Triflic imide

Aryl triflates, produced from the corresponding hydroxy arene using triflic anhydride or triflic imide with microwave heating [77] (or by other means)... 

Aryl trifiates, which are readily prepared by use of microwaves [113] from the corresponding aryl alcohol using triflic anhydride or triflic imide, are important halide alternatives but are, occasionally, poorly reactive. Nevertheless, Zhang and Neumeyer have reported palladium-catalyzed activation of trifiates in nitrile couplings for preparation of different K-opioid receptor ligands [109]. As shown in Scheme 15.54, a reaction time of 15 min at 200 °C, in sealed reaction vessels, was sufficient for complete displacement, generating yields between 86 and 92%. 

Although [2+2] cycloaddition of alkyl enol ether with acrylate was promoted in the presence of TMSNTf2, it is hard to handle and isolate TMSNTf2 owing to its moisture sensitivity. As an alternative and concise method, in situ generated silyl triflic imides were available in the [2+2] cycloaddition of alkyl enol ethers. Thus, after mixing EtsSiH and Tf2NH to... 

A possible mechanism for the catalytic [2+2] cycloaddition reaction catalyzed by Tf2NH is depicted in Scheme 4.9. The Mukaiyama-type Michael addition of silyl enol ether to enoate catalyzed by silyl triflic imide aHbrds the corresponding silyl ketene acetal, and then it proceeds successively to the intramolecular silyl oxonium carbon to... 

SCHEME 4.8 [2+2] Cycloaddition of alkyl enol ether using in situ generated silyl triflic imide from triethylsUane and Tf2NH. 

The problem of the nucleophilicity of amides in glycosylation reactions is not limited to the sulfoxide method and has been shown to result in the formation of glycosyl imidates from intermolecular reaction with activated donors. It appears that this problem may be suppressed by the prior silylation of the amide [348,349]. Accordingly, it may be sufficient to operate the sulfoxide method with an excess of triflic anhydride when amides are present so as to convert all amides into O-triflyl imidates, which are then hydrolyzed on work-up. Despite these problems, several examples have been published of successful sulfoxide glycosylation reactions with acceptors carrying remote peptide bonds [344,345] and with donors coupled to resins via amide-based linkages [346,347], with no apparent problems reported. Sulfonamides and tertiary amides appear to be well tolerated by the sulfoxide method [340,350],... 

A reagent composed of tetra-n-butylammonium nitrate and TFAA in methylene chloride has been used to nitrate a series of A-alkyl and A-aryl amides (40-90 %). The formation of significant amounts of A-nitrosamides was noted. Tetra-n-butylammonium nitrate and triflic anhydride in methylene chloride has been used to successfully nitrate a variety of heterocyclic amides, imides and ureas (66). ... 

Benzyl ethers.2 Benzyl ethers of sugar alcohols can be obtained in 82-98% isolated yield by reaction with 1 and catalytic amounts of triflic acid under these conditions isopropylidene and benzylidene acetal groups are stable, as well as ester and imide groups. The reagent thus is comparable to benzyl triflate (6,44). 

Benzylation with benzyl trichloroacetimidate and a catalytic amount of triflic acid (TfOH) is a mild and efficient procedure (Scheme 2.1c).5 The acid protonates the nitrogen of the imidate moiety converting it into a very good leaving group. Nucleophilic attack by an alcohol introduces a benzyl ether. The procedure is often compatible with base- and acid-sensitive functionalities with esters, (7-isopropylidene and (7-benzylidene acetals. Benzyl trichloroacetimidate is commercially available but can easily be prepared by reaction of benzyl alcohol with trichloroacetonitrile in the presence of a mild base. 

Almost all types of leaving groups have been explored in sialyl donors with, until recently, two notable exceptions the venerable imidates and the sulfoxides. While the preparation of stable, isolable sialyl trichloroacetimidates has still to be demonstrated, the recent innovation of the Biao Yu group—the (V-phenyltrifluoroacctimidatcs—has proven equal to the task and has provided access to new potent class of sialyl donors [27], Stable sulfoxides of sialyl thioglycosides have also been described recently and employed as glycosyl donors on activation with triflic anhydride (Tf20) [28], The S-benzoxazolyl (.S -Box) thiosialosides constitute another recent addition to the armory of sialyl donors [29, 30],... 

In their initial report on the use of the 5-V-acetyl Neu5 Ac donors, Demchenko and Boons observed that the addition of the second acetyl group to the standard donor 6, resulting in the imide 7, increased the reactivity of the donor considerably on activation with. V-iodosuccinimide (NIS) and triflic acid (TfOH) at -40°C in acetonitrile (Scheme 5.3). The precise origins of this increased activity were not identified,... 

Charette recently described an innovative activation protocol in which lactams, in the presence of triflic anhydride (33), react with pyridines to afford the pyridinium imidate 107 in good yield. Subsequent addition of metal enolates to this species leads to 2-substituted tricyclic dihydropyridines, advanced intermediates for the total synthesis of the natural alkaloid ( )-tetraponerine T4 (109, Scheme 16) [107]. 

There are also several examples of imidate-derived azomethine yhdes reported in the Hterature. For example, the Gin group described a clever use of these 1,3-dipoles in an approach to the azatricychc core of some stemofoline members of the stemona alkaloid family. The formation of the azomethine ylide 164 occurred upon exposure of pyrroUdine 163 to triflic anhydride and tetrabutylammonium triphenyldifluorosihcate (TBAT Scheme 35) (2008T3629). Cycloaddition of the resulting dipole across the pendant vinyl sulfide fiomished 165 in 71% yield. Enol triflate 165 was then reduced to give the saturated side chain in 166 in 89% yield by the action of Pd/C under an H.2 atmosphere. The enolate derived from 166 was treated with ethyl iodoa-cetate in the presence of hexamethylphosphoramide (HMPA) followed by... 

Several styrene derivatives can be used, but the presence of an electron donating group in the benzene ring diminishes the yield. The reaction time is highly dependent on the steric bulk of the cyclic imide which should be used in excess as it is in part quenched by triflic acid generated during the reaction. 

Later a modified procedure for the preparation of 3,6-bis(trifluoromethyl) phthalodinitrile 83b was elaborated [67] (Scheme 23), which starts from 2,5-bis(trifluoromethyl)benzoyl chloride 86 and includes its conversion to N,N-diethylamide 87, carboxylation of the latter in the presence of 2,2,6,6-tetramethylpiperidine, followed by direct formation of the imide 81b ( 59 % overall yield). The diamide 82b obtained with liquid NH3 treatment (28 % yield), was then converted to dinitrile 83b with triflic anhydride in dioxane (yield... 

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