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

Thermochemistry and photochemistry of spiroketals derived from indan-2-one: Stepwise processes versus coarctate fragmentations

• Götz Bucher,
• Gernot Heitmann and
• Rainer Herges

Beilstein J. Org. Chem. 2013, 9, 1668–1676, doi:10.3762/bjoc.9.191

• -one and propane-1,3-diol and cis-2-butene-1,4-diol, respectively. Indan-2-one ethylene ketal (1): IR (Ar, 10 K) ν: 3109.2 (vw), 3084.4 (vw), 3057.7 (vw), 3034.8 (w), 2993.3 (w), 2989.6 (w), 2962.3 (w), 2928.9 (vw), 2898.5 (w), 2894.8 (w), 2878.1 (w), 2834.1 (vw), 1598.6 (vw), 1485.5 (m), 1472.5 (vw

• −1. Synthesis of 2: Indan-2-one propane-1,3-diol ketal (2) was prepared as described for the synthesis of 1, with the exception of the use of toluene rather than benzene as solvent. Indan-2-one (2.0 g, 0.015 mol) and 1,3-propanediol (1.4 g, 0.018 mol) were heated under reflux in 100 mL toluene

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

• stereoselective fashion from displacement of a leaving group at C10, a means for the selective formation of a syn-1,3-diol at C11 and C13 is required. Rychnovsky has demonstrated that alkylation of 4-cyano-1,3-dioxanes (cyanohydrin acetonides) constitutes a practical and valuable approach to syn-1,3-diol

• synthesis [66]. The lithiated cyanohydrin acetonides react as nucleophiles with alkyl, allyl, and propargyl halides, as well as with epoxides. Although the alkylation itself is highly stereoselective in favor of the axial nitrile, the syn-1,3-diol stereochemistry is ultimately set in a subsequent reductive

Some aspects of radical chemistry in the assembly of complex molecular architectures

• Béatrice Quiclet-Sire and
• Samir Z. Zard

Beilstein J. Org. Chem. 2013, 9, 557–576, doi:10.3762/bjoc.9.61

• be easily constructed. Spiroketals 119 and 120 are two such examples. The former was used in the total enantioselective synthesis of (+)-broussonetine G (121) [50]. If one of the alkenes contains a masked aldehyde, a bis-spiroketal such as 122 may be accessed. Furthermore, placing a 1,2- or a 1,3

• -diol on one of the alkenes would in principle result in the formation of a cyclic ketal. Spiro and cyclic ketals are ubiquitous in pheromones and in marine natural products [51]. The comparatively long effective lifetime of radicals generated under the conditions of the xanthate transfer may be

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

• . From the 1,3-diol, a bimolecular elimination (TS2) leads to the allylic alcohol as the first channel. In the second channel, the 1,3-diol was converted via TS3 into an unprecedented hemiacetal intermediate, HO–CH2–O–CH(R)–CH2–CH2–OH. This intermediate undergoes ring closure (TS4), affording the 1,3

• hydrolyzed to form the 1,3-diol by stirring the former in a 2% (or lower) sulfuric acid solution under reflux [4]. However, the hydrolysis yield on the dioxane charged is only 8–17% depending on the alkene reactants. The result was interpreted in terms of a reversible reaction shown in Scheme 3. On the other

• ][11][12][13][14][15][16][17][18] to afford 1,3-dioxane, 1,3-diol and allylic alcohol, where the carbocation intermediate (X) is included (Scheme 5). In the second step, X is formed. From X, two routes, (i) and (ii), are possible. In the route (i), a water molecule is linked with the cation center

Thermotropic and lyotropic behaviour of new liquid-crystalline materials with different hydrophilic groups: synthesis and mesomorphic properties

• Alexej Bubnov,
• Miroslav Kašpar,
• Věra Hamplová,
• Ute Dawin and
• Frank Giesselmann

Beilstein J. Org. Chem. 2013, 9, 425–436, doi:10.3762/bjoc.9.45

• of 2-(1-(6-(4'-(6-(3-hydroxy-2-(hydroxymethyl)-2-methylpropoxy)hexyloxy)biphenyl-4-yloxy)hexyloxy)methyl)-2-methylpropane-1,3-diol (TL3). General procedure for the synthesis of chiral (E)-2-methyl-2-((2-(2-(2-(4-((4-((4-(2-methylbutoxy)phenyl)diazenyl)phenoxy)methyl)phenoxy)ethoxy)ethoxy)ethoxy

