Stereoselective synthesis of the C79–C97 fragment of symbiodinolide

• Hiroyoshi Takamura,
• Takayuki Fujiwara,
• Isao Kadota and
• Daisuke Uemura

Beilstein J. Org. Chem. 2013, 9, 1931–1935, doi:10.3762/bjoc.9.228

• Sharpless asymmetric dihydroxylation were utilized as the key transformations. Keywords: Julia–Kocienski olefination; polyol marine natural product; Sharpless asymmetric dihydroxylation; spiroacetalization; symbiodinolide; Findings A 62-membered polyol marine natural product, symbiodinolide (1, Figure 1

• the Birch reduction to afford the trans-alkene 6, wherein the benzyl moiety was deprotected. The alkene 6 was derivatized to the spiroacetal C79–C96 fragment 7 in four steps including the benzyl protection and Sharpless asymmetric dihydroxylation (AD). Although the desired spiroacetal fragment 7 was

• Information File 1). In conclusion, we have achieved the stereoselective synthesis of the C79–C97 fragment. The synthetic route has featured a stereoselective spiroacetalization, a Julia–Kocienski olefination, and a Sharpless asymmetric dihydroxylation. This synthesis of the spiroacetal fragment, wherein the

De novo synthesis of D- and L-fucosamine containing disaccharides

• Daniele Leonori and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2013, 9, 332–341, doi:10.3762/bjoc.9.38

• blocks Our retrosynthetic analysis of D-fucosamine envisioned the installation of the syn-1,2-diol unit by osmium-catalysed dihydroxylation of allylic ether A. It was anticipated that the conformation adopted by the molecule would allow for the formation of the required anti relationship between C3 and

• commercially available starting materials. The two different O-protecting groups, namely naphthyl ether (Nap) [57][58][59] and benzoate ester (Bz), were introduced to gain access to two sets of electronically different and orthogonally protected derivatives (Scheme 2A). Dihydroxylation of aldehyde 6a under

• a 3JH3–H4 coupling of 3.5 Hz. When the same sequence of dihydroxylation–peracetylation was performed on Bz-substituted aldehyde 6b, compound D-8b was formed in 71% as a single diastereomer (Scheme 3). This product was crystallized from n-hexane/EtOAc solvent mixture, and the stereochemical

Iron-containing mesoporous aluminosilicate catalyzed direct alkenylation of phenols: Facile synthesis of 1,1-diarylalkenes

• Satyajit Haldar and
• Subratanath Koner

Beilstein J. Org. Chem. 2013, 9, 49–55, doi:10.3762/bjoc.9.6

• ]. Furthermore, a variety of available reactions to functionalize the double bond, such as reductive (hydrogenation, hydrosilylation, etc.), oxidative (epoxidation, halogenations, dihydroxylation, etc.) or cycloaddition transformations, encourage such vinylation process as an attractive primary tool in organic

Total synthesis and biological evaluation of fluorinated cryptophycins

• Christine Weiß,
• Tobias Bogner,
• Benedikt Sammet and
• Norbert Sewald

Beilstein J. Org. Chem. 2012, 8, 2060–2066, doi:10.3762/bjoc.8.231

• 11 could then be directly employed without purification in the asymmetric dihydroxylation with osmium tetroxide and (DHQD)2PHAL, in close analogy to a previously published procedure [23]. The initially formed vicinal diol cyclizes under the reaction conditions to give lactone 12 in enantiomerically

A new approach toward the total synthesis of (+)-batzellaside B

• Jolanta Wierzejska,
• Shin-ichi Motogoe,
• Yuto Makino,
• Tetsuya Sengoku,
• Masaki Takahashi and
• Hidemi Yoda

Beilstein J. Org. Chem. 2012, 8, 1831–1838, doi:10.3762/bjoc.8.210

• (+)-batzellaside B from naturally abundant L-pyroglutamic acid is presented in this article. The key synthetic step involves Sharpless asymmetric dihydroxylation of an olefinic substrate functionalized with an acetoxy group to introduce two chiral centres diastereoselectively into the structure. Heterocyclic

