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N-Alkylindoles undergo Friedel-Crafts addition to aryl and secondary alkyl nitrones in the presence of trimethylsilyl trifluoromethanesulfonate and trialkylamine to produce 3-(1-(silyloxyamino)alkyl)indoles. Spontaneous conversion to bisindolyl(aryl)methanes, which is thermodynamically favored for nitrones derived from aromatic aldehydes, is suppressed under the reaction conditions. The silyloxyamino group can be deprotected with tetrabutylammonium fluoride to yield hydroxylamines.

Trimethylsilyl trifluoromethanesulfonate mediated dimerization reaction of vinylogous carbamates of carbazoles gave highly fluorescent pyridocarbazoles through a Povarov-type formal [4 + 2] cycloaddition-retro-aza-Michael cascade. The developed strategy was used to access indolo pyridocarbazole and quinolizinocarbazolone in an expeditious manner. Various coupling reactions were successfully performed on synthesized pyridocarbazoles to study the effect of electronics of substitution on photophysical properties. Synthesized carbazoles possess excellent photophysical properties with high quantum yields (ΦF). Fluorescent carbazole dicarboxylic acid showed potential as a pH probe to give a linear response to pH over a very wide range (7.0-3.0) reflecting high efficiency.

The stoichiometric reactions of antimony trichloride, trimethylsilyl trifluoromethanesulfonate, and diiminopyridine ligands lead to the formation of N,N′,N′′-chelated SbCl2 cationic complexes. Methyl and phenyl substituents on the imine carbons of the ligand yielded structures with a lone pair on antimony and the hydrogen substituted variant was notably different as it forms a Menshutkin complex with meta-xylene in the solid-state.

The preparation of anomeric tetrabutylammonium sulphates of glucose and galactose derivatives is reported and their role as donors in glycosylation reactions is studied. Metal triflates showed good performance in activating sulphate as a leaving group. Among them, ytterbium triflate in stoichiometric amounts gave the best results. Basic conditions using barium oxide in combination with trimethylsilyl trifluoromethanesulfonate (TMSOTf) were also shown to give good results. Benzylated sulphates were much more reactive than benzoylated donors when activated either by ytterbium triflate or by BaO and TMSOTf. Different acceptors were tested, such as isopropanol, cholesterol, and other common sugar derivatives. High reaction rates and excellent glycosylation yields were obtained under mild reaction conditions. The α/β anomeric ratio suggests a predominant SN2-like reaction mechanism.

α,β-Unsaturated esters were selectively protected in situ in the presence of α,β-unsaturated Weinreb amides using PEt3 and trimethylsilyl trifluoromethanesulfonate (TMSOTf) in toluene under reflux. Diisobutylaluminium hydride (DIBAL-H) reduction of the mixture followed by tetra-n-butylammonium fluoride (TBAF) treatment produced α,β-unsaturated aldehydes in good yields along with the recovered α,β-unsaturated esters.

PhI(OTf)2 has been used for the past 30 years as a strong I(III) oxidant for organic and inorganic transformations. It has been reported to be generated in situ from the reactions of either PhI(OAc)2 or PhI=O with two equivalents of trimethylsilyl trifluoromethanesulfonate (TMS-OTf). In this report it is shown that neither of these reactions generate a solution with spectroscopic data consistent with PhI(OTf)2 , with supporting theoretical calculations, and thus this compound should not be invoked as the species acting as the oxidant for transformations that have been associated with its use.

A new selenophosphoramide-catalyzed diamination of terminal- and trans-1,2-disubstituted olefins is presented. Key to the success of this transformation was the introduction of a fluoride scavenger, trimethylsilyl trifluoromethanesulfonate (TMSOTf), to prevent a competitive syn-elimination pathway, as was the use of a phosphoramide ligand on selenium to promote the desired substitution reaction. A screen of catalysts revealed that more electron-rich phosphine ligands resulted in higher yields of the desired product, with selenophosphoramides giving the optimal results. A broad range of substrates and functional groups were tolerated and yields were generally good to excellent. For (E)-1,2-disubstituted olefins, diastereoselectivities were always high, giving exclusively anti products. The conditions were also applied to substrates bearing internal nucleophiles such as esters and carbonates, giving rise to 1,2-aminoesters and cyclic carbonates, respectively.

