Multigramme synthesis and asymmetric dihydroxylation of a 4-fluorobut-2E-enoate

• James A. B. Laurenson,
• John A. Parkinson,
• Jonathan M. Percy,
• Giuseppe Rinaudo and
• Ricard Roig

Beilstein J. Org. Chem. 2013, 9, 2660–2668, doi:10.3762/bjoc.9.301

• multigramme scale using a free radical procedure. A phase transfer catalysed fluorination transformed these species to the 4-fluorobut-2E-enoates reproducibly and at scale (48–53%, ca. 300 mmol). Asymmetric dihydroxylation reactions were then used to transform the butenoate, ultimately into all four

• d-chloroform/diisopropyl tartrate showed distinct baseline separated signals for different enantiomers. Keywords: asymmetric; dihydroxylation; ee determination; fluorination; fluorosugars; organo-fluorine; Introduction Selective fluorination can be used to make subtle but decisive modifications of

• and enantioselectivities [25]. Figure 2 shows the panel of ligands used for the asymmetric transformations. Scheme 5 shows the initial dihydroxylation carried out on 25, and Table 1 summarises the method development. The asymmetric dihydroxylation conditions were subject to some optimization; the

Garner’s aldehyde as a versatile intermediate in the synthesis of enantiopure natural products

• Mikko Passiniemi and
• Ari M.P. Koskinen

Beilstein J. Org. Chem. 2013, 9, 2641–2659, doi:10.3762/bjoc.9.300

• -selectivity (Table 1, entry 20). Olefination of Garner’s aldehyde Olefination of 1 provides an easy access to chiral 2-aminohomoallylic alcohols A (Scheme 24). The intermediate can be derivatized further, thus providing a route for greater molecular diversity. Diastereoselective dihydroxylation of A with OsO4

The total synthesis of D-chalcose and its C-3 epimer

• Jun Sun,
• Song Fan,
• Zhan Wang,
• Guoning Zhang,
• Kai Bao and
• Weige Zhang

Beilstein J. Org. Chem. 2013, 9, 2620–2624, doi:10.3762/bjoc.9.296

• C3 via Grignard reaction, the introduction of the stereogenic center on C2 by Sharpless asymmetric dihydroxylation, the protection of the C1 and C2 hydroxy groups with tert-butyldimethylsilyl trifluoromethanesulfonate (TBSOTf), and the selective cleavage of the primary OTBS ether using catalytic DL

• -10-camphorsulfonic acid (CSA) in MeOH. Keywords: asymmetric dihydroxylation; chalcose; epimer; total synthesis; Introduction Chalcose (4,6-dideoxy-3-O-methyl-D-xylo-hexose, I [1][2]) is a structural component of many macrolide antibiotics, such as chalcomycin [3], neutramycin [4], and lankamycin [5

• retrosynthetic analysis of I and I′ is presented in Scheme 1. Diol II and II′ arose from a Sharpless asymmetric dihydroxylation that form the C2 stereogenic center. The installation of the C3 stereocenter on vinyl ether III was proposed to utilize a Grignard reaction followed by chromatographic separation

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265

The chemistry of isoindole natural products

• Klaus Speck and
• Thomas Magauer

Beilstein J. Org. Chem. 2013, 9, 2048–2078, doi:10.3762/bjoc.9.243

• , dihydroxylation and a final deprotection step. Macrocyclic polyketides: The first cytochalasan alkaloids, cytochalasin A (51) and B (52), originally named phomins [39], were isolated in 1966 [39][40][41][42]. Since then, the number of natural products belonging to this family has increased to over 80. Some

A concise enantioselective synthesis of the guaiane sesquiterpene (−)-oxyphyllol

• Martin Zahel and
• Peter Metz

Beilstein J. Org. Chem. 2013, 9, 2028–2032, doi:10.3762/bjoc.9.239

• shown in Scheme 2, we first planned to use the known diol 7, which is available by diastereoselective dihydroxylation of 4 [6]. Since a chemoselective deoxygenation of the secondary alcohol of 7 would give rise to the desired intermediate 3, we investigated a radical defunctionalization strategy [8]. To

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