Synthesis of the B-seco limonoid core scaffold

• Hanna Bruss,
• Hannah Schuster,
• Rémi Martinez,
• Markus Kaiser,
• Andrey P. Antonchick and
• Herbert Waldmann

Beilstein J. Org. Chem. 2014, 10, 194–208, doi:10.3762/bjoc.10.15

• ], which can be explained by the strong conformational rigidity of the butane-2,3-diacetal (BDA) protected trans-diequatorial diols [43] and the stereoelectronic preference for axial attack on the electron-rich C13. Luche reduction with stereoelectronically preferred axial attack of the hydride gave

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

• sulfonamide which can accelerate hydrolysis and catalytic turnover was also added to the reaction mixtures [26]. Yields for the dihydroxylation chemistry were variable (44–80%); even though they are diols, these small molecules proved volatile. Reproducible yields (>55%) could be achieved if care was taken

• % respectively. The ee's were measured after conversion of the diols to the dibenzoates 29 upon stirring overnight with benzoic anhydride, DMAP and polyvinylpyridine (PVP) at room temperature. The removal of the base by filtration was facile (Scheme 6). Genuine racemate 28c was synthesised via the Upjohn

• the fluorinated diols 28a and 28b could not be achieved by the HPLC method. The very low absorbance of light at 235 nm resulted in unreliable data; small peak areas were observed for the desired compound with comparatively large peak areas for the background and trace impurities (as judged by 1H and

Flexible synthesis of anthracycline aglycone mimics via domino carbopalladation reactions

• Markus Leibeling and
• Daniel B. Werz

Beilstein J. Org. Chem. 2013, 9, 2194–2201, doi:10.3762/bjoc.9.258

• trimethylsilyl moiety. Another approach of selective silyl ether cleavage was employed by utilization of Cs2CO3 (5.0 equiv) in methanol at 100 °C. Hydrolysis of the respective domino products 13a and 13f with in situ formed HCl in methanol furnished the diols 26a and 26b under loss of the terminal TMS group [46

A reductive coupling strategy towards ripostatin A

• Kristin D. Schleicher and
• Timothy F. Jamison

Beilstein J. Org. Chem. 2013, 9, 1533–1550, doi:10.3762/bjoc.9.175

• carry out the reaction with diisopropylamine as a substitute for the thiourea catalyst. This modification afforded both the syn and anti diols in roughly a 1:1 ratio and a combined yield of 40–45%, albeit without recovery of starting material. The syn and anti diastereomers could be separated by

Development of an additive-controlled, SmI₂-mediated stereoselective sequence: Telescoped spirocyclisation, lactone reduction and Peterson elimination

• Brice Sautier,
• Karl D. Collins and
• David J. Procter

Beilstein J. Org. Chem. 2013, 9, 1443–1447, doi:10.3762/bjoc.9.163

• . Following a screen of reaction conditions, moderate but consistent yields were obtained when eliminations were performed in an open vessel, using undried solvents. When combined with the spirocyclisation and lactone reduction sequence, the Peterson elimination gave diols 5, with good overall yields

Thiourea-catalyzed Diels–Alder reaction of a naphthoquinone monoketal dienophile

• Carsten S. Kramer and
• Stefan Bräse

Beilstein J. Org. Chem. 2013, 9, 1414–1418, doi:10.3762/bjoc.9.158

• carbenes, guanidines, thioureas, amidinium ions, diols, and Brønsted acids showed their value to give densely functionalized Diels–Alder products in high selectivities [1][2][3][4][5][6][7]. In addition, some organocatalysts enabled even the formation of quaternary centers in Diels–Alder cycloadditions [3

Copper-catalyzed aerobic aliphatic C–H oxygenation with hydroperoxides

• Pei Chui Too,
• Ya Lin Tnay and
• Shunsuke Chiba

Beilstein J. Org. Chem. 2013, 9, 1217–1225, doi:10.3762/bjoc.9.138

• aerobic oxygenation of aliphatic C–H bonds with hydroperoxides, which proceeds by 1,5-H radical shift of putative oxygen-centered radicals (O-radicals) derived from hydroperoxides followed by trapping of the resulting carbon-centered radicals with molecular oxygen. Keywords: copper; 1,4-diols; free

• could be trapped by O2 to form the new C–O bonds. Herein, we report the realization of this concept mainly for the aerobic synthesis of 1,4-diols from hydroperoxides, which could be catalyzed by the Cu(OAc)2-1,10-phenanthroline system in the presence of Et3N as a terminal reductant of the Cu(II) species

• present aerobic strategy for the synthesis of 1,4-diols by targeting methylene C–H oxygenation with various tertiary hydroperoxides 1 (Table 2). Generally, oxygenation of benzylic methylene C–H bonds proceeded smoothly to give the corresponding 1,4-diols 3 in good to moderate yields (77–51% yields) (Table