N-(3-Phenylprop-2-yn-1-yl)-sulfonamides derived from serine and threonine were synthesized using solid-phase synthesis and subjected to reaction with trimethylsilyl trifluoromethanesulfonate (TMSOTf). In contrast to the previously reported formation of 1,4-oxazepanes, this reaction afforded pyrrolidin-3-ones. A mechanistic explanation for this unexpected outcome is proposed, and the limitations and scope of the rearrangement are outlined.

Upon stabilization by 5,6-bis(diisopropylphosphino)acenaphthene to form compound 1, the fugitive antimony (I) cation exhibited nucleophilic behavior towards coinage metals. Compound 1 was strategically synthesized at room temperature from SbCl3 , the bis(phosphine), and trimethylsilyl trifluoromethanesulfonate taken in a 1:2:3 ratio, whereby the bis(phosphine) plays the dual role of a reductant and a supporting ligand. The generation of 1 involves two-electron oxidation of the ligand to form a P-P bonded diphosphonium dication. Compound 1 was separated from this dication to give both products in pure form in moderate yields. Despite the overall positive charge, the SbI site in 1 was found to bind to metal centers, forming complexes with AuI , AgI and CuI . Compound 1 reduced CuII to CuI and formed a coordination complex with the resulting CuI species. The effects of the electron-rich bis(phosphine) and the constrained peri geometry in stabilizing and enhancing the nucleophilicity of 1 have been rationalized through computational studies.

Aryl alkyl ketones, acetate esters, and acetamides undergo facile one-pot enol silane formation, Mukaiyama aldol addition, and dehydrosilyloxylation in the presence of an amine base and excess trimethylsilyl trifluoromethanesulfonate. The chalcone and cinnamate products are generally recovered in high yield. The relative stoichiometry of the trimethylsilyl trifluoromethanesulfonate and amine base reagents determines whether the reaction yields the β-silyloxy carbonyl product or the α,β-unsaturated carbonyl.

In the presence of trimethylsilyl trifluoromethanesulfonate (TMSOTf) and triethylamine, 3-(trimethylsilyl)propargyl carboxylates undergo a one-pot alkylation-cyclization-desilylation reaction with ketones to produce 2-methylfurans. Alkylation at 0 °C in methylene chloride, followed by acid-catalyzed cyclization at room temperature, provides the furans in 52-86% yield. Cyclization and desilylation appear to be promoted by triflic acid generated in situ from the exposure of the reaction mixture to water upon completion of the initial substitution reaction.

(Trimethylsilyl)acetonitrile reacts smoothly with dimethyl acetals in the presence of stoichiometric trimethylsilyl trifluoromethanesulfonate (TMSOTf) to yield β-methoxynitriles. The ideal substrates for this reaction are acetals derived from aromatic aldehydes. Elimination to the corresponding α,β-unsaturated nitriles is observed as the major product in the case of electron-rich acetals. A mechanistic hypothesis that includes isomerization of the silylnitrile to a nucleophilic N-silyl ketene imine is presented.

A combination of I2, iodosylbenzene, and trimethylsilyl trifluoromethanesulfonate (TMSOTf) is effective for single-step synthesis of iodinated oxazoles from N-propargyl amides via the aromatization of the iodocyclized intermediates, which has difficulty proceeding through conventional iodocyclization methods. Compared to the former method consisting of the metal-catalyzed cyclization of N-propargyl amides followed by halogenation of alkylideneoxazolines, the present reaction provides a facile and metal-free procedure.

