Enol amidation with acetamide

Scheme 9.19 Amidation of the enol triflate with acetamide.

Molecules that contain two or three bulky aryl groups. An example is 2,2-dimesitylethenol (112). In this case, the keto content at equilibrium is only In cases such as this steric hindrance (p. 189) destabilizes the keto form. In 112 the two aryl groups are 120° apart, but in 113 they must move closer together (w 109.5°). Such compounds are often called Fuson-type enols ° There is one example of an amide with a bulky aryl group, A-methyl l w(2,4,6-triisopropylphenyl)acetamide, that has a measurable enol content, in sharp contrast to most amides. 

Most of the information on simple a-arylation reactions on the enolates of amides comes from a single study by Rossi and Alonso.128 They showed that with acetamide itself no arylation reactions took place, presumably on account of ionization of the N—H rather than the C—H bond and the observation that the... 

Amides. Despite many investigations in the 1970s and 1980s on Pd-catalyzed a-arylation of carboxylic acid derivatives, that of amides had not been studied until recently. In 1998, the reaction of potassium enolates of 7V,7V-dimethylacetamide (DMA) and other amides with aryl bromides in the presence of catalytic amounts of Pd(dba)2 and bidentate phosphines, such as BINAP and dppf, was shown to provide the desired a-arylated products in up to roughly 70% yields, as shown in Table Diarylation competed with monoaryladon to the extent of up to 18%. Under the conditions used, the intermolecular reactions of amides other than acetamides were rather disappointing, as indicated by the last two entries in Table 5. Clearly, additional development is desirable. Its intramolecular cyclic version, however, is considerably more favorable, as discussed in the following subsection. 

The first starting material for building benzodiazepines was prepared inadvertently in a synthesis aimed at the benzodiazoxepine (6-1). The oxime acetamide (6-2) from 2-aminobenzophenone was thus treated with hydrogen chloride in the expectation that the new heterocycle would form by the elimination of water between the oxime and the enol form of the amide. The product mrned out in fact to be the quinazoline A-oxide (6-3), the product from the addition of the nucleophilic oxime nitrogen to the amide carbonyl group. 

N, A-Dialkylacetamide enolate ions (143) were proved to react with aryl halides in liquid ammonia giving A,A-dimethyl-a-arylacetamides together with some A,A-dimethyl-a, a-diarylacetamides189. In order to synthesize some herbicides of the amide family, a series of A,A-dimethyl a-aryl and a,a-diaryl acetamides were prepared by the reaction of aryl halides (Phi, /7-iodoanisole, / -iodotoluene, 1-iodonaphthalene, 9-bromophenan-threne, 9-bromoanthracene and/ -iodobenzoic acid) with 143 (equation 95)190. The product distribution was shown to be dependent on the 143/aryl halide ratio. With a ratio of 5, approximately 50% of 144 and 20% of 145 were obtained. 

A similar conformational analysis has been done with formamide derivatives, with secondary amides, and for hydroxamide acids. It is known that thioformamide has a larger rotational barrier than formamide, which can be explained by a traditional picture of amide resonance that is more appropriate for the thioformamide than formamide itself. Torsional barriers in a-keto amides have been reported, and the C—N bond of acetamides, thioa-mides, enamides carbamates (R2N—C02R), and enolate anions derived... 

Bis(trimethylsilyl)acetamide (1). Mol. wt. 203.44, b.p. 71-73735 mm. Prepared in 80% yield by reaction of acetamide with trimethylchlorosilane with triethylamine as catalyst, the reagent effects trimethylsilyUuion of amides, ureas, amino acids, phenols, carboxylic acids, enols. ... 

Thus, for instance, the formation of trimethylsilyl esters, alcohols and phenols or other hydroxyl-containing compounds not only improves chromatographic separations, but also is a method for the analysis of hydroxyl groups. The reagents used in this instance are, however, not very selective as they react with several classes of compounds. For instance, N,0-bis(trimethyl)acetamide also reacts with organic acids, amines, aromatic amides, urea derivatives and some enols [19, 20]. Therefore, this technique should desirably be used in combination with other methods or for converting involatile... 

Peterson reactions of the lithium enolate 124 derived from N,N-dimethyl-(trimethylsilyl)acetamide with carbonyl compounds furnish the corresponding ,/ -unsaturated amides (Scheme 2.75) [210]. Although the amides are obtained in good yields in the reactions with ketones and with non-enolizable aldehydes, the reactions with enoli2able aldehydes give only negligible yields with predominant recovery of the starting amides. There appears to be little stereoselectivity in the... 

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