TMSOTf Research Articles

Factorizing the Nephelauxetic Effect in Heteroleptic Molecular Rubies.

The interest in chromium(III) complexes has been renewed over the past decade for the design of efficient earth-abundant phosphorescent red-to-near-infrared spin-flip emitters and photocatalysts with long excited state lifetimes. In this context, we report the energy tuning of spin-flip excited states based on heteroleptic bis(tridentate) polypyridine chromium(III) complexes [3X,Y]3+, namely, [3NMe,CH2]3+, [3NMe,S]3+ and [3CH2,S]3+ with the tridentate ligands LX and LY [X/Y = NMe, N,N'-dimethyl-N,N'-dipyridin-2-ylpyridine-2,6-diamine; X/Y = CH2, 2,6-bis(2-pyridylmethyl)pyridine and X/Y = S, 2,6-bis(pyridine-2-ylthio)pyridine]. The heteroleptic complexes [3X,Y]3+ are obtained via a novel synthetic approach toward the required intermediate labile triflato complexes Cr(LX)(OTf)3 (2X) from the respective chlorido precursors CrCl3(LX) (1X) using trimethylsilyl trifluoromethanesulfonate. Spin-flip energies were experimentally detected by vis/near-infrared absorption and emission spectroscopy as well as computationally derived by multireference calculations. Together with the known homoleptic molecular ruby complexes, the three resulting series of luminescent complexes [3X,X]3+/[3X,Y]3+/[3Y,Y]3+ allow delineation of an additive nephelauxetic effect of the ligands with chromium(III) ions and thus prediction of spin-flip emission energies of derived molecular rubies.

Synthesis of the pyruvic acid acetal containing tetrasaccharide repeating unit corresponding to the K82 capsular polysaccharide of Acinetobacter baumannii LUH5534 strain

An efficient synthetic strategy has been developed to achieve a pyruvic acid acetal containing tetrasaccharide repeating unit corresponding to the K82 capsular polysaccharide of Acinetobacter baumannii LUH5534 strain in very good yield. The synthetic scheme involves the use of suitably functionalized monosaccharide thioglycosides as glycosyl donors and a combination of N-iodosuccinimide (NIS) and trimethylsilyl trifluoromethanesulfonate (TMSOTf) as thiophilic glycosylation activator to furnish satisfactory yield of the products with appropriate stereochemistry at the glycosidic linkages. Incorporation of the (R)-pyruvic acid acetal in the D-galactose moiety was achieved in very good yield by the treatment of the diol derivative with methyl 2,2-bis(p-methylphenylthio)propionate in the presence of a combination of NIS and triflic acid.

Friedel–crafts alkylations of indoles, furans, and thiophenes with arylmethyl acetates promoted by trimethylsilyl trifluoromethanesulfonate

Various indoles undergo Friedel–Crafts alkylation at the 3-position when treated with secondary arylmethyl acetates in the presence of trimethylsilyl trifluoromethanesulfonate (TMSOTf) and 2,6-lutidine. Tertiary benzylic alcohols are also effective alkylating agents, undergoing TMSOTf-promoted activation to yield alkylated indoles that feature quaternary centers. A related study shows that benzofuran reacts under similar conditions to yield 2-alkylated benzofurans when treated with similar alkylating agents, and the reaction has been extended to include other representative heteroarenes. Yields for these Friedel–Crafts alkylation products range from 43%–99% over a wide range of substrate combinations.

Synthesis of β-Carbonyl α-Iminoamides by Double Insertion of Isocyanides into Aldehydes.

An unprecedented trimethylsilyl trifluoromethanesulfonate (TMSOTf)-promoted selective double insertion of isocyanides into aldehydes was developed, providing an efficient protocol for synthetically challenging β-carbonyl α-iminoamides. The given approach is applicable for a diverse selection of readily accessible aldehydes, along with isocyanides serving as essential precursors for "amide" and "imine" scaffolds. The versatile transformations of the given products were demonstrated, and the pivotal intermediates for the plausible mechanism were identified.

Use of an oxazolidinone derivative of a sialyl thioglycoside as a useful glycosyl donor for α-favorable glycosidation with simple alcohols

An efficient synthesis of lauryl thioglycoside of oxazolidinones derived from N-acetyl neuraminic acid was accomplished from a known thioglycoside of Neu5Ac. The O-glycosidation reactivities of the oxazolidinones were evaluated by means of trimethylsilyl trifluoromethanesulfonate (TMSOTf) and N-iodosuccinimide (NIS) as a combined-mediator system. The glycosidation reaction of the lauryl thioglycoside with simple alcohols proceeded smoothly to yield the corresponding α-glycosides in good yields after isolation. The results suggested that the glycosylation reaction using the oxazolidinone derivative of sialic acid has excellent α-stereoselectivity and enables easy isolation of the desired product from the reaction mixture.

