Presence Of Trimethylsilyl Triflate Research Articles

Stereoselective Synthesis of Trisubstituted Alkenes by Nickel-Catalyzed Benzylation and Alkene Isomerization.

Catalytic strategies that provide stereoselective access to highly substituted alkenes from abundant monosubstituted substrates are exceedingly sought-after but rare. Here, we show that a N-heterocyclic carbene-NiI catalytic species mediates efficient union of electronically polarized terminal olefins with benzyl chlorides, in the presence of trimethylsilyl triflate and trimethylamine additives, to generate trisubstituted boron- and arene-containing trans alkenes in excellent regio- and stereoselectivities. Control experiments provide evidence for a mechanism involving branched-selective Heck-type benzylation that overrides substrate control, followed by trans-selective 1,3-hydrogen shift. The method represents a significant addition to the toolbox of reactions for the concise synthesis of unsaturated biologically active compounds.

Stereoselective Synthesis of Trisubstituted Alkenes by Nickel‐Catalyzed Benzylation and Alkene Isomerization

AbstractCatalytic strategies that provide stereoselective access to highly substituted alkenes from abundant monosubstituted substrates are exceedingly sought‐after but rare. Here, we show that a N‐heterocyclic carbene‐NiI catalytic species mediates efficient union of electronically polarized terminal olefins with benzyl chlorides, in the presence of trimethylsilyl triflate and trimethylamine additives, to generate trisubstituted boron‐ and arene‐containing trans alkenes in excellent regio‐ and stereoselectivities. Control experiments provide evidence for a mechanism involving branched‐selective Heck‐type benzylation that overrides substrate control, followed by trans‐selective 1,3‐hydrogen shift. The method represents a significant addition to the toolbox of reactions for the concise synthesis of unsaturated biologically active compounds.

Total Synthesis of Natural Disaccharide Sambubiose.

A practical and robust synthetic method to obtain the natural disaccharide sambubiose (2-O-β-D-xylopyranosyl-D-glucopyranose) is reported, exploring the key step in the synthesis, i.e., stereoselective O-glycosylation. Specifically, the best combinations of glycoside donors and acceptors were identified, stereospecific control of the reaction was achieved by screening several catalysts and protection/deprotection steps were evaluated and improved. The best result was obtained by coupling allyl 3,5,6-tri-O-benzyl-β-D-glucofuranoside with 2,3,4-tri-O-acetyl-D-xylopiranosyl-α-trichloro acetimidate in the presence of trimethylsilyl triflate as a catalyst giving the corresponding protected target compound as a correct single isomer. The latter was transformed accordingly into the desired final product by deprotection steps (deallylation, deacetylation, and debenzylation). Sambubiose was synthesized into a satisfactory and higher overall yield than previously reported and was also characterized.

Synthesis of oligo(spiroketal)s by polycondensation of silyl ethers derived from naturally occurring myo‐inositol with 1,4‐cyclohexanedione

ABSTRACTOligo(spiroketal)s (OSKs) were synthesized from myo‐inositol, a naturally occurring cyclic compound bearing six hydroxyl groups. The successful synthesis of OSKs was achieved using silyl ethers 2 derived from 1,4‐di‐O‐alkylated myo‐inositol 1 as monomers, which underwent polycondensation with 1,4‐cyclohexanedione (CHD) at 0 °C in the presence of trimethylsilyl triflate as a catalyst. Because of the irreversible nature of the condensation reaction of silyl ethers with ketones, the resulting OSKs 7 had higher molecular weights than previously reported OSKs that were obtained by polycondensation of tetraols 1 with CHD, where backward hydrolysis of the ketal functions occurred. In addition, another series of OSKs, 8, were synthesized using silyl ethers 3 derived from 2,5‐di‐O‐alkylated myo‐inositol 6, which are more symmetric monomers than silyl ethers 2. Silyl ethers 3 underwent efficient polycondensation with CHD, whereas tetraol 6 did not, demonstrating that the derivation of such tetraols into the corresponding silyl ethers is a powerful strategy to access OSKs. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 2407–2414

Synthesis of new five-membered N-heterocycle derivatives of mono- and bis-phosphonic acids

The new functionalized hydroxymethylphosphonic and methylenebis(phosphonic) acids are synthesized via reaction of tris(trimethylsilyl) phosphite and N-formyl derivatives of five-membered N-heterocycles in the presence of trimethylsilyl triflate.

ChemInform Abstract: A General Metal Free Approach to α‐Ketoamides via Oxidative Amidation—Diketonization of Terminal Alkynes.

