Amides from ketenes

Without additional reagents Synthesis of carboxylic acid amides from ketene aminals via amidinium salts... 

While wanning the catalysis mixture to 55 C (Step D, Scheme 1) leads to no other observable reaction intermediates, the generation of intermediate 8 would allow the series of steps shown in Scheme 1. Insertion of the coordinated CO into the palladium-carbon bond would lead to the overall coupling of acid chloride, imine and carbon monoxide in conq>lex 10. The subsequent loss of HCl from 10, either via direct deprotonation or P-H elimination, would form the a-amide substituted ketene 11. The latter is known to be in rapid equilibrium with its cyclic mesoionic l,3-oxazolium-5-oxide tautomeric 12 (14). These steps would lead to the liberation of the Pd(0) catalyst, which can return to the catalytic cycle. 

Isopropenyl acetate, obtained from ketene and acetone, reacts as an activated ester of acetic acid and, like its generator ketene, acetylates amides highly exothermally at room temperature.784 Even 1-acetylimidazole, which is difficult to prepare in other ways, is thus obtained from imidazole in 94% yield.785... 

Fatty acids are raw materials for fatty amines, ethoxylated fatty amines, quaternary ammonium compounds (Quats), fatty acid-polyamine condensates, fabric softeners based on esterquats, fatty add amides, alkyl keten dimers for paper sizing and amphoteric surfactants. Binding of oleic add anhydride to cellulose fibre by chemical grafting is a recently introduced sustainable process to protect construction timber for outdoor use, such as pinewood shutters, from moisture and outside attack. Impregnation of the wood involves two stages firstly in an autoclave, where vacuum and pressure ensure its penetration, and then in a tank where the wood is soaked in a bath of anhydride, to encourage grafting of the anhydride on the wood. ... 

Methylthio-l,2-dithiolium perchlorates may be obtained directly from keten mercaptals, for example (31), by the action of phosphorus pentasulphide and subsequent treatment of the insoluble residue with perchloric acid. Similar treatment of /3-keto-amides (32) yields 3-arylimino-l,2-dithiole perchlorates (27 R = Ar, X = CIO4). The method succeeds with amides (32 R = alkyl) and thus serves as a route to the previously inaccessible 5-alkyl-l,2-dithiol-3-imines. Demethylation of 3-methylthio-5-phenyl-l,2-dithiolium cation, to give 3-phenyl-l,2-dithiole-3-thione, occurs when the iodide is heated in xylene. 

In contrast, ketenes insert into chloramines to give amides From sulfur dichloride and disulfur monochloride, respectively, the acid chloride insertion products are formed Arylsulfenyl chloridesand acetylsulfenyl chloride react similarly with ketene. 

Another valuable derivatization was realized via the treatment with A,C)-dimethylhydroxylamine under pyridone catalyzed acyl transfer conditions, followed by reduction with Zn(OTf>2/NaBH4, giving Weinreb amide 105 in 99% ee and 46% yield over three steps from ketene 89 (Scheme 3.22). 

The mechanism of the reaction probably involves the production of bivalent carbon during the initial loss of nitrogen the group R shifte from an adjacent position to this carbon leading to the production of a keten the latter then reacts with the solvent to give an acid, an amide or an ester. 

The intermediacy of ketenes in some enamine acylation reactions using acid chlorides was described above (386,387). Direct addition of ketene to enamines was studied simultaneously by several groups (414-420). The initially formed aminocyclobutanone products could be isolated in some instances, depending on the substitution of the initial enamine. Opening to give either the acylated enamine or the alternative vinylogous amide was found to occur spontaneously or on heating, particularly in adducts derived from enamines with an olefinic proton. 

The reactions of vinylogous amides and vinylogous urethanes with excess ketene were found to give a-pyrones (421), which could also be obtained from further reactions of acylated enamines with ketene (383,421). 

The ketocarbene 4 that is generated by loss of Na from the a-diazo ketone, and that has an electron-sextet, rearranges to the more stable ketene 2 by a nucleophilic 1,2-shift of substituent R. The ketene thus formed corresponds to the isocyanate product of the related Curtius reaction. The ketene can further react with nucleophilic agents, that add to the C=0-double bond. For example by reaction with water a carboxylic acid 3 is formed, while from reaction with an alcohol R -OH an ester 5 is obtained directly. The reaction with ammonia or an amine R -NHa leads to formation of a carboxylic amide 6 or 7 ... 

Photodriven reactions of Fischer carbenes with alcohols produces esters, the expected product from nucleophilic addition to ketenes. Hydroxycarbene complexes, generated in situ by protonation of the corresponding ate complex, produced a-hydroxyesters in modest yield (Table 15) [103]. Ketals,presumably formed by thermal decomposition of the carbenes, were major by-products. The discovery that amides were readily converted to aminocarbene complexes [104] resulted in an efficient approach to a-amino acids by photodriven reaction of these aminocarbenes with alcohols (Table 16) [105,106]. a-Alkylation of the (methyl)(dibenzylamino)carbene complex followed by photolysis produced a range of racemic alanine derivatives (Eq. 26). With chiral oxazolidine carbene complexes optically active amino acid derivatives were available (Eq. 27). Since both enantiomers of the optically active chromium aminocarbene are equally available, both the natural S and unnatural R amino acid derivatives are equally... 

Whilst the addition of a chiral NHC to a ketene generates a chiral azolium enolate directly, a number of alternative strategies have been developed that allow asymmetric reactions to proceed via an enol or enolate intermediate. For example, Rovis and co-workers have shown that chiral azolium enolate species 225 can be generated from a,a-dihaloaldehydes 222, with enantioselective protonation and subsequent esterification generating a-chloroesters 224 in excellent ee (84-93% ee). Notably, in this process a bulky acidic phenol 223 is used as a buffer alongside an excess of an altemativephenoliccomponentto minimise productepimerisation (Scheme 12.48). An extension of this approach allows the synthesis of enantiomericaUy emiched a-chloro-amides (80% ee) [87]. 

The stereochemistry of the silyl ketene acetal can be controlled by the conditions of preparation. The base that is usually used for enolate formation is lithium diisopropyl-amide (LDA). If the enolate is prepared in pure THF, the F-enolate is generated and this stereochemistry is maintained in the silyl derivative. The preferential formation of the F-enolate can be explained in terms of a cyclic TS in which the proton is abstracted from the stereoelectronically preferred orientation perpendicular to the carbonyl plane. The carboxy substituent is oriented away from the alkyl groups on the amide base. 

Amides prepared from carboxylic acids and primary amines using azolides obtained from acid chloride/imidazolea) or ketene/imidazole systems.b)... 

In the presence of cyclohexyl amine the photolysis of the dienone (58) gives the cyclohexyl amide expected from dienone ring fission and reaction of cyclohexyl amine with the ketene. However, in the presence of weaker nucleophiles the ring opened product is not trapped and instead there is a relatively slow formation of phenols<36,44) ... 

At low temperatures cyclopropenones and enamines or ketene acetals were shown to yield 2-azonia-bicyclo(3,l, 0)hex-3-enolates-3 (371, X=0), which can be isomerized thermally to penta-2,4-diene amides(372, X=0). At elevated temperatures the amides were found to be the principal products arising from C-N-insertion 237) (insertion of the cyclopropenone three-carbon unit into the C-N bond of the enamine). These were accompanied in some cases by 3-aminoenones 373 arising from C-C-insertion 237) (insertion of the cyclopropenone into the C-C double bond of the enamine) and a-amino cyclopentenones 375 formed by Stevens rearrangement of the ylide 369 and cyclopentenones 374 ( condensation 237)). 

---