Coupled chemo(enzymatic) reactions in continuous flow

• Ruslan Yuryev,
• Simon Strompen and
• Andreas Liese

Beilstein J. Org. Chem. 2011, 7, 1449–1467, doi:10.3762/bjoc.7.169

• at 56% of overall conversion was achieved. In the continuous sequential synthesis of vic-diols in a multicatalyst system described by Liese [2], the incompatible reaction steps were successfully separated in a cascade of two enzyme membrane reactors as well. The first reactor contained benzoyl

Development of the titanium–TADDOLate-catalyzed asymmetric fluorination of β-ketoesters

• Lukas Hintermann,
• Mauro Perseghini and
• Antonio Togni

Beilstein J. Org. Chem. 2011, 7, 1421–1435, doi:10.3762/bjoc.7.166

• prepared in situ from Me2AlCl and several chiral diols, were not catalytically active. However, the well-established Lewis acid [(R,R-TADDOLato)TiCl2] [82] (Scheme 1) displayed good catalytic activity (5 mol %, 1→1-F in 4 h) and gave (S)-1-F with an enantiomeric excess of 28% (for a complex incorporating

• 6), the reagents induced similar enantioselectivity. Ligand variations in the asymmetric titanium-catalyzed fluorination reaction We tested several chiral diols in the titanium-catalyzed asymmetric fluorination, but notable success was only achieved with TADDOL ligands [91]. We obtained several

Efficient and selective chemical transformations under flow conditions: The combination of supported catalysts and supercritical fluids

• M. Isabel Burguete,
• Eduardo García-Verdugo and
• Santiago V. Luis

Beilstein J. Org. Chem. 2011, 7, 1347–1359, doi:10.3762/bjoc.7.159

• processes. Furthermore, the catalyst lifetime can, in many cases, be dramatically improved under supercritical conditions, owing to reduced coking [69][70]. The selective monoprotection of 1,n-terminal diols is a characteristic example of how mono-substituted ethers can be selectively prepared versus the

• bis-substituted ones [71]. The use of an acid catalyst (Amberlyst 15) allows the formation of the corresponding mono-ethers by reaction of 1,6-hexanediol and other diols with simple alcohols under flow conditions (scCO2, 150 °C, 20 MPa, 1.15 mL·min−1). One of the most interesting results found was the

Carbamate-directed benzylic lithiation for the diastereo- and enantioselective synthesis of diaryl ether atropisomers

• Abigail Page and
• Jonathan Clayden

Beilstein J. Org. Chem. 2011, 7, 1327–1333, doi:10.3762/bjoc.7.156

• ), two diols 8 and 9, available from previous work, were converted to the biscarbamates 10 and 11. The metallation of O-benzylcarbamates has been studied extensively by Hoppe [1][24][25][26], and the deprotonation of 10 was achieved with sec-BuLi in ether and the addition of acetone, returning 12 as a

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

• groups. The optimization and scope of this reaction are discussed, and the utility of this process is demonstrated in the one-pot preparation of a number of chiral diols as well as a short synthesis of the chiral ligand Vivol. Keywords: chiral diol; directed ortho-metalation; hydrobenzoin; Introduction

• The discovery of new chiral ligands and auxiliaries continues to expand the frontiers of catalytic asymmetric synthesis. In particular, C2-symmetric diols, such as (S)-BINOL (1) [1] and (−)-TADDOL (2) [2] (Figure 1), have garnered considerable attention owing to the wide variety of asymmetric

• . Importantly, a wide variety of chiral diols (e.g., Vivol (4)) are now readily accessible in optically pure form following this one-pot reaction. Although the range of electrophiles that engage in synthetically useful reactions with the tetralithio intermediate 8 is limited, the diiodohydrobenzoin 12 and bis

Lithium phosphonate umpolung catalysts: Do fluoro substituents increase the catalytic activity?