• hemiaminal 4, which could be converted from the resulting product, was found to provide stereospecific access to enantiomerically enriched allylated intermediate, offering better prospects for the total synthesis of this natural product. Keywords: asymmetric dihydroxylation; (+)-batzellaside B; iminosugar

• transformation will involve Sharpless asymmetric dihydroxylation to install stereoselectively the hydroxy groups at C3 and C4 positions of the olefinic substrate 6, and an intramolecular cyclization of aldehyde generated in situ from 5 to construct the piperidine ring system. The present publication describes

Synthesis and ring openings of cinnamate-derived N-unfunctionalised aziridines

• Alan Armstrong and
• Alexandra Ferguson

Beilstein J. Org. Chem. 2012, 8, 1747–1752, doi:10.3762/bjoc.8.199

• dihydroxylation, conversion to a cyclic sulfate, ring opening with azide, and finally ring closure to afford the NH-aziridine [18]. We recently reported [21][22] a nucleophilic aziridination methodology [23][24][25][26][27][28][29][30] that allows access to NH-aziridines in a single step from α,β-unsaturated

On the proposed structures and stereocontrolled synthesis of the cephalosporolides

• Sami F. Tlais and
• Gregory B. Dudley

Beilstein J. Org. Chem. 2012, 8, 1287–1292, doi:10.3762/bjoc.8.146

• C9, as opposed to the n-heptyl chain in cephalosporolide H. Synthesis of cephalosporolide E started with the known alcohol 12, which was prepared from the commercially available diester 11 (Scheme 4) [34]. PMB protection of alcohol 12 followed by Sharpless dihydroxylation afforded diol 14 [35][36

• tracing back to the Sharpless dihydroxylation reaction). Spectroscopic data for our synthetic material was in full agreement with the reported data for cephalosporolide E [28][29][30]. Conclusion We have completed the stereocontrolled synthesis of the reported structure of cephalosporolide H and three

Chiral multifunctional thiourea-phosphine catalyzed asymmetric [3 + 2] annulation of Morita–Baylis–Hillman carbonates with maleimides

• Hong-Ping Deng,
• De Wang,
• Yin Wei and
• Min Shi

Beilstein J. Org. Chem. 2012, 8, 1098–1104, doi:10.3762/bjoc.8.121

• desired catalytic cycle. To illustrate the synthetic utility of these products 3 obtained from the above asymmetric [3 + 2] annulation, the further transformation of 3c was performed in the presence of RuCl3 and NaIO4 under mild conditions (Scheme 3) [22][60]. Upon dihydroxylation of 3c, the corresponding

• /EtOAc 10:1–4:1) to provide compound 3. The ORTEP plot of compound 3r. 31P NMR spectra (161.9 MHz, CDCl3) of control experiments. Paths to the formation of 1,3-dipolar synthons by using a catalytic amount of phosphines. Proposed transition models. Dihydroxylation of 3c. Optimization of the reaction

Directed ortho,ortho'-dimetalation of hydrobenzoin: Rapid access to hydrobenzoin derivatives useful for asymmetric synthesis

• Inhee Cho,
• Labros Meimetis,
• Lee Belding,
• Michael J. Katz,
• Travis Dudding and
• Robert Britton

Beilstein J. Org. Chem. 2011, 7, 1315–1322, doi:10.3762/bjoc.7.154

• (S,S)-hydrobenzoin are relatively inexpensive [18], or can be readily prepared on kilogram-scale from trans-stilbene through Sharpless asymmetric dihydroxylation (SAD) [19][20], the synthesis of ortho,ortho'-functionalized derivatives of hydrobenzoin typically requires several steps that include

Amine-linked diglycosides: Synthesis facilitated by the enhanced reactivity of allylic electrophiles, and glycosidase inhibition assays

