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

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

• 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

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

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

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

• 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

• equipped with a magnetic stirrer was added the silyl enol ether 11 (0.101 mmol) followed by nitromethane (1 mL) and [L1AuNCMe][SbF6] (0.005 mmol). After stirring overnight, the reaction mixture was concentrated in vacuo and the crude mixture was purified by flash chromatography (1–5% ethyl acetate/hexanes

Bidirectional cross metathesis and ring-closing metathesis/ring opening of a C₂-symmetric building block: a strategy for the synthesis of decanolide natural products

• Bernd Schmidt and
• Oliver Kunz

Beilstein J. Org. Chem. 2013, 9, 2544–2555, doi:10.3762/bjoc.9.289

• with silane to regenerate the Cu-hydride. Alternatively, the Cu-enolate might enter a competing catalytic cycle by reacting with silane, furnishing a silyl enol ether and the catalytically active Cu-hydride species. The silyl enol ether is inert to protonation by tert-butanol, and therefore the

• competing secondary cycle will result in a decreased yield of reduction product. This reasoning prompted us to run the reaction in toluene without any protic co-solvent, which should exclusively lead to the silyl enol ether, and add TBAF as a desilylating agent after complete consumption of the starting

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

• synthesized (Scheme 8). Strategic bond disconnections revealed the common isoindolinone precursor 73. The synthesis of the latter commenced from N,N-dibenzylphenylalanine (71) to afford the Diels–Alder substrate 72 in four steps. The envisioned intramolecular Diels–Alder cyclization of the silyl enol ether 72

• provided the depicted endo-diastereomer in good yield. Exchange of the N-benzyl for a Boc-protecting group and cleavage of the silyl enol ether gave the corresponding ketone, which was first converted to an enol-triflate and then to the tricyclic alkene 73. At this stage, the syntheses of cytochalasin B

Asymmetric synthesis of a highly functionalized bicyclo[3.2.2]nonene derivative

• Toshiki Tabuchi,
• Daisuke Urabe and
• Masayuki Inoue

Beilstein J. Org. Chem. 2013, 9, 655–663, doi:10.3762/bjoc.9.74

• heptenone 12 [17][18][19][20][21]. The more thermodynamically stable silyl enol ether 13 was regioselectively formed from 12 under Holton’s conditions [22], and DDQ-mediated oxidation of 13 resulted in the formation of α,β-unsaturated ketone 14. Asymmetric reduction of ketone 14 was in turn realized by

• due to the unfavorable interaction of the two proximal TBS groups in TS-B, allowing formation of 8 as the major compound. Having synthesized the optically active 8, the next task was the preparation of C2-symmetric bicyclo[3.3.2]decene 1 from 8 (Scheme 5). The silyl enol ether formation of aldehyde 8

• chromatography (silica gel 200 g, pentane only) to afford silyl enol ether 13 (3.3 g, 16 mmol) and its regioisomer (344 mg, 1.64 mmol) in 70% and 7% yield, respectively. The synthesized silyl enol ether 13 was immediately subjected to the next reaction: colorless oil; 1H NMR (500 MHz, C6D6) δ 0.17 (9H, s, CH3 of

Facile isomerization of silyl enol ethers catalyzed by triflic imide and its application to one-pot isomerization–(2 + 2) cycloaddition

• Kazato Inanaga,
• Yu Ogawa,
• Yuuki Nagamoto,
• Akihiro Daigaku,
• Hidetoshi Tokuyama,
• Yoshiji Takemoto and
• Kiyosei Takasu

Beilstein J. Org. Chem. 2012, 8, 658–661, doi:10.3762/bjoc.8.73

• mol % of Tf2NH, −10 °C, CH2Cl2). The results are summarized in Table 2. All the kinetically favourable silyl enol ethers 1 were smoothly isomerized to the thermodynamically stable 2 in the presence of Tf2NH. A plausible mechanism for the catalytic isomerization is shown in Scheme 1. Silyl enol ether 1

• is rapidly protonated by a catalytic amount of Tf2NH to give the corresponding siloxonium cation 4, and, then, another molecule of silyl enol ether 1 deprotonates the α-position of 4. Equilibration results in the selective production of the thermodynamically more stable 2. As a side reaction, the

Recent developments in gold-catalyzed cycloaddition reactions

• Fernando López and
• José L. Mascareñas

Beilstein J. Org. Chem. 2011, 7, 1075–1094, doi:10.3762/bjoc.7.124

• is regenerated. When using a dienol silyl ether such as 21 (Scheme 12) as the diene component, the formation of the (4 + 2) products can be justified in terms of an alternative mechanism consisting of a 5-exo nucleophilic attack of the silyl enol ether moiety on the electrophilically activated alkyne

Gold-catalyzed alkylation of silyl enol ethers with ortho-alkynylbenzoic acid esters

