Silver and gold-catalyzed multicomponent reactions

• Giorgio Abbiati and
• Elisabetta Rossi

Beilstein J. Org. Chem. 2014, 10, 481–513, doi:10.3762/bjoc.10.46

Ambient gold-catalyzed O-vinylation of cyclic 1,3-diketone: A vinyl ether synthesis

• Yumeng Xi,
• Boliang Dong and
• Xiaodong Shi

Beilstein J. Org. Chem. 2013, 9, 2537–2543, doi:10.3762/bjoc.9.288

• as essential tools in organic synthesis. Generally with the unique reactivity and mild reaction conditions, this type of transformation has found widespread applications in complex molecule synthesis [10][11]. Among those reactions, the gold-catalyzed hydration of alkynes is regarded as one of the

• signature reactions in the field (known as Teles hydration) [12]. This reaction usually utilized the combination of methanol and water, wherein methanol served as the nucleophile to attack the triple bond, forming the vinyl ether intermediate. This vinyl ether then collapsed to give a ketone as the final

• 1,3-diketones with unactivated alkynes at ambient temperature. Results and Discussion As indicated in Scheme 1, the main challenge for the intermolecular O-nucleophile addition to alkynes is the competitive hydration side reaction. Although, theoretically, strictly anhydrous conditions shall prevent

Recent advances in transition metal-catalyzed Csp²-monofluoro-, difluoro-, perfluoromethylation and trifluoromethylthiolation

• Grégory Landelle,
• Armen Panossian,
• Sergiy Pazenok,
• Jean-Pierre Vors and
• Frédéric R. Leroux

Beilstein J. Org. Chem. 2013, 9, 2476–2536, doi:10.3762/bjoc.9.287

• fluorine, its hydration and thus reduced nucleophilicity [21]. The importance of this developing research field is reflected by the various review articles which have been published dealing with transition metal mediated or catalyzed fluorination [22][23][24], difluoromethylation [24], and

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

• condensation of primary amines with o-diacylbenzene 19 (Scheme 2) [13]. After initial formation of 20, isomerization to 21 and 22 can occur through a sequential dehydration–hydration process. Dimerization of 21 and 22 generates 23, the substrate for a formal retro-Aldol reaction. Loss of formaldehyde gives 24

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

• the total synthesis of the anticancer guaiane (−)-englerin A. A regio- and diastereoselective Co(II)-catalyzed hydration of the olefin and a transannular epoxide opening were used as the key reactions. Keywords: asymmetric synthesis; hydration; natural products; terpenes; transannular epoxide opening

• completion of the synthesis of (−)-oxyphyllol (1) from 4. To our delight, a direct regio- and diastereoselective Co(II)-catalyzed hydration [12] of the olefin in 4 succeeded to give the required α-stereoisomer 3 in 58% isolated yield after chromatographic separation of the minor β-alcohol. Compared to the

Synthesis of enantiomerically pure (2S,3S)-5,5,5-trifluoroisoleucine and (2R,3S)-5,5,5-trifluoro-allo-isoleucine

• Holger Erdbrink,
• Elisabeth K. Nyakatura,
• Susanne Huhmann,
• Ulla I. M. Gerling,
• Dieter Lentz,
• Beate Koksch and
• Constantin Czekelius

Beilstein J. Org. Chem. 2013, 9, 2009–2014, doi:10.3762/bjoc.9.236

• stereoisomers of Ile are less hydrophobic than Aha. F6Leu is similar to Aha in hydrophobicity, while exhibiting a much larger volume. In a free energy perturbation study, the hydration energy of F6Leu was shown to be 1.1 kcal/mol higher than that of leucine [29]. This, together with our previous and new

• findings, suggests that there are two factors determining the overall hydrophobicity of fluorinated amino acids [26]. On one hand, substitutions of hydrogen by fluorine increase the solvent accessible surface area and thus lead to an increase in hydration energy. On the other hand, the C–F bond is more

A practical synthesis of long-chain iso-fatty acids (iso-C₁₂–C₁₉) and related natural products

