropylidene acetal. In the next step, after removal of the TBS group and mesylation, attempted substitution with NaN3 resulted

A stereoselective and flexible synthesis to access both enantiomers of N-acetylgalactosamine and peracetylated N-acetylidosamine

• Bettina Riedl and
• Walther Schmid

Beilstein J. Org. Chem. 2018, 14, 856–860, doi:10.3762/bjoc.14.71

• )- or (S)-2,3-isopropylideneglyceraldehyde with a second chiral building block containing the amine function, followed by dihydroxylation [13][14]. Despite the compounds already available through these and other approaches, novel synthetic concepts to fill the remaining methodological gaps for accessing

Acid-catalyzed ring-opening reactions of a cyclopropanated 3-aza-2-oxabicyclo[2.2.1]hept-5-ene with alcohols

• Katrina Tait,
• Alysia Horvath,
• Nicolas Blanchard and
• William Tam

Beilstein J. Org. Chem. 2017, 13, 2888–2894, doi:10.3762/bjoc.13.281

• includes the reduction to form alkane 8 [3], oxidative cleavage of the C=C bond to form 9 [4], ring-opening metathesis to form functionalized alkenes 10 and 11 [4], dihydroxylation to form diol 12 [5], ruthenium-catalyzed [2 + 2] cycloaddition with unsymmetrical alkynes to form regioisomers 13 and 14 [6

The use of 4,4,4-trifluorothreonine to stabilize extended peptide structures and mimic β-strands

• Yaochun Xu,
• Isabelle Correia,
• Tap Ha-Duong,
• Nadjib Kihal,
• Jean-Louis Soulier,
• Julia Kaffy,
• Benoît Crousse,
• Olivier Lequin and
• Sandrine Ongeri

Beilstein J. Org. Chem. 2017, 13, 2842–2853, doi:10.3762/bjoc.13.276

• ] from propargylic alcohol in ten steps, based on the trifluoromethylation key step of 1-(((E)-3-bromoallyloxy)methyl)benzene to obtain (E)-1-benzyloxy-4,4,4-trifluoro-2-butene. The sequence then involved Sharpless asymmetric dihydroxylation, nucleophilic opening of cyclic sulfate with NaN3, palladium

Fluorination of some highly functionalized cycloalkanes: chemoselectivity and substrate dependence

• Attila Márió Remete,
• Melinda Nonn,
• Santos Fustero,
• Matti Haukka,
• Ferenc Fülöp and
• Loránd Kiss

Beilstein J. Org. Chem. 2017, 13, 2364–2371, doi:10.3762/bjoc.13.233

• our synthetic investigations by selecting some cyclohexane β-amino acid esters as model compounds. Thus, diol (±)-8 [23][24][25][26] derived from dihydroxylation of cis-2-aminocyclohex-4-ene carboxylic acid was treated with 1 equiv of Deoxofluor in CH2Cl2. Again, through chemodiscrimination of the

Synthesis of ergostane-type brassinosteroids with modifications in ring A

• Vladimir N. Zhabinskii,
• Darya A. Osiyuk,
• Yuri V. Ermolovich,
• Natalia M. Chaschina,
• Tatsiana S. Dalidovich,
• Miroslav Strnad and
• Vladimir A. Khripach

Beilstein J. Org. Chem. 2017, 13, 2326–2331, doi:10.3762/bjoc.13.229

• the epimerization of the hydroxy group at C-2/C-3 is the inactivation process contributing to a constant level of the active phytohormone. 2β,3β-Diols 6 are available through Woodward–Prévost cis-dihydroxylation of Δ2-steroids 3 [21]. The diaxial diols 7 can be easily synthesized by an acid-catalyzed

Difunctionalization of alkenes with iodine and tert-butyl hydroperoxide (TBHP) at room temperature for the synthesis of 1-(tert-butylperoxy)-2-iodoethanes

• Hao Wang,
• Cui Chen,
• Weibing Liu and
• Zhibo Zhu

Beilstein J. Org. Chem. 2017, 13, 2023–2027, doi:10.3762/bjoc.13.200

• dioxygenation [10][11], dihydroxylation [10][12], bisperoxidation [13], oxyamidation [14], aminohydroxylation [15], oxyphosphorylation [16], deamination [17] and carbonylation–peroxidation [18]. Several very recent reports have pertained to metal-free catalysts for difunctionalization of alkenes such as UV

The chemistry and biology of mycolactones

• Matthias Gehringer and
• Karl-Heinz Altmann

Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159

Urea–hydrogen peroxide prompted the selective and controlled oxidation of thioglycosides into sulfoxides and sulfones

• Adesh Kumar Singh,
• Varsha Tiwari,
• Kunj Bihari Mishra,
• Surabhi Gupta and
• Jeyakumar Kandasamy