N-Aryl-protecting groups were introduced in glucosamines to achieve β-selective glycosylation. Various N-aryl aminosugars were synthesized via Buchwald–Hartwig reaction. Glycosylation using glycosyl trichloroacetimidates of N-aryl aminosugars smoothly proceeded in the presence of trimethylsilyl trifluoromethanesulfonate. Use of a glycosyl donor comprising an electron-donating 2,4-dimethoxyphenyl (DMP) group led to the glycosylation proceeding with high β selectivity. This stereoselectivity seemed to be derived from the formation of an aziridine intermediate. The DMP-protecting group can be removed immediately by using ammonium hexanitratocerate (IV).

The synthesis of naproxen-containing diaryliodonium salts has been realized from naproxen methyl ester and ArI(OH)OTs activated by trimethylsilyl trifluoromethanesulfonate (TMSOTf) in a solvent mixture comprising dichloromethane and 2,2,2-trifluoroethanol (TFE). Those iodonium salts have been successfully used in the functionalization of an aromatic ring of naproxen methyl ester, including fluorination, iodination, alkynylation, arylation, thiophenolation, and amination and esterification reactions. Moreover, further hydrolysis of the obtained 5-iodo-naproxen methyl ester afforded 5-iodo-naproxen.

Development of a scalable synthesis of an oxazine class of β-secretase inhibitor is described. Trifluoromethylated acyloin synthesis by the reaction of a mandelic acid with trifluoroacetic anhydride in the presence of pyridine (Dakin–West reaction) was used as an efficient strategy to install the key trifluoromethyl substituent on the oxazine ring. Diastereoselective addition of methyl magnesium bromide to a cyclic sulfamidate imine and trimethylsilyl trifluoromethanesulfonate catalyzed intramolecular amidine formation to yield oxazine-3-amine are some of the significant, novel synthetic methods developed in this synthesis. These critical transformations allowed a concise 11-step route to the target compound with excellent overall yields.

The convenient syntheses of new aryl-substituted hydroxymethylphosphonic and methylenediphosphonic acids from the aromatic aldehydes, their derivatives, and phosphorous acid esters in the presence of the effective catalysts (trimethylsilyl trifluoromethanesulfonate, zinc chloride, and cadmium iodide) were developed.

Reactive acyl trifluoromethanesulfonates are formed from the reaction of acyl fluorides with trimethylsilyl trifluoromethanesulfonate (TMSOTf). These electrophiles undergo Friedel–Crafts reactions with electron-rich aromatics at room temperature. When a sulfur atom is present at their γ position, their cyclization to acylsulfonium cations is observed and is followed by a rearrangement leading to benzothiepinones (or dibenzo[b,e]thiepinones) in 40–85% yield.

The Lewis acceptor chemistry of Me3SiOTf with p-block Lewis bases has been explored and a library of complexes has been characterized by spectroscopic and, where possible, crystallographic methods. Compounds with the generic formula [Me3Si(L)][OTf] (L = 4-dmap, pyr, imz, OPMe3, OPCy3, OPPh3, OpyrMe, dmso, PMe3) were isolated from 1:1 mixtures of Me3SiOTf and the respective ligand in CH2Cl2. Characterization by NMR spectroscopy confirmed the solution stability of all but [Me3Si(PMe3)][OTf], with indications that the latter dissociates into PMe3 and Me3SiOTf. Solid-state structures of [Me3Si(4-dmap)][OTf], [Me3Si(pyr)][OTf], [Me3Si(OPCy3)][OTf], [Me3Si(OPPh3)][OTf], [Me3Si(OpyrMe)][OTf], and [Me3Si(PMe3)][OTf] were elucidated by single crystal X-ray diffraction, confirming the envisaged ionic formulations resulting from the displacement of the OTf anion from the silicon center of Me3SiOTf by the incoming ligand. Mixtures of Me3SiOTf with other related donors, including ChPPh3 (Ch = S or Se), NEt3, SMe2, PPh3, 2,2′-bipy, or Me2CO, show no evidence of reaction under ambient conditions, reflecting the lower basicity and (or) greater steric encumbrance of these ligands. Reactions of Me3SiOTf with bis-donor ligands yielded complexes of the generic formulae [Me3Si(L–L)SiMe3][OTf]2 (L–L = 4,4′-bipy, tmeda, dmpe) and [Me3Si(L–L)][OTf] (L–L = 4,4′-bipy, tmeda, dmpe). The tmeda and dmpe complexes, however, were found to dissociate in solution, with complexes only prevailing in the solid phase. X-ray diffraction studies of [Me3Si(4,4′-bipy)SiMe3][OTf]2 and [Me3Si(dmpe)SiMe3][OTf]2 confirmed the expected connectivities and ionic formulations, with Si–ligand bond lengths comparable to those observed in [Me3Si(pyr)][OTf] and [Me3Si(PMe3)][OTf], respectively.