• )methyl)propane-1,3-diol (TL5). Chemical formulae of compounds and used abbreviations. Sequence of phases and phase-transition temperatures, T (°C), measured on cooling (5 K min−1); melting points, mp (°C), measured on heating (5 K min−1) and phase-transition enthalpies, ΔH [Jg−1], obtained by DSC for the

Removal of benzylidene acetal and benzyl ether in carbohydrate derivatives using triethylsilane and Pd/C

• Abhishek Santra,
• Tamashree Ghosh and
• Anup Kumar Misra

Beilstein J. Org. Chem. 2013, 9, 74–78, doi:10.3762/bjoc.9.9

• hydrogenation; triethylsilane; Introduction Functionalization of carbohydrate intermediates is essential for their assembly towards the synthesis of complex oligosaccharides [1][2][3][4][5][6][7][8][9]. Benzylidene acetal is a frequently used protecting group for the simultaneous protection of 1,2- and 1,3

• -diol derivatives [10][11]. It can be removed under acidic hydrolysis as well as under neutral conditions (e.g., hydrogenolysis). The benzylidene acetal can also be regioselectively opened under reductive conditions to produce partially benzylated derivatives [12][13][14]. A number of methods have been

Combined bead polymerization and Cinchona organocatalyst immobilization by thiol–ene addition

• Kim A. Fredriksen,
• Tor E. Kristensen and
• Tore Hansen

Beilstein J. Org. Chem. 2012, 8, 1126–1133, doi:10.3762/bjoc.8.125

• dithiol 5 was easily obtained from esterification of 3-mercaptopropionic acid and propane-1,3-diol [14]. Trivinyl ether 6, polyethylene glycol (PEG) dimethacrylate 7, diacrylate 8 and diallyl ether 9 are all commercially available compounds. For thiol–ene additions via the radical pathway, the order of

Asymmetric total synthesis of smyrindiol employing an organocatalytic aldol key step

• Dieter Enders,
• Jeanne Fronert,
• Tom Bisschops and
• Florian Boeck

Beilstein J. Org. Chem. 2012, 8, 1112–1117, doi:10.3762/bjoc.8.123

• intramolecular aldol reaction of O-acetonyl-salicylaldehydes was described by our research group (Scheme 3) [10]. We envisaged that this 5-enolexo aldolization could be utilized to construct the 1,3-diol moiety of smyrindiol, if a coumarin derivative of the O-acetonyl-salicylaldehyde were to be used. The

• this reason, we decided to construct the coumarin system after the proline catalyzed aldol reaction had taken place. We envisaged that the preparation of the coumarin system of smyrindiol (1) could be achieved by Lindlar reduction of the propiolate ester 5, in which the 1,3-diol would be protected as

• introduction of the methyl group by using the Imamoto protocol [13] employing cerium(III) chloride and methyllithium at −78 °C, was unreliable with highly varying yields of the 1,3-diol. This irreproducibility is probably due to the heterogeneous nature of the reaction mixture. Fortunately, the use of

Aldol elaboration of 4,5,6,7-tetrahydroisoxazolo[4,3-c]pyridin-4-ones, masked precursors to acylpyridones

• Raymond C. F. Jones,
• Abdul K. Choudhury,
• James N. Iley,
• Mark E. Light,
• Georgia Loizou and
• Terence A. Pillainayagam

Beilstein J. Org. Chem. 2012, 8, 308–312, doi:10.3762/bjoc.8.33

• 13, (LiAlH4, THF) to give the 1,3-diol 14 in 75% yield. This was followed by synthesis of the cyclic carbonate 15 by treating the 1,3-diol 14 with methyl chloroformate (Et3N, CH2Cl2; 74%). In the final step, carbonate 15 was treated with palladium dibenzylideneacetone in dry MeCN at room temperature

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

• microwave reaction conditions can be found in the literature [8]. anti-2-(N-Benzylamino)-1-(4-chlorophenyl)propan-1,3-diol (9a) Recrystallization from hexane/EtOAc (1:25), white crystals, 95%. Mp 192.3 °C; 1H NMR (300 MHz, CDCl3) δ 2.39 (s, 2H), 3.12–3.18 (m, 1H), 3.54 (dd, J = 13.0, 3.6 Hz, 1H), 3.82 (dd

• (NH), 2926, 1448, 1162, 1008, 681; MS (70 eV) m/z (%): 292/4 (M+ + 1, 100); HRMS (ESI): [M + H]+ calcd for C16H19ClNO2, 292.1104; found, 292.1112. syn-2-(N-tert-Butylamino)-1-(2-methoxyphenyl)propan-1,3-diol (12a) Rf 0.07 (EtOAc), white crystals, 30%. Mp 112.8 °C; 1H NMR (300 MHz, CDCl3) δ 1.03 (s, 9H