Convergent synthesis of the pentasaccharide repeating unit corresponding to the cell wall O-polysaccharide of Salmonella milwaukee (group U) O:43 strain

Synthesis of the pentasaccharide repeating unit of the cell O-polysaccharide produced by Salmonella milwaukee O:43 strain (group U) has been achieved in very good yield adopting a convergent stereoselective [3 + 2] block glycosylation strategy. Thioglycosides and glycosyl trichloroacetimidate derivative were used as glycosyl donors in the presence of a combination of N-iodosuccinimide (NIS) and trimethylsilyl trifluoromethanesulfonate (TMSOTf) as thiophilic activator and TMSOTf as trichloroacetimidate activator respectively. The stereochemical outcome of all glycosylation reactions was excellent.

Convergent Synthesis of a Pentasaccharide Containing a Rare Sugar 4‐amino‐4‐deoxy‐D‐fucose Related to the Cell Wall O‐polysaccharide of Acinetobacter baumannii 90

AbstractA convenient synthetic strategy has been developed for the synthesis of a pentasaccharide related to the cell wall O‐polysaccharide of Acinetobacter baumannii (A. baumannii) 90 in very good yield applying a stereoselective [3+2] block glycosylation reaction. The synthesis of the target pentasaccharide was challenging due to the presence of a rare sugar, 4‐amino‐4‐deoxy‐D‐fucose and several α‐glycosidic linkages in it. The construction of 1,2‐cis glycosyl linkages were achieved using a combination of copper(II) bromide and tetra‐n‐butylammonium bromide (TBAB) or a combination of N‐iodosuccinimide (NIS) and trimethylsilyl trifluoromethanesulfonate (TMSOTf) as thiophilic glycosylation activator. Perchloric acid supported over silica (HClO4‐SiO2) mediated orthogonal glycosylation reaction has been carried out using glycosyl trichloroacetimidate derivative as donor and thioglycoside as acceptor.

MSTFA as an Effective TMS Source for the TMSOTf-Catalzyed Synthesis of Cyclic Acetals.

Commercially and readily available MSTFA [2,2,2-trifluoro-N-methyl-N-(trimethylsilyl)acetamide] was identified as a highly effective TMS (trimethylsilyl) source for the convenient preparation of cyclic acetals under modified Noyori's conditions. The reactions proceeded smoothly under mild conditions, affording a wide range of the corresponding cyclic acetals with excellent yields in the presence of catalytic TMSOTf (trimethylsilyl trifluoromethanesulfonate). The present method does not require a large excess of diols that can be valuable and does not require presynthesized silylated diols. In contrast to other silylating reagents such as BSA [N,O-bis(trimethylsilyl)acetamide] and BSTFA [N,O-bis(trimethylsilyl)trifluoroacetamide], the application of MSTFA avoided the inhibition of catalytic acetalization by the side product 2,2,2-trifluoro-N-methylacetamide.

Diastereoselective Synthesis of High Functionalized 4‐Imidazolidinone‐Tetrahydro‐β‐Carboline Hybrids via Divergent Post‐Ugi Transformation

AbstractAn easily scalable and highly diastereoselective synthesis of challenging 1,2,5,6,11,11b‐hexahydro‐3H‐imidazo[1′,2′:1,2]pyrido[3,4‐b]indol‐3‐ones is accomplished through divergent transformation of Ugi 4‐CR products. The trimethylsilyl trifluoromethanesulfonate (TMSOTf) mediated intramolecular condensation of a series of Ugi 4‐CR adducts generates a N‐acylimidinium intermediate which undergoes ring closure to selectively afford the target title compounds in good to high yields.

Synthesis of the Pentasaccharide of the K14 Capsular Polysaccharide of Antibiotic Resistant ST25 Acinetobacter baumannii isolate, D46 and O‐Polysaccharide of Acinetobacter baumannii O11

AbstractSynthesis of the pentasaccharide corresponding to the K14 capsular polysaccharide from ST25 Acinetobacter baumannii isolate, D46 and O‐polysaccharide of Acinetobacter baumannii O11 has been achieved in very good yield using a convergent stereoselective [3+2] block glycosylation strategy. The synthetic scheme includes several regio‐ and stereose lective glycosylations as well as orthogonal glycosylation with high yield. Thioglycosides have been used as glycosyl donors using a combination of copper(II) bromide and tetra‐n‐butylammonium bromide (TBAB) as thiophilic activator for 1,2‐cis glycosylation and a combination of N‐iodosuccinimide (NIS) and trimethylsilyl trifluoromethanesulfonate (TMSOTf) as thiophilic activator for 1,2‐trans glycosylation. Glycosyl trichloroacetimidate derivative was used as glycosyl donor using perchloric acid supported on silica (HClO4–SiO2) as activator. A catalytic transfer hydrogenation reaction has been carried out for the removal of benzyloxy and benzylidene functional groups using triethylsilane as hydrogen source.

