New approaches to organocatalysis based on C–H and C–X bonding for electrophilic substrate activation

• Pavel Nagorny and
• Zhankui Sun

Beilstein J. Org. Chem. 2016, 12, 2834–2848, doi:10.3762/bjoc.12.283

• catalyst with X = I, and R = Oct promoted the reaction between 1-chloroisochroman and silyl enol ether at 0.5 mol % catalyst loadings (70% yield, 6 h). A good correlation was observed between the catalytic activity and halogen affinity, and the Ka of L22 with X = I, R = Oct with bromide anion was

Rh-Catalyzed reductive Mannich-type reaction and its application towards the synthesis of (±)-ezetimibe

• Motoyuki Isoda,
• Kazuyuki Sato,
• Yurika Kunugi,
• Satsuki Tokonishi,
• Atsushi Tarui,
• Masaaki Omote,
• Hideki Minami and
• Akira Ando

Beilstein J. Org. Chem. 2016, 12, 1608–1615, doi:10.3762/bjoc.12.157

• asymmetric Mannich reaction using a Lewis acid catalyst [1]. (L)-Proline is known as an excellent promoter for the Mannich reaction [2][3][4][5][6], and besides this, the reaction of the silyl enol ether derivatives with imines was used as an effective method [7][8][9]. In this situation, a wide variety of

Catalytic asymmetric synthesis of biologically important 3-hydroxyoxindoles: an update

• Bin Yu,
• Hui Xing,
• De-Quan Yu and
• Hong-Min Liu

Beilstein J. Org. Chem. 2016, 12, 1000–1039, doi:10.3762/bjoc.12.98

• -workers in 2014 (Scheme 34) [51]. After activation by the tertiary amine catalysts (cat. 19 and 20), the monofluorinated silyl enol ether then reacted with isatins to generate 3-hydroxyoxindoles bearing two adjacent chiral carbon centers. The reactions were performed in acetonitrile with 10 mol % of

• value under the same conditions, suggesting that the NH moiety is critical for achieving good results. Under the same conditions, the α-fluorotetralone-derived silyl enol ether gave the corresponding product in 37% yield and with 82% ee. More recently, Miao and co-workers reported the quinidine (cat. 21

1H-Imidazol-4(5H)-ones and thiazol-4(5H)-ones as emerging pronucleophiles in asymmetric catalysis

• Antonia Mielgo and
• Claudio Palomo

Beilstein J. Org. Chem. 2016, 12, 918–936, doi:10.3762/bjoc.12.90

• analogous they do not show the Cα/Cγ selectivity problem [56][57][58]. 1.1 Synthesis of 1H-imidazol-4(5H)-ones 1 1H-Imidazol-4(5H)-ones 1 (R = SBn) are prepared by S-alkylation of the corresponding thiohydantoins [55][59] (Scheme 1a) prior trimethylsilyl enol ether formation which is necessary to avoid O

(Thio)urea-mediated synthesis of functionalized six-membered rings with multiple chiral centers

• Giorgos Koutoulogenis,
• Nikolaos Kaplaneris and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2016, 12, 462–495, doi:10.3762/bjoc.12.48

Facile synthesis of 4H-chromene derivatives via base-mediated annulation of ortho-hydroxychalcones and 2-bromoallyl sulfones

• Srinivas Thadkapally,
• Athira C. Kunjachan and
• Rajeev S. Menon

Beilstein J. Org. Chem. 2016, 12, 16–21, doi:10.3762/bjoc.12.3

•  1, path a). Bromoallyl sulfones 2a,b partake in a cesium carbonate-mediated formal vinylic substitution reaction with heteronucleophiles to afford valuable multifunctional building blocks [23]. For example, the reaction of 2a with 4-chlorophenol afforded the enol ether 3 in 84% yield (Scheme 1, path

Catalytic asymmetric formal synthesis of beraprost

• Yusuke Kobayashi,
• Ryuta Kuramoto and
• Yoshiji Takemoto

Beilstein J. Org. Chem. 2015, 11, 2654–2660, doi:10.3762/bjoc.11.285

• [4][5]. However, PGI2 possesses an unstable enol ether moiety, which can be hydrolyzed even under neutral aqueous conditions, resulting in a loss of pharmacological action [6][7][8]. Therefore, an increasing number of more stable PGI2 derivatives have been developed. Among these, beraprost (1) has

Stereoselective synthesis of hernandulcin, peroxylippidulcine A, lippidulcines A, B and C and taste evaluation

• Marco G. Rigamonti and
• Francesco G. Gatti

Beilstein J. Org. Chem. 2015, 11, 2117–2124, doi:10.3762/bjoc.11.228

• oxidation of 8 to give the enone 1 in DMSO at high temperature (80 °C) resulted unsuccessful [24]. The hydrogenation of silyl enol ether derivatives in the presence of the IBX-N-oxide complex gives the corresponding enones, usually with better conversion and under milder conditions (room temperature) [25

