Triflic Anhydride Research Articles

Synthesis and application of polytetrahydrofuran-grafted polystyrene (PS–PTHF) resin supports for organic synthesis

Cross-linked polystyrene (PS) with polytetrahydrofuran (PTHF) chains were prepared for use in solid phase organic synthesis (SPOS). The resins were prepared from styrene, styrene–PTHF macromonomers and cross-linkers 1,4-bis[4-vinylphenoxy]butane or divinylbenzene by suspension polymerization. The styrene–PTHF macromonomers were prepared by cationic polymerization of 4-vinylbenzyl bromide and 4-(4-vinylphenoxy)butyl iodide activated by silver hexafluoroantimonate and 4-(5-hydroxypentyl)styrene activated by triflic anhydride. Alternatively, polytetrahydrofuran–grafted polystyrene (PS–PTHF) resins could also be directly prepared from 5-hydroxypentyl Janda Jel by cationic polymerization using triflic anhydride as the initiator. These PS–PTHF resins exhibited good swelling characteristics across a wide spectrum of polar and non-polar solvents. These resins were used in the synthesis of 3-methyl-1-phenyl-2-pyrazolin-5-one, which requires β-ketoester formation at low temperature (−78 °C), resulting in good yield and product purity; whereas the same synthesis carried out on PEG–grafted PS (PS–PEG) resin resulted in incomplete synthesis.

A Facile One‐Pot Benzylation of Sodium Enolates Using Trifluoromethanesulfonic Anhydride and Diphenyl Sulfoxide.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Regioselective Conversion of the Secondary Hydroxyl Groups of D‐Glucuronic Acid without the Requirement of O‐Protecting Groups

Trifluoromethanesulfonic acid anhydride (triflic acid anhydride) transforms the bicyclic thiazolidinlactam 1 a into the crystalline elimination product 2, in which all four secondary hydroxyl groups of 1 a are differently functionalized. Compound 2 can then add nucleophiles with high chemo- and stereoselectivity. Altogether, the four secondary hydroxyl groups of D-glucuronic acid are selectively transformed without the need for any O-protecting groups. Minimizing the number of O-protecting groups is a prerequisite for the use of sugar scaffolds in molecular libraries. The hapalosin analogues 15, 16, 19, and 22 outline the strategy towards O-diversified glucose derivatives.

Synthetic studies on thiostrepton family of peptide antibiotics: synthesis of the dihydroquinoline portion of thiostrepton, the siomycins, and the thiopeptins

Synthesis of the dihydroquinoline portion of thiostrepton, the siomycins, and the thiopeptins, members of the thiostrepton family of peptide antibiotics, has been achieved featuring the one-pot olefination via the Matsumura–Boekelheide rearrangement “using trifluoromethanesulfonic anhydride and triethylamine” and the stereoselective addition reaction controlled by the stereocenter of the peri-position.

Improved Synthesis of 1‐Benzenesulfinyl Piperidine and Analogs for the Activation of Thioglycosides in Conjunction with Trifluoromethanesulfonic Anhydride*

An improved protocol for the large‐scale production of 1‐benzenesulfinyl piperidine and other sulfinamides is described. It is demonstrated that 1‐benzenesulfinyl pyrrolidine and N,N‐diethyl benzenesulfinamide function analogously to 1‐benzenesulfinyl piperidine in the trifluoromethanesulfonic anhydride‐mediated activation of thioglycosides, and that their less crystalline nature enables them to be used at −78°C as opposed to the −60°C required to keep 1‐benzenesulfinyl piperidine in solution. N,N-Dicyclohexyl benzenesulfinamide does not activate thioglycosides in combination with trifluoromethanesulfonic anhydride, which is attributed to its greater steric bulk. * Dedicated with respect to the memory of Professor Jacques H. Van Boom.

Facile Synthesis of Aryl- and Alkyl-bis(trifluoromethylsulfonyl)methanes

Abstract Various arylbis(trifluoromethylsulfonyl)methanes (1) have been synthesized by reacting the corresponding benzylic halides with sodium trifluoromethanesulfinate and then with triflic anhydride. In addition, when the aryl group of 1 is a pentafluorophenyl group, the nucleophilic para-substitution of the aryl group with alkyllithiums and sodium alkoxides occurs. This reaction is useful for the design of new Brønsted acids.

Glycosylation with Sulfoxides and Sulfinates as Donors or Promoters

AbstractFor Abstract see ChemInform Abstract in Full Text.