Synthesis and Derivatives of Beryllium Triflate.

Various pathways for the synthesis of beryllium triflate were investigated. The reaction of triflic acid or trimethylsilyl triflate with beryllium metal in liquid ammonia led to the formation of mono-, di-, and tetra-nuclear beryllium ammine complexes. Utilization of SMe2 as a solvent gave homoleptic Be(OTf)2. Various beryllium triflate complexes with N- and O-donor ligands as well as the complex anions [Be(OTf)4]2- and [Be2(OTf)6]2- were synthesized to evaluate the reactivity and solution properties of beryllium triflate. This showed that OTf- is not a weakly coordinating anion for Be2+ cations and that it exhibits good bridging properties.

C-SuFEx linkage of sulfonimidoyl fluorides and organotrifluoroborates

Sulfur(VI) fluoride exchange, a new type of linkage reaction, has excellent potential for application in functional molecule linkage to prepare pharmaceuticals, biomolecules, and polymers. Herein, a C-SuFEx reaction is established to achieve fast (in minutes) linkage between sulfonimidoyl fluorides and aryl/alkyl organotrifluoroborates. Potassium organotrifluoroborates are instantaneously activated via a substoichiometric amount of trimethylsilyl triflate to afford organodifluoroboranes, releasing BF3 as an activating reagent in situ. This sulfur(VI) fluoride exchange technique is capable of forming S(VI)-C(alkyl), S(VI)-C(alkenyl) and S(VI)-C(aryl) bonds, demonstrating its broad scope. Natural products and pharmaceuticals with sensitive functional groups, such as valdecoxib, celecoxib and diacetonefructose, are compatible with this protocol, allowing the formation of diverse sulfoximines.

Towards an efficient methodology for the synthesis of functionalized dihydropyrans by silyl-Prins cyclization: access to truncated natural products.

We herein present a selective methodology for the synthesis of disubstituted dihydropyrans by silyl-Prins cyclization of Z-vinylsilyl alcohols mediated by trimethylsilyl trifluoromethanesulfonate (TMSOTf). The reaction features broad substrate scope, short reaction times and ease of process scale-up. Moreover, to showcase the applicability of the proposed method, we also report a facile and linear synthesis of analogues of rhopaloic acid and natural doremox fragrance.

Expeditious Synthesis of the Hexasaccharide Repeating Unit of the Capsular Polysaccharide of Streptococcus pneumoniae Type 7A

AbstractThe hexasaccharide repeating unit corresponding to the capsular polysaccharide of Streptococcus pneumoniae type 7A has been synthesized in good yield using [3+2+1] block synthetic strategy. The synthetic strategy involved a number of challenging stereoselective glycosylation steps, which include β-selective glycosylation of l-rhamnosyl thioglycoside donor, α-selective glycosylations of 2-azido-2-deoxy-d-glucopyranosyl thioglycoside donor and d-galactopyranosyl donor together with the formation of β-glycoside of d-galactosamine moiety and α-glycoside of l-rhamnosyl moiety. Suitably functionalized thioglycosides have been used as glycosyl donors and a combination of N-iodosuccinimide (NIS) and trimethylsilyl trifluoromethanesulfonate (TMSOTf­) has been used as glycosylation promoter.

Ru(OAc)3-Catalyzed Regioselective Difunctionalization of Alkynes: Access to (E)-2-Bromo-1-alkenyl Sulfonates.

A new approach is proposed for the divergent and regioselective synthesis of (E)-2-bromo-1-phenylvinyl trifluoromethanesulfonates through alkyne difunctionalization by employing a compatible system of abundantly available alkynes, N-bromosuccinimide (NBS), and trimethylsilyl trifluoromethanesulfonate (TMSOTf) catalyzed by ruthenium(III) acetate [Ru(OAc)3]. It is a novel method for the preparation of vinyl triflate and it offers a fundamental basis for the development of advanced functional compounds, including drugs and organic functional materials. Unlike previously reported methods, the proposed protocol can tolerate a broad range of functional groups. Alkynes derived from bioactive molecules, such as l(-)-borneol, demonstrate the potential value of this new reaction in organic synthesis.