• kinetic enol ether 10 in 91% yield ([α]D +19.7° (c 1.4, CHCl3)). The latter was submitted to the oxidative step with the IBX-N-oxide, but even in this case the results were unsatisfactory since only traces of enone 11 were detected. In contrast, the Pd based Saegusa–Larock methodology resulted successful

• Pd(TFA)2 catalyzed dehydrogenation on the silyl enol ether 10 and in the presence of Na2HPO4 buffer, in order to mitigate the detrimental acidity of TFA. However, 11 was produced in a modest yield of 21%, because, even at these mild conditions, 10 reconverted to the initial ketone 9 faster than its

Preparative semiconductor photoredox catalysis: An emerging theme in organic synthesis

• David W. Manley and
• John C. Walton

Beilstein J. Org. Chem. 2015, 11, 1570–1582, doi:10.3762/bjoc.11.173

• compounds, that could be isolated on a gram scale, came from the research group of Kisch [39]. Additions of allylic alkenes and enol ethers to 1,2-diazines, mediated by photolyses of methanolic suspensions of CdS, resulted in the formation of alkenyl diazanes 3 (Scheme 2) [40]. Oxidation of the alkene/enol

• ether component by h+ from the CdS furnished radical cations. On deprotonation the derived allylic radicals added to the N=N bonds of the diazines resulting in modest yields of substituted diazanes 3. Functionalized N-benzylanilines 4 were also obtained from an analogous process in which alkenes added

Structure and conformational analysis of spiroketals from 6-O-methyl-9(E)-hydroxyiminoerythronolide A

• Ana Čikoš,
• Irena Ćaleta,
• Dinko Žiher,
• Mark B. Vine,
• Ivaylo J. Elenkov,
• Marko Dukši,
• Dubravka Gembarovski,
• Marina Ilijaš,
• Snježana Dragojević,
• Ivica Malnar and
• Sulejman Alihodžić

Beilstein J. Org. Chem. 2015, 11, 1447–1457, doi:10.3762/bjoc.11.157

• undergo skeletal transformations such as epimerisations, spiroketalisation, translactonisation, dehydroxylations, etc. [57]. Grover et al. [58] have previously shown that during the oximation of erythromycin A, unexpected side reactions led to the formation of a 6,9-intramolecular enol ether

• whole equilibrium process most likely consists of a series of hemiketal and enol ether transformations. Thus the elusive intermediate A in acidic media forms a hemiketal B (B1 or B2). From our data and literature precedents it is not clear if the 6-membered (B1) or the 5-membered (B2) intermediate is

• formed first. Based on chemical calculations Hassanzadeh et al. suggested 12-O-enol ether formation (type C2) and final spiroketalisation [42] via the corresponding oxocarbenium type transition state. Carreira et al. on the other hand isolated a 6-membered enol ether (type C1) and further transformed it

Selected synthetic strategies to cyclophanes

• Sambasivarao Kotha,
• Mukesh E. Shirbhate and
• Gopalkrushna T. Waghule

Beilstein J. Org. Chem. 2015, 11, 1274–1331, doi:10.3762/bjoc.11.142

• synthesis of polyunsaturated [10]paracyclophane annulated by two azulene rings by using the McMurry reaction [100][101]. The bis(trimethylsilyl)enol ether 74 was reacted with 3-methoxycarbonyl-2H-cyclohepta[b]furan-2-one (75) in refluxing decaline to generate the 1,4-diazulenobenzene derivative 76. Double

Photovoltaic-driven organic electrosynthesis and efforts toward more sustainable oxidation reactions

• Bichlien H. Nguyen,
• Robert J. Perkins,
• Jake A. Smith and
• Kevin D. Moeller

Beilstein J. Org. Chem. 2015, 11, 280–287, doi:10.3762/bjoc.11.32

• was generated from the enol ether, it was rapidly trapped by the alcohol nucleophile. This generated a radical that was in turn trapped by an allylsilane. The loss of a second electron and elimination of the silyl group led to the final product. To be successful, the reaction needed to overcome the

• reaction flask (Figure 1a). Alternatively, several 6 V solar photovoltaic cells can be connected in series to generate the equivalent amount of current (Figure 1b). Representative procedure for solar-driven direct electrochemical reactions (Scheme 2a) The enol ether substrate was dissolved in anhydrous

Formal total syntheses of classic natural product target molecules via palladium-catalyzed enantioselective alkylation

• Yiyang Liu,
• Marc Liniger,
• Ryan M. McFadden,
• Jenny L. Roizen,
• Jacquie Malette,
• Corey M. Reeves,
• Douglas C. Behenna,
• Masaki Seto,
• Jimin Kim,
• Justin T. Mohr,
• Scott C. Virgil and
• Brian M. Stoltz