• Ian Cumpstey,
• Jens Frigell,
• Elias Pershagen,
• Tashfeen Akhtar,
• Elena Moreno-Clavijo,
• Inmaculada Robina,
• Dominic S. Alonzi and
• Terry D. Butters

Beilstein J. Org. Chem. 2011, 7, 1115–1123, doi:10.3762/bjoc.7.128

• carbohydrate into an unsaturated derivative with an allylic alcohol as leaving group [16]. After the coupling reaction, dihydroxylation of the C=C double bond would restore the carbohydrate structure (Scheme 1) [17]. As well as Mitsunobu chemistry [18], the allylic nature of the electrophile opens up the way

• achieved the coupling, we turned to the refunctionalisation of the C=C bond (Scheme 4). Osmium-catalysed dihydroxylation of the double bond in erythro configured pseudodisaccharide 13 proceeded to give a single diastereomer of product 16. The configuration of the dihydroxylated product 16 was most

• consistent with the α-manno configuration, and inconsistent with the alternative α-allo configuration. Hence dihydroxylation proceeded from the opposite side to the two neighbouring substituents (at C-1 and C-4), as expected in a sterically controlled reaction, and consistent with previous results [35]. The

Metathesis access to monocyclic iminocyclitol-based therapeutic agents

• Ileana Dragutan,
• Valerian Dragutan,
• Carmen Mitan,
• Hermanus C.M. Vosloo,
• Lionel Delaude and
• Albert Demonceau

Beilstein J. Org. Chem. 2011, 7, 699–716, doi:10.3762/bjoc.7.81

• the core cyclic olefin; and (iii) dihydroxylation of the endocyclic double bond in a highly diastereoselective manner to form the target product. In comparison to the traditional, lengthier syntheses of iminocyclitols, the metathesis approach has emerged as a highly advantageous method in terms of

• ) and ester group reduction (LiBH4), a protected racemic diene 16 was obtained; RCM cyclization of the latter using the Grubbs catalyst Cl2(PCy3)2Ru=CH–CH=CPh2 (3) led to the racemic dehydroprolinol derivative 17 in high yield. Subsequent O-protection with trityl chloride and dihydroxylation (with OsO4

• dihydroxylation with simultaneous deprotection of (+)-22 gave the final product (−)-23 in good yield. In an interesting work by Rao and co-workers [54] a Grignard reaction was employed to design the diene with desired stereochemistry for the synthesis of 1,4-dideoxy-1,4-imino-D-allitol (29) and the formal

Brønsted acid-promoted azide–olefin [3 + 2] cycloadditions for the preparation of contiguous aminopolyols: The importance of disiloxane ring size to a diastereoselective, bidirectional approach to zwittermicin A

• Hubert Muchalski,
• Ki Bum Hong and
• Jeffrey N. Johnston

Beilstein J. Org. Chem. 2010, 6, 1206–1210, doi:10.3762/bjoc.6.138

• alkene functionalization such as aminohydroxylation [3] and dihydroxylation [4] reactions, or by methods that forge the carbon–carbon bond such as the glycolate Mannich reaction [5]. Recently, we developed a Brønsted acid-promoted azide–olefin reaction as an alternative to metal catalyzed

Tandem catalysis of ring-closing metathesis/atom transfer radical reactions with homobimetallic ruthenium–arene complexes

• Yannick Borguet,
• Xavier Sauvage,
• Guillermo Zaragoza,
• Albert Demonceau and
• Lionel Delaude

Beilstein J. Org. Chem. 2010, 6, 1167–1173, doi:10.3762/bjoc.6.133

• ][13][14], ATRP [15][16][17][18], cyclopropanation [19], dihydroxylation [20], hydrogenation [21][22][23], hydrovinylation [24], isomerization [25][26][27][28], oxidation [29], or Wittig reactions [30], to name just a few [31]. In this contribution, we investigate the tandem catalysis of RCM/ATRC