1-n-Butyl-3-methylimidazolium-2-carboxylate: a versatile precatalyst for the ring-opening polymerization of ε-caprolactone and rac-lactide under solvent-free conditions

• Astrid Hoppe,
• Faten Sadaka,
• Claire-Hélène Brachais,
• Gilles Boni,
• Jean-Pierre Couvercelle and
• Laurent Plasseraud

Beilstein J. Org. Chem. 2013, 9, 647–654, doi:10.3762/bjoc.9.73

• concept was extended to the synthesis of aliphatic polycarbonates, involving the transesterification of DMC with linear alkane diols under solvent-free conditions, and based on a two-step polymerization process [50]. The high reactivity of imidazolium-2-carboxylates can be explained by their facile

A new intermediate in the Prins reaction

• Shinichi Yamabe,
• Takeshi Fukuda and
• Shoko Yamazaki

Beilstein J. Org. Chem. 2013, 9, 476–485, doi:10.3762/bjoc.9.51

• reactions were investigated by the use of DFT calculations. A model composed of R–CH=CH2 + H3O+(H2O)13 + (H2C=O)2, R = Me and Ph, was adopted to trace reaction paths. For both alkenes, the concerted path forming 1,3-diols was obtained as the rate determining step (TS1). TS stands for a transition state

Polar reactions of acyclic conjugated bisallenes

• Reiner Stamm and
• Henning Hopf

Beilstein J. Org. Chem. 2013, 9, 36–48, doi:10.3762/bjoc.9.5

• atom absorbs as a singlet at δ 71.5 ppm. All other spectroscopic data (see Supporting Information File 1) also agree with the structure proposal. The other two alcohols, 24 and 25, both of them diols, are obviously bisalkylation products and involve the generation of anionic intermediates with a

The chemistry of bisallenes

• Henning Hopf and
• Georgios Markopoulos

Beilstein J. Org. Chem. 2012, 8, 1936–1998, doi:10.3762/bjoc.8.225

• coming close to a general route to introduce functionality into bisallenes at the present time seems to be the double SN2'-reaction of 2,4-hexadiyne-1,6-diol (63, e.g. R1 to R4 = aryl) and its derivatives with various nucleophiles (Scheme 13) [49][50]. Thus, heating the diols 63 with an aromatic or

• heteroaromatic thiol 64 provides the sulfur-substituted bisallene derivative 65 in good yields. Likewise, the stable diallenes 66 carrying phosphorus-containing substituents were obtained by heating the diols 63 with R52PCl [51][52][53][54]. How critically the substituents in the 3- and 4-position determine the

• at room temperature failed because they easily isomerized to the dienynes 69. The derivatives 71 can also be obtained from the isomeric diols 70 under comparable conditions, as shown by Braverman and co-workers. However, in only one case could these bisallene derivatives actually be isolated; all

Asymmetric desymmetrization of meso-diols by C₂-symmetric chiral 4-pyrrolidinopyridines

• Hartmut Schedel,
• Keizo Kan,
• Yoshihiro Ueda,
• Kenji Mishiro,
• Keisuke Yoshida,
• Takumi Furuta and
• Takeo Kawabata

Beilstein J. Org. Chem. 2012, 8, 1778–1787, doi:10.3762/bjoc.8.203

• pyrrolidinopyridine framework as a catalytic site. Some of these organocatalysts effectively promoted asymmetric desymmetrization of meso-diols via enantioselective acylation. Keywords: acylation; desymmetrization; hydrogen bond; meso-diol; nucleophilic catalyst; organocatalysis; Introduction Since the pioneering

• racemic diols (s: up to 12) [8] and amino alcohol derivatives (s: up to 54) [9]. Catalyst 2, readily prepared from L-proline, could be employed for the kinetic resolution of amino alcohol derivatives (s: up to 11) [10]. Chiral PPY catalysts with dual functional side chains at C(2) and C(4) of the

• pyrrolidine ring such as 3 were prepared from trans-4-hydroxy-L-proline. These catalysts were found to be moderately effective for the asymmetric desymmetrization of meso-diols [11]. C2-Symmetric PPY-catalyst 4 was found to be effective for the chemo- and regioselective acylation of carbohydrates [12][14][16

Synthesis of 5-oxyquinoline derivatives for reversal of multidrug resistance

• Torsten Dittrich,
• Nils Hanekop,
• Nacera Infed,
• Lutz Schmitt and
• Manfred Braun

Beilstein J. Org. Chem. 2012, 8, 1700–1704, doi:10.3762/bjoc.8.193

• purification in the coupling reaction with epoxide (R)-16. The spirocyclic compounds 6c–13c were obtained by standard acid-catalyzed reaction with the corresponding diols for the formation of acetals 6c–12c and propanedithiol for 13c, starting from N-acetyl-4-piperidone. Basic hydrolysis was found to be

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

• alkyne 5 with (S)-1,2 epoxynonane. Gold-catalyzed cycloisomerization (with desilylation) provided spiroketal diols 10a and 10b in a 32:68 ratio and in 89% total yield. Major spiroketal 10b could be converted to 10a in 15:1 dr by zinc-catalyzed isomerization. Both isomers (10a and 10b) were independently