One-pot silyl imidate formation-N-alkylation reactions of amides with propargyl propionates

The combination of trimethylsilyl trifluoromethanesulfonate (TMSOTf) and i-Pr2NEt promotes the N-alkylation of primary and secondary amides with propargyl propionates. The amide substrates are believed to undergo conversion to nucleophilic silyl imidates in the presence of TMSOTf and the amine base, conditions which also promote propargyl cation formation in the same flask through the loss of trimethylsilyl propionate, leading to N-propargylation of the amide. A range of amides and propargyl propionates react efficiently in this reliable one-pot process with yields ranging from 19 to 99%.

Synthesis and Reactivity of Trifluoromethylthiophosphonium Salts†

Comprehensive SummaryThis article described an unprecedented synthesis of trifluoromethylthiophosphonium salts from allyl trifluoromethyl sulfoxide and phosphines in the presence of trimethylsilyl trifluoromethanesulfonate (TMSOTf) through Mislow‐Evans‐type rearrangement. The resulting trifluoromethylthiophosphonium salts were firstly isolated and fully characterized. These fluoroalkylphosphonium salts, as exemplified by trifluoromethylthio triphenylphosphonium salt (6a), exhibited unique and versatile reaction with nucleophiles and deoxygenative trifluoromethylthiolation reaction of carboxylic acids. Furthermore, the photoredox catalytic tunable radical hydrotrifluoromethylation and hydrotrifluoromethythiolation of unactivated alkenes with 6a was successfully developed.

Residue-selective C-H sulfenylation enabled by acid-activated S-acetamidomethyl cysteine sulfoxide with application to one-pot stapling and lipidation sequence.

A tyrosine (Tyr)- or tryptophan (Trp)-selective metal-free C-H sulfenylation reaction using an acid-activated S-acetamidomethyl cysteine (Cys) sulfoxide, Cys(Acm)(O), has been achieved. The dually protonated intermediate produced from the Cys(Acm)(O) under acidic conditions allows the sulfenylation of Tyr. Significantly, the reaction in the presence of trimethylsilyl trifluoromethanesulfonate (TMSOTf) mainly affords a Cys-Tyr-linked peptide even in the presence of Trp residues. In contrast, a Cys-Trp-linked peptide was selectively obtained from the reaction in the presence of guanidine hydrochloride (Gn·HCl) under acidic conditions. Established Tyr- and Trp-selective sulfenylation methods were used in the Cys-Tyr stapling and Trp-lipidation of glucagon-like peptides in a one-pot/stepwise manner. Investigation of the mechanism showed that orbital- and charge-controlled reactions are responsible for the Trp and Tyr selectivity, respectively.

Cationic Complexes of 3a,6a-Diaza-1,4-diphosphapentalenes

The reactions of annulated 1,4-dichloro-3a,6a-diaza-1,4-diphosphapentalenes (DDPCl2) with 1 equiv. of trimethylsilyl triflate (TMSOTf) lead to replacement of one chlorine atom with the triflate group, thus giving cationic diazadiphosphapentalenes [ClDDP]+[TfO]−. In the presence of 2 equiv. of TMSOTf and 2 equiv. of 4‑dimethylaminopyridine (DMAP), the DDP dication stabilized by two DMAP molecules, [DDP(DMAP)2]2+[(CF3SO3)−]2, is formed. The DMAP molecules are located on one side of the DDP skeleton and lie in parallel planes. Free diazadiphosphapentalene was detected in solutions of [DDP(DMAP)2]2+[(CF3SO3)−]2 in CH2Cl2 by UV-Vis spectroscopy and CV. This implies that this compound disproportionates under these conditions; it is unstable in dilute solutions and decomposes to give [DMAP∙HOTf] in a quantitative yield. Crystallographic data for the obtained compounds: CCDC nos. 2182881–2182883.

Stability Effects of Selective Anion Abstraction from Cesium Lead Halide Perovskite Nanocrystals

The dynamic surface chemistry and stabilization of cesium lead halide perovskite nanocrystals (NCs) remain principal challenges for the use of these materials in many applications. Here, trimethylsilyl trifluoromethanesulfonate (Me3SiOTf) was used as a Lewis acidic reagent for quantitative and irreversible silylation and removal of anionic ligands from colloidal oleate- and oleylamine-capped CsPbBr3 and CsPbCl3 NCs. 1H NMR and FTIR spectroscopies, combined with elemental analysis, show strong binding of a population of anionic ligands to the NC surfaces. Surface anion exchange for trifluoromethanesulfonate also results in an increase in photoluminescence quantum yields. For CsPbCl3 NCs, Me3SiOTf treatment abstracts chlorides and destabilizes the NC lattice. The thermodynamic differences between these reactions and their implications are discussed.