Beilstein J. Org. Chem. 2014, 10, 2501–2512, doi:10.3762/bjoc.10.261

• bromolactonization of 22 to build in the requisite syn relationship between the carboxylate group and the 3-hydroxy group, ultimately leading to quinic acid. Unlike the allylic alkylations in Scheme 1, which form all-carbon stereocenters, we envisioned a unique modification of the silyl enol ether version to access

• Novak routes to quinic acid (21). Conversion of dioxanone 25 to a cyclohexylimine enabled alkylation via a metalloenamine. On acidic work-up, imine hydrolysis furnished an alkylated dioxanone in good yield. The targeted silyl enol ether 26 was prepared by thermodynamic silylation in 66% yield [43

• ]. Optimal conversions and enantioselectivities were achieved from triethylsilyl enol ether 26 on exposure to [Pd(dmdba)2] (5 mol %), (S)-t-BuPHOX (5, 5.5 mol %), and diallyl carbonate (1.05 equiv) at 25 °C, in PhMe with an equivalent of Bu4NPh3SiF2 (TBAT) [43]. Recognizing that enantioenriched α,ω-dienes

Synthesis of rigid p-terphenyl-linked carbohydrate mimetics

• Maja Kandziora and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2014, 10, 1749–1758, doi:10.3762/bjoc.10.182

• this case. The mechanism of the rearrangement 4 → 11 can be described as an aldol-type cyclization process. The Lewis acid coordinates to the sterically less hindered oxygen atom of the dioxolane ring of 4 opening this ring and forming a carbenium ion that intramolecularly attacks the enol ether moiety

C–H-Functionalization logic guides the synthesis of a carbacyclopamine analog

• Sebastian Rabe,
• Johann Moschner,
• Marina Bantzi,
• Philipp Heretsch and
• Athanassios Giannis

Beilstein J. Org. Chem. 2014, 10, 1564–1569, doi:10.3762/bjoc.10.161

• inexpensive dehydroepiandrosterone (5) by the means of a copper-mediated C–H hydroxylation in the 12-position and a palladium-catalyzed coupling of methyl acrylate to an activated enol ether in the 17-position. In synthetic direction (Scheme 2), dehydroepiandrosterone (5) was protected as its

4-Hydroxy-6-alkyl-2-pyrones as nucleophilic coupling partners in Mitsunobu reactions and oxa-Michael additions

• Michael J. Burns,
• Thomas O. Ronson,
• Richard J. K. Taylor and
• Ian J. S. Fairlamb

Beilstein J. Org. Chem. 2014, 10, 1159–1165, doi:10.3762/bjoc.10.116

• could find only limited precedent for this procedure being used previously in this way [15][16][17]. In our case, we were able to further modify the resulting pyronyl ether forming a trisubstituted enol ether, which then underwent a Suzuki–Miyaura cross-coupling or direct arylation-type reaction. As

• of pyronyl ethers is useful in itself, the ability to introduce an unsaturated group onto the oxygen, leading to a pyronyl enol ether, would have additional value. This is a highly unusual motif found in some marine polyketide natural products (such as compound 1, Figure 1). Conjugate addition to α,β

• methodology, we explored the addition of hydroxypyrones to both an allene and an internal alkyne to furnish a trisubstituted enol ether. Addition of 4-hydroxy-6-methyl-2-pyrone (3a) to the terminal allene 8 under the optimised conditions proceeded smoothly to give the trans-trisubstituted enol ether 9 in 52

Use of activated enol ethers in the synthesis of pyrazoles: reactions with hydrazine and a study of pyrazole tautomerism

• Denisa Tarabová,
• Stanislava Šoralová,
• Martin Breza,
• Marek Fronc,
• Wolfgang Holzer and
• Viktor Milata

Beilstein J. Org. Chem. 2014, 10, 752–760, doi:10.3762/bjoc.10.70

• enol ether/hydrazine is 1:1, as in the case of the reaction with 3c, the formation of 7-aminopyrazolo[1,5-a]pyrimidine-3,6-dicarbonitrile could be expected as a byproduct [24][25]. When hydrazine hydrochloride is used [14], ethyl 3-ethoxypyrazole-4-carboxylate was obtained in 41% yield and the expected

• ethyl 3-oxo-2,3-dihydropyrazole-4-carboxylate (5c, oxo form) in 37% yield. The first product was obtained as an oil, whereas compound 5c was afforded as a white powder. The reversal of the addition by adding hydrazine hydrate dropwise to the stirred enol ether led to the bis-N,N´-product 6a in 60% yield

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

Synthesis of new enantiopure poly(hydroxy)aminooxepanes as building blocks for multivalent carbohydrate mimetics