• -spiroketals 21a and 21b was obtained in 71% overall yield from 20. The mixture of diols 21a and 21b converged to 21a (epimer 21b no longer observable by 1H NMR) upon treatment with zinc chloride. TEMPO oxidation of diol 21a led to the formation of cephalosporolide E (2, admixed with a minor diastereomer

Synthesis of functionalized macrocyclic derivatives of trioxabicyclo[3.3.0]nonadiene

• Sabine Leber,
• Gert Kollenz and
• Curt Wentrup

Beilstein J. Org. Chem. 2012, 8, 738–743, doi:10.3762/bjoc.8.83

• and Discussion Functional group manipulation on aromatic rings often starts with the nitro group. Therefore, a synthesis of suitable nitro-aromatic diols for combination with the diacid dichloride 3 was required. The desired 2-nitro-1,4-phenylene derivative 7 was prepared by treatment of hydroquinone

• with 3-bromopropanol followed by nitration of the resulting diol 6 (Scheme 2). The isomeric 1,2,3-trisubstituted aromatic 10 was obtained by etherification of nitroresorcinol (Scheme 3). The two diols 7 and 10 reacted readily with the diacid dichloride 3 in boiling toluene in the presence of

Aryl nitrile oxide cycloaddition reactions in the presence of pinacol boronic acid ester

• Sarah L. Harding,
• Sebastian M. Marcuccio and
• G. Paul Savage

Beilstein J. Org. Chem. 2012, 8, 606–612, doi:10.3762/bjoc.8.67

• alkenes [15], alkynes [16][17], and benzyne [18][19], to give Δ2-isoxazolines and isoxazoles. These are interesting sources of bioactive compounds in their own right, but isoxazoles are particularly valuable for their latent functionality as β-hydroxyketones, β-aminoalcohols, 1,3-diols, and a range of

Synthesis and mesomorphic properties of calamitic malonates and cyanoacetates tethered to 4-cyanobiphenyls

• Katharina C. Kress,
• Martin Kaller,
• Kirill V. Axenov,
• Stefan Tussetschläger and
• Sabine Laschat

Beilstein J. Org. Chem. 2012, 8, 371–378, doi:10.3762/bjoc.8.40

• . Starting from the corresponding diols 6a,b, 6-bromohexan-1-ol (7a) and 10-bromodecan-1-ol (7b) were obtained in moderate yields by bromination with aqueous HBr in toluene [35]. The bromides 7a,b were reacted with 4-cyano-1,1'-biphenol (8) in acetone in the presence of K2CO3 giving compounds 9a,b, bearing

Synthesis of 2-amino-3-arylpropan-1-ols and 1-(2,3-diaminopropyl)-1,2,3-triazoles and evaluation of their antimalarial activity

• Matthias D’hooghe,
• Stéphanie Vandekerckhove,
• Karen Mollet,
• Karel Vervisch,
• Stijn Dekeukeleire,
• Liesbeth Lehoucq,
• Carmen Lategan,
• Peter J. Smith,
• Kelly Chibale and
• Norbert De Kimpe

Beilstein J. Org. Chem. 2011, 7, 1745–1752, doi:10.3762/bjoc.7.205

• variety of 2-amino-3-arylpropan-1-ols, anti-2-amino-3-aryl-3-methoxypropan-1-ols and anti-2-amino-1-arylpropan-1,3-diols were prepared selectively through elaboration of trans-4-aryl-3-chloro-β-lactams. In addition, a number of 2-(azidomethyl)aziridines was converted into novel 2-[(1,2,3-triazol-1-yl

• ). Furthermore, in order to provide access to the class of 2-aminopropan-1,3-diols, aziridines 7 were evaluated for the first time as substrates for a water-induced aziridine ring opening in an acidic medium. Thus, treatment of trans-2-aryl-3-(hydroxymethyl)aziridines 7 with one equiv of para-toluenesulfonic

• acid in a H2O/THF (1/1) solvent system [32] furnished novel anti-2-amino-1-arylpropan-1,3-diols 9a–d in good yields after 3 h at 40 °C, again in a regio- and stereospecific way (Scheme 1). The observed regio- and stereoselectivity in aminopropanols 8 and 9 can be rationalized by considering the ring

Planar-bilayer activities of linear oligoester bolaamphiphiles

• Jonathan K. W. Chui,
• Thomas M. Fyles and
• Horace Luong

Beilstein J. Org. Chem. 2011, 7, 1562–1569, doi:10.3762/bjoc.7.184

• -bromoalcohols prepared by mono-brominating the corresponding diols as described [16]. This gave the bis-bromides, which were subsequently displaced by the protected carboxylate anion of BOC-protected aniline 14 to give precursors 15, 16 and 17. Deprotection of the carbamate protecting groups under various

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