Enol trifluoroacetates, from

C-Acylation of the lithium enolates derived from 4-methoxybut-3-en-2-ones is achieved with acid chlorides without any significant O-acylation. A general route to pyranones results which avoids the acidic conditions frequently associated with other synthetic methods (80TL1197). Cyclization of these products, which exist in an enolic form, occurs at room temperature in benzene in the presence of a trace of trifluoroacetic acid (Scheme 135). 

Initial reports on the use of simple enolates as nucleophiles in TT-allylpalladium chemistry met with only limited success.77 106 The enolate of acetophenone reacted with allyl acetate in the presence of Pd(PPh3)4, but gave predominantly dialkylated product.106 The use of the enol silyl ether of acetophenone gave only monoalkylated product with allyl acetate and Pd° catalysis, but substituted allyl acetates did not function in this reaction.106 Enol stannanes, however, have been found to give monoalkylated products with a wide variety of allyl acetates (equation 19).106 In situ generation of enol stannanes from lithium enolates and trialkylstannyl trifluoroacetates followed by Pd°-catalyzed allylation has been demonstrated.107... 

Nitridomanganese Complexes. Stoichiometric amounts of chiral complexes of type 43 react with silyl enol ethers in the presence of trifluoroacetic or /Moluenesulfonic anhydride to give a-(A-trifluroacetyl)amino- and a-(N-p-tosylamino) ketones, respectively (see Eq. 160).350 - 353 With glycals, the 1-hydroxy-2-( A -trifluoroacetyljamino derivatives are formed (see Eq. 83).354 A mechanism involving approach of the enol ether from the least hindered side of the 43-TFA complex has been proposed.353... 

Isocoumarin formation from an indanone has been effected through involvement of an enol trifluoroacetate followed by ozonolysis. 

If aqueous conditions are to be avoided, the 2-nitrophenylsulfenyI group can be installed using triethylamine as base in an aprotic solvent. In the example shown in Scheme 8.148, the sulfenamide product 148 was converted to the N sulfenyl imine derivative 148.3 by oxidation with N-chlorosuccinimide. After nucleophilic addition of the enolate derived from 2-acetylpyridine, the tert-buty ester and 2-nitrophenylsulfenyl groups were removed with trifluoroacetic acid to give the y-keto-a-amino acid 148.4. 

Mechanistically, the authors proposed that this reaction most probably proceeds by cyclodehydration of 499 with TFAA to afford a mesoionic 1,3-oxazolium-5-olate 505. Trilluoroacetylation of 505 yields 506, which is ring opened with trifluoroacetate to produce 507 from which the enol trifluoroacetate 508 is produced by decarboxylation (Scheme 1.137). Cyclization of508 gives the IV-alkyloxazolium salt 509 that is dealkylated by trifluoroactate to furnish 500. This dealkylation is consistent with the observation that 499 (Rj = Bn) are better substrates than 499... 

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 spirobenzylisoquinoline 171b derived from berberine (15) (Section IV,A,1) was oxidized with m-chloroperbenzoic acid to the /V-oxide 389, which was treated with trifluoroacetic anhydride to afford dehydrohydrastine (370) in 56% overall yield (Scheme 71) through the Polonovski reaction (187). Holland et al. (188,189) reported the reverse reaction from dehydrophthalides to spirobenzylisoquinolines, namely, 370 was reduced with diisobutylalu-minum hydride to give a mixture of two diastereoisomeric spirobenzylisoquinolines 320 and 348 via the enol aldehyde. This reaction was applied to synthesis of various spirobenzylisoquinoline alkaloids such as (+)-sibiricine (352), ( + )-corydaine (347), (+ )-raddeanone (354), ( )-yenhusomidine (359), (+ )-ochrobirine (343), and ( )-yenhusomine (323). 

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... 

Nitration of the potassium enolates of cycloalkanones with pentyl nitrate81 or nitration of silyl enol ethers with nitronium tetrafluoroborate82 provides a method for the preparation of cyclic a-nitro ketones. Trifluoroacetyl nitrate generated from trifluoroacetic anhydride and ammonium nitrate is a mild and effective nitrating reagent for enol acetates (Eq. 2.41).83... 