• Anca Gliga,
• Bernd Goldfuss and
• Jörg M. Neudörfl

Beilstein J. Org. Chem. 2011, 7, 1189–1197, doi:10.3762/bjoc.7.138

• analyze the effect of fluoro substituents on the catalytic activity by using different fluorinated and nonfluorinated phosphonates as precatalysts in the benzoin coupling. Results and Discussion As precursors for six, seven and nine membered ring phosphonates, diols 1–4, and 6–8 were synthesized (Scheme 3

• nine ring phosphonates. The synthesis of these diols was realized by a double ortho lithiation of biphenyl and subsequent addition to the corresponding carbonyl compound. By this procedure, two asymmetric carbon centres and a chiral axis, which is fixed by intramolecular hydrogen bonds (6

• ) [31][32]. The energy differences of the terpene-based conformers are between 5.1 and 5.8 kcal/mol [32][33] (B3LYP/6-31++G**:AM1). The conversion of diols 1–5, 7, and 8 to the desired phosphonates can be achieved by twofold addition to phosphorus trichloride and subsequent hydrolysis. Diol 6 could not

Functionalization of anthracene: A selective route to brominated 1,4-anthraquinones

• Kiymet Berkil Akar,
• Osman Cakmak,
• Orhan Büyükgüngör and
• Ertan Sahin

Beilstein J. Org. Chem. 2011, 7, 1036–1045, doi:10.3762/bjoc.7.118

• towards the base for the hydroxy and the methoxy compounds. For example, the methoxy compounds aromatize to give 10 and 11, but the diols convert either to the epoxides by cyclization (Scheme 1 and Scheme 5) or to the alkene by elimination of 1 mol HBr (Scheme 6). In addition, however, the base-induced

Recent advances in the gold-catalyzed additions to C–C multiple bonds

• He Huang,
• Yu Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2011, 7, 897–936, doi:10.3762/bjoc.7.103

• from suitably substituted (Z)-2-en-4-yn-1-ols 5 [20]. A similar strategy has been applied to an efficient formation of substituted furans 9 through gold-catalyzed selective cyclization of enyne-1,6-diols 8 [21]. Nucleophilic attack of the hydroxy oxygen atom on 1-position to a gold-coordinated C–C

• available heteroatom-substituted propargyl alcohols 10 has been developed by Aponick and co-workers [22]. For the formation of tetrahydropyran analogs 13 and 15, the gold(I)-catalyzed cyclization of monoallylic diols 12 and 14 is an efficient method (Scheme 2) [23][24]. In addition to common organic

A comparative study of the Au-catalyzed cyclization of hydroxy-substituted allylic alcohols and ethers

• Berenger Biannic,
• Thomas Ghebreghiorgis and
• Aaron Aponick

Beilstein J. Org. Chem. 2011, 7, 802–807, doi:10.3762/bjoc.7.91

• able to make comparisons between how well different substrates function in the reaction. Previous papers detail the results with diols and include a variety of substrates with yields and reaction times [23][24][25]. While the isolated yield is the ultimate measure of how well the system has performed

• to vary the nature of the allylic leaving group and olefin geometry. These conditions are slightly different to those employed in the study of diols [23][24][25], differing in catalyst identity and loading (1 mol % (Ph3P)AuCl/AgOTf versus 5 mol % Au[P(t-Bu)2(o-biphenyl)]SbF6). As mentioned above, the

• reaction shown in black, which proceeded to 96% conversion, while the reactions quenched at 1, 3, and 5 minutes went to 23%, 41%, and 52% conversion, respectively. Subsequently, a comparison between cis- and trans-diols 10 and 7 was made. As can be seen in Figure 3, both reactions were fairly rapid, with

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

• in a rather selective manner, a similar route to deoxymannojirimycin (63) and 1-deoxyallonojirimycin (66) did not achieve the same degree of selectivity, presumably due to difficulties in transforming the endocyclic double bond of the RCM product 72 into the targeted trans diols. Clean epoxide

• modified Upjohn conditions, Scheme 22). For iminocyclitols containing trans diols at the 3- and 4-positions an epoxy functionality at the double bond in 125 was introduced. While the syn epoxide 128 led to a mixture of fagomine (129) and 3,4-di-epi-fagomine (130), the anti epoxide 127 gave 129 selectively

Synthesis, reactivity and biological activity of 5-alkoxymethyluracil analogues

• Lucie Brulikova and
• Jan Hlavac

Beilstein J. Org. Chem. 2011, 7, 678–698, doi:10.3762/bjoc.7.80

• styrene to afford nucleoside 147. The oxidation of alkene function in 147 with OsO4 led to a mixture of diastereomers of vicinal diols 148. For the introduction of the oligodeoxynucleotide 146, the dihydroxynucleoside 147 was converted to the corresponding phosphoramidite. This was carried out as follows