Sequential Aminodiene Diels−Alder Approach to the Ergoline Skeleton

Through a novel sequence of aminodiene Diels-Alder reactions, several substituted amidofurans were readily converted to tricyclic ketones in good yield. The formation of the tricyclic ketone system is the result of a ring opening and dehydration of a transient oxabicyclic adduct formed by an intramolecular Diels-Alder cycloaddition of an amidofuran with a cyclohexenone moiety tethered such that it participates in the cycloaddition as the 2pi component. A convenient way to construct the cyclohexenone is to make use of some aminodiene chemistry developed by Rawal. An angular carbomethoxy group is required in order to activate the olefin toward cycloaddition with Rawal's diene. The presence of this activating group not only prevents the isomerization of the advanced ergoline intermediate to a naphthalene but can also be leveraged for an oxidation to provide Uhle's ketone (13). The easily formed Kornfeld ketone analogue 25 was readily transformed into the corresponding triflate 41 by the action of triflic anhydride and a base. Oxidative addition of vinyl triflate 41 to Pd(0) and the ability of the resulting vinyl palladium species to undergo cross-coupling with terminal alkynes prompted us to devise an expeditious route to lysergic acid. Unfortunately, our inability to carry out a regioselective Heck reaction using vinyl triflate 41 and the methylene amino acrylate ester 48 thwarted the completion of the synthesis of lysergic acid.

Sulfonium Triflate Mediated Glycosidations of Aryl 2‐Azido‐2‐deoxy‐1‐thio‐D‐mannosides.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Sulfonium Triflate Mediated Glycosidations of Aryl 2‐Azido‐2‐deoxy‐1‐thio‐D‐mannosides

AbstractThe effectiveness in terms of yield and stereoselectivity of (phenylsulfinyl)piperidine (BSP) 1b/ trifluoromethanesulfonic anhydride (Tf2O) and diphenyl sulfoxide (DPS) 1c/Tf2O‐mediated glycosidations of 2‐azido‐3‐O‐benzyl‐4,6‐O‐benzylidene‐2‐deoxy‐D‐thiomannosides 2a/b is described. Application of the BSP/Tf2O activator led to productive condensations using p‐methoxyphenyl 2‐azido‐3‐O‐benzyl‐4,6‐O‐benzylidene‐2‐deoxy‐D‐thiomannoside (2b) as a donor, while the more powerful DPS/Tf2O combination gave similar results using both p‐methoxyphenyl and phenyl 2‐azido‐3‐O‐benzyl‐4,6‐O‐benzylidene‐2‐deoxy‐D‐thiomannosides 2a/b. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

A Facile One-Pot Benzylation of Sodium Enolates Using Trifluoromethanesulfonic Anhydride and Diphenyl Sulfoxide

A facile one-pot C-benzylation of various sodium enolates derived from methyl malonate, beta-ketoesters, a beta-cyanoester, a beta-cyanosulfone, ketones and a carboxylic ester is reported. Reaction of alkoxydiphenylsulfonium salts formed by treating various benzyl alcohols with diphenyl sulfide bis(trifluoromethanesulfonate) (derived from trifluoromethanesulfonic anhydride and diphenyl sulfoxide) proceeded smoothly, and the corresponding C-benzylated products were afforded in good to high yields.

Preparation of star block co-polymers by combination of cationic ring opening polymerization and atom transfer radical polymerization

The synthesis of star block co-polymers with polytetrahydrofuran (PTHF) core and poly(tert-butyl acrylate) (PtBA) shell was performed using a dual initiator, 4-hydroxy butyl bromoisobutyrate, by combination of cationic ring-opening polymerization (CROP) and atom transfer radical polymerization (ATRP). The in situ reaction of the hydroxyl groups originating from the dual initiator with trifluoromethane sulfonic anhydride provides a triflate ester initiating group for the CROP of THF. PTHF star polymers having three arms with tertiary bromide end groups (PTHF)3 have been prepared by reaction of living PTHF chains with tris(2-aminoethyl)amine (TAEA) in the presence of 2,2,6,6-tetramethylpiperidine (TMP) as a proton trap. Subsequently, the star polymers were used as macroinitiators for the ATRP of tBA using the CuBr/N,N,N′,N″,N″-pentamethyldiethylenetriamine (PMDETA) catalyst system to obtain the tri-armed star block co-polymers (PTHF-b-PtBA)3. The polymers were characterized with gel-permeation chromatography (GPC) and1H-NMR. Both techniques demonstrated the formation of tri-armed star block co-polymers.

On the activation of valerolactam with triflic anhydride: the synthesis of ω-trifluorosulfonamido dipeptides using a transpeptidation reaction under mild conditions

The activation of valerolactam with triflic anhydride is studied in detail, initially producing an O-triflated lactam, which rearranges, following the addition of base at higher temperatures, to an N-triflated derivative. This reacts with a series of nucleophiles to produce esters and amides, which are formally dipeptides of omega-amino acids.

The first carborane triflates: synthesis and reactivity of 1-trifluoromethanesulfonylmethyl- and 1,2-bis(trifluoromethanesulfonylmethyl)-o-carborane

The first carborane triflates, namely, 1-trifluoromethanesulfonylmethyl-o-carborane (2) and 1,2-bis(trifluoromethanesulfonylmethyl)-o-carborane (7), were obtained in high yields in the reactions of 1-hydroxymethyl-o-carborane (1) or 1,2-bis(hydroxymethyl)-o-carborane (6) with triflic anhydride (Tf2O) in CH2Cl2 in the presence of pyridine. When an excess of pyridine is employed, 1-o-carboranylmethylpyridinium triflate (3), which retains a closo-icosahedral structure, or a pyridinium salt (4) with a zwitterionic nido-dicarbaundecaborate anion are obtained from 1, while the nido compound 8 is formed from 6. The reaction of compound 2 or 7 with excess pyridine also gave 3 or 8, respectively. Compound 2 proved to be a convenient carboranylmethylating agent which reacts with nucleophiles (e.g., potassium phthalimide, PPh3 or KCN) to give the corresponding substitution products N-[(o-carboranyl-1-yl)methyl]phthalimide (9), o-carboranylmethylphosphonium salt 10, and 1-cyanomethyl-o-carborane (11). All compounds were characterized by 1H and 11B NMR spectroscopy. The structures of compounds 4, 7 and 8 were established by X-ray analysis.

