Triflate with amines

The palladium-catalyzed amination of aryl halides has recently emerged as a powerful alternative to other methods for the synthesis of aryl amines.5 This method allows for the cross-coupling of aryl halides arrd triflates with amines in the presence of a stoichiometric amount of a base and catalytic amounts of palladium complexes bearing tertiary phosphine ligands. As shown in Tables I and II, the Pd/BlNAP catalyst is highly effective for reactions of aryl bromides and triflates with primary and cyclic... 

Conversion of aldehydes into the corresponding enol silyl ethers can be accomplished with a number of enolization-silylation reagents KH/DME-TMS-Cl/EtsN, TMS triflate with amines or bis(tri-methylsilyl)acetamide ° among them. In the specific case of siloxyethylene, it has been prepared by the fragmentation of tetrahydrofuran with butyllithium and silylation of the resulting enolate anion (Scheme... 

Aryl sulfonates are often an alternative in cross-coupling reactions, if the corresponding hahdes are not available. In this context, the coupling of aryl triflates with amines catalyzed by the BINAP (1) system is a well-established methodology [18] to access valuable compounds (Scheme 13.29) [90]. 

Allylic amines are coupled to halides giving either allylic amines or enamines depending on the reaction condition. Reaction of steroidal dienyl triflate with Boc-diprotected allylamine affords allylamine. Use of AcOK as a base is crucial for the clean coupling[102]. The tert-allylic amine 123 reacts with an aryl halide to give the enamine 125 in DMF and allylic amine 124 in nonpolar solvents[103]. 

Imidazolides can also be activated by N-alkylation with methyl triflate.116 Imidazolides react with alcohols on heating to give esters and react at room temperature with amines to give amides. Imidazolides are particularly appropriate for acylation of acid-sensitive materials. 

The silyl ketene acetal rearrangement can also be carried out by reaction of the ester with a silyl triflate and tertiary amine, without formation of the ester enolate. Optimum results are obtained with bulky silyl triflates and amines, e.g., f-butyldimethylsilyl triflate and (V-methyl-Af, /V-dicyclohcxylaminc. Under these conditions the reaction is stereoselective for the Z-silyl ketene acetal and the stereochemistry of the allylic double bond determines the syn or anti configuration of the product.243... 

Amino-squaraines 39 (Z1 = O, Z2 = R1R2) are synthesized by etherification of the oxo-squaraine oxygen using dimethylsulfate or methyl triflate followed by substitution of the methoxy group with amines [52] (Fig. 10). 

To investigate the feasibility of employing 3-oxidopyridinium betaines as stabilized 1,3-dipoles in an intramolecular dipolar cycloaddition to construct the hetisine alkaloid core (Scheme 1.8, 77 78), a series of model cycloaddition substrates were prepared. In the first (Scheme 1.9a), an ene-nitrile substrate (i.e., 83) was selected as an activated dipolarophile functionality. Nitrile 66 was subjected to reduction with DIBAL-H, affording aldehyde 79 in 79 % yield. This was followed by reductive amination of aldehyde x with furfurylamine (80) to afford the furan amine 81 in 80 % yield. The ene-nitrile was then readily accessed via palladium-catalyzed cyanation of the enol triflate with KCN, 18-crown-6, and Pd(PPh3)4 in refluxing benzene to provide ene-nitrile 82 in 75 % yield. Finally, bromine-mediated aza-Achmatowicz reaction [44] of 82 then delivered oxidopyridinium betaine 83 in 65 % yield. 

Mannich and related readions provide one of the most fundamental and useful methods for the synthesis of p-amino carbonyl compounds, which constitute various pharmaceuticals, natural products, and versatile synthetic intermediates.1271 Conventional protocols for three-component Mannich-type readions of aldehydes, amines, and ketones in organic solvents indude some severe side reactions and have some substrate limitations, espedally for enolizable aliphatic aldehydes. The dired synthesis of P-amino ketones from aldehydes, amines, and silyl enolates under mild conditions is desirable from a synthetic point of view. Our working hypothesis was that aldehydes could read with amines in a hydro-phobic reaction fidd created in water in the presence of a catalytic amount of a metal triflate and a surfactant to produce imines, which could then read with hydrophobic silyl enolates. 

The catalyst choice was based on several unique properties of the rare-earth Lewis acids (1) ready availability, (2) a large number of triflates with varied Lewis acidity, (3) compatibility with amine nucleophiles and (4) potential for reactions in aqueous medium. 

The is-boron enolates of some ketones can be preferentially obtained with the use of dialkylboron chlorides.17 The data in Table 2.3 pertaining to 3-pentanone and 2-methyl-3-pentanone illustrate this method. Use of boron triflates with a more hindered amine favors the Z-enolate. The contrasting stereoselectivity of the boron triflates and chlorides has been discussed in terms of reactant conformation and the stereoelectronic requirement for perpendicular alignment of the hydrogen being removed with the carbonyl group.18 The... 

There has been a summary of the use of insertion reactions of arynes into a-bonds to prepare nrt/io-disubs tituted arenes. A key to the success of these processes is the ability to generate benzyne under mild conditions by the reaction of readily available o-(trimethylsilyl)phenyl triflate with fluoride ions.61 Reaction of amines and their derivatives with benzynes generated in this way has been shown to be an efficient method for the production of N-arylated derivatives, as illustrated in Scheme 8. The method also works well in the O-arylation reactions of phenols and carboxylic acids 62... 

A dry two-neck flask was charged with amine (1.00 mmol), triflate or bromide (1.20 mmol), base (1.40 mmol), ligand (10 mol%), palladium acetate (Pd(OAc)2) or tris-(dibenzylidene-acetone)dipalladium (0) (Pd2dba3) (5 mol%), and toluene (2.00 mL/mmol of amine). The reaction was flushed with N2 and heated at 80 °C. The mixture was diluted with ether, filtered through a pad of Celite, and the volatile components were removed reduced pressure to give a crude product, which was purified by flash column chromatography on silica gel. 

The same differential behavior can be observed with amine nucleophiles. For example, calcium triflate promotes the aminolysis of propene oxide 84 with benzylamine to give 1-(A -benzyl)amino-2-propanol 85, the result of attack at the less substituted site <03T2435>, and which is also seen in the solventless reaction of epoxides with heterocyclic amines under the catalysis of ytterbium(III) triflate <03SC2989>. Conversely, zinc chloride directs the attack of aniline on styrene oxide 34 at the more substituted carbon center <03TL6026>. A ruthenium catalyst in the presence of tin chloride also results in an SNl-type substitution behavior with aniline derivatives (e.g., 88), but further provides for subsequent cyclization of the intermediate amino alcohol, thus representing an interesting synthesis of 2-substituted indoles (e.g., 89) <03TL2975>. 

An effective control of the simple diastereoselectivity in boron-mediated aldol reactions of various propionate esters (162) was achieved by Abiko and coworkers (equation 45) °. They could show that under usual enolization conditions (dialkylboron triflate and amine) enol borinates are formed, which allowed the selective synthesis of 5yw-configured aldol products (Table 11). The enolization at low temperature (—78 °C) generated a (Z)-enolate selectively, which afforded mainly the syn diastereomer 164 after reaction with isobu-tyraldehyde (163), following a Zimmerman-Traxler transition-state. The anti diastereomer 164 instead was obtained only in small amounts (5-20%). 

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