Addition of lithiated enol ethers to nitrones and subsequent Lewis acid induced cyclizations to enantiopure 3,6-dihydro-2H-pyrans – an approach to carbohydrate mimetics

• Fabian Pfrengle and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2010, 6, No. 75, doi:10.3762/bjoc.6.75

• dihydroxylation or bromination. Bicyclic enol ether 19 was oxidatively cleaved to provide the highly functionalized ten-membered ring lactone 20. The synthesized enantiopure aminopyrans 24, 26, 28 and 30 can be regarded as carbohydrate mimetics. Trimeric versions of 24 and 28 were constructed via their attachment

• and Scheme 6). Starting from cis-5a, acidic hydrolysis with concurrent loss of the TBS-group by treatment with saturated methanolic HCl followed by the addition of a saturated solution of NaHCO3 in water gave ketone 8 in good yield (Scheme 5 and Scheme 6). Dihydroxylation using the K2OsO4/N

• dihydroxylation reagent OsO4, from the sterically less hindered side, leading to incorporation of the bromo substituent trans to the hydroxymethyl and the bulky hydroxylamine moiety. The partial removal of the TBS-group is undoubtedly caused by HBr formed in the course of the reaction. When these reaction

Synthesis of a new class of aminocyclitol analogues with the conduramine D-2 configuration

• Latif Kelebekli,
• Yunus Kara and
• Murat Celik

Beilstein J. Org. Chem. 2010, 6, No. 15, doi:10.3762/bjoc.6.15

• theoretically form two complexes 15 and 16 after ionization. We assume that the formation of complex 15 is hindered due to the presence of an acetate group in the endo position. cis-Dihydroxylation of 13 with KMnO4 at −15 °C gave a single diol 17, which was converted into the tetraacetate by treatment with

Can we measure catalyst efficiency in asymmetric chemical reactions? A theoretical approach

• Shaimaa El-Fayyoumy,
• Matthew H. Todd and
• Christopher J. Richards

Beilstein J. Org. Chem. 2009, 5, No. 67, doi:10.3762/bjoc.5.67

• anecdotally refer to a “good“ or “bad“ reaction, there is no system for comparing those reactions with each other. Well-known examples of asymmetric catalysis such as the Sharpless asymmetric dihydroxylation, the Corey oxazaborolidine ketone reduction or the proline-catalysed aldol reaction are almost

Mitomycins syntheses: a recent update

• Jean-Christophe Andrez

Beilstein J. Org. Chem. 2009, 5, No. 33, doi:10.3762/bjoc.5.33

• . Functionalization of the olefin in compound 38 was accomplished first by dihydroxylation with osmium tetroxide. The reaction was stereospecific, resulting in formation of the diol 39 derived from attack of the reagent from the concave face of the molecule. Diol 39 was found to have the undesired stereochemistry for

• sequence using dihydroxylation with osmium tetroxide, mesylation and displacement with azide was used to produce leucoaziridinomitosane 45, whose spectral data matched those of an authentic sample derived from natural mitomycin C. 3.3. Williams. Mitsunobu reaction R.M. Williams successfully used this

• (Scheme 23). First, the phenol acetate was replaced by a benzyl group. Among the different oxidants screened for dihydroxylation, osmium tetroxide was preferred, since it did not effect aromatization of the indoline ring and gave diol 83 as a single isomer. Dihydroxylation occurred selectively from the

Recent progress on the total synthesis of acetogenins from Annonaceae

• Nianguang Li,
• Zhihao Shi,
• Yuping Tang,
• Jianwei Chen and
• Xiang Li

Beilstein J. Org. Chem. 2008, 4, No. 48, doi:10.3762/bjoc.4.48

• materials (e.g. amino acids, sugars, tartaric acid, etc.) or on asymmetric reactions {e.g. Sharpless asymmetric epoxidation (AE), Sharpless asymmetric dihydroxylation (AD), diastereoselective Williamson etherification, etc.}. Semi-synthesis of natural ACGs as well as derivatised ACGs (e.g. amines, esters

