Amines, reaction with trifluoroacetic

The hydroxy lactams are postulated to be intermediates in transformations of enol lactones to ene lactams. This hypothesis was proved by synthesis. For example, treatment of N-methylhydrastine (98) with dilute ammonium hydroxide resulted in hydroxy lactam 148, which by the action of hydrochloric acid underwent dehydration to produce fumaridine (113) (5). Similarily, fumschleicherine (120) in reaction with trifluoroacetic acid gave fumaramine (111) 121). Narceine amide (149) was prepared from (Z)-narceine enol lactone (101) in likewise fashion 100,122) and dehydrated to narceine imide (116). A large number of N-alkylated narceine amides was synthesized from (Z)-narceine enol lactone (101) and primary amines by Czech investigators for... 

Sigman and Jacobsen reported the first example of a metal-catalyzed enantioselective Strecker-type reaction using a chiral Alnl-salen complex (salen = N,N -bis(salicyhdene)-ethylenediamine dianion) [4]. A variety of N-allylimines 4 were evaluated in the reaction catalyzed by complex 5 to give products 6, which were isolated as trifluoroacetamides in good yields and moderate-to-excellent enantioselectivities (Scheme 3). Substituted arylimines 4 were the best substrates, while alkyl-substituted imines afforded products with considerably lower ee values. Jacobsen and co-workers also reported that non-metal Schiff base catalysts 8 and 9 proved to be effective in the Strecker reaction of imines 7 with hydrogen cyanide to afford trifluoroacetamides 10 after reaction with trifluoroacetic anhydride, since the free amines were not stable to chromatography (Scheme 4) [5]. 

Trifluoromethyl derivatives of thiochromone are also available from thiosalicylic acid by conversion to alkyl 2-mercaptophenyl ketones followed by a Baker-Venkataraman reaction with trifluoroacetic anhydride in triethyl-amine (Scheme 205) <2005PS(180)1315>. 

Methyleneimmonium salts 31 are conveniently prepared from mcihylene-bis-amines, formaldehyde-N,0-acetals, or methylene halogenides. Electrochemical reactions on various alkylamines have also been used to generate methyleneimmonium salts, and trimethylamine N-oxide 34 (Fig. 20) is reported as a source of the corresponding methyleneimmonium salt by reaction with trifluoroacetic anhydride. ... 

Iminium ion cycUzations such as the Pictet-Spengler reaction have been widely used in alkaloid chemistry to create a carbon-carbon bond between the carbon a to the basic nitrogen and an aromatic ring. The requisite iminium ions in these reactions are often readily available via the modified Polonov-ski reaction. Although two steps, IV-oxide formation and reaction with trifluoroacetic anhydride, are involved, this approach is often preferable to the reaction of a tertiary amine with mercury(II) acetate, in which it is necessary to destroy the amine-mercury complex at the end of the reaction. In this way the secoheteroyohimbinoidiV-oxide (34) was cyclized selectively to uammigine (35 equation 12). Using mercuiy(II) acetate a nearly equal mixture of (35) and its C-3 P-H epimer tetrahydroalstonine is obtained. 

In a variation of the known conversion of phthalideisoquinolines into rhoeadines, the -lactone 1 derived from jS-hydrastine was converted to its iV-oxide. The secondary amine 2 was obtained from the iV-oxide by reaction with trifluoroacetic anhydride, in a modified Polonovski reaction. The papaverrubine 3 was then generated from the amine 2 as shown below ... 

Scheme 2.12 shows some representative Mannich reactions. Entries 1 and 2 show the preparation of typical Mannich bases from a ketone, formaldehyde, and a dialkylamine following the classical procedure. Alternatively, formaldehyde equivalents may be used, such as l>is-(di methyl ami no)methane in Entry 3. On treatment with trifluoroacetic acid, this aminal generates the iminium trifluoroacetate as a reactive electrophile. lV,A-(Dimethyl)methylene ammonium iodide is commercially available and is known as Eschenmoser s salt.192 This compound is sufficiently electrophilic to react directly with silyl enol ethers in neutral solution.183 The reagent can be added to a solution of an enolate or enolate precursor, which permits the reaction to be carried out under nonacidic conditions. Entries 4 and 5 illustrate the preparation of Mannich bases using Eschenmoser s salt in reactions with preformed enolates. 

The best results in the imidazole synthesis were obtained by microwave-assisted reaction of an eightfold excess of the polymer-supported isonitrile suspended in 1,2-dimethoxyethane (DME) with the appropriate amines. Cleavage with 50% trifluoroacetic acid in dichloromethane afforded the desired heterocyclic scaffolds in moderate yields. 

Furthermore, multicomponent reactions can also be performed under fluorous-phase conditions, as shown for the Ugi four-component reaction [96], To improve the efficiency of a recently reported Ugi/de-Boc/cyclization strategy, Zhang and Tempest introduced a fluorous Boc group for amine protection and carried out the Ugi multicomponent condensation under microwave irradiation (Scheme 7.84). The desired fluorous condensation products were easily separated by fluorous solid-phase extraction (F-SPE) and deprotected by treatment with trifluoroacetic acid/tet-rahydrofuran under microwave irradiation. The resulting quinoxalinones were purified by a second F-SPE to furnish the products in excellent purity. This methodology was also applied in a benzimidazole synthesis, employing benzoic acid as a substrate. 

Another example is provided by the application of the modified Polonovski reaction to A3-piperideines. Treatment of amine oxides (141) with trifluoroacetic anhydride results in the formation of iminium ion (142). These compounds can behave as useful synthetic intermediates, reacting with a number of nucleophiles such as cyanide ion (80JA1064). 

Reaction of the imidazole (7-4) with the benzofuran derivative (6-7) leads to the displacement of the benzylic halogen and the formation of the alkylation product (8-1). Treatment of that intermediate with trifluoroacetic acid breaks open the urethane to afford the corresponding free amine. This is allowed to react with ttiflic anhydride to afford the trifluoromethyl sulfonamide (8-2). The ester group on the imdidazole is then saponified, and the newly formed acid is reacted with carbonyl diimidazole. Reaction with ammonia converts the activated carboxyl group to the amide. There is thus obtained the angiotensin antagonist saprisartan (8-3) [6]. 

The presence of an internal salt, a zwitterion or betaine, in cephalosporins enhances their solubity in water, making such agents particularly suitable for parenteral administration. The preparation of one such dmg first involves the replacement of allyl oxygen in the tert-butylcarbonyloxy protected 7-ACA derivative (23-1) by nitrogen in azaindan (23-2) to afford the betaine (23-3). The protecting group is then removed so as to free the amine on the azetidone (23-4) by treatment with trifluoroacetic acid. Reaction with the thiazole free acid (23-5) in the presence of DCC then affords cefpirone (23-6) [26]. 

When double bonds are reduced by lithium in ammonia or amines, the mechanism is similar to that of the Birch reduction (5-10).320 The reduction with trifluoroacetic acid and Et3SiH has an ionic mechanism, with H+ coming in from the acid and H from the silane.248 In accord with this mechanism, the reaction can be applied only to those olefins which when... 

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