Addition to linear 1,1-disubstituted allylic acetates is slower than addition to monosubstituted allylic esters. Additions to allylic trifluoroacetates or phosphates are faster than additions to allylic carbonates or acetates, and reactions of branched allylic esters are faster than additions to linear allylic esters. Aryl-, vinyl, alkynyl, and alkyl-substituted allylic esters readily undergo allylic substitution. Amines and stabilized enolates both react with these electrophiles in the presence of the catalyst generated from an iridium precursor and triphenylphosphite. 

Cycloheptanes.— The C-1—C-2 bond in -y-thujaplicin is essentially single, Co"-/3-thujaplicin-amine complexes have been described, and thermodynamic data on the U -/3-thujaplicin complex have been calculated. The biomimetic cyclization of the silyl enol ether (191) to karahanaenone (192), using methyl-aluminium bis(trifluoroacetate) is almost quantitative (192) is also synthesized by thermolysis followed by desilylation of the silyl enol ether (193) which is readily available from l-bromo-2-methyl-2-vinylcyclopropane and isobutyraldehyde. Dehalogenation of 3-bromo-l-iodo-3-methylbutan-2-one with Zn-Cu couple on alumina in the presence of isoprene yields (192) and minor amounts of the isomers (194) and (195) however, dehalogenation with Fc2(CO)9 favours (195). Acetolysis of karahanaenol tosylate yields anticipated p-menthane derivatives and no filifolene. ... 

Similar arguments apply to the six a-carboxy-substituted ketones that have been studied by Kresge and coworkers (entries acetoacetate to oxocyclobutane-2-carboxylate in Table 1). Kresge already noted that the rate constants kucK observed for the uncatalyzed ketonization of some of these compounds would give unrealistically high calculated values for k e near or above 1011 m-1 s-1 using Equation (18). Indeed, these calculated values of k are about two orders of magnitude above those expected from the Marcus relation except that for 4,4,4-trifluoroacetate. The rate constants k c observed for the formation of these a-carboxy-substituted ketones are, however, close to those expected for the protonation of the neutral enols by water, k = kf. 

The transformation could also be performed using a chiral enantiopure enol ether as dienophile. The best results were achieved with the isopropenyl ether 182b derived from cheap and commercially available (—)-(lR,2S,5R)-menthol. The cycloadduct was obtained with an endo/exo-selectivity of 4.1 1 and an induced dia-stereoselectivity of 88 12. Treatment of 178b with trifluoroacetic acid/water 19 1 provided (S)-warfarin 175 in an overall yield of 61% referred to 4-hydroxy coumarin 55 and an enantiomeric excess of 76% (HPLC), which could be increased to 95% ee by recrystallization using the purified endo-product 178b as substrate for the hydrolysis. In the same manner (S)-coumachlor 176 and (S)-acenocoumarol 177 were obtained with 56% overall yield and 93% ee and 59% overall yield and 95% ee, respectively. 

Dihydro-3-methylenethiopyran-4-one is available from the TMS enol ether of 2//-thiopyran4-one by conversion to the 2,3-dihydro-3-methoxymethylthiopyran4-one and successive treatment with trifluoroacetic acid and triethyl-amine (Scheme 219) <1996SL261>. 

Titanium(iv) benzylidenes (Schlock carbenes) 4 react with resin-bound esters 5 to generate the resin-bound enol ethers 6. Treatment of the enol ethers with a mixture of trifiuoroacetic acid (TEA) and trifluoroacetic anhydride (TFAA) leads to cleavage from the resin, removal of the Bu Me2Si group, and subsequent cyclization to give the benzothiophenes 7 (Scheme 2) <2004JOC6145>. 

The synthesis, starting from a bifunctional initiator followed by quenching the double-headed living ends, gives homotelechelic polymers (method B). Carboxylate-capped telechelic poly(isobutyl vinyl ether) has been obtained in this way [82], where the adduct of a bifunctional vinyl ether with trifluoroacetic acid is the initiator, and the quencher is the malonate anion. For method C, a bifunctional trimethylsilyl enol ether, CH2=C[OSi(CH3)3]C6H4OCH2CH20C6H4[(CH3)3SiO]C=CH2, is a useful terminator (chain coupler) for vinyl ethers [142,147] and a-methyl-styrene [159] (see also Section VI.B.4). 

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