AbstractIn the presence of trimethylsilyl triflate and catalytic amounts of iodine, the first metal free oxidative amidation—diketonization of terminal alkynes leads to a wide variety of α‐ketoamides.

Synthesis of Purine Nucleosides from D‐Glucuronic Acid Derivatives and Evaluation of Their Cholinesterase‐Inhibitory Activities

AbstractGlucuronolactones were used as precursors for N9 and N7 purine nucleosides containing glucuronic acid derivatives in their structures. Acetylated N‐benzylglucofuran‐ and glucopyranuronamides were synthesized in a few steps from glucofuranurono‐6,3‐lactone. They were converted into the corresponding furanosyl and pyranosyl uronamide‐based nucleosides by N‐glycosylation with silylated 2‐acetamido‐6‐chloropurine in the presence of trimethylsilyl triflate. The triacetylated bicyclic lactone was coupled itself with the nucleobase to give bicyclic N9,N7 nucleosides. Tri‐O‐acetylglucopyranurono‐6,1‐lactone was used for the first time as a glycosyl donor for N‐glycosylation, and led to β‐configured N9‐ and N7‐linked purinylglucuronides under reaction conditions similar to those used with the 1‐O‐acetyl‐substituted glycosyl donors. The cholinesterase inhibitory profiles of the synthetic nucleosides bearing glucuronic acid derivatives as glycons were evaluated, and they showed moderate selective acetylcholinesterase inhibitory activities (Ki = 14.78–50.53 μM). The best inhibition was shown by the furanosyl N9‐linked uronamide‐based purine nucleoside.

Mechanism of the Pummerer Reaction: A Computational Study

DFT calculations are used to investigate the mechanism of the Pummerer reaction between a chiral sulfoxide and acetic anhydride under classical and stereoselective reaction conditions (without and with additives, respectively). The first step involving acetylation of the sulfoxide with release of acetate is found to be rate-determining in both cases. For the stereoselective Pummerer reaction in the presence of trimethylsilyl triflate (TMSOTf) and N,N-dimethylacetamide (DMAC), TMSOTf- and DMAC-assisted transition states as well as ion exchange reactions are considered to account for the role of TMSOTf and DMAC.

Synthesis of tetra- and hexasaccharide fragments corresponding to the O-antigenic polysaccharide of Klebsiella pneumoniae

The preparation of linear tetra- (1) and hexasaccharides (2), containing the repeating unit [→3)-β-Galf-(1→3)-α-Galp-(1→] present in the O-polysaccharide of the lipopolysaccharide of Klebsiella pneumoniae is described. The key step in their synthesis is the α-selective galactopyranosylation of 3-OH di- and tetrasaccharide acceptors (20 and 22) with a disaccharide trichloroacetimidate donor 19 in the presence of trimethylsilyl triflate in a diethyl ether–CH2Cl2 mixture as solvent.

ChemInform Abstract: Synthesis of 2′,3′-Dideoxynucleosides from 5-Alkoxymethyluracils.

A modified synthesis of protected 2,3-dideoxyribose5 starting fromL-glutamic acid (1) is described. Reaction of5 with silylated 5-hydroxymethyluracil7 a and 5-alkoxymethyluracils7 b–e in the presence of trimethylsilyl triflate afforded an anomeric mixture of 2′,3′-dideoxyuridine derivatives8 a–e and9 a–e. Deprotection with methanolic ammonia and separation by chromatography gave the corresponding nucleosides10 a–e and11 a–e. Treatment of9 b–e with tri(1H-1,2,4-triazol-1-yl)phosphine oxide and subsequent reaction of12 b–e with ammonia in dioxane afforded the cytosine derivatives13 b–e which on treatment with methanolic ammonia gave the corresponding 2′,3′-dideoxycytidine derivatives14 b–e and15 b–e. In contrast with the parent compounds, these alkoxymethyl derivatives had no appreciable activity against human immunodeficiency virus (HIV-1).

ChemInform Abstract: Stereoselective Synthesis of trans-2,6-Diaryl-4-piperidones by Using Benzaldiminetricarbonylchromium Derivatives.

Stereoselective synthesis of trans-2,6-diaryl-4-piperidones has been carried out by cycloaddition of benzaldiminetricarbonylchromium derivatives 1 with 2-silyloxybuta-1,3-diene in the presence of trimethylsilyl triflate as a Lewis acid. The tricarbonylchromium moiety played an important role in increasing the stereoselectivities of the products.