6-Halouridine derivatives were synthesized regiospecifically through the coupling of N3-protected 6-halouracil to a ribose derivative. The combination of the silylating reagent N,O -bis(trimethylsilyl)acetamide and Lewis acid catalyst trimethylsilyl trifluoromethanesulfonate is unique in their ability to facilitate the coupling of sterically hindered pyrimidine bases to ribose to form nucleoside derivatives.

An efficient route to acylated acyclic nucleosides containing a branched hemiaminal ether moiety is reported via three-component alkylation of N-heterocycle (purine nucleobase) with acetal (cyclic or acyclic, variously branched) and anhydride (preferentially acetic anhydride). The procedure employs cheap and easily available acetals, acetic anhydride, and trimethylsilyl trifluoromethanesulfonate (TMSOTf). The multi-component reaction is carried out in acetonitrile at room temperature for 15 min and provides moderate to high yields (up to 88%) of diverse acyclonucleosides branched at the aliphatic side chain. The procedure exhibits a broad substrate scope of N-heterocycles and acetals, and, in the case of purine derivatives, also excellent regioselectivity, giving almost exclusively N-9 isomers.

A convenient procedure for the synthesis of aryl(trifloxyalkenyl)iodonium triflate salts from commercially available (diacetoxyiodo)benzene, trimethylsilyl trifluoromethanesulfonate, and acetylenes under mild conditions was developed. The obtained multifunctional hypervalent vinyliodonium salts equipped with electrophilic and nucleophilic functions could serve as novel C2 synthons for organic transformations. The structure of the iodonium salts was identified by multidimensional NMR spectroscopy and X-ray crystallography.

© The Author(s)., Naturally occurring nootkatone, with reported insecticidal and acaricidal properties, has been used as a lead to generate molecular diversity and, consequently, new insect antifeedant and ixodicidal compounds. A total of 22 derivatives were generated by subjecting this molecule to several reactions including dehydrogenation with the iodine/DMSO system, oxidation with SeO2, epoxidation with mCPBA, oxidation or carbon homologations of the α-carbonyl position with TMSOTf (trimethylsilyl trifluoromethanesulfonate) followed by Rubottom and Dess Martin periodane oxidations, condensation with formaldehyde using Yb(OTf)3 as catalyst and dehydroxilation using the Grieco protocol. The insect antifeedant (against Myzus persicae and Ropaloshysum padi) and ixodicidal (against the tick Hyalomma lusitanicum) activities of these compounds were tested. Compound 20 was the most active substance against M. persicae and R. padi, and twice more efficient than nootkatone in the antitick test., This research was funded by Grant CTQ-2015-64049-C3-3-R / CTQ2015-64049-C3-1-R; Ministerio de Economía y Competitividad, Spain (MINECO/FEDER).

Bismuth trifluoromethanesulfonate can be efficiently used for the preparation of dihydropyrans from β-allenols and aldehydes by oxonium-ene reaction in good yields. The reaction is highly regioselective. On the other hand, the same reaction with trimethylsilyl trifluoromethanesulfonate at -45 °C affords the hexahydropyrano[4,3- b]pyran skeleton in moderate yields.