• Mark B. Richardson and
• Spencer J. Williams

Beilstein J. Org. Chem. 2013, 9, 1807–1812, doi:10.3762/bjoc.9.210

• triethylsilane and BF3·Et2O [53], affording 11. Oxidative cleavage of 11 with KMnO4/Bu4NBr [54] afforded iso-C12 acid 1. Alternatively, anti-Markovnikov hydration of 11, using I2/NaBH4 then hydrogen peroxide [55], afforded the alcohol 12, and oxidation of 12 with KMnO4/Bu4NBr afforded iso-C13 acid 2

Gold(I)-catalyzed formation of furans from γ-acyloxyalkynyl ketones

• Marie Hoffmann,
• Solène Miaskiewicz,
• Jean-Marc Weibel,
• Patrick Pale and
• Aurélien Blanc

Beilstein J. Org. Chem. 2013, 9, 1774–1780, doi:10.3762/bjoc.9.206

• formation of the hydration product 3 (Table 1, entries 2 and 3 versus entry 1). We found out that running the reaction at 70 °C instead of at room temperature completely prevented the byproduct formation. At this temperature good to quantitative yields of furans 2a were achieved in less than 30 min, and 5

• °C, no trace of furan 2a could be detected by 1H NMR analysis. Interestingly, decreasing the catalytic loading from 5 to 1 mol % still provided the furan in less than 1 h and in high yields (Table 1, entries 6 and 7 versus entry 5). However, hydration started to compete again at low loading, as

• hydration product, the reaction took 6 h to reach almost full conversion. Beside the expected furan 2d, its corresponding regioisomer 2d’ arising from 1,3-migration of the pivaloyl group is formed in this reaction and both products were obtained in a combined yield of 68% (Table 2, entry 4). We next varied

Aerobic radical multifunctionalization of alkenes using tert-butyl nitrite and water

• Daisuke Hirose and
• Tsuyoshi Taniguchi

Beilstein J. Org. Chem. 2013, 9, 1713–1717, doi:10.3762/bjoc.9.196

• hydroxy group arising from hydration of the olefin (entry 6). Functionalization reactions involving oxygenation of methylene C–H bonds of alkenes 11–13 also proceeded to afford secondary nitrate compounds 21–23, though no diastereoselectivity was observed (Table 2, entries 7–9). Unfortunately, no tertiary

Anionic cascade reactions. One-pot assembly of (Z)-chloro-exo-methylenetetrahydrofurans from β-hydroxyketones

• István E. Markó and
• Florian T. Schevenels

Beilstein J. Org. Chem. 2013, 9, 1319–1325, doi:10.3762/bjoc.9.148

• 13 was treated with aqueous hydrochloric acid, in the hope of generating the corresponding dihydrofuran carbaldehyde 33. Instead, the diol 34 was obtained in 52% yield as a 1:1 mixture of diastereoisomers. It thus transpires that protonation and hydration of the exo-methylene double bond of 13

• of two new dimers. Formation of (Z)-chloro-exo-methyleneketals. Mechanism of formation of (Z)-chloro-exo-methylenetetrahydrofurans. Stepwise formation of (Z)-chloro-exo-methylenetetrahydrofurans. Optimized protocols to form (Z)-chloro-exo-methylenetetrahydrofurans. Hydration of (Z)-chloro-exo

A computational study of base-catalyzed reactions of cyclic 1,2-diones: cyclobutane-1,2-dione

• Nargis Sultana and
• Walter M. F. Fabian

Beilstein J. Org. Chem. 2013, 9, 594–601, doi:10.3762/bjoc.9.64

• transition states, intermediates and products shown in Scheme 3, hydration by six water molecules is implied. Relative Gibbs free energies with respect to the separated reactants 1·(H2O)2 + [OH(H2O)4]– including bulk aqueous solvation energies (SMD solvation model [21]) obtained by various computational