• Haruo Aikawa,
• Tetsuro Kaneko,
• Naoki Asao and
• Yoshinori Yamamoto

Beilstein J. Org. Chem. 2011, 7, 648–652, doi:10.3762/bjoc.7.76

• -induced in situ construction of leaving groups and subsequent nucleophilic attack on the silyl enol ethers. The generated leaving compound abstracts a proton to regenerate the silyl enol ether structure. Keywords: alkylation; gold catalysis; leaving group; silyl enol ether; substitution reaction

• reaction of silyl enol ethers with ortho-alkynylbenzoic acid esters which leads to the formation of α-alkylated silyl enol ethers (path b). We examined the reactions of silyl enol ether 1a with ortho-alkynylbenzoic acid benzyl esters 2 in the presence of gold catalysts under several reaction conditions and

• the results are summarized in Table 1 [18][19][20][21]. With a cationic gold catalyst, derived from Ph3PAuCl and AgClO4, the reaction of 1a with 2a proceeded at 80 °C over 2 h and the benzylated silyl enol ether 3a was obtained in 35% yield, along with the eliminated isocoumarin 4a and recovered 2a in

Shelf-stable electrophilic trifluoromethylating reagents: A brief historical perspective

• Norio Shibata,
• Andrej Matsnev and
• Dominique Cahard

Beilstein J. Org. Chem. 2010, 6, No. 65, doi:10.3762/bjoc.6.65

• trifluoromethylating power of chalcogenium salts increased in the order Te < Se < S while nitro-substituted reagents showed higher reactivity than non-nitrated reagents [14]. Matching the power of the trifluoromethylating agent with the nucleophile (carbanion, silyl enol ether, enamine, phenol, aniline, phosphine

Fused bicyclic piperidines and dihydropyridines by dearomatising cyclisation of the enolates of nicotinyl-substituted esters and ketones

• Heloise Brice,
• Jonathan Clayden and
• Stuart D. Hamilton

Beilstein J. Org. Chem. 2010, 6, No. 22, doi:10.3762/bjoc.6.22

• Heloise Brice Jonathan Clayden Stuart D. Hamilton School of Chemistry, University of Manchester, Oxford Rd., Manchester M13 9PL, United Kingdom 10.3762/bjoc.6.22 Abstract The silyl enol ether derivatives of ketones or esters tethered by a hydrocarbon or ether linkage to the 3-position of a

• it into a silyl enol ether 9. Silyl enol ethers and ketene acetals are known to add effectively to pyridinium species in an intermolecular manner [42][43][44][45][46]. Thus 7 was converted to silyl enol ether 9 in excellent yield under standard conditions. A single geometrical isomer was obtained

• however that these yields were not consistently reproducible and yields around 25% were more commonly observed. However, scrupulous avoidance of contact with oxygen before the hydrogenation step improved the yield of 20a to 41%. Attempted cyclisation without formation of the silyl enol ether (i.e

Mitomycins syntheses: a recent update

• Jean-Christophe Andrez

Beilstein J. Org. Chem. 2009, 5, No. 33, doi:10.3762/bjoc.5.33

End game strategies towards the total synthesis of vibsanin E, 3-hydroxyvibsanin E, furanovibsanin A, and 3-O-methylfuranovibsanin A

• Brett D. Schwartz,
• Craig M. Williams and
• Paul V. Bernhardt

Beilstein J. Org. Chem. 2008, 4, No. 34, doi:10.3762/bjoc.4.34

• ) by a Claisen rearrangment (via the silyl enol ether) was not high yielding and produced many side products. Ozonolysis of 25 afforded the acetone sidechain (i.e. 26) in acceptable yield (50%). Other methods to unmask the ketone functionality failed, for example, dihydroxylation followed by oxidative

Sordarin, an antifungal agent with a unique mode of action

• Huan Liang

Beilstein J. Org. Chem. 2008, 4, No. 31, doi:10.3762/bjoc.4.31

• (Swern), which was converted to the corresponding silyl enol ether. Saegusa oxidation [23] of the latter occurred regioselectively to afford 15, which underwent intramolecular cycloaddtion in benzene at 40 °C. A final deprotection gave sordaricin methyl ester (3) in 16 linear steps from 8 and 9 with an

• silylation / cycloaddition conditions that had successfully advanced 94 to 95, and it was recovered unchanged after many such attempts. Thus, extensive studies were performed to find suitable conditions for the silylation reaction. Silyl enol ether formation failed to occur under Corey-Gross (LDA, R3SiCl

Contemporary organosilicon chemistry

• Steve Marsden

Beilstein J. Org. Chem. 2007, 3, No. 4, doi:10.1186/1860-5397-3-4

• . Notwithstanding the earlier, pioneering work of chemists such as Eaborn, 1968 was notable for many innovations we now take for granted, including the development of silyl enol ether chemistry by Stork and Hudrlik, and the eponymous olefination reaction by Peterson. These landmark papers triggered a massive growth