• ). Asymmetric dihydroxylation with AD-mix-β on 11 and subsequent acid-catalyzed cyclization with camphorsulfonic acid (CSA) resulted in THF ring-containing building block 12, which was converted into alkyne 13. The alkylation of iodide 14 with the sodium enolate of 15 afforded 16. Transformation of 16 following

• ). 130 was obtained by using the Sharpless epoxidation and dihydroxylation of 129. Compound 130 was then subjected to the Mitsunobu inversion to afford 131, which was transformed into 125. Then the THF moiety 125 and γ-lactone moiety 132 were coupled by a Sonogashira cross-coupling, and diimide reduction

End game strategies towards the total synthesis of vibsanin E, 3-hydroxyvibsanin E, furanovibsanin A, and 3-O-methylfuranovibsanin A

• Brett D. Schwartz,
• Craig M. Williams and
• Paul V. Bernhardt

Beilstein J. Org. Chem. 2008, 4, No. 34, doi:10.3762/bjoc.4.34

• ) by a Claisen rearrangment (via the silyl enol ether) was not high yielding and produced many side products. Ozonolysis of 25 afforded the acetone sidechain (i.e. 26) in acceptable yield (50%). Other methods to unmask the ketone functionality failed, for example, dihydroxylation followed by oxidative

Total synthesis of the indolizidine alkaloid tashiromine

• Stephen P. Marsden and
• Alison D. McElhinney

Beilstein J. Org. Chem. 2008, 4, No. 8, doi:10.1186/1860-5397-4-8

• the resulting carbonyl function and the amide. In the event, attempts to form a C5 aldehyde using either ozonolytic or dihydroxylation/periodate alkene cleavage protocols were unsuccessful, with complex mixtures being obtained in both cases. We suspected that the problem lay in the potential for the

An asymmetric synthesis of all stereoisomers of piclavines A1-4 using an iterative asymmetric dihydroxylation

• Yukako Saito,
• Naoki Okamoto and
• Hiroki Takahata

Beilstein J. Org. Chem. 2007, 3, No. 37, doi:10.1186/1860-5397-3-37

• dihydroxylation with enantiomeric enhancement. Background Indolizidine units are frequently found in many natural products and designed bioactive molecules. [1] Among these alkaloids, piclavines A1-4 (Figure 1), extracted from the tunicate Clavelina picta and the first indolizidine alkaloids to be found in the

• challenge. Our interest in this field has been focused on potential strategies based on the enantiomeric enhancement caused by the twofold or more application of the Sharpless asymmetric dihydroxylation (AD) [5][6] or Brown's asymmetric allylboration[7] reactions. In general, the enantiomeric excesses (ees

• all stereoisomers of piclavines A1-4 using an iterative asymmetric dihydroxylation. Experimental data which includes experimental details on the spectral instruments. Acknowledgements This work was supported in part by the High Technology Research Program from the Ministry of Education, Sciences

Single and double stereoselective fluorination of (E)-allylsilanes

• Marcin Sawicki,
• Angela Kwok,
• Matthew Tredwell and
• Véronique Gouverneur

Beilstein J. Org. Chem. 2007, 3, No. 34, doi:10.1186/1860-5397-3-34

• difluorinated alkene 7 (Scheme 4). The key steps necessary to perform this conversion were a dihydroxylation, the reduction of the ester group and the benzylation of the resulting primary alcohol. Preliminary work revealed that the order of steps was important and that protecting group manipulations were

• required for clean product outcome. The cis-dihydroxylation of 3 was performed employing NMO and catalytic OsO4 in DCM.[35] In the event, the diastereoselectivity was controlled by the two fluorine substituents. Four successful operations separated the newly formed unsymmetrical diol from 7, namely the