When cyclopropenes meet gold catalysts

• Frédéric Miege,
• Christophe Meyer and
• Janine Cossy

Beilstein J. Org. Chem. 2011, 7, 717–734, doi:10.3762/bjoc.7.82

• . With the optically pure chiral alcohol (R)-PhMeCHCH2OH as a nucleophile, the reaction was not diastereoselective and led to the tertiary allylic ether 9k (65%) as a 1:1 mixture of diastereomers. An unprotected primary and tertiary 1,3-diol reacted chemoselectively with the primary alcohol to furnish

An overview of the key routes to the best selling 5-membered ring heterocyclic pharmaceuticals

• Marcus Baumann,
• Ian R. Baxendale,
• Steven V. Ley and
• Nikzad Nikbin

Beilstein J. Org. Chem. 2011, 7, 442–495, doi:10.3762/bjoc.7.57

• atorvastatin this important syn-1,3-diol moiety is connected to the other functional constituents through a fully substituted pyrrole ring instead of the more elaborate systems which are encountered in other members of this family. The initial synthesis of atorvastatin was reported by the Warner–Lambert

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

• Structural motifs such as 1,2-aminoalcohol, 1,2- and 1,3-diol are very prevalent features in natural products, especially polyketides. The structures of some of these, such as sorbistin A1 [1] or zwittermicin A [2], contain mostly aminopolyol moieties. Aminoalcohol and diol motifs are often constructed via

• , diastereoselective sequence of two [3 + 2] cycloaddition reactions promoted by triflic acid where the large 1,3-diol protecting group – the 1,1,3,3-tetraisopropoxydisiloxanylidene group (TIPDS) – plays a crucial role in facial discrimination. Results and Discussion Our approach to the preparation of enantiomerically

• alcohol protecting group at the central anti-1,3-diol (C11 and C13 in zwittermicin A). Our study of the diastereoselective reaction of benzyl azide with the bis(imide) is presented in Table 1. We began with a thermal reaction of the bis(imide) 5 that used the common di(tert-butylsilyl) functionality as a

A short stereoselective synthesis of (+)-(6R,2′S)-cryptocaryalactone via ring- closing metathesis

• Palakodety Radha Krishna,
• Krishnarao Lopinti and
• K. L. N. Reddy

Beilstein J. Org. Chem. 2009, 5, No. 14, doi:10.3762/bjoc.5.14

• undergoes a reductive ring-opening reaction with Red-Al under standard reaction conditions to furnish the 1,3-diol 9 in 88% yield. Traces of 1,2-diol were oxidatively cleaved with NaIO4 in presence of catalytic amount of saturated NaHCO3 solution. Diol 9 was protected with anisaldehyde dimethylacetal in

• . Confirmation of absolute configuration The structure of compound 7 was confirmed by 1H NMR and 13C spectral analysis (Scheme 2). The absolute stereochemistry was assigned based on Rychnovsky’s analogy [42][43][44]. According to literature precedent, the relative configuration of a secondary 1,3-diol can be

• confirmed the anti configuration of the 1,3-diol. Since the first hydroxyl center was obtained through an unambiguous method, the stereochemistry of the newly created hydroxyl functionality could be confirmed as that depicted in Scheme 2. The propargylic alcohol 7 was chemoselectively reduced with LiAlH4 in

Stereoselective synthesis of (2S,3S,4Z)-4-fluoro- 1,3-dihydroxy- 2-(octadecanoylamino)octadec- 4-ene, [(Z)-4-fluoroceramide], and its phase behavior at the air/water interface

• Gergana S. Nikolova and
• Günter Haufe

Beilstein J. Org. Chem. 2008, 4, No. 12, doi:10.3762/bjoc.4.12

• diastereomeric 4-fluoro-4,5-dihydroceramides, which we synthesized recently [28]. We became interested in studying the properties and report in this paper the stereoselective synthesis of (Z)-2-amino-4-fluorooctadec-4-ene-1,3-diol (4-fluorosphingosine, 1b) and (Z)-2-octadecanoylamino-4-fluorooctadec-4-ene-1,3

• -diol (4-fluoroceramide, 2b) having the D-erythro-configuration (2S,3S) and the trans-configured C(4)-C(5) double bond of the natural compounds 1a and 2a (Figure 1). Our first investigations on the phase behavior at the air/water interface of 4-fluoroceramide (2b) and its non-fluorinated analogue 2a by