A gold-catalyzed alkyne-diol cycloisomerization for the synthesis of oxygenated 5,5-spiroketals

• Sami F. Tlais and
• Gregory B. Dudley

Beilstein J. Org. Chem. 2011, 7, 570–577, doi:10.3762/bjoc.7.66

• 5,5-spiroketals, including cyclocondensation of ketone diols [6][7], the cycloisomerization of alkyne diols (Scheme 1) [8][9][10][11][12][13][14][15][16], oxidative spirocyclization of tetrahydrofuryl propanols [17][18][19][20], and others. Cyclocondensation of ketone diols is perhaps the most

• straighforward and the most used method, but the alternative procedures offer specific advantages. For example, the cycloisomerization of alkyne diols is more exothermic (Scheme 1) [21] and atom economical [22], and non-polar alkyne π-bonds are more compatible than ketones (kinetically stable) towards a number

• cyclocondensation of alkyne diols to give substituted furans (Scheme 3, Reaction 3) [35]. Our objective, laid out in Scheme 4, was to initiate cycloisomerization with a 5-endo-dig cyclization of the homopropargyl alcohol 6, followed by 5-exo-trig cyclization onto the resulting dihydrofuran, whilst avoiding

The preparation of 3-substituted-1,5-dibromopentanes as precursors to heteracyclohexanes

• Bryan Ringstrand,
• Martin Oltmanns,
• Jeffrey A. Batt,
• Aleksandra Jankowiak,
• Richard P. Denicola and
• Piotr Kaszynski

Beilstein J. Org. Chem. 2011, 7, 386–393, doi:10.3762/bjoc.7.49

• ], while the latter from p-toluenesulfonyl chloride in the presence of a base such as pyridine [13][17][18][19][20]. Dibromides I can also be obtained by the ring-opening of tetrahydropyrans VIII under the same conditions employed for the diols VII [2][12][21][22], or via phase-transfer catalysis

• are listed in Table 1. For completeness, thianes IV, diols VII, and tetrahydropyrans VIII are also included. Diols VII represent a convenient intermediate for the preparation of dibromides I or ditosylates II, and four routes to VII are presented in Scheme 1. The first route (Method 1A) involves six

• steps starting from alkylation of malonate diester followed by reduction of the esters, tosylation of the alcohols, carbon homologation with NaCN, hydrolysis of the cyano groups to carboxylic acids, and lastly a second reduction to VII. Overall yields of diols VII using Method 1A are around 10% [27][28

Palladium-catalyzed formation of oxazolidinones from biscarbamates: a mechanistic study

• Benan Kilbas and
• Metin Balci

Beilstein J. Org. Chem. 2011, 7, 246–253, doi:10.3762/bjoc.7.33

• palladium-catalyzed reaction. To test the proposed mechanism of this reaction, first, bicyclonorcarene endoperoxides derived from cyano and carbomethoxy cycloheptatrienes were synthesized and converted into the corresponding diols. The reaction of diols with toluenesulfonyl isocyanate followed by a

• than the trans-coupling [23][24], we assigned the exo-configuration to the cyano group in 12. Selective reduction of the peroxide linkages in 12 and 13 with thiourea under very mild conditions afforded the diols 14 and 18a, respectively. For further characterization, the diols were converted to the

• diacetates 15 and 18b. The isomeric diols 14 and 18a were treated with 2 equiv of toluenesulfonyl isocyanate as described above to give the corresponding biscarbamates 16 and 19. Treatment of 16 and 19 with the palladium catalyst (as described above) resulted in the formation of oxazolidinone derivatives 17

Miniemulsion polymerization as a versatile tool for the synthesis of functionalized polymers

• Daniel Crespy and
• Katharina Landfester

Beilstein J. Org. Chem. 2010, 6, 1132–1148, doi:10.3762/bjoc.6.130

• is the formation of polyurethanes. Originally, there was considerable interest in producing water-borne polyurethane dispersions to replace the solvent-borne formulations and therefore much effort was expended in investigating the synthesis of polyurethane in aqueous miniemulsions. Hydrophobic diols