Preparation and Characterization of a Ligand‐Stabilized Trimethylphosphane Dication

AbstractThe ditriflate salt of the DMAP‐stabilized trimethylphosphane dication is formed from the reaction of chlorotrimethylphosphonium triflate with DMAP (4‐dimethylaminopyridine) in the presence of trimethylsilyltriflate and also from the reaction of DMAP‐dimethylphosphenium triflate with methyltriflate. The coordinative nature of the DMAP–phosphorus bond is demonstrated by a ligand exchange of DMAP for PMe3 to give the hexamethyldiphosphonium dication. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

Synthesis, Structure, and Electrochemistry of Di- and Zerovalent Nickel, Palladium, and Platinum Monomers and Dimers Derived from an Enantiopure (S,S)-Tetra(tertiary Phosphine)

The ligand (S,S)-1,1,4,7,10,10-hexaphenyl-1,4,7,10-tetraphosphadecane, (S,S)-tetraphos, reacts with hexa(aqua)nickel(II) chloride in the presence of trimethylsilyl triflate (TMSOTf) in dichloromethane to give the yellow square-planar complex [Ni{(R,R)-tetraphos}](OTf)2, which has been crystallographically characterized as the square-pyramidal, acetonitrile adduct [Ni(NCMe){(R,R)-tetraphos}]OTf. Cyclic voltammograms of the nickel(II) complex in dichloromethane and acetonitrile at 20 degrees C showed two reduction processes at negative potentials with oxidative (E(p)(ox)) and reductive (E(p)(red)) peak separations similar to those observed for ferrocene/ferrocenium under identical conditions, suggesting two one-electron steps. The cyclic voltammetric data for the divalent nickel complex in acetonitrile at temperatures below -20 degrees C were interpreted according to reversible coordination of acetonitrile to the nickel(I) and nickel(0) complexes. The divalent palladium and platinum complexes [M{(R,R)-tetraphos}](PF6)2 and [M2{(R,R)-tetraphos}2](OTf)4 have been prepared. The reduction potentials for the complexes [M{(R,R)-tetraphos}](PF6)2 increase in the order nickel(II) < palladium(II) < platinum(II). The reaction of (S,S)-tetraphos with bis(cycloocta-1,5-diene)nickel(0) in benzene affords orange [Ni{(R,R)-tetraphos}], which slowly rearranges into the thermodynamically more stable, yellow, double-stranded helicate [Ni2{(R,R)-tetraphos}2]; the crystal structures of both complexes have been determined. The reactions of (S,S)-tetraphos with [M(PPh3)4] in toluene (M = Pd) or benzene (M = Pt) furnish the double-stranded helicates [M2{(R,R)-tetraphos}2]; the palladium complex crystallizes from hot benzene as the 2-benzene solvate and was structurally characterized by X-ray crystallography. In each of the three zerovalent complexes, the coordinated (R,R)-tetraphos stereospecifically generates tetrahedral M(PP)2 stereocenters of M configuration.

A new route to furanoeremophilane sesquiterpenoids. Synthesis of Senecio metabolites (±)-6-hydroxyeuryopsin, (±)-1,10-epoxy-6-hydroxyeuryopsin, (±)-toluccanolide A and (±)-toluccanolide C

A new strategy for the synthesis of sesquiterpenoids of the furanoeremophilane family was developed in which the tricyclic nucleus was assembled in an A + C → A–C → A–B–C sequence. The A–C connection was made via coupling of a cyclohexenylmethyl bromide with a stannylfuran under “ligandless” Stille conditions, and the key cyclization which closed ring B was accomplished with complete stereocontrol by intramolecular formylation of a 2-silylfuran in the presence of trimethylsilyl triflate. This route was used to complete the first total syntheses of the furanoeremophilane 6-hydroxyeuryopsin and the eremophilenolides toluccanolide A and toluccanolide C, as well as a formal synthesis of 1,10-epoxy-6-hydroxyeuryopsin.

Diastereoselective Allylation of Imines with &amp;#947;-Silyloxyallylstannanes Promoted by Trimethylsilyl Triflate and Application to the Synthesis of Erythro-Sphingosine

Addition of γ-silyloxyallylstannanes to imines in the presence of trimethylsilyl triflate was studied. Allylation of α-imino ester with (Z)-allylstannane proceeded to give anti-adduct as a major product, which was transformed into N,O,O-triacetyl erythro-sphingposine via appropriate functional group transformations. Keywords: silyloxyallylstannane, imines, allylation, erythro-sphingosine

Solid-phase Parallel Synthesis of 4-β-D-Ribofuranosylpyrazolo[4,3-d]pyrimidine Nucleosides