Beilstein J. Org. Chem. 2017, 13, 1139–1144, doi:10.3762/bjoc.13.113

• within 1.5 h. However, corresponding sulfone was obtained in a moderated yield due to instability which undergoes partial amount of decomposition. In general, olefins functional groups are known to undergo epoxidation or dihydroxylation with different oxidizing agents (e.g. m-CPBA, t-BuOOH, oxone, etc

Synthesis of D-manno-heptulose via a cascade aldol/hemiketalization reaction

• Yan Chen,
• Xiaoman Wang,
• Junchang Wang and
• You Yang

Beilstein J. Org. Chem. 2017, 13, 795–799, doi:10.3762/bjoc.13.79

• followed by dihydroxylation [10][11][12][13][23][24][25][26][27]. Remarkably, Thiem et al. reported the highly efficient synthesis of D-manno-heptulose from D-mannose in 59% overall yield over five steps [26]. However, the synthesis of D-manno-heptulose and its derivatives from the common differentially

Exploring endoperoxides as a new entry for the synthesis of branched azasugars

• Svenja Domeyer,
• Mark Bjerregaard,
• Henrik Johansson and
• Daniel Sejer Pedersen

Beilstein J. Org. Chem. 2017, 13, 644–647, doi:10.3762/bjoc.13.63

• sufficient material of dienes 14–16 was available to proceed to the critical cycloaddition and dihydroxylation steps and thus no further optimisation was performed. The cycloaddition reaction of dienes 14–16 with singlet oxygen was performed in a modified photochemical reactor that had been fitted with a gas

• set for the central dihydroxylation reaction that would give access to key intermediates 20 and 21 (Scheme 4). To our delight dihydroxylation with potassium osmate in the presence of citric acid was smooth and gave excellent yields of diols 20 and 21 [11]. Diols 20 and 21 were found to be unstable

• mercury lamp was replaced with three 100 W halogen bulbs. Dihydroxylation and protection of endoperoxides 18 and 19 to provide novel building blocks 20–23 for azasugar synthesis. Preliminary exploration of the chemistry of endoperoxides 18–23 was encouraging and gave access to a variety of derivatives

Studies directed toward the exploitation of vicinal diols in the synthesis of (+)-nebivolol intermediates

• Runjun Devi and
• Sajal Kumar Das

Beilstein J. Org. Chem. 2017, 13, 571–578, doi:10.3762/bjoc.13.56

• Runjun Devi Sajal Kumar Das Department of Chemical Sciences, Tezpur University, Napaam, Tezpur, Assam-784028, India 10.3762/bjoc.13.56 Abstract While the exploitation of the Sharpless asymmetric dihydroxylation as the source of chirality in the synthesis of acyclic molecules and saturated

• heterocycles has been tremendous, its synthetic utility toward chiral benzo-annulated heterocycles is relatively limited. Thus, in the search for wider applications of Sharpless asymmetric dihydroxylation-derived diols for the synthesis of benzo-annulated heterocycles, we report herein our studies in the

• that a large number of racemic and asymmetric syntheses of nebivolol and their intermediates have been described in the literature, however, the Sharpless asymmetric dihydroxylation has never been employed as the sole source of chirality for this purpose. Keywords: dihydroxylation; epoxide-ring

Synthesis of polyhydroxylated decalins via two consecutive one-pot reactions: 1,4-addition/aldol reaction followed by RCM/syn-dihydroxylation

• Michał Malik and
• Sławomir Jarosz

Beilstein J. Org. Chem. 2016, 12, 2602–2608, doi:10.3762/bjoc.12.255

• -dihydroxylation. The stereochemical outcome of these reactions is discussed. Keywords: carbasugars; one-pot reactions; ring-closing metathesis; syn-dihydroxylation; Introduction Derivatives of carbohydrates, in which the endocyclic oxygen atom is replaced with a methylene group are known as carbasugars [1]. Due

• ruthenium catalyst in the subsequent syn-dihydroxylation. As a result, the polyhydroxylated decalin derivative 12 was obtained. The syn-dihydroxylation of cyclic alkenes is among the most widely used methods for the introduction of hydroxy groups onto the ring. Such transformations are usually conducted

• Snapper [41][42]. Both groups described a methodology, in which the ring-closing metathesis (RCM) reaction is followed by the reuse of the Ru catalyst in the syn-dihydroxylation step. In our recent papers [43][44], we extended this concise and effective approach to the synthesis of bicyclic iminosugars

Enduracididine, a rare amino acid component of peptide antibiotics: Natural products and synthesis

• Darcy J. Atkinson,
• Briar J. Naysmith,
• Daniel P. Furkert and
• Margaret A. Brimble

Beilstein J. Org. Chem. 2016, 12, 2325–2342, doi:10.3762/bjoc.12.226

• to orthogonally protected amino acids 46 and 47 (Scheme 7) [58]. Installation of the C-2 stereocentre again began with Garner’s aldehyde 48 and Wittig olefination, followed by Sharpless dihydroxylation to stereoselectively afford diol 49 [59][60]. The C-2 epimer was accessed via Still–Gennari