• miniemulsion. For example, castor oil (a triol) has been used as the monomer [102]. Li et al. showed that short diols can be also replaced efficiently by poly(tetramethylene glycol) [103]. The polyaddition reaction to form urethane bonds was also carried out with a cyclodextrin derivative and IPDI as the

• parameters were found to play a role in increasing the yield. The yield was higher if a) more hydrophobic monomers and b) diols with electron-donating groups were polymerized. The polycondensation of a diamine and sebacoyl chloride was carried out in direct miniemulsions in the presence of silica

β-Hydroxy carbocation intermediates in solvolyses of di- and tetra-hydronaphthalene substrates

• Jaya S. Kudavalli and
• Rory A. More O'Ferrall

Beilstein J. Org. Chem. 2010, 6, 1035–1042, doi:10.3762/bjoc.6.118

• ratio of cis to trans diols from cis and trans reactants together with a small amount of 2-tetralone. The product distribution for the trans isomer is shown in Scheme 3. The corresponding figures for the cis isomer are 76% cis and 20% trans dihydrodiols plus 4% 2-tetralone. The similarity of the product

Redox-active tetrathiafulvalene and dithiolene compounds derived from allylic 1,4-diol rearrangement products of disubstituted 1,3-dithiole derivatives

• Filipe Vilela,
• Peter J. Skabara,
• Christopher R. Mason,
• Thomas D. J. Westgate,
• Asun Luquin,
• Simon J. Coles and
• Michael B. Hursthouse

Beilstein J. Org. Chem. 2010, 6, 1002–1014, doi:10.3762/bjoc.6.113

• carboxaldehydes affords the corresponding bisalcohol products 2 in good yield (75–90%). Under ambient conditions, these diols decompose slowly. However, on treatment with a few drops of perchloric acid to solutions of 2 in dichloromethane (CH2Cl2), the rate of decomposition of the starting materials greatly

• increases and in all cases the diol is consumed within 24 h. Dihydrofurans, such as 5 (87% yield), were isolated from the corresponding diols as mixtures of stereoisomers, whereas the 4-methoxyphenyl substituted diol gave the rearrangement product 6 in 44% yield. The rearrangement products from 2 were all

• –carbon or carbon–hydrogen bonds followed by formation of new ones via alkyl, hydride and allylic shifts. However, one cannot assume that the mechanism is pinacol-like. Saturated 1,4-diols favour the formation of tetrahydrofuran derivatives, whilst allylic cations will involve some degree of stabilisation

Novel 2-(ω-phosphonooxy-2-oxaalkyl)acrylate monomers for self-etching self-priming one part adhesive

• Joachim E. Klee and
• Uwe Lehmann

Beilstein J. Org. Chem. 2010, 6, 766–772, doi:10.3762/bjoc.6.95

• acrylate and formaldehyde, and subsequent etherification of the obtained product with diols and phosphorylation using POCl3. The polymerization enthalpy of 2-(ω-phosphonooxy-2-oxaalkyl)acrylates 3 as measured by DSC ranges from −29 to −53 kJ·mol−1. The shear bond strength of adhesive compositions 4

• , comprising of phosphoric acid ester moieties, were synthesized via a three step synthesis via Baylis–Hillman reaction of ethyl acrylate and formaldehyde, and subsequent etherification of the obtained product with diols and phosphorylation using POCl3 (Scheme 1, Table 1). The double bonds in 3 are evident in

• -phosphonooxy-2-oxaalkyl)acrylate monomers 3 with phosphoric acid moieties and alkyl as well as oxyalkyl spacers were synthesized in three steps via Baylis–Hillman reaction of ethyl acrylate and formaldehyde, and subsequent etherification of the obtained product with diols and phosphorylation using POCl3. The

Systematic investigations on the reduction of 4-aryl-4-oxoesters to 1-aryl-1,4-butanediols with methanolic sodium borohydride

• Subrata Kumar Chaudhuri,
• Manabendra Saha,
• Amit Saha and
• Sanjay Bhar

Beilstein J. Org. Chem. 2010, 6, 748–755, doi:10.3762/bjoc.6.94

• the keto moiety. Results of a detailed and systematic investigation of the reaction are described. Keywords: diols; esters; lactones; reduction; Introduction Chemoselective reductions of aldehydes, ketones and imines are generally accomplished using NaBH4 in methanol where other reducible functional