Ketones readily undergo conversion to enol silanes in the presence of a trialkylamine base and trimethylsilyl trifluoromethanesulfonate (TMSOTf) and add to propargyl cations to yield β-alkynyl ketones. The propargyl cations are generated in the same reaction flask through the TMSOTf-promoted ionization of propargyl acetates or propargyl propionates. A range of enol silane precursors and propargyl carboxylates reacts efficiently (20 examples, up to 99% yield). Cyclization of a representative product in the presence of TMSOTf provided 61% yield of the trisubstituted furan.

The use of trimethylsilyl trifluoromethanesulfonate as a mild means to unite epoxy-carvone silyl ethers with anisole derivatives to yield products that are structurally similar to the CBD scaffold is reported. Importantly, unlike related methods, this process can utilize both epoxy-carvone diastereomers and does not require the use of air/moisture-sensitive organometallic reagents. Several examples of aryl nucleophiles as well as mechanistic insight based on in silico computational analysis are presented.

This paper reports the application of hexamethyldisilazane-trimethylsilyl trifluoromethanesulfonate (HMDS-TMSOTf) for the simultaneous silylation of 3-monochloro-1,2-propanediol (3-MCPD) and 1,3-dicholoropropanol (1,3-DCP) in solid and liquid food samples. 3-MCPD and 1,3-DCP are chloropropanols that have been established as Group 2B carcinogens in clinical testing. They can be found in heat-processed food, especially when an extended high-temperature treatment is required. However, the current AOAC detection method is time-consuming and expensive. Thus, HMDS-TMSOTf was used in this study to provide a safer, and cost-effective alternative to the HFBI method. Three important steps are involved in the quantification of 3-MCPD and 1,3-DCP: extraction, derivatization and quantification. The optimization of the derivatization process, which involved focusing on the catalyst volume, derivatization temperature, and derivatization time was performed based on the findings obtained from both the Box-Behnken modeling and a real experimental set up. With the optimized conditions, the newly developed method was used for actual food sample quantification and the results were compared with those obtained via the standard AOAC method. The developed method required less samples and reagents but it could be used to achieve lower limits of quantification (0.0043 mg L-1 for 1,3-DCP and 0.0011 mg L-1 for 3-MCPD) and detection (0.0028 mg L-1 for 1,3-DCP and 0.0008 mg L-1 for 3-MCPD). All the detected concentrations are below the maximum tolerable limit of 0.02 mg L-1. The percentage of recovery obtained from food sample analysis was between 83% and 96%. The new procedure was validated with the AOAC method and showed a comparable performance. The HMDS-TMSOTf derivatization strategy is capable of simultaneously derivatizing 1,3-DCP and 3-MCPD at room temperature, and it also serves as a rapid, sensitive, and accurate analytical method for food samples analysis.

In the presence of trimethylsilyl trifluoromethanesulfonate and trialkylamine base, thioesters are readily converted into silyl ketene acetals in situ and undergo Mukaiyama–Mannich addition to N-phenylimines in one pot. The silyl triflate appears to play two roles, activating both the thioester and the imine. This process also works well when thioesters are replaced with amides, esters, or ketones. Products are isolated as desilylated anilines without the necessity of a deprotection step. Yields range from 65 to 99 %.

A mild and convenient synthesis of carbazoles by TfOTMS (trimethylsilyl trifluoromethanesulfonate)-catalyzed ring-opening annulation of 2-amidodihydrofurans is presented with a high degree of chemoselectivity and regioselectivity. This procedure was also scaled up to a gram-scale synthesis. The reaction could involve an iminonium intermediate through a series of C-O, C-N bond cleavages, C-C bond formations, and a 1,2-migration process.