Alkyne hydroarylation with Au N-heterocyclic carbene catalysts

• Cristina Tubaro,
• Marco Baron,
• Andrea Biffis and
• Marino Basato

Beilstein J. Org. Chem. 2013, 9, 246–253, doi:10.3762/bjoc.9.29

• selectivity compared to the previously published complex AuCl(PPh3). Preliminary results on intramolecular hydroarylations using this catalytic system indicate, however, that alkyne hydration by traces of water may become a serious competing reaction. Keywords: alkyne; C–H functionalization; cyclisation

• VI moderate to very good conversions of the substrates were obtained, but the main reaction product was invariably the product of hydration of the triple bond 8, whereas the 6-endo-dig cyclisation product 7 was present in minor amounts. Gold(I) NHC complexes such as VI are known to be extremely

• efficient catalysts for alkyne hydration [61], hence it can be expected that alkyne hydration by traces of water may become a serious competitive reaction despite the low concentration of water in the reaction mixture. On the basis of the above, it can be hypothesised that in order to steer the reaction

Presence or absence of a novel charge-transfer complex in the base-catalyzed hydrolysis of N-ethylbenzamide or ethyl benzoate

• Shinichi Yamabe,
• Wei Guan and
• Shigeyoshi Sakaki

Beilstein J. Org. Chem. 2013, 9, 185–196, doi:10.3762/bjoc.9.22

• water molecules in the first hydration shell of an alanine molecule was found to be seven [44]. Thus, more than seven water molecules would be required to examine the reaction paths of hydrolyses reliably. However, less than six water molecules are included in the precedent computational studies [26][27

• TS1(es) is enlarged appreciably (= +17.87 kcal/mol) in spite of the positional assumption (ii) in Figure 7. Thus, the counter ion works unfavorably on the rate-determining step TS1(es). The Na+ ion has a very large hydration energy (= −97 kcal/mol), and the cation needs to be surrounded by many water

• molecules in the hydration shell far from the reaction region. Figure 8 shows energy changes for the amide hydrolysis of Figure 5. Those of Na+-containing paths in the system, Ph–C(=O)–NH–Et + NaOH(H2O)16 in Figure S4 (Supporting Information File 1), are also shown in green. In energies of the Na+-free

Antifreeze glycopeptide diastereomers

• Lilly Nagel,
• Carsten Budke,
• Axel Dreyer,
• Thomas Koop and
• Norbert Sewald

Beilstein J. Org. Chem. 2012, 8, 1657–1667, doi:10.3762/bjoc.8.190

• position for adsorption to the ice surface; a similar situation applies to the retro-inverso peptide 7. Moreover, these conformational changes may possibly also alter the water hydration shell around the peptide, which has been suggested to be essential for the antifreeze activity of AFGPs and AFGP

• backbone as well as on the hydration shell around the peptide. Experimental All chemicals were acquired from Sigma Aldrich (Hamburg, Germany), Acros (Geel, Belgium), Alfa Aesar (Ward Hill, USA) and VWR (Darmstadt, Germany) and were employed without additional purification. Moisture- and air-sensitive

Mannose-decorated cyclodextrin vesicles: The interplay of multivalency and surface density in lectin–carbohydrate recognition

• Ulrike Kauscher and
• Bart Jan Ravoo

Beilstein J. Org. Chem. 2012, 8, 1543–1551, doi:10.3762/bjoc.8.175

• functionalized by self-assembly [27]. To this end, cyclodextrins are modified with long alkyl chains (“tails”) and short oligo(ethylene glycol) head groups. These macrocyclic amphiphiles form unilamellar bilayer vesicles in aqueous solution upon hydration of a thin film cast by evaporation from organic solution

Synthesis of a novel chemotype via sequential metal-catalyzed cycloisomerizations

• Bo Leng,
• Stephanie Chichetti,
• Shun Su,
• Aaron B. Beeler and
• John A. Porco Jr.