• implies 30 °C throughout) both the oxo- and the alkoxycarbonyl moieties were reduced to give the diols (2a–2f), as shown in Scheme 1. γ-Aryl-α,β-unsaturated-γ-ketoesters (1g and 1h), on similar treatment, furnished the saturated diols (2a and 2b) by the reduction of both the keto and the ester groups

• -oxoester to 1,4-diols was finally established (Scheme 11) when substrate 14 [40] (incapable of lactonization due to distal spatial disposition of the oxo- and methoxycarbonyl moieties imposed by the rigidity of the cyclopropane ring system) underwent selective reduction of the oxo-functionality only under

Functionalized copolyimide membranes for the separation of gaseous and liquid mixtures

• Nadine Schmeling,
• Roman Konietzny,
• Daniel Sieffert,
• Patrick Rölling and
• Claudia Staudt

Beilstein J. Org. Chem. 2010, 6, 789–800, doi:10.3762/bjoc.6.86

• groups reduces the CO2 plasticization slightly due to the hydrogen bonds between the carboxylic acid groups [23]. Copolyimides with carboxy groups can be further modified via covalent cross-linking with, e.g., diols or diamines or cross-linked ionically with aluminium acetylacetonate or zirconium

Synthesis of 6-PEtN-α-D-GalpNAc-(1–>6)-β-D-Galp-(1–>4)-β-D-GlcpNAc-(1–>3)-β-D-Galp-(1–>4)-β-D-Glcp, a Haemophilus influenzae lipopolysacharide structure, and biotin and protein conjugates thereof

• Andreas Sundgren,
• Martina Lahmann and
• Stefan Oscarson

Beilstein J. Org. Chem. 2010, 6, 704–708, doi:10.3762/bjoc.6.80

• thioglycoside 4 [14] yielded the 6-O-silylated compound 5 (92%), benzylation of which gave donor 6 (85%). A benzyl group in the 4-position was preferred to an ester group to avoid the risk of acyl migration during subsequent reactions; desilylation, glycosidation and phosphorylation. 3II,4II-Diols of lactose

Synthesis and crystallographic analysis of meso-2,3-difluoro-1,4-butanediol and meso-1,4-dibenzyloxy-2,3-difluorobutane

• Bruno Linclau,
• Leo Leung,
• Jean Nonnenmacher and
• Graham Tizzard

Beilstein J. Org. Chem. 2010, 6, No. 62, doi:10.3762/bjoc.6.62

• hypervalent iodine species [21]. Such approaches often display poor stereoselectivity or result in rearrangement products. Treatment of 1,2-diols with SF4 [22][23], DAST [24], or deoxofluor [25] also leads to vicinal difluorides. Reaction with vicinal triflates has also been successful in some cases [7][26

Preparation of pyridine-3,4-diols, their crystal packing and their use as precursors for palladium-catalyzed cross-coupling reactions

• Tilman Lechel,
• Irene Brüdgam and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2010, 6, No. 42, doi:10.3762/bjoc.6.42

• derivatives in good yields. The X-ray crystal structure analysis proved that a 1:1 mixture of pyridine-3,4-diols and their pyridin-4-one tautomers exist in the solid state. Subsequent conversion into bis(perfluoroalkanesulfonate)s were smoothly achieved. The obtained compounds were used as substrates for

• palladium-catalyzed coupling reactions. Fluorescence measurements of the biscoupled products showed a maximum of emission in the violet region of the spectrum. Keywords: bisnonaflates; fluorescence; palladium catalysis; pyridine-3,4-diols; pyridines; Introduction Pyridine scaffolds have been found in

• numerous naturally occurring compounds and are also frequently used in functional materials [1][2][3][4]. Pyridindiol derivatives are of particular interest as building blocks for the construction of dendritic nanostructures in supramolecular chemistry [5], whereas N-protected pyridine-3,4-diols find

Molecular recognition of organic ammonium ions in solution using synthetic receptors

• Andreas Späth and
• Burkhard König

Beilstein J. Org. Chem. 2010, 6, No. 32, doi:10.3762/bjoc.6.32

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

• diols in the presence of p-toluenesulfonyl isocyanate for the introduction of the amino alcohol functionality. We are currently interested in the synthesis of cyclitols and their derivatives [25]. As a part of our program directed towards the synthesis of potential glycosidase inhibitors we used a