The synthesis of pyrazolo[4,3-d]pyrimidine nucleoside library using solid-phase parallel synthesis methodology is described. Glycosylation of the trimethylsilyl (TMS) derivative of 1- and 2-(methyl)-1H and 2H-pyrazolo[4,3-d]pyrimidine-5,7-(4H,6H)-dione (5) with 1-O-acetyl-2,3,5-tri-O-benzoyl-D-ribofuranose in the presence of TMS triflate provided two novel protected nucleosides 6 and 7. The structures of 6 and 7 were assigned by 1H and 2D NMR experiments. Nucleosides 6 and 7 were then transformed to the key intermediates 12 and 15 respectively. Reaction of 12 and 15 with MMTCl resin in the presence of 2,6-lutidine afforded the necessary scaffolds B and C. Different amines (96) were introduced selectively by nucleophilic substitution on scaffolds B and C using solid-phase parallel semi-automated synthesizer. Cleavage of the products from the solid support with 30% HFIP in a parallel fashion yielded nucleoside libraries simultaneously, and they were analyzed and characterized by high-throughput LC-MS.

Addition of Metal Cyanides to Tosylhydrazones of Aldehydes in Aprotic Solvents: A New Method for One‐Carbon Homologation of Aldehydes and for the Synthesis of α‐(N2‐Tosylhydrazino)nitriles.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Addition of Metal Cyanides toTosylhydrazones of Aldehydes in Aprotic Solvents: A NewMethod for One-Carbon Homologation of Aldehydes and forthe Synthesis of α-(N 2-Tosylhydrazino)nitriles

One-carbon homologation of aldehydes to nitriles via reaction of the respective tosylhydrazones with trimethylsilyl cyanide, tributyltin cyanide and diethylaluminum cyanide with or without Lewis acid-type catalysts was examined. Representative tosylhydrazones on treatment with trimethylsilyl cyanide in the presence of trimethylsilyl triflate or scandium triflate afforded α-(N 2-tosylhydraziono)nitriles in excellent yields. The same adducts were also obtained using tributyltin cyanide/scandium triflate system or diethylaluminum cyanide at room temperature. Treatment of tosylhydrazones with trimethylsilyl cyanide/scandium triflate or with diethylaluminum cyanide in appropriate solvent at higher temperatures afforded the respective one-carbon extended nitriles in good yields. Some examples of the application of these reactions to polyfunctional compounds are given.

Conjugate addition of organozinc reagents to enones linked to a tricarbonyl iron diene unit. Asymmetric synthesis of a building block of amphotericin B

Conjugate addition of organometallics to enones linked by the ketocarbonyl to tricarbonyliron diene units can be successfully achieved with dialkylzinc reagents, when used in the presence of trimethylsilyl triflate. Organocopper reagents are not well suited, giving only incomplete and partially destructive reactions. The enone complexes are easily obtained by dehydration of aldol condensation products, which is particularly interesting when the aldol reaction is also a resolution (chiral aldehydes). The conjugate addition is not highly diastereoselective, unless the enones are substituted with polar groups (de up to 88% for γ-alkoxylated enones). This conjugate addition reaction was used to synthesize, in two practical steps from the enone 14 (two asymmetric centers), the chlorohydrin 25 (54%, five asymmetric centers), an elaborate intermediate for the synthesis of amphotericin B. Graphic

The Reaction of Nitrones with Organometallic Compounds: Scope, Limitations and Synthetic Applications

Synthetic organic chemists have widely exploited nitrones for the last 50 years as precious substrates for the assembly of complex nitrogen containing frameworks through inter and intramolecular 1,3-dipolar cycloadditions. In the last decade the interest for nitrones was further on increased by a second opportunity, offered by the nucleophilic addition of organometallic reagents to give N,N-disubstituted hydroxylamines. Grignard, lithium reagents and allylic zinc derivatives react very efficiently with nitrones in a wide temperature range, both the reaction rate and the stereochemical outcome of the process can be significantly modified by the addition of nitrone-chelating Lewis acids. The allylation of nitrones is also carried out under Sakurai conditions in the presence of trimethylsilyltriflate, and different results are obtained using allylic silanes or stannanes. Homoallylic hydroxylamines, generated by the allylation of nitrones, are exploited in 5-exo-trig iodocyclizations to give 5-iodomethyl isoxazolidines, useful precursors of hydroxylated acyclic and cyclic amino compounds. Enolates and silyl enol ethers under Mukayama conditions are also investigated. In particular, 2-trimethylsilyloxyfuran reacts with nitrones, in the presence of nitrone activators, to give 3-substituted tetrahydrofuro[2,3-d]isoxazol-5(2H)-ones, easily transformed into a variety of polyhydroxylated piperidine and indolizidine azasugars. The most recent solutions to achieve the control of stereochemistry in nucleophilic additions to nitrones will be examined.