Indoles and N-alkylindoles undergo Friedel-Crafts addition to aldehydes in the presence of trimethylsilyl trifluoromethanesulfonate and a trialkylamine to produce 3-(1-silyloxyalkyl)indoles. Neutralization of the reaction mixture with pyridine followed by deprotection under basic conditions with tetrabutylammonium fluoride provides the 1:1 adduct as the free alcohol. This method prevents spontaneous conversion of the desired products to the thermodynamically favored bisindolyl(aryl)methanes, a process typically observed when indoles are reacted with aldehydes under acidic conditions.

New analogues of acyclovir have been prepared by reacting 1,2,4-triazolo[1,5-a]pyrimidin-7-ones 1а-i and (2-acetoxyethoxy)methyl acetate 2 in the presence of trimethylsilyl trifluoromethanesulfonate as a catalyst. Thei nteraction between the compounds 1а-е and 2 has led to a mixture of N3 and N4 isomers. In contrast, the reaction of compounds 1g-i and 2 proceeded selectively to form N3 isomers. In the case of compounds 1a-c the predominant product is the one with the acyclic moiety in azine ring (N4 isomer). Interaction between 1d-f and 2 has led to mixtures comprising mainly N3 isomer. It has been found that the ratio of glycosylation products 1 and 2 are thermodynamically controlled. The structure of the obtained compounds has been proved by 1 Н, 13 С, two-dimensional 1 Н- 13 С NMR spectroscopy and X-ray analysis.

(1,3-Dioxan-4-yl)-substituted nucleoside analogues, higher homologues of antiviral and anticancer 1,3-dioxolanes, were prepared from the key intermediate (4-acetoxy-1,3-dioxan-2-yl)methyl benzoate and silylated bases. Glycosylation, carried out under Vorbruggen conditions in the presence of trimethylsilyl trifluoromethanesulfonate (TMSOTf) as a catalyst, afforded the desired compounds with high stereoselectivity and regioselectivity, with only the desired β-anomeric N-1 pyrimidine and N-9 purin nucleosides being obtained. 1H NMR experiments established that the β-anomers were diequatorial, and this assignment was confirmed by single-crystal X-ray diffraction. Despite their structural similarities with natural nucleosides, none of the synthesized nucleosides showed antiviral activity.

A two-step chemical method for the synthesis of β-nicotinamide riboside (NR) is described. NR has achieved wide use as an NAD+ precursor (vitamin B3) and can significantly increase central metabolite NAD+ concentrations in mammalian cells. β-NR can be prepared with an efficient two-step procedure. The synthesis is initiated via coupling of commercially available 1,2,3,5-tetra-O-acetyl-β-D-ribofuranose with ethyl nicotinate in the presence of trimethylsilyl trifluoromethanesulfonate (TMSOTf). 1 H NMR showed that the product was formed with complete stereoselectivity to produce only the β-isomer in high yield (>90% versus starting sugar). The clean stereochemical result suggests that the coupling proceeds via a cationic cis-1,2-acyloxonium-sugar intermediate, which controls addition by nucleophiles to generate predominantly β-stereochemistry. The subsequent deprotection of esters in methanolic ammonia generates the desired product in 85% overall yield versus sugar. © 2017 by John Wiley & Sons, Inc.

Trimethylsilyl trifluoromethanesulfonate (TMSOTf) and a trialkylamine base promote the conversion of acetonitrile to its silyl ketene imine in situ when acetonitrile is employed as solvent. Residual TMSOTf acts as a Lewis acid catalyst to activate acetals and nitrones in the reaction mixture, yielding β-methoxynitriles and β-(silyloxy)aminonitriles, respectively. Some reaction products undergo elimination under the reaction conditions to provide the α,β-unsaturated nitrile directly.