Development of a Generic Stereocontrolled Pathway to Fully Hydroxylated Spirocarbocyclic Nucleosides as a Prelude to RNA Targeting

Osmylation of the enantiopure conjugated enones 4 and 15 proceeded predominantly or exclusively from the α-face to give the 2',3'-diols 6 and 16. Ensuing conversion into the acetonide allowed for sequential stereocontrolled reduction with L-Selectride, and esterification with triflic anhydride was utilized to form triflates 11 and 19. The heightened electrophilicity of these intermediates made possible S N 2 displacements with several nucleobases as promoted with potassium hydride in N,N-dimethylformamide at room temperature. Suitable deprotection measures led to the targeted compounds.

Facile One‐Pot Syntheses of Amidines and Enamines from Oximes via Beckmann Rearrangement Using Trifluoromethanesulfonic Anhydride.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Novel Polymer‐Supported Coupling/Dehydrating Reagents for Use in Organic Synthesis.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Gadolinium triflate: an efficient and convenient catalyst for acetylation of alcohols and amines

Abstract Gadolinium triflate (Gd(OTf)3) was found to be a simple and efficient catalyst for the acetylation of alcohols and amines. Acetylation reactions using acetic anhydride as the reagent proceed in excellent yields, in the presence of catalytic amounts (0.01–0.1 mol%) of Gd(OTf)3, at ambient temperature. Aliphatic alcohols as well as phenols and amines undergo acetylations under mild conditions. The intermediate formation of the mixed anhydride, acetic trifluoromethanesulfonic anhydride was demonstrated by 13C NMR spectroscopy experiments.

Phosphaalkynes from Acid Chlorides via P for O(Cl) Metathesis: A Recyclable Niobium Phosphide (P3-) Reagent that Effects C−P Triple-Bond Formation

Reported herein is a new, metathetical P for O(Cl) exchange mediated by an anionic niobium phosphide complex that furnished phosphaalkynes (RCP) from acid chlorides (RC(O)Cl) under mild conditions. The niobaziridine hydride complex, Nb(H)(tBu(H)C=NAr)(N[Np]Ar)2 (1, Np = neopentyl, Ar = 3,5-Me2C6H3), has been shown previously to react with elemental phosphorus (P4), affording the mu-diphosphide complex, (mu2:eta2,eta2-P2)[Nb(N[Np]Ar)3]2, (2), which can be subsequently reduced by sodium amalgam to the anonic, terminal phosphide complex, [Na][PNb(N[Np]Ar)3] (3). It is now shown that treatment of 3 with either pivaloyl (t-BuC(O)Cl) or 1-adamantoyl (1-AdC(O)Cl) chloride provides the thermally unstable niobacyles, (t-BuC(O)P)Nb(N[Np]Ar)3 (4-t-Bu) and (1-AdC(O)P)Nb(N[Np]Ar)3 (4-1-Ad), which are intermediates along the pathway to ejection of the known phosphaalkynes t-BuCP (5-t-Bu) and 1-AdCP(5-1-Ad). Phosphaalkyne ejection from 4-t-Bu and 4-1-Ad proceeds with formation of the niobium(V) oxo complex ONb(N[Np]Ar)3 (6) as a stable byproduct. Preliminary kinetic measurements for fragmentation of 4-t-Bu to 5-t-Bu and 6 in C6D6 solution are consistent with a first-order process, yielding the thermodynamic parameters DeltaH = 24.9 +/- 1.4 kcal mol-1 and DeltaS = 2.4 +/- 4.3 cal mol-1 K-1 over the temperature range 308-338 K. Separation of volatile 5-t-Bu from 6 after thermolysis has been readily achieved by vacuum transfer in yields of 90%. Pure 6 is recovered after vacuum transfer and can be treated with 1.0 equiv of triflic anhydride (Tf2O, Tf = O2SCF3) to afford the bistriflate complex, Nb(OTf)2(N[Np]Ar)3 (7), in high yield. Complex 7 provides direct access to 1 upon reduction with magnesium anthracene, thus completing a cycle of element activation, small-molecule generation via metathetical P-atom transfer, and deoxygenative recycling of the final niobium(V) oxo product.

Stereoselective One‐Pot Synthesis of Substituted (4Z)‐2‐Alkyl‐4‐benzylidene‐4H‐1,3‐benzothiazines.

AbstractFor Abstract see ChemInform Abstract in Full Text.