Beilstein J. Org. Chem. 2012, 8, 1338–1343, doi:10.3762/bjoc.8.153

• , evaluating a number of metal catalysts in the presence of diethyl malonate. From this focused reaction screen we identified three types of reactivity: (1) no reaction; (2) alkyne hydration (4); and (3) cycloisomerization leading to isochromene (5) (Figure 1). Many catalysts resulted in no reaction, including

• ones that might have been expected to catalyze cycloisomerization, such as AgOTf. Two catalysts, Cu(OTf)2 and Pd(MeCN)2Cl2, afforded only hydration of the alkyne. Interestingly, hydration was regioselective, which is possibly due to direction from the ether oxygen. We were most interested in metal

Continuous-flow hydration–condensation reaction: Synthesis of α,β-unsaturated ketones from alkynes and aldehydes by using a heterogeneous solid acid catalyst

• Magnus Rueping,
• Teerawut Bootwicha,
• Hannah Baars and
• Erli Sugiono

Beilstein J. Org. Chem. 2011, 7, 1680–1687, doi:10.3762/bjoc.7.198

• Magnus Rueping Teerawut Bootwicha Hannah Baars Erli Sugiono Institute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, D-52074 Aachen, Germany 10.3762/bjoc.7.198 Abstract A simple, practical and efficient continuous-flow hydration–condensation protocol was developed for the synthesis

• of valuable differently substituted chalcones. Starting from commercially available alkynes and aldehydes, a continuous-flow hydration–condensation protocol leads to the desired products in good to excellent yields. The reactions were sequentially introduced into the flow cell and performed several

• General procedure for hydration–condensation reaction of phenylacetylene (1a) and benzaldehyde (2a). A solution of phenylacetylene (1a) (0.4 mmol) and benzaldehyde (2a) (1.6 mmol) was pumped through the flow cell filled with amberlyst-15 resin (16–50 mesh) (10.0 g) and dry 1,2-dichloroethane at a flow

Gold-catalyzed propargylic substitutions: Scope and synthetic developments

• Olivier Debleds,
• Eric Gayon,
• Emmanuel Vrancken and
• Jean-Marc Campagne

Beilstein J. Org. Chem. 2011, 7, 866–877, doi:10.3762/bjoc.7.99

• , whereas in refluxing dichloroethane the substitution product 16 led to a mixture of products via triple bond hydration to give 17 [49][50][56] and furan formation to afford 18 (Scheme 7). The furan may possibly result from intramolecular addition of the enol form of acetylacetone. Related experiments have

• obtain these isoxazolines would be to realize the propargylic substitution first of all (and consume all of the hydroxylamine) and subsequently perform the cyclization. Since iron(III) was known to be inefficient in the hydration of triple bonds [64][65], we anticipated that its use would lead only to

• even after prolonged reaction at reflux (Scheme 14). Very recently, Darcel described the iron(III) hydration of terminal alkynes [65]. These conditions were attempted to cyclize 22a but in our hands only extensive decomposition was observed. We thus turned our attention to gold-catalyzed cyclization of

Gold-catalyzed oxidation of arylallenes: Synthesis of quinoxalines and benzimidazoles

• Dong-Mei Cui,
• Dan-Wen Zhuang,
• Ying Chen and
• Chen Zhang

Beilstein J. Org. Chem. 2011, 7, 860–865, doi:10.3762/bjoc.7.98

• /hydration and oxidative cleavage of allenes to form α-diketones and aldehydes, and the synthesis of quinoxalines and benzimidazoles via the condensation of the resulting α-diketones and aldehydes with benzene-1,2-diamine [45][46][47][48][49][50][51][52][53][54][55][56]. Results and Discussion Our initial

• of quinoxalines and benzimidazoles via the condensation of the resulting α-diketones and aldehydes with benzene-1,2-diamine was achieved in high yields. This reaction appears to proceed via oxidation/hydration and oxidative cleavage of the allene, and investigations into the mechanism of this

Fine-tuning alkyne cycloadditions: Insights into photochemistry responsible for the double-strand DNA cleavage via structural perturbations in diaryl alkyne conjugates

• Wang-Yong Yang,
• Samantha A. Marrone,
• Nalisha Minors,
• Diego A. R. Zorio and
• Igor V. Alabugin