Living organisms employ glycans as recognition elements because of their large structural information density. Well-defined sugar structures are needed to fully understand and take advantage of glycan functions, but sufficient quantities of these compounds cannot be readily obtained from natural sources and have to be synthesized. Among the bottlenecks in the chemical synthesis of complex glycans is the preparation of suitably protected monosaccharide building blocks. Thus, easy, rapid, and efficient methods for building-block acquisition are desirable. Herein, we describe routes directly starting from the free sugars toward notable monosaccharide derivatives through microwave-assisted one-pot synthesis. The procedure followed the in situ generation of per-O-trimethylsilylated monosaccharide intermediates, which provided 1,6-anhydrosugars or thioglycosides upon treatment with either trimethylsilyl trifluoromethanesulfonate or trimethyl(4-methylphenylthio)silane and ZnI2, respectively, under microwave irradiation. We successfully extended the methodology to regioselective protecting group installation and manipulation toward a number of thioglucosides and the glycosylation of persilylated derivatives, all of which were conducted in a single vessel. These developed approaches open the possibility for generating arrays of suitably protected building blocks for oligosaccharide assembly in a short period with minimal number of purification stages.

Two different mechanism pathways are observed for the reaction of allylsilyl alcohols 1 and aldehydes in the presence of trimethylsilyl trifluoromethanesulfonate (TMSOTf). In the case of allylsilyl alcohols without allylic substituents, the reaction gives dioxaspirodecanes, which are the products of a tandem Sakurai-Prins cyclization. In contrast, allylsilyl alcohols with an allylic substituent (R(2)≠H) selectively provide oxepanes, thus corresponding to a direct silyl-Prins cyclization. Both types of product are obtained with excellent stereoselectivity. Theoretical studies have been performed to obtain some rationalization for the observed stereoselectivity.

The selectivities of nucleophilic substitution reactions of tetrahydropyran acetals promoted by trimethylsilyl trifluoromethanesulfonate depend upon the reaction solvent. Polar solvents favor the formation of S(N)1 products, while nonpolar solvents favor S(N)2 products. Trichloroethylene was identified as the solvent most likely to give S(N)2 products in both C- and O-glycosylation reactions.

Thioperoxide (1) in combination with trimethylsilyl trifluoromethanesulfonate (TMSOTf) provides a powerful thiophilic promoter system, capable of activating different thioglycosides. Both armed and disarmed thioglycosides were activated effectively in the presence of different glycosyl acceptors, giving glycosidation products in high to excellent yields. A plausible activation pathway was also proposed and supported by isolating side-products trifluoromethylphenyl disulfide (CF3SSPh) and alkene (42).

An efficient asymmetric synthesis of -sulfinylamino isocyanides is reported on the basis of the highly diastereoselective addition of 9-isocyanofluorene to optically pure N-tert-butanesulfinimines. The resulting optically pure isocyanides readily cyclized to give optically pure 2-imidazolines upon removal of the sulfinyl group. Furthermore, the -sulfinylamino isocyanides were used as chiral inputs in Ugi and Passerini multicomponent reactions to generate new types of (pseudo)peptide scaffolds. Optically pure -sulfinylamino isocyanides are synthesized in a highly diastereoselective addition of 9-isocyanofluorene with N-tert-butanesulfinimines. Follow-up chemistry demonstrates that they are excellent precursors for the preparation of optically pure 2-imidazolines. Furthermore, they are applied in Ugi and Passerini multicomponent reactions; TMSOTf = trimethylsilyl trifluoromethanesulfonate, DIPEA = N,N- diisopropylethylamine. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Trimethylsilyl trifluoromethanesulfonate (TMSOTf) and a trialkylamine base promote both in situ enol silane/silyl ketene acetal formation and Mukaiyama aldol addition reactions between a variety of reaction partners in a single reaction flask. Isolation of the required enol silane or silyl ketene acetal is not necessary. For example, crossed aldol reactions between α-disubstituted aldehydes and non-enolizable aldehydes yield β-hydroxy aldehydes in good yield. In a related reaction, the common laboratory solvent ethyl acetate functions as both an enolate precursor and a green reaction solvent. When thioesters are employed as enolate precursors, high yields for additions to non-enolizable aldehydes are routinely observed.