• Léa Bouché,
• Maja Kandziora and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2014, 10, 213–223, doi:10.3762/bjoc.10.17

• single diastereomer) which may be due to the stabilized carbenium ion formed at the benzylic position. This rearrangement presents a relatively rare example of an intramolecular aldol-like reaction of an enol ether with an activated acetal (which may also be regarded as a special case of a Prins reaction

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

• , entry 1). Intermediary, the silyl enol ether and the silyl ketene acetal are formed. However, after the rearrangement, the keto-functionality can be set free again during an acidic work-up. In terms of yield and diastereoselectivity there was no difference observed between rearrangements with

• alkylation of the lithium enolate of 15 with alkyl halides under several conditions. They incorporated an α-allyl side chain via an α-bromo-enone, which can be obtained from an initially formed silyl enol ether, and subsequent reaction with NBS. Keck allylation of the α-bromo-enone using allyltributyltin and

• the corresponding silyl enol ether 81 followed by esterification with TMSCHN2 furnished the ester aldehyde that was reduced to the primary alcohol and protected to give TBDPS ether 82. After selective cleavage of the acetal group by treatment with perchloric acid, installation of the double bond via

Recent applications of the divinylcyclopropane–cycloheptadiene rearrangement in organic synthesis

• Sebastian Krüger and
• Tanja Gaich

Beilstein J. Org. Chem. 2014, 10, 163–193, doi:10.3762/bjoc.10.14

• to give tricycle 111. The enol ether moiety was reduced using NaCNBH3, followed by allylic Riley oxidation and PCC-mediated enone formation. Copper-catalyzed conjugate addition in the presence of TMSCl [105] yielded silyl enol ether 112. Subsequent introduction of the side chain in 113 via a Claisen

• of silyl enol ether 188 furnished the desired cis-divinylcyclopropane, which underwent smooth DVCPR under mild conditions to give bridged bicycle 189. The alcohol was deprotected and oxidized to aldehyde 190. The aldehyde was transferred into the corresponding cyanohydrin trimethylsilyl ether using

Synthesis of five- and six-membered cyclic organic peroxides: Key transformations into peroxide ring-retaining products

• Alexander O. Terent'ev,
• Dmitry A. Borisov,
• Vera A. Vil’ and
• Valery M. Dembitsky

Beilstein J. Org. Chem. 2014, 10, 34–114, doi:10.3762/bjoc.10.6

Diastereoselectivity in the Staudinger reaction of pentafluorosulfanylaldimines and ketimines

• Alexander Penger,
• Cortney N. von Hahmann,
• Alexander S. Filatov and
• John T. Welch

Beilstein J. Org. Chem. 2013, 9, 2675–2680, doi:10.3762/bjoc.9.303

• of SF5Cl to the enol ether 2 instead of the previously described additions to enol acetates [16] (Scheme 1). In earlier studies, it was found that the yield of SF5Cl addition to enol acetates was highly dependent upon the purity of the enol acetate substrate, compounds surprisingly difficult to

Gold(I)-catalyzed domino cyclization for the synthesis of polyaromatic heterocycles

• Mathieu Morin,
• Patrick Levesque and
• Louis Barriault

Beilstein J. Org. Chem. 2013, 9, 2625–2628, doi:10.3762/bjoc.9.297

• , the cyclization of cyclic enol ether 1 using σ-donor ligands such as IPr (L1) [19] was exceptionally selective for the 5-exo-dig pathway (1→2) whereas bulky Me4XPhos (L2) [12] gave mainly 6-endo-dig-cyclized product 3. Results and Discussion During the course of our investigation, we examined the

• cyclization of non-cyclic enol ethers. As expected, the cyclization of enol ether 4 using [L2AuNCMe][SbF6] in dichloromethane afforded the cyclohexene 5 in 79% yield (Scheme 2). However, the anticipated 5-exo-dig product 6 was not observed when the catalyst [L1AuNCMe][SbF6] was utilized. Instead, the

• cyclizations of the enol ether 11a (R1 = p-BrC6H4, R2 = H) gave the corresponding benzothiophene 12a in 83% yield. The use of electron-poor silyl enol ether 11b (R1 = p-NO2C6H4, R2 = H) gave the desired product 12b, albeit in lower yield of 63%. Di- and trisubstituted silyl enol ethers 11c (R1 and R2 = H) and

Stereodivergent synthesis of jaspine B and its isomers using a carbohydrate-derived alkoxyallene as C₃-building block

• Volker M. Schmiedel,
• Stefano Stefani and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2013, 9, 2564–2569, doi:10.3762/bjoc.9.291

• therefore leads to a stereodivergent approach to the natural product and its enantiomer. The gold-catalyzed 5-endo-cyclization affords the corresponding dihydrofurans, which after separation, azidation of the enol ether moiety and two subsequent reduction steps give the natural product and its stereoisomers