Beilstein J. Org. Chem. 2011, 7, 813–823, doi:10.3762/bjoc.7.93

• triple bond. The cyclized product, benzoxazepine 13, and the ketone product 14 were isolated. Whereas 13 was produced by a 7-endo cyclization (unprecedented in these systems), the ketone 14 can be formed either by direct hydration of the alkyne or by a known pathway that involves the corresponding six

• -membered product, a benzoxazine. The formation of benzoxazines has been previously reported by Roberts and coworkers, who suggested cyclization via triplet excitation following hydration [59][60][61][62]. The presence of vinyl peaks at 6.2 and 5.9 ppm in the reaction mixture and their quick disappearance

• undergoes further photorearrangement via a formal 1,3-shift. Photocycloaddition of amido acetylenes with 1,4-CHD. Possible mechanism for photochemical hydration of diaryl acetylene moiety catalyzed by the ortho-amide substituent. Stern–Volmer quenching constants (Et3N as a quencher) and singlet lifetimes

Gold-catalyzed heterocyclizations in alkynyl- and allenyl-β-lactams

• Benito Alcaide and
• Pedro Almendros

Beilstein J. Org. Chem. 2011, 7, 622–630, doi:10.3762/bjoc.7.73

• -azetidinone nucleus [66][67]. Treatment of the terminal alkyne 35a with the catalytic system AuCl3/PTSA gave the desired ketal 36a. Appreciable amounts of a polar ketone arising from alkyne hydration were also produced. Fortunately, the [AuClPPh3]/AgOTf/PTSA system demonstrated better activity. Interestingly

pH-Responsive chromogenic-sensing molecule based on bis(indolyl)methene for the highly selective recognition of aspartate and glutamate

• Litao Wang,
• Xiaoming He,
• Yong Guo,
• Jian Xu and
• Shijun Shao

Beilstein J. Org. Chem. 2011, 7, 218–221, doi:10.3762/bjoc.7.29

• /deprotonation of, the indolyl moiety modulate the internal charge transfer (ICT) state of bis(indolyl)methene and give rise to large color changes. In aqueous solution, the effective recognition based on strong hydrogen bonding is hardly achieved because of the strong hydration to hydrogen bonding sites of both

A short and efficient synthesis of valsartan via a Negishi reaction

• Samir Ghosh,
• A. Sanjeev Kumar and
• G. N. Mehta

Beilstein J. Org. Chem. 2010, 6, No. 27, doi:10.3762/bjoc.6.27

• and arteries causes the tissues to constrict. AT-II receptors are activated by the octapeptide AT-II. AT-II helps to maintain constant blood pressure [1] despite fluctuations in a person’s state of hydration, sodium intake and other physiological variables. AT-II also performs the regulatory tasks of

Solvent-free and time-efficient Suzuki–Miyaura reaction in a ball mill: the solid reagent system KF–Al₂O₃ under inspection

• Franziska Bernhardt,
• Ronald Trotzki,
• Tony Szuppa,
• Achim Stolle and
• Bernd Ondruschka

Beilstein J. Org. Chem. 2010, 6, No. 7, doi:10.3762/bjoc.6.7

• these results, materials were stored in a desiccator over KOH and vacuum for further applications to avoid uncontrollable uptake of water as indicated in the procedures of Kabalka et al. (“exposed to air over a period of days to allow for hydration of the surface”) [33] as well as for preventing the

Enantioselective synthesis of tricyclic amino acid derivatives based on a rigid 4-azatricyclo[5.2.1.0^2,6]decane skeleton

• Matthias Breuning,
• Tobias Häuser,
• Christian Mehler,
• Christian Däschlein,
• Carsten Strohmann,
• Andreas Oechsner and
• Holger Braunschweig

Beilstein J. Org. Chem. 2009, 5, No. 81, doi:10.3762/bjoc.5.81

• of 11 delivered the exo-configured alcohol rac-12, which was oxidized with PCC furnishing rac-9 in 79% yield. The asymmetric synthesis of the ketone 9 was realized by enantioselective hydration of the meso-alkene 11 using Hayashi’s method (Scheme 2) [25][26][27][28][29][30]: Hydrosilylation with