• olefination of aldehyde 48 to afford the Z-olefin, which underwent dihydroxylation using potassium osmate to afford diol 50 [61][62]. With both diastereomers in hand, conversion to protected amino acids 46 and 47 was effected in four steps. With amino acids 46 and 47 in hand, conversion to the corresponding

• with isothiourea 33 followed by mesyl chloride afforded cyclic guanidine 72 in 70% yield. Silyl deprotection, Swern oxidation and Still–Gennari olefination afforded Z-alkene 73. Diastereoselective dihydroxylation of 73 followed by treatment with 1,1'-thiocarbonyldiimidazole (TCDI) and sodium azide

The direct oxidative diene cyclization and related reactions in natural product synthesis

• Juliane Adrian,
• Leona J. Gross and
• Christian B. W. Stark

Beilstein J. Org. Chem. 2016, 12, 2104–2123, doi:10.3762/bjoc.12.200

• the key step (right, Scheme 8) [79]. After reduction of the ester 26, a Sharpless asymmetric dihydroxylation (AD) [86][87][88] reaction furnished diol 31 with a high degree of both regio- and enantioselectivity. Osmium-promoted oxidative type B cyclization of 31 proceeded in high yield (81%) and with

• succeeded in synthesizing cis-solamin A (29) utilizing a ruthenium tetroxide-catalyzed type A oxidative cyclization approach (Scheme 9) [80]. Silyl-protected dienediol 34, the oxidative cyclization precursor, was synthesized from all-trans-cyclododecatriene 33 in four steps including dihydroxylation, glycol

• , polyketides, amino acids, fatty acids as well as acetogenins and terpenoids) are summarized in this review article. Putative structures of geraniol 1a (R = H) or 1b (R = H) (in 1924), their expected dihydroxylation products 2a or 2b and the true structure 3 as determined by Klein and Rojahn in 1965 [8

Synthesis of the C8’-epimeric thymine pyranosyl amino acid core of amipurimycin

• Pramod R. Markad,
• Navanath Kumbhar and
• Dilip D. Dhavale

Beilstein J. Org. Chem. 2016, 12, 1765–1771, doi:10.3762/bjoc.12.165

• ] (Scheme 2). Selective protection of the C5 primary hydroxy group as PMP ether using p-methoxyphenol under Mitsunobu reaction conditions afforded 4 that on benzylation of the C3 hydroxy group (NaH and benzyl bromide in DMF) gave compound 5. Upjohn dihydroxylation of 5 using K2OsO4·2H2O followed by

Modular synthesis of the pyrimidine core of the manzacidins by divergent Tsuji–Trost coupling

• Sebastian Bretzke,
• Stephan Scheeff,
• Felicitas Vollmeyer,
• Friederike Eberhagen,
• Frank Rominger and
• Dirk Menche

Beilstein J. Org. Chem. 2016, 12, 1111–1121, doi:10.3762/bjoc.12.107

• correlations and vicinal coupling constants as shown in Scheme 7. For further conversion to key intermediates 3 and 4, the tosyl groups of 42 and 43 were removed with SmI2 [54][55] giving the free amides 44 and 45. The terminal double bonds were then oxidized by dihydroxylation with OsO4 and periodate cleavage

Efficient syntheses of climate relevant isoprene nitrates and (1R,5S)-(−)-myrtenol nitrate

• Sean P. Bew,
• Glyn D. Hiatt-Gipson,
• Graham P. Mills and
• Claire E. Reeves

Beilstein J. Org. Chem. 2016, 12, 1081–1095, doi:10.3762/bjoc.12.103

• dihydroxylation [24] afforded the inseparable (flash chromatography) (±)-3-methylbut-3-ene-1,2-diol (rac-17) and (±)-2-methylbut-3-ene-1,2-diol (rac-18) in a 3:2 ratio and unoptimized 67% yield (Scheme 3). Investigating O-nitrate ester formation the rac-17/rac-18 mixture was dissolved in dichloromethane

A novel and practical asymmetric synthesis of dapoxetine hydrochloride

• Yijun Zhu,
• Zhenren Liu,
• Hongyan Li,
• Deyong Ye and
• Weicheng Zhou

Beilstein J. Org. Chem. 2015, 11, 2641–2645, doi:10.3762/bjoc.11.283

• encompass asymmetric dihydroxylation of trans-methyl cinnamate or cinnamyl alcohol [6], chiral azetidin-2,3-dione [7], asymmetric C–H amination reactions of a prochiral sulfamate [8], oxazaborolidine reduction of 3-chloropropiophenone or ketone [9], and an imidazolidin-2-one chiral auxiliary mediated