The oxanorbornene approach to 3-hydroxy, 3,4-dihydroxy and 3,4,5-trihydroxy derivatives of 2-aminocyclohexanecarboxylic acid

• Ishmael B. Masesane,
• Andrei S. Batsanov,
• Judith A. K. Howard,
• Raju Mondal and
• Patrick G. Steel

Beilstein J. Org. Chem. 2006, 2, No. 9, doi:10.1186/1860-5397-2-9

• . 3,4,5-Trihydroxy-2-aminocyclohexanecarboxylic acids The final group of targets we wished to generate was the trihydroxy analogs. Initial attempts addressed the generation of the syn 4,5 set. Consequently, OsO4 mediated dihydroxylation and subsequent peracylation of dienes 4 and 5 proved to be facio

• -specific and afforded cyclohexenyl derivatives 18 and 20 in 75 % yield over the two steps, Scheme 4. Reduction, as previously, afforded the trihydroxy β-aminoacid derivatives in excellent yields. At this stage it is instructive to address the interesting stereochemical outcome of this dihydroxylation

• reaction. Concurring with our results, Donohoe has reported that cyclic homoallylic carbamates give high levels of syn selectivity in the OsO4 mediated dihydroxylation reactions.[25][26] On the other hand, Kishi has established that the OsO4 mediated oxidation of cyclic allylic alcohols led preferentially

Synthesis and glycosidase inhibitory activity of new hexa- substituted C8-glycomimetics

• Olivia Andriuzzi,
• Christine Gravier-Pelletier,
• Gildas Bertho,
• Thierry Prangé and
• Yves Le Merrer

Beilstein J. Org. Chem. 2005, 1, No. 12, doi:10.1186/1860-5397-1-12

• enzymes. The synthesis of these new C8-glycomimetics is described from enantiomerically pure C2-symmetrical polyhydroxylated cyclooctenes. Their obtention notably involved a syn-dihydroxylation, and more extended functionalization through formation of a cis-cyclic sulfate followed by amination and

• cyclic double bond were explored to reach hexa-substituted C8-glycomimetics. Results and discussion From the C2-symmetrical L-ido- or D-manno- cyclooctene, 1 or 2, to obtain the C8 hexa-substitued carbasugars a straightfoward approach seemed to be a dihydroxylation, whereas to obtain the corresponding

• accomplished the synthesis of a range of new hexa-substituted C8-glycomimetics in enantiopure form. Transformation of the cyclic double bond involved syn-dihydroxylation, then introduction of an azido group by opening of a cyclic sulfate followed by reduction and eventual alkylation of the resulting amine

Methods for the synthesis of polyhydroxylated piperidines by diastereoselective dihydroxylation: Exploitation in the two-directional synthesis of aza-C-linked disaccharide derivatives

• Andrew Kennedy,
• Adam Nelson and
• Alexis Perry

Beilstein J. Org. Chem. 2005, 1, No. 2, doi:10.1186/1860-5397-1-2

• these enzymes. Results The scope, limitations and diastereoselectivity of the dihydroxylation of stereoisomeric 2-butyl-1-(toluene-4-sulfonyl)-1,2,3,6-tetrahydro-pyridin-3-ols is discussed. In the absence of a 6-substituent on the piperidine ring, the Upjohn (cat. OsO4, NMO, acetone-water) and Donohoe

• corresponding difuran. Selective substitution of its N,O acetal was possible. The stereochemical outcome of a two-directional Luche reduction step was different in the two heterocyclic rings, and depended on the conformation of the ring. Finally, two-directional diastereoselective dihydroxylation yielded seven

• paper, the final products are labelled according the configuration of the piperidine (A-D) and tetrahydropyran (d, d' or e) ring systems. Note that the ring systems d and d' are enantiomeric.) Results and discussion Synthesis of substrates for model dihydroxylation reactions Methods for the